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1608.03464
Alan Paris
Alan Paris, George Atia, Azadeh Vosoughi, Stephen Berman
A New Statistical Model of Electroencephalogram Noise Spectra for Real-time Brain-Computer Interfaces
Revised submission to IEEE EMBS Trans. Biomed. Eng. 12 pages, 9 figures
null
10.1109/TBME.2016.2606595
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
$Objective$: A characteristic of neurological signal processing is high levels of noise from sub-cellular ion channels up to whole-brain processes. In this paper, we propose a new model of electroencephalogram (EEG) background periodograms, based on a family of functions which we call generalized van der Ziel--McWhorter (GVZM) power spectral densities (PSDs). To the best of our knowledge, the GVZM PSD function is the only EEG noise model which has relatively few parameters, matches recorded EEG PSD's with high accuracy from 0 Hz to over 30 Hz, and has approximately $1/f^\theta$ behavior in the mid-frequencies without infinities. $Methods$: We validate this model using three approaches. First, we show how GVZM PSDs can arise in population of ion channels in maximum entropy equilibrium. Second, we present a class of mixed autoregressive models, which simulate brain background noise and whose periodograms are asymptotic to the GVZM PSD. Third, we present two real-time estimation algorithms for steady-state visual evoked potential (SSVEP) frequencies, and analyze their performance statistically. $Results$: In pairwise comparisons, the GVZM-based algorithms showed statistically significant accuracy improvement over two well-known and widely-used SSVEP estimators. $Conclusion$: The GVZM noise model can be a useful and reliable technique for EEG signal processing. $Significance$: Understanding EEG noise is essential for EEG-based neurology and applications such as real-time brain-computer interfaces (BCIs), which must make accurate control decisions from very short data epochs. The GVZM approach represents a successful new paradigm for understanding and managing this neurological noise.
[ { "created": "Sun, 24 Jul 2016 06:36:59 GMT", "version": "v1" } ]
2016-11-17
[ [ "Paris", "Alan", "" ], [ "Atia", "George", "" ], [ "Vosoughi", "Azadeh", "" ], [ "Berman", "Stephen", "" ] ]
$Objective$: A characteristic of neurological signal processing is high levels of noise from sub-cellular ion channels up to whole-brain processes. In this paper, we propose a new model of electroencephalogram (EEG) background periodograms, based on a family of functions which we call generalized van der Ziel--McWhorter (GVZM) power spectral densities (PSDs). To the best of our knowledge, the GVZM PSD function is the only EEG noise model which has relatively few parameters, matches recorded EEG PSD's with high accuracy from 0 Hz to over 30 Hz, and has approximately $1/f^\theta$ behavior in the mid-frequencies without infinities. $Methods$: We validate this model using three approaches. First, we show how GVZM PSDs can arise in population of ion channels in maximum entropy equilibrium. Second, we present a class of mixed autoregressive models, which simulate brain background noise and whose periodograms are asymptotic to the GVZM PSD. Third, we present two real-time estimation algorithms for steady-state visual evoked potential (SSVEP) frequencies, and analyze their performance statistically. $Results$: In pairwise comparisons, the GVZM-based algorithms showed statistically significant accuracy improvement over two well-known and widely-used SSVEP estimators. $Conclusion$: The GVZM noise model can be a useful and reliable technique for EEG signal processing. $Significance$: Understanding EEG noise is essential for EEG-based neurology and applications such as real-time brain-computer interfaces (BCIs), which must make accurate control decisions from very short data epochs. The GVZM approach represents a successful new paradigm for understanding and managing this neurological noise.
1510.03224
Matteo Figliuzzi
Matteo Figliuzzi, Herv\'e Jacquier, Alexander Schug, Olivier Tenaillon, Martin Weigt
Coevolutionary landscape inference and the context-dependence of mutations in beta-lactamase TEM-1
14 pages, 5 figures. Supplementary files on the publisher's website: http://mbe.oxfordjournals.org/content/early/2015/10/06/molbev.msv211.short?rss=1
Mol Biol Evol (2015) doi: 10.1093/molbev/msv211
10.1093/molbev/msv211
null
q-bio.QM cond-mat.stat-mech q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The quantitative characterization of mutational landscapes is a task of outstanding importance in evolutionary and medical biology: It is, e.g., of central importance for our understanding of the phenotypic effect of mutations related to disease and antibiotic drug resistance. Here we develop a novel inference scheme for mutational landscapes, which is based on the statistical analysis of large alignments of homologs of the protein of interest. Our method is able to capture epistatic couplings between residues, and therefore to assess the dependence of mutational effects on the sequence context where they appear. Compared to recent large-scale mutagenesis data of the beta-lactamase TEM-1, a protein providing resistance against beta-lactam antibiotics, our method leads to an increase of about 40% in explicative power as compared to approaches neglecting epistasis. We find that the informative sequence context extends to residues at native distances of about 20{\AA} from the mutated site, reaching thus far beyond residues in direct physical contact.
[ { "created": "Mon, 12 Oct 2015 11:05:22 GMT", "version": "v1" } ]
2015-10-13
[ [ "Figliuzzi", "Matteo", "" ], [ "Jacquier", "Hervé", "" ], [ "Schug", "Alexander", "" ], [ "Tenaillon", "Olivier", "" ], [ "Weigt", "Martin", "" ] ]
The quantitative characterization of mutational landscapes is a task of outstanding importance in evolutionary and medical biology: It is, e.g., of central importance for our understanding of the phenotypic effect of mutations related to disease and antibiotic drug resistance. Here we develop a novel inference scheme for mutational landscapes, which is based on the statistical analysis of large alignments of homologs of the protein of interest. Our method is able to capture epistatic couplings between residues, and therefore to assess the dependence of mutational effects on the sequence context where they appear. Compared to recent large-scale mutagenesis data of the beta-lactamase TEM-1, a protein providing resistance against beta-lactam antibiotics, our method leads to an increase of about 40% in explicative power as compared to approaches neglecting epistasis. We find that the informative sequence context extends to residues at native distances of about 20{\AA} from the mutated site, reaching thus far beyond residues in direct physical contact.
0902.2404
Eugene Shakhnovich
Muyoung Heo, Louis Kang and Eugene Shakhnovich
Adaptation through stochastic switching into transient mutators in finite asexual populations
null
null
null
null
q-bio.BM q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The importance of mutator clones in the adaptive evolution of asexual populations is not fully understood. Here we address this problem by using an ab initio microscopic model of living cells, whose fitness is derived directly from their genomes using a biophysically realistic model of protein folding and interactions in the cytoplasm. The model organisms contain replication controlling genes (DCGs) and genes modeling the mismatch repair (MMR) complexes. We find that adaptation occurs through the transient fixation of a mutator phenotype, regardless of particular perturbations in the fitness landscape. The microscopic pathway of adaptation follows a well-defined set of events: stochastic switching to the mutator phenotype first, then mutation in the MMR complex that hitchhikes with a beneficial mutation in the DCGs, and finally a compensating mutation in the MMR complex returning the population to a non-mutator phenotype. Similarity of these results to reported adaptation events points out to robust universal physical principles of evolutionary adaptation.
[ { "created": "Fri, 13 Feb 2009 22:10:40 GMT", "version": "v1" } ]
2009-02-17
[ [ "Heo", "Muyoung", "" ], [ "Kang", "Louis", "" ], [ "Shakhnovich", "Eugene", "" ] ]
The importance of mutator clones in the adaptive evolution of asexual populations is not fully understood. Here we address this problem by using an ab initio microscopic model of living cells, whose fitness is derived directly from their genomes using a biophysically realistic model of protein folding and interactions in the cytoplasm. The model organisms contain replication controlling genes (DCGs) and genes modeling the mismatch repair (MMR) complexes. We find that adaptation occurs through the transient fixation of a mutator phenotype, regardless of particular perturbations in the fitness landscape. The microscopic pathway of adaptation follows a well-defined set of events: stochastic switching to the mutator phenotype first, then mutation in the MMR complex that hitchhikes with a beneficial mutation in the DCGs, and finally a compensating mutation in the MMR complex returning the population to a non-mutator phenotype. Similarity of these results to reported adaptation events points out to robust universal physical principles of evolutionary adaptation.
2006.12536
Yannick Tchaptchie Kouakep
S. Y. Tchoumi, Y. T. Kouakep, D. J. Fotsa Mbogne, J. C. Kamgang, J. M. Tchuenche
Optimal Control of a Malaria Model with Long-Lasting Insecticide-Treated Nets
Submitted to a scientific journal
null
null
null
q-bio.PE math.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A deterministic multi-stage malaria model with a non-therapeutic control measure, the use of mosquito bednet is formulated and analyzed. The model basic reproduction number is derived, and analytical results show that the models equilibria are locally and globally asymptotically stable when certain threshold conditions are satisfied. Pontryagin's Maximum Principle with respect to a time dependent constant is used to derive the necessary conditions for the optimal usage of the Long-Lasting Insecticide-treated bednets(LLINs) to mitigate the malaria transmission dynamics. This is accomplished by introducing biologically admissible control and e-approximate sub-optimal control. The results from this study could help public health planners and policy decision-makers to design reachable and more practical malaria prevention programs "close" to the optimal strategy.
[ { "created": "Mon, 22 Jun 2020 18:06:57 GMT", "version": "v1" }, { "created": "Sat, 18 Jul 2020 11:11:11 GMT", "version": "v2" } ]
2020-07-21
[ [ "Tchoumi", "S. Y.", "" ], [ "Kouakep", "Y. T.", "" ], [ "Mbogne", "D. J. Fotsa", "" ], [ "Kamgang", "J. C.", "" ], [ "Tchuenche", "J. M.", "" ] ]
A deterministic multi-stage malaria model with a non-therapeutic control measure, the use of mosquito bednet is formulated and analyzed. The model basic reproduction number is derived, and analytical results show that the models equilibria are locally and globally asymptotically stable when certain threshold conditions are satisfied. Pontryagin's Maximum Principle with respect to a time dependent constant is used to derive the necessary conditions for the optimal usage of the Long-Lasting Insecticide-treated bednets(LLINs) to mitigate the malaria transmission dynamics. This is accomplished by introducing biologically admissible control and e-approximate sub-optimal control. The results from this study could help public health planners and policy decision-makers to design reachable and more practical malaria prevention programs "close" to the optimal strategy.
0906.5028
Mari Watanabe
Tomofumi Kimotsuki (Saint Louis University), Noriko Niwa (Washington Univ. St. Louis), Martin N. Hicks (Glasgow University), Michael Dunne (Glasgow University), Stuart M. Cobbe (Glasgow University), Mari A. Watanabe (Saint Louis University)
Isoprenaline increases Excursive Restitution Slope in the Conscious Rabbit with Ischaemic Heart Failure
27 pages
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Background: An increased QT/RR slope is hypothesized to be predictive of sudden cardiac death after myocardial infarction. Previous studies have shown that beta-adrenergic stimulation increases QT/RR slope, but the effects of beta-adrenergic stimulation on QT/RR slope in heart failure are unknown. Methods: New Zealand White rabbits underwent coronary ligation (n=15) or sham surgery (n=11), and implantation of a pediatric pacemaker lead in the right ventricle for chronic ECG recording. Eight weeks after surgery, unsedated rabbits were given intravenous administrations of 0.25 to 2.0 ml of 1 micromol/l isoprenaline, while peak QRS to QRS (RR) and Q to T peak (QT) intervals were measured. Results: Ligated rabbits (n=6) had lower LVEF than sham rabbits (n=7, p<.0001), but similar baseline RR (269 +/- 15 vs 292 +/- 23 ms, p=.07), QT (104 +/- 17 vs 91 +/- 9 ms, p=.1) and minimum RR (204 +/- 11 vs 208 +/- 6 ms, p=.4) intervals induced by isoprenaline (0.79 +/- 0.18 vs 0.73 +/- 0.14 ml, p=.6). Hysteresis in QT vs TQ interval plots displayed biphasic restitution and regions of negative slope. The slope of the positive slope region was >1 in ligated rabbits (1.27 +/- 0.66) and <1 in sham rabbits (0.35 +/- 0.14, p=.004). Absolute value of the negative slope was greater in ligated rabbits (-0.81 +/- 0.52 vs -0.35 +/- 0.14, p=.04). Conclusion: Ischaemic heart failure produces steeper restitution slopes during beta-adrenergically induced QT/TQ hysteresis. This could underlie the propensity of failing hearts to arrhythmias.
[ { "created": "Sat, 27 Jun 2009 02:31:20 GMT", "version": "v1" } ]
2009-06-30
[ [ "Kimotsuki", "Tomofumi", "", "Saint Louis University" ], [ "Niwa", "Noriko", "", "Washington\n Univ. St. Louis" ], [ "Hicks", "Martin N.", "", "Glasgow University" ], [ "Dunne", "Michael", "", "Glasgow University" ], [ "Cobbe", "Stuart M.", "", "Glasgow University" ], [ "Watanabe", "Mari A.", "", "Saint Louis University" ] ]
Background: An increased QT/RR slope is hypothesized to be predictive of sudden cardiac death after myocardial infarction. Previous studies have shown that beta-adrenergic stimulation increases QT/RR slope, but the effects of beta-adrenergic stimulation on QT/RR slope in heart failure are unknown. Methods: New Zealand White rabbits underwent coronary ligation (n=15) or sham surgery (n=11), and implantation of a pediatric pacemaker lead in the right ventricle for chronic ECG recording. Eight weeks after surgery, unsedated rabbits were given intravenous administrations of 0.25 to 2.0 ml of 1 micromol/l isoprenaline, while peak QRS to QRS (RR) and Q to T peak (QT) intervals were measured. Results: Ligated rabbits (n=6) had lower LVEF than sham rabbits (n=7, p<.0001), but similar baseline RR (269 +/- 15 vs 292 +/- 23 ms, p=.07), QT (104 +/- 17 vs 91 +/- 9 ms, p=.1) and minimum RR (204 +/- 11 vs 208 +/- 6 ms, p=.4) intervals induced by isoprenaline (0.79 +/- 0.18 vs 0.73 +/- 0.14 ml, p=.6). Hysteresis in QT vs TQ interval plots displayed biphasic restitution and regions of negative slope. The slope of the positive slope region was >1 in ligated rabbits (1.27 +/- 0.66) and <1 in sham rabbits (0.35 +/- 0.14, p=.004). Absolute value of the negative slope was greater in ligated rabbits (-0.81 +/- 0.52 vs -0.35 +/- 0.14, p=.04). Conclusion: Ischaemic heart failure produces steeper restitution slopes during beta-adrenergically induced QT/TQ hysteresis. This could underlie the propensity of failing hearts to arrhythmias.
1301.7254
Michael B\"orsch
Nawid Zarrabi, Caterina Clausen, Monika G. Dueser, Michael Boersch
Manipulating freely diffusing single 20-nm particles in an Anti-Brownian Electrokinetic Trap (ABELtrap)
11 pages, 6 figures
null
10.1117/12.2002952
null
q-bio.QM physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Conformational changes of individual fluorescently labeled proteins can be followed in solution using a confocal microscope. Two fluorophores attached to selected domains of the protein report fluctuating conformations. Based on F\"orster resonance energy transfer (FRET) between these fluorophores on a single protein, sequential distance changes between the dyes provide the real time trajectories of protein conformations. However, observation times are limited for freely diffusing biomolecules by Brownian motion through the confocal detection volume. A. E. Cohen and W. E. Moerner have invented and built microfluidic devices with 4 electrodes for an Anti-Brownian Electrokinetic Trap (ABELtrap). Here we present an ABELtrap based on a laser focus pattern generated by a pair of acousto-optical beam deflectors and controlled by a programmable FPGA chip. Fluorescent 20-nm beads in solution were used to mimic freely diffusing large proteins like solubilized FoF1-ATP synthase. The ABELtrap could hold these nanobeads for about 10 seconds at the given position. Thereby, observation times of a single particle were increased by a factor of 1000.
[ { "created": "Wed, 30 Jan 2013 15:22:13 GMT", "version": "v1" } ]
2015-06-12
[ [ "Zarrabi", "Nawid", "" ], [ "Clausen", "Caterina", "" ], [ "Dueser", "Monika G.", "" ], [ "Boersch", "Michael", "" ] ]
Conformational changes of individual fluorescently labeled proteins can be followed in solution using a confocal microscope. Two fluorophores attached to selected domains of the protein report fluctuating conformations. Based on F\"orster resonance energy transfer (FRET) between these fluorophores on a single protein, sequential distance changes between the dyes provide the real time trajectories of protein conformations. However, observation times are limited for freely diffusing biomolecules by Brownian motion through the confocal detection volume. A. E. Cohen and W. E. Moerner have invented and built microfluidic devices with 4 electrodes for an Anti-Brownian Electrokinetic Trap (ABELtrap). Here we present an ABELtrap based on a laser focus pattern generated by a pair of acousto-optical beam deflectors and controlled by a programmable FPGA chip. Fluorescent 20-nm beads in solution were used to mimic freely diffusing large proteins like solubilized FoF1-ATP synthase. The ABELtrap could hold these nanobeads for about 10 seconds at the given position. Thereby, observation times of a single particle were increased by a factor of 1000.
0911.0215
Manuel Rivas
Manuel A. Rivas, Mark J. Daly, Itsik Pe'er
Age, Sex, and Genetic Architecture of Human Gene Expression in EBV Transformed Cell Lines
27 pages, 3 figures
null
null
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Individual expression profiles from EBV transformed cell lines are an emerging resource for genomic investigation. In this study we characterize the effects of age, sex, and genetic variation on gene expression by surveying public datasets of such profiles. We establish that the expression space of cell lines maintains genetic as well as non-germline information, in an individual-specific and cross-tissue manner. Age of donor is associated with the expression of 949 genes in the derived cell line. Age-associated genes include over-representation of immune-related genes, specifically MHC Class I genes, a phenomenon that replicates across tissues and organisms. Sex associated genes in these cell lines include likely candidates, such as genes that escape X-inactivation,testis specific expressed genes, androgen and estrogen specific genes, but also gene families previously unknown to be sex associated such as common microRNA targets (MIR-490, V_ARP1_01, MIR-489). Finally, we report 494 transcripts whose expression levels are associated with a genetic variant in cis, overlapping and validating previous reports. Incorporating age in analysis of association facilitates additional discovery of trans-acting regulatory genetic variants. Our findings promote expression profiling of transformed cell lines as a vehicle for understanding cellular systems beyond the specific lines.
[ { "created": "Sun, 1 Nov 2009 23:17:06 GMT", "version": "v1" } ]
2009-11-03
[ [ "Rivas", "Manuel A.", "" ], [ "Daly", "Mark J.", "" ], [ "Pe'er", "Itsik", "" ] ]
Individual expression profiles from EBV transformed cell lines are an emerging resource for genomic investigation. In this study we characterize the effects of age, sex, and genetic variation on gene expression by surveying public datasets of such profiles. We establish that the expression space of cell lines maintains genetic as well as non-germline information, in an individual-specific and cross-tissue manner. Age of donor is associated with the expression of 949 genes in the derived cell line. Age-associated genes include over-representation of immune-related genes, specifically MHC Class I genes, a phenomenon that replicates across tissues and organisms. Sex associated genes in these cell lines include likely candidates, such as genes that escape X-inactivation,testis specific expressed genes, androgen and estrogen specific genes, but also gene families previously unknown to be sex associated such as common microRNA targets (MIR-490, V_ARP1_01, MIR-489). Finally, we report 494 transcripts whose expression levels are associated with a genetic variant in cis, overlapping and validating previous reports. Incorporating age in analysis of association facilitates additional discovery of trans-acting regulatory genetic variants. Our findings promote expression profiling of transformed cell lines as a vehicle for understanding cellular systems beyond the specific lines.
1305.7411
Jiapu Zhang
Jiapu Zhang
The Methicillin-Resistant Staphylococcus Aureus Infection Controls
null
Journal Review of Bioinformatics and Biometrics (RBB) 2(4), pp.83-87 (2013)
null
null
q-bio.OT
http://creativecommons.org/licenses/by-nc-sa/3.0/
Multi-resistant organisms (MROs), the bacteria that are resistant to a number of different antibiotics, have been very popular around the world in recent years. They are very difficult to treat but highly infectious in humans. MRSA (Methicillin-Resistant Staphylococcus Aureus) is one of the MROs. It is believed that in 2007 more people died of MRSA than of AIDS worldwide. In Australia "there are about 2000 people per year who have a bloodstream infection with the MRSA germ and the vast majority of those get them from health care procedure" (Nader, 2005). It is acknowledged as a significant challenge to Australian hospitals for MRSA infection control. Nursing professionals are in urgent need of the study of MRSA nosocomial infection controls. This review provides insight into the hand washing and isolation infection-control strategies for MRSA. The important technologies on those two aspects worldwide are well surveyed, compared, contrasted, and discussed. The review is to do a complete survey on the hand washing and isolation technologies of infection controls for MRSA and try to provide some possible recommendations for Australian hospitals.
[ { "created": "Thu, 30 May 2013 12:33:57 GMT", "version": "v1" } ]
2013-12-09
[ [ "Zhang", "Jiapu", "" ] ]
Multi-resistant organisms (MROs), the bacteria that are resistant to a number of different antibiotics, have been very popular around the world in recent years. They are very difficult to treat but highly infectious in humans. MRSA (Methicillin-Resistant Staphylococcus Aureus) is one of the MROs. It is believed that in 2007 more people died of MRSA than of AIDS worldwide. In Australia "there are about 2000 people per year who have a bloodstream infection with the MRSA germ and the vast majority of those get them from health care procedure" (Nader, 2005). It is acknowledged as a significant challenge to Australian hospitals for MRSA infection control. Nursing professionals are in urgent need of the study of MRSA nosocomial infection controls. This review provides insight into the hand washing and isolation infection-control strategies for MRSA. The important technologies on those two aspects worldwide are well surveyed, compared, contrasted, and discussed. The review is to do a complete survey on the hand washing and isolation technologies of infection controls for MRSA and try to provide some possible recommendations for Australian hospitals.
1509.02816
John Platig
John Platig, Peter Castaldi, Dawn DeMeo, and John Quackenbush
Bipartite Community Structure of eQTLs
null
null
10.1371/journal.pcbi.1005033
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Genome Wide Association Studies (GWAS) and eQTL analyses have produced a large and growing number of genetic associations linked to a wide range of human phenotypes. As of 2013, there were more than 11,000 SNPs associated with a trait as reported in the NHGRI GWAS Catalog. However, interpreting the functional roles played by these SNPs remains a challenge. Here we describe an approach that uses the inherent bipartite structure of eQTL networks to place SNPs into a functional context. Using genotyping and gene expression data from 163 lung tissue samples in a study of Chronic Obstructive Pulmonary Disease (COPD) we calculated eQTL associations between SNPs and genes and cast significant associations (FDR $< 0.1$) as links in a bipartite network. To our surprise, we discovered that the highly-connected "hub" SNPs within the network were devoid of disease-associations. However, within the network we identified 35 highly modular communities, which comprise groups of SNPs associated with groups of genes; 13 of these communities were significantly enriched for distinct biological functions (P $ < 5 \times 10^{-4}$) including COPD-related functions. Further, we found that GWAS-significant SNPs were enriched at the cores of these communities, including previously identified GWAS associations for COPD, asthma, and pulmonary function, among others. These results speak to our intuition: rather than single SNPs influencing single genes, we see groups of SNPs associated with the expression of families of functionally related genes and that disease SNPs are associated with the perturbation of those functions. These methods are not limited in their application to COPD and can be used in the analysis of a wide variety of disease processes and other phenotypic traits.
[ { "created": "Wed, 9 Sep 2015 15:52:09 GMT", "version": "v1" } ]
2016-09-28
[ [ "Platig", "John", "" ], [ "Castaldi", "Peter", "" ], [ "DeMeo", "Dawn", "" ], [ "Quackenbush", "John", "" ] ]
Genome Wide Association Studies (GWAS) and eQTL analyses have produced a large and growing number of genetic associations linked to a wide range of human phenotypes. As of 2013, there were more than 11,000 SNPs associated with a trait as reported in the NHGRI GWAS Catalog. However, interpreting the functional roles played by these SNPs remains a challenge. Here we describe an approach that uses the inherent bipartite structure of eQTL networks to place SNPs into a functional context. Using genotyping and gene expression data from 163 lung tissue samples in a study of Chronic Obstructive Pulmonary Disease (COPD) we calculated eQTL associations between SNPs and genes and cast significant associations (FDR $< 0.1$) as links in a bipartite network. To our surprise, we discovered that the highly-connected "hub" SNPs within the network were devoid of disease-associations. However, within the network we identified 35 highly modular communities, which comprise groups of SNPs associated with groups of genes; 13 of these communities were significantly enriched for distinct biological functions (P $ < 5 \times 10^{-4}$) including COPD-related functions. Further, we found that GWAS-significant SNPs were enriched at the cores of these communities, including previously identified GWAS associations for COPD, asthma, and pulmonary function, among others. These results speak to our intuition: rather than single SNPs influencing single genes, we see groups of SNPs associated with the expression of families of functionally related genes and that disease SNPs are associated with the perturbation of those functions. These methods are not limited in their application to COPD and can be used in the analysis of a wide variety of disease processes and other phenotypic traits.
1508.00613
Maria Kochugaeva
Martin Lange, Maria Kochugaeva and Anatoly B. Kolomeisky
Protein search for multiple targets on DNA
null
null
10.1063/1.4930113
null
q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Protein-DNA interactions are crucial for all biological processes. One of the most important fundamental aspects of these interactions is the process of protein searching and recognizing specific binding sites on DNA. A large number of experimental and theoretical investigations have been devoted to uncovering the molecular description of these phenomena, but many aspects of the mechanisms of protein search for the targets on DNA remain not well understood. One of the most intriguing problems is the role of multiple targets in protein search dynamics. Using a recently developed theoretical framework we analyze this question in detail. Our method is based on a discrete-state stochastic approach that takes into account most relevant physical-chemical processes and leads to fully analytical description of all dynamic properties. Specifically, systems with two and three targets have been explicitly investigated. It is found that multiple targets in most cases accelerate the search in comparison with a single target situation. However, the acceleration is not always proportional to the number of targets. Surprisingly, there are even situations when it takes longer to find one of the multiple targets in comparison with the single target. It depends on the spatial position of the targets, distances between them, average scanning lengths of protein molecules on DNA, and the total DNA lengths. Physical-chemical explanations of observed results are presented. Our predictions are compared with experimental observations as well as with results from a continuum theory for the protein search. Extensive Monte Carlo computer simulations fully support our theoretical calculations.
[ { "created": "Mon, 3 Aug 2015 22:21:11 GMT", "version": "v1" } ]
2015-09-30
[ [ "Lange", "Martin", "" ], [ "Kochugaeva", "Maria", "" ], [ "Kolomeisky", "Anatoly B.", "" ] ]
Protein-DNA interactions are crucial for all biological processes. One of the most important fundamental aspects of these interactions is the process of protein searching and recognizing specific binding sites on DNA. A large number of experimental and theoretical investigations have been devoted to uncovering the molecular description of these phenomena, but many aspects of the mechanisms of protein search for the targets on DNA remain not well understood. One of the most intriguing problems is the role of multiple targets in protein search dynamics. Using a recently developed theoretical framework we analyze this question in detail. Our method is based on a discrete-state stochastic approach that takes into account most relevant physical-chemical processes and leads to fully analytical description of all dynamic properties. Specifically, systems with two and three targets have been explicitly investigated. It is found that multiple targets in most cases accelerate the search in comparison with a single target situation. However, the acceleration is not always proportional to the number of targets. Surprisingly, there are even situations when it takes longer to find one of the multiple targets in comparison with the single target. It depends on the spatial position of the targets, distances between them, average scanning lengths of protein molecules on DNA, and the total DNA lengths. Physical-chemical explanations of observed results are presented. Our predictions are compared with experimental observations as well as with results from a continuum theory for the protein search. Extensive Monte Carlo computer simulations fully support our theoretical calculations.
q-bio/0603036
Otger Camp\`as
Otger Campas, Jaume Casademunt, Ignacio Pagonabarraga
Dynamic stability of spindles controlled by molecular motor kinetics
4 pages, 3 figures
null
null
null
q-bio.SC physics.bio-ph
null
We analyze the role of the force-dependent kinetics of motor proteins in the stability of antiparallel arrays of polar filaments, such as those in the mitotic spindle. We determine the possible stable structures and show that there exists an instability associated to the collective behavior of motors that leads to the collapse of the spindle. Our analysis provides a general framework to understand several experimental observations in eukaryotic cell division.
[ { "created": "Thu, 30 Mar 2006 19:11:43 GMT", "version": "v1" } ]
2007-05-23
[ [ "Campas", "Otger", "" ], [ "Casademunt", "Jaume", "" ], [ "Pagonabarraga", "Ignacio", "" ] ]
We analyze the role of the force-dependent kinetics of motor proteins in the stability of antiparallel arrays of polar filaments, such as those in the mitotic spindle. We determine the possible stable structures and show that there exists an instability associated to the collective behavior of motors that leads to the collapse of the spindle. Our analysis provides a general framework to understand several experimental observations in eukaryotic cell division.
1401.6207
Huisheng Liu
Huisheng Liu, Hua Bai, Enfu Hui, Lu Yang, Chantell Evans, Zhao Wang, Sung Kwon, and Edwin Chapman
Synaptotagmin 7 Functions as a Ca2+-sensor for Synaptic Vesicle Replenishment
41 pages, 17 Figures
null
10.7554/eLife.01524
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Synaptotagmin (syt) 7 is one of three syt isoforms found in all metazoans; it is ubiquitously expressed, yet its function in neurons remains obscure. Here, we resolved Ca2+-dependent and Ca2+-independent synaptic vesicle (SV) replenishment pathways, and found that syt 7 plays a selective and critical role in the Ca2+-dependent pathway. Mutations that disrupt Ca2+-binding to syt 7 abolish this function, suggesting that syt 7 functions as a Ca2+-sensor for replenishment. The Ca2+-binding protein calmodulin (CaM) has also been implicated in SV replenishment, and we found that loss of syt 7 was phenocopied by a CaM antagonist. Moreover, we discovered that syt 7 binds to CaM in a highly specific and Ca2+-dependent manner; this interaction requires intact Ca2+-binding sites within syt 7. Together, these data indicate that a complex of two conserved Ca2+-binding proteins, syt 7 and CaM, serve as a key regulator of SV replenishment in presynaptic nerve terminals.
[ { "created": "Thu, 23 Jan 2014 22:48:27 GMT", "version": "v1" } ]
2014-01-27
[ [ "Liu", "Huisheng", "" ], [ "Bai", "Hua", "" ], [ "Hui", "Enfu", "" ], [ "Yang", "Lu", "" ], [ "Evans", "Chantell", "" ], [ "Wang", "Zhao", "" ], [ "Kwon", "Sung", "" ], [ "Chapman", "Edwin", "" ] ]
Synaptotagmin (syt) 7 is one of three syt isoforms found in all metazoans; it is ubiquitously expressed, yet its function in neurons remains obscure. Here, we resolved Ca2+-dependent and Ca2+-independent synaptic vesicle (SV) replenishment pathways, and found that syt 7 plays a selective and critical role in the Ca2+-dependent pathway. Mutations that disrupt Ca2+-binding to syt 7 abolish this function, suggesting that syt 7 functions as a Ca2+-sensor for replenishment. The Ca2+-binding protein calmodulin (CaM) has also been implicated in SV replenishment, and we found that loss of syt 7 was phenocopied by a CaM antagonist. Moreover, we discovered that syt 7 binds to CaM in a highly specific and Ca2+-dependent manner; this interaction requires intact Ca2+-binding sites within syt 7. Together, these data indicate that a complex of two conserved Ca2+-binding proteins, syt 7 and CaM, serve as a key regulator of SV replenishment in presynaptic nerve terminals.
2104.02881
Seung Ki Baek
Sanghun Lee, Yohsuke Murase, and Seung Ki Baek
Local stability of cooperation in a continuous model of indirect reciprocity
13 pages, 3 figures
Sci. Rep. 11, 14225 (2021)
10.1038/s41598-021-93598-7
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Reputation is a powerful mechanism to enforce cooperation among unrelated individuals through indirect reciprocity, but it suffers from disagreement originating from private assessment, noise, and incomplete information. In this work, we investigate stability of cooperation in the donation game by regarding each player's reputation and behaviour as continuous variables. Through perturbative calculation, we derive a condition that a social norm should satisfy to give penalties to its close variants, provided that everyone initially cooperates with a good reputation, and this result is supported by numerical simulation. A crucial factor of the condition is whether a well-reputed player's donation to an ill-reputed co-player is appreciated by other members of the society, and the condition can be reduced to a threshold for the benefit-cost ratio of cooperation which depends on the reputational sensitivity to a donor's behaviour as well as on the behavioural sensitivity to a recipient's reputation. Our continuum formulation suggests how indirect reciprocity can work beyond the dichotomy between good and bad even in the presence of inhomogeneity, noise, and incomplete information.
[ { "created": "Wed, 7 Apr 2021 03:14:22 GMT", "version": "v1" }, { "created": "Fri, 9 Jul 2021 13:18:57 GMT", "version": "v2" } ]
2021-07-12
[ [ "Lee", "Sanghun", "" ], [ "Murase", "Yohsuke", "" ], [ "Baek", "Seung Ki", "" ] ]
Reputation is a powerful mechanism to enforce cooperation among unrelated individuals through indirect reciprocity, but it suffers from disagreement originating from private assessment, noise, and incomplete information. In this work, we investigate stability of cooperation in the donation game by regarding each player's reputation and behaviour as continuous variables. Through perturbative calculation, we derive a condition that a social norm should satisfy to give penalties to its close variants, provided that everyone initially cooperates with a good reputation, and this result is supported by numerical simulation. A crucial factor of the condition is whether a well-reputed player's donation to an ill-reputed co-player is appreciated by other members of the society, and the condition can be reduced to a threshold for the benefit-cost ratio of cooperation which depends on the reputational sensitivity to a donor's behaviour as well as on the behavioural sensitivity to a recipient's reputation. Our continuum formulation suggests how indirect reciprocity can work beyond the dichotomy between good and bad even in the presence of inhomogeneity, noise, and incomplete information.
2307.00253
Rahul Biswas
Rahul Biswas and SuryaNarayana Sripada
Application of Time-Aware PC algorithm to compute Causal Functional Connectivity in Alzheimer's Disease from fMRI data
null
null
null
null
q-bio.NC q-bio.QM stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Functional Connectivity between brain regions is known to be altered in Alzheimer's disease, and promises to be a biomarker for early diagnosis of the disease. While several approaches for functional connectivity obtain an un-directed network representing stochastic associations (correlations) between brain regions, association does not necessarily imply causation. In contrast, Causal Functional Connectivity is more informative, providing a directed network representing causal relationships between brain regions. In this paper, we obtained the causal functional connectome for the whole brain from recordings of resting-state functional magnetic resonance imaging (rs-fMRI) for subjects from three clinical groups: cognitively normal, mild cognitive impairment, and Alzheimer's disease. We applied the recently developed Time-aware PC (TPC) algorithm to infer the causal functional connectome for the whole brain. TPC supports model-free estimation of whole brain causal functional connectivity based on directed graphical modeling in a time series setting. We then perform an exploratory analysis to identify the causal brain connections between brain regions which have altered strengths between pairs of subject groups, and over the three subject groups, based on edge-wise p-values from statistical tests. We used the altered causal brain connections thus obtained to compile a comprehensive list of brain regions impacted by Alzheimer's disease according to the current data set. The brain regions thus identified are found to be in agreement with literature on brain regions impacted by Alzheimer's disease, published by researchers from clinical/medical institutions.
[ { "created": "Sat, 1 Jul 2023 07:20:04 GMT", "version": "v1" }, { "created": "Tue, 20 Feb 2024 00:18:19 GMT", "version": "v2" } ]
2024-02-21
[ [ "Biswas", "Rahul", "" ], [ "Sripada", "SuryaNarayana", "" ] ]
Functional Connectivity between brain regions is known to be altered in Alzheimer's disease, and promises to be a biomarker for early diagnosis of the disease. While several approaches for functional connectivity obtain an un-directed network representing stochastic associations (correlations) between brain regions, association does not necessarily imply causation. In contrast, Causal Functional Connectivity is more informative, providing a directed network representing causal relationships between brain regions. In this paper, we obtained the causal functional connectome for the whole brain from recordings of resting-state functional magnetic resonance imaging (rs-fMRI) for subjects from three clinical groups: cognitively normal, mild cognitive impairment, and Alzheimer's disease. We applied the recently developed Time-aware PC (TPC) algorithm to infer the causal functional connectome for the whole brain. TPC supports model-free estimation of whole brain causal functional connectivity based on directed graphical modeling in a time series setting. We then perform an exploratory analysis to identify the causal brain connections between brain regions which have altered strengths between pairs of subject groups, and over the three subject groups, based on edge-wise p-values from statistical tests. We used the altered causal brain connections thus obtained to compile a comprehensive list of brain regions impacted by Alzheimer's disease according to the current data set. The brain regions thus identified are found to be in agreement with literature on brain regions impacted by Alzheimer's disease, published by researchers from clinical/medical institutions.
q-bio/0603021
Ovidiu Radulescu
O.Radulescu, A.Siegel, E. Pecou, and S.Lagarrigue
A model for regulated fatty acid metabolism in liver; equilibria and their changes
null
null
null
null
q-bio.CB
null
We build a model for the hepatic fatty acid metabolism and its metabolic and genetic regulations. The model has two functioning modes: synthesis and oxidation of fatty acids. We provide a sufficient condition (the strong lipolytic condition) for the uniqueness of its equilibrium. Under this condition, modifications of the glucose input produce equilibrium shifts, which are gradual changes from one functioning mode to the other. We also discuss the concentration variations of various metabolites during equilibrium shifts. The model can explain a certain amount of experimental observations, assess the role of poly-unsaturated fatty acids in genetic regulation, and predict the behavior of mutants. The analysis of the model is based on block elimination of variables and uses a modular decomposition of the system dictated by mathematical global univalence conditions.
[ { "created": "Sat, 18 Mar 2006 22:30:57 GMT", "version": "v1" } ]
2007-05-23
[ [ "Radulescu", "O.", "" ], [ "Siegel", "A.", "" ], [ "Pecou", "E.", "" ], [ "Lagarrigue", "S.", "" ] ]
We build a model for the hepatic fatty acid metabolism and its metabolic and genetic regulations. The model has two functioning modes: synthesis and oxidation of fatty acids. We provide a sufficient condition (the strong lipolytic condition) for the uniqueness of its equilibrium. Under this condition, modifications of the glucose input produce equilibrium shifts, which are gradual changes from one functioning mode to the other. We also discuss the concentration variations of various metabolites during equilibrium shifts. The model can explain a certain amount of experimental observations, assess the role of poly-unsaturated fatty acids in genetic regulation, and predict the behavior of mutants. The analysis of the model is based on block elimination of variables and uses a modular decomposition of the system dictated by mathematical global univalence conditions.
2011.08024
Shailaja Akella
Shailaja Akella, Ali Mohebi, Kiersten Riels, Andreas Keil, Karim Oweiss, Jose C. Principe
Local power estimation of neuromodulations using point process modeling
6 pages
null
null
null
q-bio.NC eess.SP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Extracellular electrical potentials (EEP) recorded from the brain are an active manifestation of all cellular processes that propagate within a volume of brain tissue. A standard approach for their quantification are power spectral analyses methods that reflect the global distribution of signal power over frequency. However, these methods incorporate analysis windows to achieve locality and therefore, are limited by the inherent trade - off between time and frequency resolutions. In this paper, we present a novel approach to estimate local power more precisely at a resolution as high as the sampling frequency. Our methods are well grounded on established neurophysiology of the bio-signals where we model EEPs as comprising of two components: neuromodulations and background activity. A local measure of power, we call Marked Point Process (MPP) spectrogram, is then derived as a power - weighted intensity function of the point process for neuromodulations. We demonstrate our results on two datasets: 1) local field potentials recorded from the prefrontal cortex of 3 rats performing a working memory task and 2) EEPs recorded via electroencephalography from the visual cortex of human subjects performing a conditioned stimulus task. A detailed analysis of the power - specific marked features of neuromodulations confirm high correlation between power spectral density and power in neuromodulations establishing the aptness of MPP spectrogram as a finer measure of power where it is able to track local variations in power while preserving the global structure of signal power distribution.
[ { "created": "Mon, 16 Nov 2020 15:20:33 GMT", "version": "v1" } ]
2020-11-17
[ [ "Akella", "Shailaja", "" ], [ "Mohebi", "Ali", "" ], [ "Riels", "Kiersten", "" ], [ "Keil", "Andreas", "" ], [ "Oweiss", "Karim", "" ], [ "Principe", "Jose C.", "" ] ]
Extracellular electrical potentials (EEP) recorded from the brain are an active manifestation of all cellular processes that propagate within a volume of brain tissue. A standard approach for their quantification are power spectral analyses methods that reflect the global distribution of signal power over frequency. However, these methods incorporate analysis windows to achieve locality and therefore, are limited by the inherent trade - off between time and frequency resolutions. In this paper, we present a novel approach to estimate local power more precisely at a resolution as high as the sampling frequency. Our methods are well grounded on established neurophysiology of the bio-signals where we model EEPs as comprising of two components: neuromodulations and background activity. A local measure of power, we call Marked Point Process (MPP) spectrogram, is then derived as a power - weighted intensity function of the point process for neuromodulations. We demonstrate our results on two datasets: 1) local field potentials recorded from the prefrontal cortex of 3 rats performing a working memory task and 2) EEPs recorded via electroencephalography from the visual cortex of human subjects performing a conditioned stimulus task. A detailed analysis of the power - specific marked features of neuromodulations confirm high correlation between power spectral density and power in neuromodulations establishing the aptness of MPP spectrogram as a finer measure of power where it is able to track local variations in power while preserving the global structure of signal power distribution.
0903.4491
Aleksandra Walczak
Gasper Tkacik, Aleksandra M. Walczak, and William Bialek
Optimizing information flow in small genetic networks. I
null
Phys. Rev. E 80, 031920 (2009)
10.1103/PhysRevE.80.031920
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In order to survive, reproduce and (in multicellular organisms) differentiate, cells must control the concentrations of the myriad different proteins that are encoded in the genome. The precision of this control is limited by the inevitable randomness of individual molecular events. Here we explore how cells can maximize their control power in the presence of these physical limits; formally, we solve the theoretical problem of maximizing the information transferred from inputs to outputs when the number of available molecules is held fixed. We start with the simplest version of the problem, in which a single transcription factor protein controls the readout of one or more genes by binding to DNA. We further simplify by assuming that this regulatory network operates in steady state, that the noise is small relative to the available dynamic range, and that the target genes do not interact. Even in this simple limit, we find a surprisingly rich set of optimal solutions. Importantly, for each locally optimal regulatory network, all parameters are determined once the physical constraints on the number of available molecules are specified. Although we are solving an over--simplified version of the problem facing real cells, we see parallels between the structure of these optimal solutions and the behavior of actual genetic regulatory networks. Subsequent papers will discuss more complete versions of the problem.
[ { "created": "Thu, 26 Mar 2009 00:12:20 GMT", "version": "v1" }, { "created": "Sun, 1 Nov 2009 22:39:25 GMT", "version": "v2" } ]
2013-08-01
[ [ "Tkacik", "Gasper", "" ], [ "Walczak", "Aleksandra M.", "" ], [ "Bialek", "William", "" ] ]
In order to survive, reproduce and (in multicellular organisms) differentiate, cells must control the concentrations of the myriad different proteins that are encoded in the genome. The precision of this control is limited by the inevitable randomness of individual molecular events. Here we explore how cells can maximize their control power in the presence of these physical limits; formally, we solve the theoretical problem of maximizing the information transferred from inputs to outputs when the number of available molecules is held fixed. We start with the simplest version of the problem, in which a single transcription factor protein controls the readout of one or more genes by binding to DNA. We further simplify by assuming that this regulatory network operates in steady state, that the noise is small relative to the available dynamic range, and that the target genes do not interact. Even in this simple limit, we find a surprisingly rich set of optimal solutions. Importantly, for each locally optimal regulatory network, all parameters are determined once the physical constraints on the number of available molecules are specified. Although we are solving an over--simplified version of the problem facing real cells, we see parallels between the structure of these optimal solutions and the behavior of actual genetic regulatory networks. Subsequent papers will discuss more complete versions of the problem.
1509.08158
Sara Clifton
Sara M. Clifton, Rosemary I. Braun, Daniel M. Abrams
Handicap principle implies emergence of dimorphic mating displays
7 pages, 4 figures, supplementary information included
Proceedings of the Royal Society B 283, 1970: November 30 2016
10.1098/rspb.2016.1970
null
q-bio.PE math.DS nlin.AO physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Species spanning the animal kingdom have evolved extravagant and costly ornaments to attract mating partners. Zahavi's handicap principle offers an elegant explanation for this: ornaments signal individual quality, and must be costly to ensure honest signalling, making mate selection more efficient. Here we incorporate the assumptions of the handicap principle into a mathematical model and show that they are sufficient to explain the heretofore puzzling observation of bimodally distributed ornament sizes in a variety of species.
[ { "created": "Sun, 27 Sep 2015 22:35:32 GMT", "version": "v1" }, { "created": "Mon, 9 May 2016 18:20:21 GMT", "version": "v2" }, { "created": "Tue, 1 Nov 2016 00:44:29 GMT", "version": "v3" } ]
2016-12-02
[ [ "Clifton", "Sara M.", "" ], [ "Braun", "Rosemary I.", "" ], [ "Abrams", "Daniel M.", "" ] ]
Species spanning the animal kingdom have evolved extravagant and costly ornaments to attract mating partners. Zahavi's handicap principle offers an elegant explanation for this: ornaments signal individual quality, and must be costly to ensure honest signalling, making mate selection more efficient. Here we incorporate the assumptions of the handicap principle into a mathematical model and show that they are sufficient to explain the heretofore puzzling observation of bimodally distributed ornament sizes in a variety of species.
1809.02849
Eli Cornblath
Eli J. Cornblath, Arian Ashourvan, Jason Z. Kim, Richard F. Betzel, Rastko Ciric, Azeez Adebimpe, Graham L. Baum, Xiaosong He, Kosha Ruparel, Tyler M. Moore, Ruben C. Gur, Raquel E. Gur, Russell T. Shinohara, David R. Roalf, Theodore D. Satterthwaite, and Danielle S. Bassett
Temporal sequences of brain activity at rest are constrained by white matter structure and modulated by cognitive demands
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A diverse white matter network and finely tuned neuronal membrane properties allow the brain to transition seamlessly between cognitive states. However, it remains unclear how static structural connections guide the temporal progression of large-scale brain activity patterns in different cognitive states. Here, we analyze the brain's trajectories through a high-dimensional activity space at the level of single time point activity patterns from functional magnetic resonance imaging data acquired during passive visual fixation (rest) and an n-back working memory task. We find that specific state space trajectories, which represent temporal sequences of brain activity, are modulated by cognitive load and related to task performance. Using diffusion-weighted imaging acquired from the same subjects, we use tools from network control theory to show that linear spread of activity along white matter connections constrains the brain's state space trajectories at rest. Additionally, accounting for stimulus-driven visual inputs explains the different trajectories taken during the n-back task. We also used models of network rewiring to show that these findings are the result of non-trivial geometric and topological properties of white matter architecture. Finally, we examine associations between age and time-resolved brain state dynamics, revealing new insights into functional changes in the default mode and executive control networks. Overall, these results elucidate the structural underpinnings of cognitively and developmentally relevant spatiotemporal brain dynamics.
[ { "created": "Sat, 8 Sep 2018 18:14:29 GMT", "version": "v1" }, { "created": "Mon, 30 Sep 2019 23:14:02 GMT", "version": "v2" } ]
2019-10-02
[ [ "Cornblath", "Eli J.", "" ], [ "Ashourvan", "Arian", "" ], [ "Kim", "Jason Z.", "" ], [ "Betzel", "Richard F.", "" ], [ "Ciric", "Rastko", "" ], [ "Adebimpe", "Azeez", "" ], [ "Baum", "Graham L.", "" ], [ "He", "Xiaosong", "" ], [ "Ruparel", "Kosha", "" ], [ "Moore", "Tyler M.", "" ], [ "Gur", "Ruben C.", "" ], [ "Gur", "Raquel E.", "" ], [ "Shinohara", "Russell T.", "" ], [ "Roalf", "David R.", "" ], [ "Satterthwaite", "Theodore D.", "" ], [ "Bassett", "Danielle S.", "" ] ]
A diverse white matter network and finely tuned neuronal membrane properties allow the brain to transition seamlessly between cognitive states. However, it remains unclear how static structural connections guide the temporal progression of large-scale brain activity patterns in different cognitive states. Here, we analyze the brain's trajectories through a high-dimensional activity space at the level of single time point activity patterns from functional magnetic resonance imaging data acquired during passive visual fixation (rest) and an n-back working memory task. We find that specific state space trajectories, which represent temporal sequences of brain activity, are modulated by cognitive load and related to task performance. Using diffusion-weighted imaging acquired from the same subjects, we use tools from network control theory to show that linear spread of activity along white matter connections constrains the brain's state space trajectories at rest. Additionally, accounting for stimulus-driven visual inputs explains the different trajectories taken during the n-back task. We also used models of network rewiring to show that these findings are the result of non-trivial geometric and topological properties of white matter architecture. Finally, we examine associations between age and time-resolved brain state dynamics, revealing new insights into functional changes in the default mode and executive control networks. Overall, these results elucidate the structural underpinnings of cognitively and developmentally relevant spatiotemporal brain dynamics.
2104.01458
Mar\'ia Vallet-Regi
M. Natividad Gomez-Cerezo, Juan Pena, Saso Ivanovski, Daniel Arcos, Maria Vallet-Regi, Cedryck Vaquette
Multiscale porosity in mesoporous bioglass 3D-printed scaffolds for bone regeneration
34 pages, 10 figures
Materials Science and Engineering: C, Volume 120, January 2021, 111706
10.1016/j.msec.2020.111706
null
q-bio.TO
http://creativecommons.org/licenses/by-nc-nd/4.0/
In order to increase the bone forming ability of MBG-PCL composite scaffold, microporosity was created in the struts of 3D-printed MBG-PCL scaffolds for the manufacturing of a construct with a multiscale porosity consisting of meso-, micro- and macro-pores. 3D-printing imparted macroporosity while the microporosity was created by porogen removal from the struts, and the MBG particles were responsible for the mesoporosity. The scaffolds were 3D-printed using a mixture of PCL, MBG and phosphate buffered saline (PBS) particles, subsequently leached out. Microporous-PCL (pPCL) as a negative control, microporous MBG-PCL (pMBG-PCL) and non-microporous-MBG-PCL (MBG-PCL) were investigated. Scanning electron microscopy, mercury intrusion porosimetry and micro-computed tomography demonstrated that the PBS removal resulted in the formation of micropores inside the struts with porosity of around 30% for both pPCL and pMBG-PCL, with both constructs displaying an overall porosity of 80-90%. In contrast, the MBG-PCL group had a microporosity of 6% and an overall porosity of 70%. Early mineralisation was found in the pMBG-PCL post-leaching out and this resulted in the formation a more homogeneous calcium phosphate layer when using a biomimetic mineralisation assay. Mechanical properties ranged from 5 to 25 MPa for microporous and non-microporous specimens, hence microporosity was the determining factor affecting compressive properties. MC3T3-E1 metabolic activity was increased in the pMBG-PCL along with an increased production of RUNX2. Therefore, the microporosity within a 3D-printed bioceramic composite construct may result in additional physical and biological benefits.
[ { "created": "Sat, 3 Apr 2021 18:34:03 GMT", "version": "v1" } ]
2021-04-06
[ [ "Gomez-Cerezo", "M. Natividad", "" ], [ "Pena", "Juan", "" ], [ "Ivanovski", "Saso", "" ], [ "Arcos", "Daniel", "" ], [ "Vallet-Regi", "Maria", "" ], [ "Vaquette", "Cedryck", "" ] ]
In order to increase the bone forming ability of MBG-PCL composite scaffold, microporosity was created in the struts of 3D-printed MBG-PCL scaffolds for the manufacturing of a construct with a multiscale porosity consisting of meso-, micro- and macro-pores. 3D-printing imparted macroporosity while the microporosity was created by porogen removal from the struts, and the MBG particles were responsible for the mesoporosity. The scaffolds were 3D-printed using a mixture of PCL, MBG and phosphate buffered saline (PBS) particles, subsequently leached out. Microporous-PCL (pPCL) as a negative control, microporous MBG-PCL (pMBG-PCL) and non-microporous-MBG-PCL (MBG-PCL) were investigated. Scanning electron microscopy, mercury intrusion porosimetry and micro-computed tomography demonstrated that the PBS removal resulted in the formation of micropores inside the struts with porosity of around 30% for both pPCL and pMBG-PCL, with both constructs displaying an overall porosity of 80-90%. In contrast, the MBG-PCL group had a microporosity of 6% and an overall porosity of 70%. Early mineralisation was found in the pMBG-PCL post-leaching out and this resulted in the formation a more homogeneous calcium phosphate layer when using a biomimetic mineralisation assay. Mechanical properties ranged from 5 to 25 MPa for microporous and non-microporous specimens, hence microporosity was the determining factor affecting compressive properties. MC3T3-E1 metabolic activity was increased in the pMBG-PCL along with an increased production of RUNX2. Therefore, the microporosity within a 3D-printed bioceramic composite construct may result in additional physical and biological benefits.
2408.03942
Davood Karimi
Camilo Calixto, Matheus D. Soldatelli, Bo Li, Lana Pierotich, Ali Gholipour, Simon K. Warfield, Davood Karimi
White matter tract crossing and bottleneck regions in the fetal brain
null
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by-nc-nd/4.0/
There is a growing interest in using diffusion MRI to study the white matter tracts and structural connectivity of the fetal brain. Recent progress in data acquisition and processing suggests that this imaging modality has a unique role in elucidating the normal and abnormal patterns of neurodevelopment in utero. However, there have been no efforts to quantify the prevalence of crossing tracts and bottleneck regions, important issues that have been extensively researched for adult brains. In this work, we determined the brain regions with crossing tracts and bottlenecks between 23 and 36 gestational weeks. We performed probabilistic tractography on 59 fetal brain scans and extracted a set of 51 distinct white tracts, which we grouped into 10 major tract bundle groups. We analyzed the results to determine the patterns of tract crossings and bottlenecks. Our results showed that 20-25% of the white matter voxels included two or three crossing tracts. Bottlenecks were more prevalent. Between 75-80% of the voxels were characterized as bottlenecks, with more than 40% of the voxels involving four or more tracts. The results of this study highlight the challenge of fetal brain tractography and structural connectivity assessment and call for innovative image acquisition and analysis methods to mitigate these problems.
[ { "created": "Sat, 20 Jul 2024 21:20:50 GMT", "version": "v1" } ]
2024-08-09
[ [ "Calixto", "Camilo", "" ], [ "Soldatelli", "Matheus D.", "" ], [ "Li", "Bo", "" ], [ "Pierotich", "Lana", "" ], [ "Gholipour", "Ali", "" ], [ "Warfield", "Simon K.", "" ], [ "Karimi", "Davood", "" ] ]
There is a growing interest in using diffusion MRI to study the white matter tracts and structural connectivity of the fetal brain. Recent progress in data acquisition and processing suggests that this imaging modality has a unique role in elucidating the normal and abnormal patterns of neurodevelopment in utero. However, there have been no efforts to quantify the prevalence of crossing tracts and bottleneck regions, important issues that have been extensively researched for adult brains. In this work, we determined the brain regions with crossing tracts and bottlenecks between 23 and 36 gestational weeks. We performed probabilistic tractography on 59 fetal brain scans and extracted a set of 51 distinct white tracts, which we grouped into 10 major tract bundle groups. We analyzed the results to determine the patterns of tract crossings and bottlenecks. Our results showed that 20-25% of the white matter voxels included two or three crossing tracts. Bottlenecks were more prevalent. Between 75-80% of the voxels were characterized as bottlenecks, with more than 40% of the voxels involving four or more tracts. The results of this study highlight the challenge of fetal brain tractography and structural connectivity assessment and call for innovative image acquisition and analysis methods to mitigate these problems.
2309.06636
Chaoqian Wang
Chaoqian Wang
Evolution of trust in structured populations
14 pages, 2 figures, accepted for publication in Applied Mathematics and Computation
Applied Mathematics and Computation, Volume 471, 15 June 2024, 128595
10.1016/j.amc.2024.128595
null
q-bio.PE nlin.AO physics.soc-ph
http://creativecommons.org/publicdomain/zero/1.0/
The trust game, derived from an economics experiment, has recently attracted interest in the field of evolutionary dynamics. In a recent version of the evolutionary trust game, players adopt one of three strategies: investor, trustworthy trustee, or untrustworthy trustee. Trustworthy trustees enhance and share the investment with the investor, whereas untrustworthy trustees retain the full amount, betraying the investor. Following this setup, we investigate a two-player trust game, which is analytically feasible under weak selection. We explore the evolution of trust in structured populations, factoring in four strategy updating rules: pairwise comparison (PC), birth-death (BD), imitation (IM), and death-birth (DB). Comparing structured populations with well-mixed populations, we arrive at two main conclusions. First, in the absence of untrustworthy trustees, there is a saddle point between investors and trustworthy trustees, with collaboration thriving best in well-mixed populations. The collaboration diminishes sequentially from DB to IM to PC/BD updating rules in structured populations. Second, an invasion of untrustworthy trustees makes this saddle point unstable and leads to the extinction of investors. The 3-strategy system stabilizes at an equilibrium line where the trustworthy and untrustworthy trustees coexist. The stability span of trustworthy trustees is maximally extended under the PC and BD updating rules in structured populations, while it decreases in a sequence from IM to DB updating rules, with the well-mixed population being the least favorable. This research thus adds an analytical lens to the evolution of trust in structured populations.
[ { "created": "Tue, 12 Sep 2023 22:54:45 GMT", "version": "v1" }, { "created": "Sun, 17 Dec 2023 02:44:09 GMT", "version": "v2" }, { "created": "Sat, 10 Feb 2024 03:08:42 GMT", "version": "v3" } ]
2024-02-13
[ [ "Wang", "Chaoqian", "" ] ]
The trust game, derived from an economics experiment, has recently attracted interest in the field of evolutionary dynamics. In a recent version of the evolutionary trust game, players adopt one of three strategies: investor, trustworthy trustee, or untrustworthy trustee. Trustworthy trustees enhance and share the investment with the investor, whereas untrustworthy trustees retain the full amount, betraying the investor. Following this setup, we investigate a two-player trust game, which is analytically feasible under weak selection. We explore the evolution of trust in structured populations, factoring in four strategy updating rules: pairwise comparison (PC), birth-death (BD), imitation (IM), and death-birth (DB). Comparing structured populations with well-mixed populations, we arrive at two main conclusions. First, in the absence of untrustworthy trustees, there is a saddle point between investors and trustworthy trustees, with collaboration thriving best in well-mixed populations. The collaboration diminishes sequentially from DB to IM to PC/BD updating rules in structured populations. Second, an invasion of untrustworthy trustees makes this saddle point unstable and leads to the extinction of investors. The 3-strategy system stabilizes at an equilibrium line where the trustworthy and untrustworthy trustees coexist. The stability span of trustworthy trustees is maximally extended under the PC and BD updating rules in structured populations, while it decreases in a sequence from IM to DB updating rules, with the well-mixed population being the least favorable. This research thus adds an analytical lens to the evolution of trust in structured populations.
2201.09647
Alex Zhavoronkov
Feng Ren, Xiao Ding, Min Zheng, Mikhail Korzinkin, Xin Cai, Wei Zhu, Alexey Mantsyzov, Alex Aliper, Vladimir Aladinskiy, Zhongying Cao, Shanshan Kong, Xi Long, Bonnie Hei Man Liu, Yingtao Liu, Vladimir Naumov, Anastasia Shneyderman, Ivan V. Ozerov, Ju Wang, Frank W. Pun, Alan Aspuru-Guzik, Michael Levitt, and Alex Zhavoronkov
AlphaFold Accelerates Artificial Intelligence Powered Drug Discovery: Efficient Discovery of a Novel Cyclin-dependent Kinase 20 (CDK20) Small Molecule Inhibitor
9 pages, 6 figures
null
null
null
q-bio.BM cs.AI cs.LG q-bio.MN
http://creativecommons.org/licenses/by-nc-sa/4.0/
The AlphaFold computer program predicted protein structures for the whole human genome, which has been considered as a remarkable breakthrough both in artificial intelligence (AI) application and structural biology. Despite the varying confidence level, these predicted structures still could significantly contribute to structure-based drug design of novel targets, especially the ones with no or limited structural information. In this work, we successfully applied AlphaFold in our end-to-end AI-powered drug discovery engines constituted of a biocomputational platform PandaOmics and a generative chemistry platform Chemistry42, to identify a first-in-class hit molecule of a novel target without an experimental structure starting from target selection towards hit identification in a cost- and time-efficient manner. PandaOmics provided the targets of interest and Chemistry42 generated the molecules based on the AlphaFold predicted structure, and the selected molecules were synthesized and tested in biological assays. Through this approach, we identified a small molecule hit compound for CDK20 with a Kd value of 8.9 +/- 1.6 uM (n = 4) within 30 days from target selection and after only synthesizing 7 compounds. Based on the available data, the second round of AI-powered compound generation was conducted and through which, a more potent hit molecule, ISM042-2 048, was discovered with a Kd value of 210.0 +/- 42.4 nM (n = 2), within 30 days and after synthesizing 6 compounds from the discovery of the first hit ISM042-2-001. To the best of our knowledge, this is the first reported small molecule targeting CDK20 and more importantly, this work is the first demonstration of AlphaFold application in the hit identification process in early drug discovery.
[ { "created": "Fri, 21 Jan 2022 07:35:24 GMT", "version": "v1" }, { "created": "Sun, 13 Feb 2022 04:26:30 GMT", "version": "v2" } ]
2022-02-15
[ [ "Ren", "Feng", "" ], [ "Ding", "Xiao", "" ], [ "Zheng", "Min", "" ], [ "Korzinkin", "Mikhail", "" ], [ "Cai", "Xin", "" ], [ "Zhu", "Wei", "" ], [ "Mantsyzov", "Alexey", "" ], [ "Aliper", "Alex", "" ], [ "Aladinskiy", "Vladimir", "" ], [ "Cao", "Zhongying", "" ], [ "Kong", "Shanshan", "" ], [ "Long", "Xi", "" ], [ "Liu", "Bonnie Hei Man", "" ], [ "Liu", "Yingtao", "" ], [ "Naumov", "Vladimir", "" ], [ "Shneyderman", "Anastasia", "" ], [ "Ozerov", "Ivan V.", "" ], [ "Wang", "Ju", "" ], [ "Pun", "Frank W.", "" ], [ "Aspuru-Guzik", "Alan", "" ], [ "Levitt", "Michael", "" ], [ "Zhavoronkov", "Alex", "" ] ]
The AlphaFold computer program predicted protein structures for the whole human genome, which has been considered as a remarkable breakthrough both in artificial intelligence (AI) application and structural biology. Despite the varying confidence level, these predicted structures still could significantly contribute to structure-based drug design of novel targets, especially the ones with no or limited structural information. In this work, we successfully applied AlphaFold in our end-to-end AI-powered drug discovery engines constituted of a biocomputational platform PandaOmics and a generative chemistry platform Chemistry42, to identify a first-in-class hit molecule of a novel target without an experimental structure starting from target selection towards hit identification in a cost- and time-efficient manner. PandaOmics provided the targets of interest and Chemistry42 generated the molecules based on the AlphaFold predicted structure, and the selected molecules were synthesized and tested in biological assays. Through this approach, we identified a small molecule hit compound for CDK20 with a Kd value of 8.9 +/- 1.6 uM (n = 4) within 30 days from target selection and after only synthesizing 7 compounds. Based on the available data, the second round of AI-powered compound generation was conducted and through which, a more potent hit molecule, ISM042-2 048, was discovered with a Kd value of 210.0 +/- 42.4 nM (n = 2), within 30 days and after synthesizing 6 compounds from the discovery of the first hit ISM042-2-001. To the best of our knowledge, this is the first reported small molecule targeting CDK20 and more importantly, this work is the first demonstration of AlphaFold application in the hit identification process in early drug discovery.
1809.08959
Joaquin Goni
Sumra Bari, Enrico Amico, Nicole Vike, Thomas M. Talavage, Joaqu\'in Go\~ni
Uncovering Multi-Site Identifiability Based on Resting-State Functional Connectomes
28 pages, 11 figures in main text, 5 figures in supplementary
NeuroImage, 2019, Vol 202, 115967
10.1016/j.neuroimage.2019.06.045
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Multi-site studies are becoming important to increase statistical power, enhance generalizability, and to improve the likelihood of pooling relevant subgroups together activities. Even with harmonized imaging sequences, site-dependent variability can mask the advantages of these multi-site studies. The aim of this study was to assess multi-site reproducibility in resting-state functional connectivity fingerprints, and to improve identifiability of functional connectomes. The individual fingerprinting of functional connectivity profiles is promising due to its potential as a robust neuroimaging biomarker. We evaluated, on two independent multi-site datasets, individual fingerprints in test-retest visit pairs within and across two sites and present a generalized framework based on principal component analysis to improve identifiability. Those components that maximized differential identifiability of a training dataset were used as an orthogonal connectivity basis to reconstruct the functional connectomes of training and validation sets. The optimally reconstructed functional connectomes showed a substantial improvement in individual fingerprinting within and across the two sites relative to the original data. A notable increase in ICC values for functional edges and resting-state networks was also observed. Improvements in identifiability were not found to be affected by global signal regression. Post-hoc analyses assessed the effect of the number of fMRI volumes on identifiability and showed that multi-site differential identifiability was for all cases maximized after optimal reconstruction. The generalizability of the optimal set of orthogonal basis of each dataset was evaluated through a leave-one-out procedure. Overall, results demonstrate that the framework presented in this study systematically improves identifiability in resting-state functional connectomes in multi-site studies.
[ { "created": "Mon, 24 Sep 2018 14:14:32 GMT", "version": "v1" }, { "created": "Tue, 23 Apr 2019 19:06:42 GMT", "version": "v2" } ]
2019-09-11
[ [ "Bari", "Sumra", "" ], [ "Amico", "Enrico", "" ], [ "Vike", "Nicole", "" ], [ "Talavage", "Thomas M.", "" ], [ "Goñi", "Joaquín", "" ] ]
Multi-site studies are becoming important to increase statistical power, enhance generalizability, and to improve the likelihood of pooling relevant subgroups together activities. Even with harmonized imaging sequences, site-dependent variability can mask the advantages of these multi-site studies. The aim of this study was to assess multi-site reproducibility in resting-state functional connectivity fingerprints, and to improve identifiability of functional connectomes. The individual fingerprinting of functional connectivity profiles is promising due to its potential as a robust neuroimaging biomarker. We evaluated, on two independent multi-site datasets, individual fingerprints in test-retest visit pairs within and across two sites and present a generalized framework based on principal component analysis to improve identifiability. Those components that maximized differential identifiability of a training dataset were used as an orthogonal connectivity basis to reconstruct the functional connectomes of training and validation sets. The optimally reconstructed functional connectomes showed a substantial improvement in individual fingerprinting within and across the two sites relative to the original data. A notable increase in ICC values for functional edges and resting-state networks was also observed. Improvements in identifiability were not found to be affected by global signal regression. Post-hoc analyses assessed the effect of the number of fMRI volumes on identifiability and showed that multi-site differential identifiability was for all cases maximized after optimal reconstruction. The generalizability of the optimal set of orthogonal basis of each dataset was evaluated through a leave-one-out procedure. Overall, results demonstrate that the framework presented in this study systematically improves identifiability in resting-state functional connectomes in multi-site studies.
2307.02561
Samuel Church
Samuel H. Church, Jasmine L. Mah, Casey W. Dunn
Unification of species, gene, and cell trees for single-cell expression analyses
16 pages, 4 figures
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
Comparisons of single-cell RNA sequencing (scRNA-seq) data across species can reveal links between cellular gene expression and the evolution of cell functions, features, and phenotypes. These comparisons invoke evolutionary histories, as depicted with phylogenetic trees, that define relationships between species, genes, and cells. Here we illustrate a tree-based framework for comparing scRNA-seq data, and contrast this framework with existing methods. We describe how we can use trees to identify homologous and comparable groups of genes and cells, based on their predicted relationship to genes and cells present in the common ancestor. We advocate for mapping data to branches of phylogenetic trees to test hypotheses about the evolution of cellular gene expression. We describe the kinds of data that can be compared, and the types of questions that each comparison has the potential to address. Finally, we reconcile species phylogenies, gene phylogenies, cell phylogenies, and cell lineages as different representations of the same concept: the tree of cellular life. By integrating phylogenetic approaches into scRNA-seq analyses, we can overcome challenges for building informed comparisons across species, and robustly test hypotheses about gene and cell evolution.
[ { "created": "Wed, 5 Jul 2023 18:02:17 GMT", "version": "v1" } ]
2023-07-07
[ [ "Church", "Samuel H.", "" ], [ "Mah", "Jasmine L.", "" ], [ "Dunn", "Casey W.", "" ] ]
Comparisons of single-cell RNA sequencing (scRNA-seq) data across species can reveal links between cellular gene expression and the evolution of cell functions, features, and phenotypes. These comparisons invoke evolutionary histories, as depicted with phylogenetic trees, that define relationships between species, genes, and cells. Here we illustrate a tree-based framework for comparing scRNA-seq data, and contrast this framework with existing methods. We describe how we can use trees to identify homologous and comparable groups of genes and cells, based on their predicted relationship to genes and cells present in the common ancestor. We advocate for mapping data to branches of phylogenetic trees to test hypotheses about the evolution of cellular gene expression. We describe the kinds of data that can be compared, and the types of questions that each comparison has the potential to address. Finally, we reconcile species phylogenies, gene phylogenies, cell phylogenies, and cell lineages as different representations of the same concept: the tree of cellular life. By integrating phylogenetic approaches into scRNA-seq analyses, we can overcome challenges for building informed comparisons across species, and robustly test hypotheses about gene and cell evolution.
2004.08973
Gabor Vattay
Gabor Vattay
Forecasting the outcome and estimating the epidemic model parameters from the fatality time series in COVID-19 outbreaks
null
Physical Biology 2020
10.1088/1478-3975/abac69
null
q-bio.PE physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In the absence of other tools, monitoring the effects of protective measures, including social distancing and forecasting the outcome of outbreaks is of immense interest. Real-time data is noisy and very often hampered by systematic errors in reporting. Detailed epidemic models may contain a large number of empirical parameters, which cannot be determined with sufficient accuracy. In this paper, we show that the cumulative number of deaths can be regarded as a master variable, and the parameters of the epidemic such as the basic reproduction number, the size of the susceptible population, and the infection rate can be determined. In the SIR model, we derive an explicit single variable differential equation for the evolution of the cumulative number of fatalities. We show that the epidemic in Spain, Italy, and Hubei Province, China follows this master equation closely. We discuss the relationship with the logistic growth model, and we show that it is a good approximation when the basic reproduction number is less than $2.3$. This condition is valid for the outbreak in Hubei, but not for the outbreaks in Spain, Italy, and New York. The difference is in the shorter infectious period in China, probably due to the separation policy of the infected. For more complex models, with more internal variables, such as the SEIR model, the equations derived from the SIR model remain valid approximately, due to the separation of timescales.
[ { "created": "Sun, 19 Apr 2020 22:14:17 GMT", "version": "v1" }, { "created": "Sat, 1 Aug 2020 09:53:57 GMT", "version": "v2" } ]
2020-08-11
[ [ "Vattay", "Gabor", "" ] ]
In the absence of other tools, monitoring the effects of protective measures, including social distancing and forecasting the outcome of outbreaks is of immense interest. Real-time data is noisy and very often hampered by systematic errors in reporting. Detailed epidemic models may contain a large number of empirical parameters, which cannot be determined with sufficient accuracy. In this paper, we show that the cumulative number of deaths can be regarded as a master variable, and the parameters of the epidemic such as the basic reproduction number, the size of the susceptible population, and the infection rate can be determined. In the SIR model, we derive an explicit single variable differential equation for the evolution of the cumulative number of fatalities. We show that the epidemic in Spain, Italy, and Hubei Province, China follows this master equation closely. We discuss the relationship with the logistic growth model, and we show that it is a good approximation when the basic reproduction number is less than $2.3$. This condition is valid for the outbreak in Hubei, but not for the outbreaks in Spain, Italy, and New York. The difference is in the shorter infectious period in China, probably due to the separation policy of the infected. For more complex models, with more internal variables, such as the SEIR model, the equations derived from the SIR model remain valid approximately, due to the separation of timescales.
q-bio/0605005
Willy Valdivia-Granda
Willy Valdivia-Granda and Christopher Dwan
Microarray Data Management. An Enterprise Information Approach: Implementations and Challenges
10 pages, 12 figures, To apperar in: Database Modeling in Biology: Practices and Challenges. Ma, Zongmin; Chen, Jake (Eds.) Springer Sciences & Business Media, Inc., New York, USA (2006). ISBN: 0-387-30238-7
null
null
null
q-bio.GN
null
The extraction of information form high-throughput experiments is a key aspect of modern biology. Early in the development of microarray technology, researchers recognized that the size of the datasets and the limitations of both computational and visualization techniques restricted their ability to find the biological meaning hidden in the data. In addition, most researchers wanted to make their datasets accessible to others. This resulted in the development of new and advanced data storage, analysis, and visualization tools enabling the cross-platform validation of the experiments and the identification of previously undetected patterns. In order to reap the benefits of this microarray data, researchers have needed to implement database management systems providing integration of different experiments and data types. Moreover, it was necessary to standardize the basic data structure and experimental techniques for the standardization of microarray platforms. In this chapter, we introduce the reader to the major concepts related to the use of controlled vocabularies (ontologies), the definition of Minimum Information About a Microarray Experiment (MIAME) and provide an overview of different microarray data management strategies in use today. We summarize the main characteristics of microarray data storage and sharing strategies including warehouses, datamarts, and federations. The fundamental challenges involved in the distribution, and retrieval of microarray data are presented, along with an overview of some emerging technologies.
[ { "created": "Wed, 3 May 2006 13:51:38 GMT", "version": "v1" } ]
2007-05-23
[ [ "Valdivia-Granda", "Willy", "" ], [ "Dwan", "Christopher", "" ] ]
The extraction of information form high-throughput experiments is a key aspect of modern biology. Early in the development of microarray technology, researchers recognized that the size of the datasets and the limitations of both computational and visualization techniques restricted their ability to find the biological meaning hidden in the data. In addition, most researchers wanted to make their datasets accessible to others. This resulted in the development of new and advanced data storage, analysis, and visualization tools enabling the cross-platform validation of the experiments and the identification of previously undetected patterns. In order to reap the benefits of this microarray data, researchers have needed to implement database management systems providing integration of different experiments and data types. Moreover, it was necessary to standardize the basic data structure and experimental techniques for the standardization of microarray platforms. In this chapter, we introduce the reader to the major concepts related to the use of controlled vocabularies (ontologies), the definition of Minimum Information About a Microarray Experiment (MIAME) and provide an overview of different microarray data management strategies in use today. We summarize the main characteristics of microarray data storage and sharing strategies including warehouses, datamarts, and federations. The fundamental challenges involved in the distribution, and retrieval of microarray data are presented, along with an overview of some emerging technologies.
1903.01316
Romain M. Yvinec
Fr\'ed\'erique Cl\'ement and Fr\'ed\'erique Robin and Romain Yvinec
Stochastic nonlinear model for somatic cell population dynamics during ovarian follicle activation
Accepted in Journal of Mathematical Biology
null
null
null
q-bio.CB math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In mammals, female germ cells are sheltered within somatic structures called ovarian follicles, which remain in a quiescent state until they get activated, all along reproductive life. We investigate the sequence of somatic cell events occurring just after follicle activation, starting by the awakening of precursor somatic cells, and their transformation into proliferative cells. We introduce a nonlinear stochastic model accounting for the joint dynamics of the two cell types, and allowing us to investigate the potential impact of a feedback from proliferative cells onto precursor cells. To tackle the key issue of whether cell proliferation is concomitant or posterior to cell awakening, we assess both the time needed for all precursor cells to awake, and the corresponding increase in the total cell number with respect to the initial cell number. Using the probabilistic theory of first passage times, we design a numerical scheme based on a rigorous Finite State Projection and coupling techniques to compute the mean extinction time and the cell number at extinction time. We find that the feedback term clearly lowers the number of proliferative cells at the extinction time. We calibrate the model parameters using an exact likelihood approach. We carry out a comprehensive comparison between the initial model and a series of submodels, which helps to select the critical cell events taking place during activation, and suggests that awakening is prominent over proliferation.
[ { "created": "Mon, 4 Mar 2019 15:48:38 GMT", "version": "v1" }, { "created": "Wed, 9 Dec 2020 08:07:29 GMT", "version": "v2" } ]
2020-12-10
[ [ "Clément", "Frédérique", "" ], [ "Robin", "Frédérique", "" ], [ "Yvinec", "Romain", "" ] ]
In mammals, female germ cells are sheltered within somatic structures called ovarian follicles, which remain in a quiescent state until they get activated, all along reproductive life. We investigate the sequence of somatic cell events occurring just after follicle activation, starting by the awakening of precursor somatic cells, and their transformation into proliferative cells. We introduce a nonlinear stochastic model accounting for the joint dynamics of the two cell types, and allowing us to investigate the potential impact of a feedback from proliferative cells onto precursor cells. To tackle the key issue of whether cell proliferation is concomitant or posterior to cell awakening, we assess both the time needed for all precursor cells to awake, and the corresponding increase in the total cell number with respect to the initial cell number. Using the probabilistic theory of first passage times, we design a numerical scheme based on a rigorous Finite State Projection and coupling techniques to compute the mean extinction time and the cell number at extinction time. We find that the feedback term clearly lowers the number of proliferative cells at the extinction time. We calibrate the model parameters using an exact likelihood approach. We carry out a comprehensive comparison between the initial model and a series of submodels, which helps to select the critical cell events taking place during activation, and suggests that awakening is prominent over proliferation.
1508.00623
Nicholas Noll
Nicholas Noll, Madhav Mani, Idse Heemskerk, Sebastian Streichan, Boris I. Shraiman
Active Tension Network model reveals an exotic mechanical state realized in epithelial tissues
The central argument as well as the initial reported results remain unchanged. This revision represents a restructuring of the initial arguments to make it more readable and easier to understand to a wider audience. Furthermore, additional movies were analyzed to bolster our claim made that VF formation is primarily isogonal deformations
null
null
null
q-bio.TO q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
It is now widely recognized that mechanical interactions between cells play a crucial role in epithelial morphogenesis, yet understanding the mechanisms through which stress and deformation affect cell behavior remains an open problem due to the complexity inherent in the mechanical behavior of cells and the difficulty of direct measurement of forces within tissues. Theoretical models can help by focusing experimental studies and by providing the framework for interpreting measurements. To that end, "vertex models" have introduced an approximation of epithelial cell mechanics based on a polygonal tiling representation of planar tissue. Here we formulate and analyze an Active Tension Network (ATN) model, which is based on the same polygonal representation of epithelial tissue geometry, but in addition i) assumes that mechanical balance is dominated by cortical tension and ii) introduces tension dependent local remodeling of the cortex, representing the active nature of cytoskeletal mechanics. The tension-dominance assumption has immediate implications for the geometry of cells, which we demonstrate to hold in certain types of Drosophila epithelial tissues. We demonstrate that stationary configurations of an ATN form a manifold with one degree of freedom per cell, corresponding to "isogonal" - i.e. angle preserving - deformations of cells, which dominate the dynamic response to perturbations. We show that isogonal modes account for approximately 90% of experimentally observed deformation of cells during the process of ventral furrow formation in Drosophila. Other interesting properties of our model include the exponential screening of mechanical stress and a negative Poisson ratio response to external uniaxial stress. We also provide a new approach to the problem of inferring local cortical tensions from the observed geometry of epithelial cells in a tissue
[ { "created": "Mon, 3 Aug 2015 23:53:26 GMT", "version": "v1" }, { "created": "Wed, 18 Jan 2017 23:31:46 GMT", "version": "v2" } ]
2017-01-20
[ [ "Noll", "Nicholas", "" ], [ "Mani", "Madhav", "" ], [ "Heemskerk", "Idse", "" ], [ "Streichan", "Sebastian", "" ], [ "Shraiman", "Boris I.", "" ] ]
It is now widely recognized that mechanical interactions between cells play a crucial role in epithelial morphogenesis, yet understanding the mechanisms through which stress and deformation affect cell behavior remains an open problem due to the complexity inherent in the mechanical behavior of cells and the difficulty of direct measurement of forces within tissues. Theoretical models can help by focusing experimental studies and by providing the framework for interpreting measurements. To that end, "vertex models" have introduced an approximation of epithelial cell mechanics based on a polygonal tiling representation of planar tissue. Here we formulate and analyze an Active Tension Network (ATN) model, which is based on the same polygonal representation of epithelial tissue geometry, but in addition i) assumes that mechanical balance is dominated by cortical tension and ii) introduces tension dependent local remodeling of the cortex, representing the active nature of cytoskeletal mechanics. The tension-dominance assumption has immediate implications for the geometry of cells, which we demonstrate to hold in certain types of Drosophila epithelial tissues. We demonstrate that stationary configurations of an ATN form a manifold with one degree of freedom per cell, corresponding to "isogonal" - i.e. angle preserving - deformations of cells, which dominate the dynamic response to perturbations. We show that isogonal modes account for approximately 90% of experimentally observed deformation of cells during the process of ventral furrow formation in Drosophila. Other interesting properties of our model include the exponential screening of mechanical stress and a negative Poisson ratio response to external uniaxial stress. We also provide a new approach to the problem of inferring local cortical tensions from the observed geometry of epithelial cells in a tissue
1812.08031
Gestionnaire Hal-Su
St\'ephane Epelbaum (ICM, IM2A, UPMC), Vincent Bouteloup (ISPED, BPH), Jean Mangin (CATI, NEUROSPIN), Valentina La Corte (UPD5 Psychologie, CPN - U894), Raffaela Migliaccio (ICM, IM2A, UPMC), Hugo Bertin (LIB, CATI, UPMC), Marie O. Habert (LIB, CATI, UPMC), Clara Fischer (CATI, NEUROSPIN), Chabha Azouani (CATI), Ludovic Fillon (CATI), Marie Chupin (CATI), Bruno Vellas, Florence Pasquier, Jean Dartigues (BPH, ISPED), Fr\'ed\'eric Blanc, Audrey Gabelle (CHRU Montpellier), Mathieu Ceccaldi (INS, TIMONE), Pierre Krolak-Salmon (HCL), Jacques Hugon (UPD7), Olivier Hanon (UPD5), Olivier Rouaud (CHU Dijon), Renaud David (CMRR Nice), Genevi\`eve Ch\^ene (BPH, ISPED), Bruno Dubois (IM2A, ICM, UPMC), Carole Dufouil (BPH, ISPED)
Neural correlates of episodic memory in the Memento cohort
null
Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2018, 4, pp.224-233
10.1016/j.trci.2018.03.010
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
IntroductionThe free and cued selective reminding test is used to identify memory deficits in mild cognitive impairment and demented patients. It allows assessing three processes: encoding, storage, and recollection of verbal episodic memory.MethodsWe investigated the neural correlates of these three memory processes in a large cohort study. The Memento cohort enrolled 2323 outpatients presenting either with subjective cognitive decline or mild cognitive impairment who underwent cognitive, structural MRI and, for a subset, fluorodeoxyglucose--positron emission tomography evaluations.ResultsEncoding was associated with a network including parietal and temporal cortices; storage was mainly associated with entorhinal and parahippocampal regions, bilaterally; retrieval was associated with a widespread network encompassing frontal regions.DiscussionThe neural correlates of episodic memory processes can be assessed in large and standardized cohorts of patients at risk for Alzheimer's disease. Their relation to pathophysiological markers of Alzheimer's disease remains to be studied.
[ { "created": "Wed, 19 Dec 2018 15:44:51 GMT", "version": "v1" } ]
2018-12-20
[ [ "Epelbaum", "Stéphane", "", "ICM, IM2A, UPMC" ], [ "Bouteloup", "Vincent", "", "ISPED, BPH" ], [ "Mangin", "Jean", "", "CATI, NEUROSPIN" ], [ "La Corte", "Valentina", "", "UPD5 Psychologie, CPN -\n U894" ], [ "Migliaccio", "Raffaela", "", "ICM, IM2A, UPMC" ], [ "Bertin", "Hugo", "", "LIB, CATI, UPMC" ], [ "Habert", "Marie O.", "", "LIB, CATI, UPMC" ], [ "Fischer", "Clara", "", "CATI, NEUROSPIN" ], [ "Azouani", "Chabha", "", "CATI" ], [ "Fillon", "Ludovic", "", "CATI" ], [ "Chupin", "Marie", "", "CATI" ], [ "Vellas", "Bruno", "", "BPH, ISPED" ], [ "Pasquier", "Florence", "", "BPH, ISPED" ], [ "Dartigues", "Jean", "", "BPH, ISPED" ], [ "Blanc", "Frédéric", "", "CHRU Montpellier" ], [ "Gabelle", "Audrey", "", "CHRU Montpellier" ], [ "Ceccaldi", "Mathieu", "", "INS, TIMONE" ], [ "Krolak-Salmon", "Pierre", "", "HCL" ], [ "Hugon", "Jacques", "", "UPD7" ], [ "Hanon", "Olivier", "", "UPD5" ], [ "Rouaud", "Olivier", "", "CHU Dijon" ], [ "David", "Renaud", "", "CMRR Nice" ], [ "Chêne", "Geneviève", "", "BPH,\n ISPED" ], [ "Dubois", "Bruno", "", "IM2A, ICM, UPMC" ], [ "Dufouil", "Carole", "", "BPH, ISPED" ] ]
IntroductionThe free and cued selective reminding test is used to identify memory deficits in mild cognitive impairment and demented patients. It allows assessing three processes: encoding, storage, and recollection of verbal episodic memory.MethodsWe investigated the neural correlates of these three memory processes in a large cohort study. The Memento cohort enrolled 2323 outpatients presenting either with subjective cognitive decline or mild cognitive impairment who underwent cognitive, structural MRI and, for a subset, fluorodeoxyglucose--positron emission tomography evaluations.ResultsEncoding was associated with a network including parietal and temporal cortices; storage was mainly associated with entorhinal and parahippocampal regions, bilaterally; retrieval was associated with a widespread network encompassing frontal regions.DiscussionThe neural correlates of episodic memory processes can be assessed in large and standardized cohorts of patients at risk for Alzheimer's disease. Their relation to pathophysiological markers of Alzheimer's disease remains to be studied.
1511.01810
Sebastien Benzekry
S\'ebastien Benzekry (IMB, MONC), J. M. L. Ebos
On the growth and dissemination laws in a mathematical model of metastatic growth
null
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Metastasis represents one of the main clinical challenge in cancer treatment since it is associated with the majority of deaths. Recent technological advances allow quantification of the dynamics of the process by means of noninvasive techniques such as longitudinal tracking of bioluminescent cells. The metastatic process was simplified here into two essential components -- dissemination and colonization -- which were mathematically formalized in terms of simple quantitative laws. The resulting mathematical model was confronted to in vivo experimental data of spontaneous metastasis after primary tumor resection. We discuss how much information can be inferred from confrontation of theories to the data with emphasis on identifiability issues. It is shown that two mutually exclusive assumptions for the secondary growth law (namely same or different from the primary tumor growth law) could fit equally well the data. Similarly, the fractal dimension coefficient in the dissemination law could not be uniquely determined from data on total metastatic burden only. Together, these results delimitate the range of information that can be recovered from fitting data of metastatic growth to already simplified mathematical models.
[ { "created": "Wed, 4 Nov 2015 12:59:36 GMT", "version": "v1" } ]
2015-11-06
[ [ "Benzekry", "Sébastien", "", "IMB, MONC" ], [ "Ebos", "J. M. L.", "" ] ]
Metastasis represents one of the main clinical challenge in cancer treatment since it is associated with the majority of deaths. Recent technological advances allow quantification of the dynamics of the process by means of noninvasive techniques such as longitudinal tracking of bioluminescent cells. The metastatic process was simplified here into two essential components -- dissemination and colonization -- which were mathematically formalized in terms of simple quantitative laws. The resulting mathematical model was confronted to in vivo experimental data of spontaneous metastasis after primary tumor resection. We discuss how much information can be inferred from confrontation of theories to the data with emphasis on identifiability issues. It is shown that two mutually exclusive assumptions for the secondary growth law (namely same or different from the primary tumor growth law) could fit equally well the data. Similarly, the fractal dimension coefficient in the dissemination law could not be uniquely determined from data on total metastatic burden only. Together, these results delimitate the range of information that can be recovered from fitting data of metastatic growth to already simplified mathematical models.
2308.14715
Ethan Levien
Ethan Levien
Coalescent processes emerging from large deviations
15 pages, 3 figures. Major revision incorporating comments from anonymous referees
null
null
null
q-bio.PE cond-mat.stat-mech
http://creativecommons.org/licenses/by/4.0/
The classical model for the genealogies of a neutrally evolving population in a fixed environment is due to Kingman. Kingman's coalescent process, which produces a binary tree, universally emerges from many microscopic models in which the variance in the number of offspring is finite. It is understood that power-law offspring distributions with infinite variance can result in a very different type of coalescent structure with merging of more than two lineages. Here we investigate the regime where the variance of the offspring distribution is finite but comparable to the population size. This is achieved by studying a model in which the log offspring sizes have a stretched exponential form. Such offspring distributions are motivated by biology, where they emerge from a toy model of growth in a heterogenous environment, but also mathematics and statistical physics, where limit theorems and phase transitions for sums over random exponentials have received considerable attention due to their appearance in the partition function of Derrida's Random Energy Model (REM). We find that the limit coalescent is a $\beta$-coalescent -- a previously studied model emerging from evolutionary dynamics models with heavy-tailed offspring distributions. We also discuss the connection to previous results on the REM.
[ { "created": "Mon, 28 Aug 2023 17:15:54 GMT", "version": "v1" }, { "created": "Tue, 5 Sep 2023 01:22:17 GMT", "version": "v2" }, { "created": "Mon, 4 Dec 2023 16:13:45 GMT", "version": "v3" } ]
2023-12-05
[ [ "Levien", "Ethan", "" ] ]
The classical model for the genealogies of a neutrally evolving population in a fixed environment is due to Kingman. Kingman's coalescent process, which produces a binary tree, universally emerges from many microscopic models in which the variance in the number of offspring is finite. It is understood that power-law offspring distributions with infinite variance can result in a very different type of coalescent structure with merging of more than two lineages. Here we investigate the regime where the variance of the offspring distribution is finite but comparable to the population size. This is achieved by studying a model in which the log offspring sizes have a stretched exponential form. Such offspring distributions are motivated by biology, where they emerge from a toy model of growth in a heterogenous environment, but also mathematics and statistical physics, where limit theorems and phase transitions for sums over random exponentials have received considerable attention due to their appearance in the partition function of Derrida's Random Energy Model (REM). We find that the limit coalescent is a $\beta$-coalescent -- a previously studied model emerging from evolutionary dynamics models with heavy-tailed offspring distributions. We also discuss the connection to previous results on the REM.
2307.16231
R\'edoane Daoudi
R\'edoane Daoudi
Strategies for targeting chondrosarcomas in vivo and molecular dissection of oncogenic events in chondrosarcomas: is epigenetics the culprit?
21 pages, 1 figure, 1 table
null
null
null
q-bio.MN q-bio.SC
http://creativecommons.org/licenses/by/4.0/
It is obvious that both epigenetic and non-epigenetic actors contribute to tumorigenesis in chondrosarcomas and more generally in other cancers. Thus, the main altered pathways in chondrosarcomas are now well established and include both epigenetic and non-epigenetic pathways such as the PI3K-AKT signaling, EGFR overexpression, SPARC overexpression, c-myc overexpression, IHH/GLI1 axis, loss of Rb function, HIF1-alpha stabilization, IDH1 mutations, hypermethylation and SIRT1. This review aims to provide a detailed analysis of these pathways and highlights recurrent interactions between non-epigenetic and epigenetic actors in chondrosarcomas, raising the intriguing possibility of developing therapeutics targeting both epigenetic and non-epigenetic actors and supporting data from previous studies. Finally, we propose some strategies for targeting chondrosarcomas in vivo based on properties of this tumor.
[ { "created": "Sun, 30 Jul 2023 13:43:33 GMT", "version": "v1" } ]
2023-08-01
[ [ "Daoudi", "Rédoane", "" ] ]
It is obvious that both epigenetic and non-epigenetic actors contribute to tumorigenesis in chondrosarcomas and more generally in other cancers. Thus, the main altered pathways in chondrosarcomas are now well established and include both epigenetic and non-epigenetic pathways such as the PI3K-AKT signaling, EGFR overexpression, SPARC overexpression, c-myc overexpression, IHH/GLI1 axis, loss of Rb function, HIF1-alpha stabilization, IDH1 mutations, hypermethylation and SIRT1. This review aims to provide a detailed analysis of these pathways and highlights recurrent interactions between non-epigenetic and epigenetic actors in chondrosarcomas, raising the intriguing possibility of developing therapeutics targeting both epigenetic and non-epigenetic actors and supporting data from previous studies. Finally, we propose some strategies for targeting chondrosarcomas in vivo based on properties of this tumor.
1511.04001
Burkhard Morgenstern
Lars Hahn, Chris-Andr\'e Leimeister, Rachid Ounit, Stefano Lonardi, Burkhard Morgenstern
RasBhari: optimizing spaced seeds for database searching, read mapping and alignment-free sequence comparison
null
null
10.1371/journal.pcbi.1005107
null
q-bio.GN cs.DS q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Many algorithms for sequence analysis rely on word matching or word statistics. Often, these approaches can be improved if binary patterns representing match and don't-care positions are used as a filter, such that only those positions of words are considered that correspond to the match positions of the patterns. The performance of these approaches, however, depends on the underlying patterns. Herein, we show that the overlap complexity of a pattern set that was introduced by Ilie and Ilie is closely related to the variance of the number of matches between two evolutionarily related sequences with respect to this pattern set. We propose a modified hill-climbing algorithm to optimize pattern sets for database searching, read mapping and alignment-free sequence comparison of nucleic-acid sequences; our implementation of this algorithm is called rasbhari. Depending on the application at hand, rasbhari can either minimize the overlap complexity of pattern sets, maximize their sensitivity in database searching or minimize the variance of the number of pattern-based matches in alignment-free sequence comparison. We show that, for database searching, rasbhari generates pattern sets with slightly higher sensitivity than existing approaches. In our Spaced Words approach to alignment-free sequence comparison, pattern sets calculated with rasbhari led to more accurate estimates of phylogenetic distances than the randomly generated pattern sets that we previously used. Finally, we used rasbhari to generate patterns for short read classification with CLARK-S. Here too, the sensitivity of the results could be improved, compared to the default patterns of the program. We integrated rasbhari into Spaced Words; the source code of rasbhari is freely available at http://rasbhari.gobics.de/
[ { "created": "Thu, 12 Nov 2015 18:48:08 GMT", "version": "v1" }, { "created": "Wed, 20 Jul 2016 13:06:46 GMT", "version": "v2" } ]
2017-02-08
[ [ "Hahn", "Lars", "" ], [ "Leimeister", "Chris-André", "" ], [ "Ounit", "Rachid", "" ], [ "Lonardi", "Stefano", "" ], [ "Morgenstern", "Burkhard", "" ] ]
Many algorithms for sequence analysis rely on word matching or word statistics. Often, these approaches can be improved if binary patterns representing match and don't-care positions are used as a filter, such that only those positions of words are considered that correspond to the match positions of the patterns. The performance of these approaches, however, depends on the underlying patterns. Herein, we show that the overlap complexity of a pattern set that was introduced by Ilie and Ilie is closely related to the variance of the number of matches between two evolutionarily related sequences with respect to this pattern set. We propose a modified hill-climbing algorithm to optimize pattern sets for database searching, read mapping and alignment-free sequence comparison of nucleic-acid sequences; our implementation of this algorithm is called rasbhari. Depending on the application at hand, rasbhari can either minimize the overlap complexity of pattern sets, maximize their sensitivity in database searching or minimize the variance of the number of pattern-based matches in alignment-free sequence comparison. We show that, for database searching, rasbhari generates pattern sets with slightly higher sensitivity than existing approaches. In our Spaced Words approach to alignment-free sequence comparison, pattern sets calculated with rasbhari led to more accurate estimates of phylogenetic distances than the randomly generated pattern sets that we previously used. Finally, we used rasbhari to generate patterns for short read classification with CLARK-S. Here too, the sensitivity of the results could be improved, compared to the default patterns of the program. We integrated rasbhari into Spaced Words; the source code of rasbhari is freely available at http://rasbhari.gobics.de/
1801.04825
Radha Srinivasan
Kiran Vishwasrao, Yasmin Khan and S. Radha
The cellular uptake mechanism of SPIONs: an in-vitro study
8 pages, 3 figures, Part of work presented at International Conference of Magnetism 2012 (Busan, S.Korea)
null
null
null
q-bio.CB cond-mat.soft physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The Superparamagnetic Iron Oxide Nanoparticles (SPIONs) of sizes ranging from 10-50 nm are being used in a large number of biological studies because of their peculiar characteristics of inducing local hyperthermia, MR imaging, specific targeting and drug delivery. An in-vitro study of the cytotoxicity and an understanding of the specific pathway of cellular uptake will enable manipulation of conditions for optimal cellular uptake of SPIONs for targeted therapy. The objective of the present study was to identify the endocytotic pathway through which the SPIONs are taken up by C6 glioma cells. The cells were pre-incubated with different concentrations of pharmacological inhibitors and then exposed to SPIONs for a few hours. The endocytosed particles were localized and quantitatively estimated using Perl's or Prussian Blue reaction. There was significant reduction in the uptake of SPIONs when incubated with the inhibitor indicating the uptake of nanoparticles is being inhibited. This reduction in SPION uptake was found to be dependent on the concentration of the inhibitors and also the nature of the inhibitors. By a systematic study of choosing various inhibitors, the data can be narrowed down to the final pathway that may be involved in the SPION uptake. The present preliminary investigation is expected to provide insight of testing the possible mechanisms with complementary techniques.
[ { "created": "Mon, 15 Jan 2018 14:40:35 GMT", "version": "v1" } ]
2018-01-16
[ [ "Vishwasrao", "Kiran", "" ], [ "Khan", "Yasmin", "" ], [ "Radha", "S.", "" ] ]
The Superparamagnetic Iron Oxide Nanoparticles (SPIONs) of sizes ranging from 10-50 nm are being used in a large number of biological studies because of their peculiar characteristics of inducing local hyperthermia, MR imaging, specific targeting and drug delivery. An in-vitro study of the cytotoxicity and an understanding of the specific pathway of cellular uptake will enable manipulation of conditions for optimal cellular uptake of SPIONs for targeted therapy. The objective of the present study was to identify the endocytotic pathway through which the SPIONs are taken up by C6 glioma cells. The cells were pre-incubated with different concentrations of pharmacological inhibitors and then exposed to SPIONs for a few hours. The endocytosed particles were localized and quantitatively estimated using Perl's or Prussian Blue reaction. There was significant reduction in the uptake of SPIONs when incubated with the inhibitor indicating the uptake of nanoparticles is being inhibited. This reduction in SPION uptake was found to be dependent on the concentration of the inhibitors and also the nature of the inhibitors. By a systematic study of choosing various inhibitors, the data can be narrowed down to the final pathway that may be involved in the SPION uptake. The present preliminary investigation is expected to provide insight of testing the possible mechanisms with complementary techniques.
2204.01847
Qi Zhang
Qi Zhang, Chang Liu, Stephen Wu and Ryo Yoshida
Bayesian Sequential Stacking Algorithm for Concurrently Designing Molecules and Synthetic Reaction Networks
null
null
null
null
q-bio.BM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In the last few years, de novo molecular design using machine learning has made great technical progress but its practical deployment has not been as successful. This is mostly owing to the cost and technical difficulty of synthesizing such computationally designed molecules. To overcome such barriers, various methods for synthetic route design using deep neural networks have been studied intensively in recent years. However, little progress has been made in designing molecules and their synthetic routes simultaneously. Here, we formulate the problem of simultaneously designing molecules with the desired set of properties and their synthetic routes within the framework of Bayesian inference. The design variables consist of a set of reactants in a reaction network and its network topology. The design space is extremely large because it consists of all combinations of purchasable reactants, often in the order of millions or more. In addition, the designed reaction networks can adopt any topology beyond simple multistep linear reaction routes. To solve this hard combinatorial problem, we present a powerful sequential Monte Carlo algorithm that recursively designs a synthetic reaction network by sequentially building up single-step reactions. In a case study of designing drug-like molecules based on commercially available compounds, compared with heuristic combinatorial search methods, the proposed method shows overwhelming performance in terms of computational efficiency and coverage and novelty with respect to existing compounds.
[ { "created": "Tue, 1 Mar 2022 14:55:32 GMT", "version": "v1" } ]
2022-04-06
[ [ "Zhang", "Qi", "" ], [ "Liu", "Chang", "" ], [ "Wu", "Stephen", "" ], [ "Yoshida", "Ryo", "" ] ]
In the last few years, de novo molecular design using machine learning has made great technical progress but its practical deployment has not been as successful. This is mostly owing to the cost and technical difficulty of synthesizing such computationally designed molecules. To overcome such barriers, various methods for synthetic route design using deep neural networks have been studied intensively in recent years. However, little progress has been made in designing molecules and their synthetic routes simultaneously. Here, we formulate the problem of simultaneously designing molecules with the desired set of properties and their synthetic routes within the framework of Bayesian inference. The design variables consist of a set of reactants in a reaction network and its network topology. The design space is extremely large because it consists of all combinations of purchasable reactants, often in the order of millions or more. In addition, the designed reaction networks can adopt any topology beyond simple multistep linear reaction routes. To solve this hard combinatorial problem, we present a powerful sequential Monte Carlo algorithm that recursively designs a synthetic reaction network by sequentially building up single-step reactions. In a case study of designing drug-like molecules based on commercially available compounds, compared with heuristic combinatorial search methods, the proposed method shows overwhelming performance in terms of computational efficiency and coverage and novelty with respect to existing compounds.
2306.08015
Reindorf Borkor
Reindorf Nartey Borkor and Adu Sakyi and Peter Amoako-Yirenkyi
Investigation of Fractional Compartmental Models with Application to Amiodarone Drug Diffusion in Pharmacokinetics
null
null
null
null
q-bio.QM cs.NA math.NA
http://creativecommons.org/licenses/by/4.0/
This paper presents three fractional models formulated from a classical Pharmacokinetics compartmental system: commensurable, non-commensurable, and implicit non-commensurable models. Their distinguishing characteristics are further examined comprehensively. Because analytic solutions for such models are typically challenging to obtain, we study the application of the Fractional Finite Difference Method (FFDM) to simulate approximate solutions. The characteristic of the non-commensurable model is shown to be incompatible with the concept of mass balance. However, it appeared to outlast fractional calculus theory when simulating anomalous kinetics. We proved this by fitting the proposed fractional and classical models to an experimental data set (amiodarone) and estimated the parameters using the least-square approach. The classical model diverged, but the non-commensurable model predicted a fit comparable to the other two fractional models. The fractional models described anomalous diffusion better than classical theories. The numerical results showed that the proposed numerical method is equally efficient in solving any complex compartmental models, as they performed well in simulations for the classic example of the model.
[ { "created": "Tue, 13 Jun 2023 12:23:26 GMT", "version": "v1" } ]
2023-06-16
[ [ "Borkor", "Reindorf Nartey", "" ], [ "Sakyi", "Adu", "" ], [ "Amoako-Yirenkyi", "Peter", "" ] ]
This paper presents three fractional models formulated from a classical Pharmacokinetics compartmental system: commensurable, non-commensurable, and implicit non-commensurable models. Their distinguishing characteristics are further examined comprehensively. Because analytic solutions for such models are typically challenging to obtain, we study the application of the Fractional Finite Difference Method (FFDM) to simulate approximate solutions. The characteristic of the non-commensurable model is shown to be incompatible with the concept of mass balance. However, it appeared to outlast fractional calculus theory when simulating anomalous kinetics. We proved this by fitting the proposed fractional and classical models to an experimental data set (amiodarone) and estimated the parameters using the least-square approach. The classical model diverged, but the non-commensurable model predicted a fit comparable to the other two fractional models. The fractional models described anomalous diffusion better than classical theories. The numerical results showed that the proposed numerical method is equally efficient in solving any complex compartmental models, as they performed well in simulations for the classic example of the model.
1611.02272
Alexander Tait
Alexander N. Tait, Thomas Ferreira de Lima, Ellen Zhou, Allie X. Wu, Mitchell A. Nahmias, Bhavin J. Shastri, and Paul R. Prucnal
Neuromorphic Silicon Photonic Networks
12 pages, 4 figures, accepted in Scientific Reports
Sci.Rep. 7 (2017) 7430
10.1038/s41598-017-07754-z
null
q-bio.NC cs.NE physics.optics
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Photonic systems for high-performance information processing have attracted renewed interest. Neuromorphic silicon photonics has the potential to integrate processing functions that vastly exceed the capabilities of electronics. We report first observations of a recurrent silicon photonic neural network, in which connections are configured by microring weight banks. A mathematical isomorphism between the silicon photonic circuit and a continuous neural network model is demonstrated through dynamical bifurcation analysis. Exploiting this isomorphism, a simulated 24-node silicon photonic neural network is programmed using "neural compiler" to solve a differential system emulation task. A 294-fold acceleration against a conventional benchmark is predicted. We also propose and derive power consumption analysis for modulator-class neurons that, as opposed to laser-class neurons, are compatible with silicon photonic platforms. At increased scale, Neuromorphic silicon photonics could access new regimes of ultrafast information processing for radio, control, and scientific computing.
[ { "created": "Sat, 5 Nov 2016 00:15:59 GMT", "version": "v1" }, { "created": "Wed, 22 Mar 2017 17:35:37 GMT", "version": "v2" }, { "created": "Mon, 12 Jun 2017 15:56:45 GMT", "version": "v3" } ]
2017-11-17
[ [ "Tait", "Alexander N.", "" ], [ "de Lima", "Thomas Ferreira", "" ], [ "Zhou", "Ellen", "" ], [ "Wu", "Allie X.", "" ], [ "Nahmias", "Mitchell A.", "" ], [ "Shastri", "Bhavin J.", "" ], [ "Prucnal", "Paul R.", "" ] ]
Photonic systems for high-performance information processing have attracted renewed interest. Neuromorphic silicon photonics has the potential to integrate processing functions that vastly exceed the capabilities of electronics. We report first observations of a recurrent silicon photonic neural network, in which connections are configured by microring weight banks. A mathematical isomorphism between the silicon photonic circuit and a continuous neural network model is demonstrated through dynamical bifurcation analysis. Exploiting this isomorphism, a simulated 24-node silicon photonic neural network is programmed using "neural compiler" to solve a differential system emulation task. A 294-fold acceleration against a conventional benchmark is predicted. We also propose and derive power consumption analysis for modulator-class neurons that, as opposed to laser-class neurons, are compatible with silicon photonic platforms. At increased scale, Neuromorphic silicon photonics could access new regimes of ultrafast information processing for radio, control, and scientific computing.
1603.09415
Benjamin Drinkwater
Benjamin Drinkwater, Angela Qiao, and Michael A. Charleston
WiSPA: A new approach for dealing with widespread parasitism
null
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Traditionally, studies of coevolving systems have considered cases where a parasite may inhabit only a single host. The case where a parasite may infect many hosts, widespread parasitism, has until recently gained little traction. This is due in part to the computational complexity involved in reconstructing the coevolutionary histories where parasites may infect only a single host, which is NP-Hard. Allowing parasites to inhabit more than one host has been seen to only further compound this computationally intractable problem. Recently however, well-established algorithms for estimating the problem instance where a parasite may infect only a single host have been extended to handle widespread parasites. Although this has offered significant progress, it has been noted that these algorithms poorly handle parasites that inhabit phylogenetically distant hosts. In this work we extend these previous algorithms to handle cases where parasites inhabit phylogenetically distant hosts using an additional evolutionary event which we call spread. Our new framework is shown to infer significantly more congruent coevolutionary histories compared to existing methods over both synthetic and biological data sets. We then apply the newly proposed algorithm, which we call WiSPA (WideSpread Parasitism Analyser), to the well studied coevolutionary system of Primates and Enterobius (pinworms), where existing methods have been unable to reconcile the widespread parasitism present without permitting additional divergence events. Using WiSPA and the new biological event, spread, we provide the first statistically significant coevolutionary hypothesis for this system.
[ { "created": "Wed, 30 Mar 2016 23:32:50 GMT", "version": "v1" } ]
2016-04-01
[ [ "Drinkwater", "Benjamin", "" ], [ "Qiao", "Angela", "" ], [ "Charleston", "Michael A.", "" ] ]
Traditionally, studies of coevolving systems have considered cases where a parasite may inhabit only a single host. The case where a parasite may infect many hosts, widespread parasitism, has until recently gained little traction. This is due in part to the computational complexity involved in reconstructing the coevolutionary histories where parasites may infect only a single host, which is NP-Hard. Allowing parasites to inhabit more than one host has been seen to only further compound this computationally intractable problem. Recently however, well-established algorithms for estimating the problem instance where a parasite may infect only a single host have been extended to handle widespread parasites. Although this has offered significant progress, it has been noted that these algorithms poorly handle parasites that inhabit phylogenetically distant hosts. In this work we extend these previous algorithms to handle cases where parasites inhabit phylogenetically distant hosts using an additional evolutionary event which we call spread. Our new framework is shown to infer significantly more congruent coevolutionary histories compared to existing methods over both synthetic and biological data sets. We then apply the newly proposed algorithm, which we call WiSPA (WideSpread Parasitism Analyser), to the well studied coevolutionary system of Primates and Enterobius (pinworms), where existing methods have been unable to reconcile the widespread parasitism present without permitting additional divergence events. Using WiSPA and the new biological event, spread, we provide the first statistically significant coevolutionary hypothesis for this system.
1402.5327
Jian-Jun Shu
Jian-Jun Shu, Kian Yan Yong and Weng Kong Chan
An improved scoring matrix for multiple sequence alignment
null
Mathematical Problems in Engineering, Vol. 2012, No. 490649, pp. 1-9, 2012
10.1155/2012/490649
null
q-bio.QM q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The way for performing multiple sequence alignment is based on the criterion of the maximum scored information content computed from a weight matrix, but it is possible to have two or more alignments to have the same highest score leading to ambiguities in selecting the best alignment. This paper addresses this issue by introducing the concept of joint weight matrix to eliminate the randomness in selecting the best multiple sequence alignment. Alignments with equal scores are iteratively rescored with the joint weight matrix of increasing level (nucleotide pairs, triplets and so on) until one single best alignment is eventually found. This method for resolving ambiguity in multiple sequence alignment can be easily implemented by use of the improved scoring matrix.
[ { "created": "Fri, 21 Feb 2014 15:44:25 GMT", "version": "v1" }, { "created": "Fri, 28 Feb 2014 14:20:00 GMT", "version": "v2" } ]
2014-03-03
[ [ "Shu", "Jian-Jun", "" ], [ "Yong", "Kian Yan", "" ], [ "Chan", "Weng Kong", "" ] ]
The way for performing multiple sequence alignment is based on the criterion of the maximum scored information content computed from a weight matrix, but it is possible to have two or more alignments to have the same highest score leading to ambiguities in selecting the best alignment. This paper addresses this issue by introducing the concept of joint weight matrix to eliminate the randomness in selecting the best multiple sequence alignment. Alignments with equal scores are iteratively rescored with the joint weight matrix of increasing level (nucleotide pairs, triplets and so on) until one single best alignment is eventually found. This method for resolving ambiguity in multiple sequence alignment can be easily implemented by use of the improved scoring matrix.
1309.3312
Armita Nourmohammad
Armita Nourmohammad, Torsten Held, Michael L\"assig
Universality and predictability in molecular quantitative genetics
null
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Molecular traits, such as gene expression levels or protein binding affinities, are increasingly accessible to quantitative measurement by modern high-throughput techniques. Such traits measure molecular functions and, from an evolutionary point of view, are important as targets of natural selection. We review recent developments in evolutionary theory and experiments that are expected to become building blocks of a quantitative genetics of molecular traits. We focus on universal evolutionary characteristics: these are largely independent of a trait's genetic basis, which is often at least partially unknown. We show that universal measurements can be used to infer selection on a quantitative trait, which determines its evolutionary mode of conservation or adaptation. Furthermore, universality is closely linked to predictability of trait evolution across lineages. We argue that universal trait statistics extends over a range of cellular scales and opens new avenues of quantitative evolutionary systems biology.
[ { "created": "Thu, 12 Sep 2013 21:30:16 GMT", "version": "v1" }, { "created": "Thu, 14 Nov 2013 15:23:28 GMT", "version": "v2" } ]
2013-11-15
[ [ "Nourmohammad", "Armita", "" ], [ "Held", "Torsten", "" ], [ "Lässig", "Michael", "" ] ]
Molecular traits, such as gene expression levels or protein binding affinities, are increasingly accessible to quantitative measurement by modern high-throughput techniques. Such traits measure molecular functions and, from an evolutionary point of view, are important as targets of natural selection. We review recent developments in evolutionary theory and experiments that are expected to become building blocks of a quantitative genetics of molecular traits. We focus on universal evolutionary characteristics: these are largely independent of a trait's genetic basis, which is often at least partially unknown. We show that universal measurements can be used to infer selection on a quantitative trait, which determines its evolutionary mode of conservation or adaptation. Furthermore, universality is closely linked to predictability of trait evolution across lineages. We argue that universal trait statistics extends over a range of cellular scales and opens new avenues of quantitative evolutionary systems biology.
2406.12625
Polina Turishcheva
Polina Turishcheva, Max Burg, Fabian H. Sinz, Alexander Ecker
Reproducibility of predictive networks for mouse visual cortex
null
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by-nc-nd/4.0/
Deep predictive models of neuronal activity have recently enabled several new discoveries about the selectivity and invariance of neurons in the visual cortex. These models learn a shared set of nonlinear basis functions, which are linearly combined via a learned weight vector to represent a neuron's function. Such weight vectors, which can be thought as embeddings of neuronal function, have been proposed to define functional cell types via unsupervised clustering. However, as deep models are usually highly overparameterized, the learning problem is unlikely to have a unique solution, which raises the question if such embeddings can be used in a meaningful way for downstream analysis. In this paper, we investigate how stable neuronal embeddings are with respect to changes in model architecture and initialization. We find that $L_1$ regularization to be an important ingredient for structured embeddings and develop an adaptive regularization that adjusts the strength of regularization per neuron. This regularization improves both predictive performance and how consistently neuronal embeddings cluster across model fits compared to uniform regularization. To overcome overparametrization, we propose an iterative feature pruning strategy which reduces the dimensionality of performance-optimized models by half without loss of performance and improves the consistency of neuronal embeddings with respect to clustering neurons. This result suggests that to achieve an objective taxonomy of cell types or a compact representation of the functional landscape, we need novel architectures or learning techniques that improve identifiability. We will make our code available at publication time.
[ { "created": "Tue, 18 Jun 2024 13:50:08 GMT", "version": "v1" } ]
2024-06-19
[ [ "Turishcheva", "Polina", "" ], [ "Burg", "Max", "" ], [ "Sinz", "Fabian H.", "" ], [ "Ecker", "Alexander", "" ] ]
Deep predictive models of neuronal activity have recently enabled several new discoveries about the selectivity and invariance of neurons in the visual cortex. These models learn a shared set of nonlinear basis functions, which are linearly combined via a learned weight vector to represent a neuron's function. Such weight vectors, which can be thought as embeddings of neuronal function, have been proposed to define functional cell types via unsupervised clustering. However, as deep models are usually highly overparameterized, the learning problem is unlikely to have a unique solution, which raises the question if such embeddings can be used in a meaningful way for downstream analysis. In this paper, we investigate how stable neuronal embeddings are with respect to changes in model architecture and initialization. We find that $L_1$ regularization to be an important ingredient for structured embeddings and develop an adaptive regularization that adjusts the strength of regularization per neuron. This regularization improves both predictive performance and how consistently neuronal embeddings cluster across model fits compared to uniform regularization. To overcome overparametrization, we propose an iterative feature pruning strategy which reduces the dimensionality of performance-optimized models by half without loss of performance and improves the consistency of neuronal embeddings with respect to clustering neurons. This result suggests that to achieve an objective taxonomy of cell types or a compact representation of the functional landscape, we need novel architectures or learning techniques that improve identifiability. We will make our code available at publication time.
2005.13692
Sergei Chekmarev F.
Sergei F. Chekmarev
First-Passage Time Distributions in Two-State Protein Folding Kinetics: Exploring the Native-Like States vs Overcoming the Free Energy Barrier
27 pages, 21 figures
null
10.1039/D0CP06560A
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Using a beta-hairpin protein as a representative example of two-state folders, we studied how the exploration of native-like states affects the folding kinetics. It has been found that the first-passage time (FPT) distributions are essentially single-exponential not only for the times to overcome the free energy barrier that separates unfolded and native-like states but also for the times to find the native state among the native-like ones. If the protein explores native-like states for a time much longer than the time to overcome the free energy barrier, which was found to be characteristic of high temperatures, the resulting FPT distribution to reach the native state remains close to exponential but the mean FPT (MFPT) is determined not by the height of the free energy barrier but by the time to explore native-like states. The mean time to overcome the free energy barrier is found to be in reasonable agreement with the Kramers rate formula and generally far shorter than the MFPT to reach the native state. The time to find the native state among native-like ones increases with temperature, which explains the known U-shape dependence of the MFPTs on temperature.
[ { "created": "Wed, 27 May 2020 22:41:53 GMT", "version": "v1" }, { "created": "Thu, 6 Aug 2020 19:13:16 GMT", "version": "v2" } ]
2021-11-16
[ [ "Chekmarev", "Sergei F.", "" ] ]
Using a beta-hairpin protein as a representative example of two-state folders, we studied how the exploration of native-like states affects the folding kinetics. It has been found that the first-passage time (FPT) distributions are essentially single-exponential not only for the times to overcome the free energy barrier that separates unfolded and native-like states but also for the times to find the native state among the native-like ones. If the protein explores native-like states for a time much longer than the time to overcome the free energy barrier, which was found to be characteristic of high temperatures, the resulting FPT distribution to reach the native state remains close to exponential but the mean FPT (MFPT) is determined not by the height of the free energy barrier but by the time to explore native-like states. The mean time to overcome the free energy barrier is found to be in reasonable agreement with the Kramers rate formula and generally far shorter than the MFPT to reach the native state. The time to find the native state among native-like ones increases with temperature, which explains the known U-shape dependence of the MFPTs on temperature.
2201.03306
Diederik Aerts
Diederik Aerts and Lester Beltran
A Planck Radiation and Quantization Scheme for Human Cognition and Language
7 figures
Frontiers in Psychology 13, 850725 (2022)
10.3389/fpsyg.2022.850725
null
q-bio.NC cs.CL quant-ph
http://creativecommons.org/licenses/by/4.0/
As a result of the identification of 'identity' and 'indistinguishability' and strong experimental evidence for the presence of the associated Bose-Einstein statistics in human cognition and language, we argued in previous work for an extension of the research domain of quantum cognition. In addition to quantum complex vector spaces and quantum probability models, we showed that quantization itself, with words as quanta, is relevant and potentially important to human cognition. In the present work, we build on this result, and introduce a powerful radiation quantization scheme for human cognition. We show that the lack of independence of the Bose-Einstein statistics compared to the Maxwell-Boltzmann statistics can be explained by the presence of a 'meaning dynamics', which causes words to be attracted to the same words. And so words clump together in the same states, a phenomenon well known for photons in the early years of quantum mechanics, leading to fierce disagreements between Planck and Einstein. Using a simple example, we introduce all the elements to get a better and detailed view of this 'meaning dynamics', such as micro and macro states, and Maxwell-Boltzmann, Bose-Einstein and Fermi-Dirac numbers and weights, and compare this example and its graphs, with the radiation quantization scheme of a Winnie the Pooh story, also with its graphs. By connecting a concept directly to human experience, we show that entanglement is a necessity for preserving the 'meaning dynamics' we identified, and it becomes clear in what way Fermi-Dirac addresses human memory. Within the human mind, as a crucial aspect of memory, in spaces with internal parameters, identical words can nevertheless be assigned different states and hence realize locally and contextually the necessary distinctiveness, structured by a Pauli exclusion principle, for human thought to thrive.
[ { "created": "Mon, 10 Jan 2022 12:13:23 GMT", "version": "v1" }, { "created": "Fri, 4 Mar 2022 10:31:22 GMT", "version": "v2" } ]
2023-02-27
[ [ "Aerts", "Diederik", "" ], [ "Beltran", "Lester", "" ] ]
As a result of the identification of 'identity' and 'indistinguishability' and strong experimental evidence for the presence of the associated Bose-Einstein statistics in human cognition and language, we argued in previous work for an extension of the research domain of quantum cognition. In addition to quantum complex vector spaces and quantum probability models, we showed that quantization itself, with words as quanta, is relevant and potentially important to human cognition. In the present work, we build on this result, and introduce a powerful radiation quantization scheme for human cognition. We show that the lack of independence of the Bose-Einstein statistics compared to the Maxwell-Boltzmann statistics can be explained by the presence of a 'meaning dynamics', which causes words to be attracted to the same words. And so words clump together in the same states, a phenomenon well known for photons in the early years of quantum mechanics, leading to fierce disagreements between Planck and Einstein. Using a simple example, we introduce all the elements to get a better and detailed view of this 'meaning dynamics', such as micro and macro states, and Maxwell-Boltzmann, Bose-Einstein and Fermi-Dirac numbers and weights, and compare this example and its graphs, with the radiation quantization scheme of a Winnie the Pooh story, also with its graphs. By connecting a concept directly to human experience, we show that entanglement is a necessity for preserving the 'meaning dynamics' we identified, and it becomes clear in what way Fermi-Dirac addresses human memory. Within the human mind, as a crucial aspect of memory, in spaces with internal parameters, identical words can nevertheless be assigned different states and hence realize locally and contextually the necessary distinctiveness, structured by a Pauli exclusion principle, for human thought to thrive.
1804.01217
Md Nafiz Hamid
Md-Nafiz Hamid
Gene Co-expression Network analysis of Lung Squamous Cell Carcinoma data
null
null
null
null
q-bio.GN q-bio.MN
http://creativecommons.org/licenses/by/4.0/
We performed a gene co-expression analysis on Lung Squamous Cell Carcinoma data to find modules (groups) of genes that may highly impact the growth of these type of tumors. Additionally, we used cancer survival data to relate modules to prognostic significance in terms of survival time. Analysis on RNA-seq data revealed modules which are significant in gene enrichment analysis. Specifically, two genes - RFC4 and ECT2 - have been found to be significant in terms of survival time. We also performed a second gene co-expression analysis on a second dataset of microarray data, and many significant genes found in this analysis could also be found in the RNA-seq data implying that these genes might indeed play a crucial role in Lung Squamous Cancer. All the R code for the analysis can be found at: \url{https://github.com/nafizh/Gene_coexpression_analysis_lung_cancer}
[ { "created": "Wed, 4 Apr 2018 02:38:26 GMT", "version": "v1" } ]
2018-04-05
[ [ "Hamid", "Md-Nafiz", "" ] ]
We performed a gene co-expression analysis on Lung Squamous Cell Carcinoma data to find modules (groups) of genes that may highly impact the growth of these type of tumors. Additionally, we used cancer survival data to relate modules to prognostic significance in terms of survival time. Analysis on RNA-seq data revealed modules which are significant in gene enrichment analysis. Specifically, two genes - RFC4 and ECT2 - have been found to be significant in terms of survival time. We also performed a second gene co-expression analysis on a second dataset of microarray data, and many significant genes found in this analysis could also be found in the RNA-seq data implying that these genes might indeed play a crucial role in Lung Squamous Cancer. All the R code for the analysis can be found at: \url{https://github.com/nafizh/Gene_coexpression_analysis_lung_cancer}
1410.4711
Sarah Hallerberg
Heike Vester, Kurt Hammerschmidt, Marc Timme, Sarah Hallerberg
Bag-of-calls analysis reveals group-specific vocal repertoire in long-finned pilot whales
under review
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Besides humans, several marine mammal species exhibit prerequisites to evolve language: high cognitive abilities, flexibility in vocal production and advanced social interactions. Here, we describe and analyse the vocal repertoire of long-finned pilot whales (Globicephalus melas) recorded in northern Norway. Observer based analysis reveals a complex vocal repertoire with 140 different call types, call sequences, call repetitions and group-specific differences in the usage of call types. Developing and applying a new automated analysis method, the bag-of-calls approach, we find that groups of pilot whales can be distinguished purely by statistical properties of their vocalisations. Comparing inter-and intra-group differences of ensembles of calls allows to identify and quantify group-specificity. Consequently, the bag-of-calls approach is a valid method to specify difference and concordance in acoustic communication in the absence of exact knowledge about signalers, which is common observing marine mammals under natural conditions.
[ { "created": "Fri, 17 Oct 2014 13:06:09 GMT", "version": "v1" }, { "created": "Fri, 12 Jun 2015 12:05:44 GMT", "version": "v2" } ]
2015-06-15
[ [ "Vester", "Heike", "" ], [ "Hammerschmidt", "Kurt", "" ], [ "Timme", "Marc", "" ], [ "Hallerberg", "Sarah", "" ] ]
Besides humans, several marine mammal species exhibit prerequisites to evolve language: high cognitive abilities, flexibility in vocal production and advanced social interactions. Here, we describe and analyse the vocal repertoire of long-finned pilot whales (Globicephalus melas) recorded in northern Norway. Observer based analysis reveals a complex vocal repertoire with 140 different call types, call sequences, call repetitions and group-specific differences in the usage of call types. Developing and applying a new automated analysis method, the bag-of-calls approach, we find that groups of pilot whales can be distinguished purely by statistical properties of their vocalisations. Comparing inter-and intra-group differences of ensembles of calls allows to identify and quantify group-specificity. Consequently, the bag-of-calls approach is a valid method to specify difference and concordance in acoustic communication in the absence of exact knowledge about signalers, which is common observing marine mammals under natural conditions.
1207.3811
Arda Halu
Arda Halu and Ginestra Bianconi
Monochromaticity in Neutral Evolutionary Network Models
8 pages, 14 figures
Phys. Rev. E 86, 066101 (2012)
10.1103/PhysRevE.86.066101
null
q-bio.MN cond-mat.dis-nn cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Recent studies on epistatic networks of model organisms have unveiled a certain type of modular property called monochromaticity in which the networks are clusterable into functional modules that interact with each other through the same type of epistasis. Here we propose and study three epistatic network models that are inspired by the Duplication-Divergence mechanism to gain insight into the evolutionary basis of monochromaticity and to test if it can be explained as the outcome of a neutral evolutionary hypothesis. We show that the epistatic networks formed by these stochastic evolutionary models have monochromaticity conflict distributions that are centered close to zero and are statistically significantly different from their randomized counterparts. In particular, the last model we propose yields a strictly monochromatic solution. Our results agree with the monochromaticity findings in real organisms and point toward the possible role of a neutral mechanism in the evolution of this phenomenon.
[ { "created": "Mon, 16 Jul 2012 20:05:55 GMT", "version": "v1" }, { "created": "Sat, 17 Nov 2012 05:12:47 GMT", "version": "v2" } ]
2013-05-30
[ [ "Halu", "Arda", "" ], [ "Bianconi", "Ginestra", "" ] ]
Recent studies on epistatic networks of model organisms have unveiled a certain type of modular property called monochromaticity in which the networks are clusterable into functional modules that interact with each other through the same type of epistasis. Here we propose and study three epistatic network models that are inspired by the Duplication-Divergence mechanism to gain insight into the evolutionary basis of monochromaticity and to test if it can be explained as the outcome of a neutral evolutionary hypothesis. We show that the epistatic networks formed by these stochastic evolutionary models have monochromaticity conflict distributions that are centered close to zero and are statistically significantly different from their randomized counterparts. In particular, the last model we propose yields a strictly monochromatic solution. Our results agree with the monochromaticity findings in real organisms and point toward the possible role of a neutral mechanism in the evolution of this phenomenon.
2007.13368
Henning Stumpf
Henning Stumpf (1), Andreja Ambriovi\'c-Ristov (2), Aleksandra Radenovic (3), Ana-Sun\v{c}ana Smith (1 and 4) ((1) PULS Group, Institute for Theoretical Physics, Interdisciplinary Center for Nanostructured Films, Friedrich-Alexander-Universit\"at Erlangen-N\"urnberg, Erlangen, Germany, (2) Laboratory for Cell Biology and Signalling, Division of Molecular Biology, Ru{\dj}er Bo\v{s}kovi\'c Institute, Zagreb, Croatia, (3) Laboratory of Nanoscale Biology, \'Ecole Polytechnique F\'ed\'erale de Lausanne, Lausanne, Switzerland, (4) Group for Computational Life Sciences, Department of Physical Chemistry, Ru{\dj}er Bo\v{s}kovi\'c Institute, Zagreb, Croatia)
Recent Advances and Prospects in the Research of Nascent Adhesions
38 pages, 2 figures, review article
null
10.3389/fphys.2020.574371
null
q-bio.SC physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Nascent adhesions are submicron transient structures promoting the early adhesion of cells to the extracellular matrix. Nascent adhesions typically consist of several tens of integrins, and serve as platforms for the recruitment and activation of proteins to build mature focal adhesions. They are also associated with early stage signalling and the mechanoresponse. Despite their crucial role in sampling the local extracellular matrix, very little is known about the mechanism of their formation. Consequently, there is a strong scientific activity focused on elucidating the physical and biochemical foundation of their development and function. Precisely the results of this effort will be summarized in this article.
[ { "created": "Mon, 27 Jul 2020 08:35:15 GMT", "version": "v1" } ]
2021-01-19
[ [ "Stumpf", "Henning", "", "1 and 4" ], [ "Ambriović-Ristov", "Andreja", "", "1 and 4" ], [ "Radenovic", "Aleksandra", "", "1 and 4" ], [ "Smith", "Ana-Sunčana", "", "1 and 4" ] ]
Nascent adhesions are submicron transient structures promoting the early adhesion of cells to the extracellular matrix. Nascent adhesions typically consist of several tens of integrins, and serve as platforms for the recruitment and activation of proteins to build mature focal adhesions. They are also associated with early stage signalling and the mechanoresponse. Despite their crucial role in sampling the local extracellular matrix, very little is known about the mechanism of their formation. Consequently, there is a strong scientific activity focused on elucidating the physical and biochemical foundation of their development and function. Precisely the results of this effort will be summarized in this article.
1906.07463
Tom Chou
Renaud Dessalles, Yunbei Pan, Mingtao Xia, Davide Maestrini, Maria R. D'Orsogna, Tom Chou
How heterogeneous thymic output and homeostatic proliferation shape naive T cell receptor clone abundance distributions
significant revision, including improved data fitting, 23 pages, 11 figures
null
null
null
q-bio.PE q-bio.TO
http://creativecommons.org/licenses/by-nc-sa/4.0/
The set of T cells that express the same T cell receptor (TCR) sequence represents a T cell clone. The number of different naive T cell clones in an organism reflects the number of different T cell receptors (TCRs) arising from recombination of the V(D)J gene segments during T cell development in the thymus. TCR diversity and more specifically, the clone abundance distribution is an important factor in immune function. Specific recombination patterns occur more frequently than others while subsequent interactions between TCRs and self-antigens are known to trigger proliferation and sustain naive T cell survival. These processes are TCR-dependent, leading to clone-dependent thymic export and naive T cell proliferation rates. Using a mean-field approximation to the solution of a regulated birth-death-immigration model and a modification arising from sampling, we systematically quantify how TCR-dependent heterogeneities in immigration and proliferation rates affect the shape of clone abundance distributions (the number of different clones that are represented by a specific number of cells, or "clone counts"). By comparing predicted clone counts derived from our heterogeneous birth-death-immigration model with experimentally sampled clone abundances, we show that although heterogeneity in immigration rates causes very little change to predicted clone-counts, significant heterogeneity in proliferation rates is necessary to generate the observed abundances with reasonable physiological parameter values. Our analysis provides constraints among physiological parameters that are necessary to yield predictions that qualitatively match the data. Assumptions of the model and potentially other important mechanistic factors are discussed.
[ { "created": "Tue, 18 Jun 2019 09:33:31 GMT", "version": "v1" }, { "created": "Thu, 5 Mar 2020 04:15:31 GMT", "version": "v2" } ]
2020-03-06
[ [ "Dessalles", "Renaud", "" ], [ "Pan", "Yunbei", "" ], [ "Xia", "Mingtao", "" ], [ "Maestrini", "Davide", "" ], [ "D'Orsogna", "Maria R.", "" ], [ "Chou", "Tom", "" ] ]
The set of T cells that express the same T cell receptor (TCR) sequence represents a T cell clone. The number of different naive T cell clones in an organism reflects the number of different T cell receptors (TCRs) arising from recombination of the V(D)J gene segments during T cell development in the thymus. TCR diversity and more specifically, the clone abundance distribution is an important factor in immune function. Specific recombination patterns occur more frequently than others while subsequent interactions between TCRs and self-antigens are known to trigger proliferation and sustain naive T cell survival. These processes are TCR-dependent, leading to clone-dependent thymic export and naive T cell proliferation rates. Using a mean-field approximation to the solution of a regulated birth-death-immigration model and a modification arising from sampling, we systematically quantify how TCR-dependent heterogeneities in immigration and proliferation rates affect the shape of clone abundance distributions (the number of different clones that are represented by a specific number of cells, or "clone counts"). By comparing predicted clone counts derived from our heterogeneous birth-death-immigration model with experimentally sampled clone abundances, we show that although heterogeneity in immigration rates causes very little change to predicted clone-counts, significant heterogeneity in proliferation rates is necessary to generate the observed abundances with reasonable physiological parameter values. Our analysis provides constraints among physiological parameters that are necessary to yield predictions that qualitatively match the data. Assumptions of the model and potentially other important mechanistic factors are discussed.
2106.14192
Jianye Pang
Kai Yi, Jianye Pang, Yungeng Zhang, Xiangrui Zeng, Min Xu
Disentangling semantic features of macromolecules in Cryo-Electron Tomography
null
null
null
null
q-bio.BM cs.CV
http://creativecommons.org/licenses/by-nc-sa/4.0/
Cryo-electron tomography (Cryo-ET) is a 3D imaging technique that enables the systemic study of shape, abundance, and distribution of macromolecular structures in single cells in near-atomic resolution. However, the systematic and efficient $\textit{de novo}$ recognition and recovery of macromolecular structures captured by Cryo-ET are very challenging due to the structural complexity and imaging limits. Even macromolecules with identical structures have various appearances due to different orientations and imaging limits, such as noise and the missing wedge effect. Explicitly disentangling the semantic features of macromolecules is crucial for performing several downstream analyses on the macromolecules. This paper has addressed the problem by proposing a 3D Spatial Variational Autoencoder that explicitly disentangle the structure, orientation, and shift of macromolecules. Extensive experiments on both synthesized and real cryo-ET datasets and cross-domain evaluations demonstrate the efficacy of our method.
[ { "created": "Sun, 27 Jun 2021 10:41:26 GMT", "version": "v1" } ]
2021-06-29
[ [ "Yi", "Kai", "" ], [ "Pang", "Jianye", "" ], [ "Zhang", "Yungeng", "" ], [ "Zeng", "Xiangrui", "" ], [ "Xu", "Min", "" ] ]
Cryo-electron tomography (Cryo-ET) is a 3D imaging technique that enables the systemic study of shape, abundance, and distribution of macromolecular structures in single cells in near-atomic resolution. However, the systematic and efficient $\textit{de novo}$ recognition and recovery of macromolecular structures captured by Cryo-ET are very challenging due to the structural complexity and imaging limits. Even macromolecules with identical structures have various appearances due to different orientations and imaging limits, such as noise and the missing wedge effect. Explicitly disentangling the semantic features of macromolecules is crucial for performing several downstream analyses on the macromolecules. This paper has addressed the problem by proposing a 3D Spatial Variational Autoencoder that explicitly disentangle the structure, orientation, and shift of macromolecules. Extensive experiments on both synthesized and real cryo-ET datasets and cross-domain evaluations demonstrate the efficacy of our method.
1905.01933
Maria Masoliver
Maria Masoliver and Cristina Masoller
Neuronal coupling benefits the encoding of weak periodic signals in symbolic spike patterns
null
null
10.1016/j.cnsns.2019.105023
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A good understanding of how neurons use electrical pulses (i.e, spikes) to encode the signal information remains elusive. Analyzing spike sequences generated by individual neurons and by two coupled neurons (using the stochastic FitzHugh-Nagumo model), recent theoretical studies have found that the relative timing of the spikes can encode the signal information. Using a symbolic method to analyze the spike sequence, preferred and infrequent spike patterns were detected, whose probabilities vary with both, the amplitude and the frequency of the signal. To investigate if this encoding mechanism is plausible also for neuronal ensembles, here we analyze the activity of a group of neurons, when they all perceive a weak periodic signal. We find that, as in the case of one or two coupled neurons, the probabilities of the spike patterns, now computed from the spike sequences of all the neurons, depend on the signal's amplitude and period, and thus, the patterns' probabilities encode the information of the signal. We also find that the resonances with the period of the signal or with the noise level are more pronounced when a group of neurons perceive the signal, in comparison with when only one or two coupled neurons perceive it. Neuronal coupling is beneficial for signal encoding as a group of neurons is able to encode a small-amplitude signal, which could not be encoded when it is perceived by just one or two coupled neurons. Interestingly, we find that for a group of neurons, just a few connections with one another can significantly improve the encoding of small-amplitude signals. Our findings indicate that information encoding in preferred and infrequent spike patterns is a plausible mechanism that can be employed by neuronal populations to encode weak periodic inputs, exploiting the presence of neural noise.
[ { "created": "Mon, 6 May 2019 11:25:24 GMT", "version": "v1" } ]
2019-10-23
[ [ "Masoliver", "Maria", "" ], [ "Masoller", "Cristina", "" ] ]
A good understanding of how neurons use electrical pulses (i.e, spikes) to encode the signal information remains elusive. Analyzing spike sequences generated by individual neurons and by two coupled neurons (using the stochastic FitzHugh-Nagumo model), recent theoretical studies have found that the relative timing of the spikes can encode the signal information. Using a symbolic method to analyze the spike sequence, preferred and infrequent spike patterns were detected, whose probabilities vary with both, the amplitude and the frequency of the signal. To investigate if this encoding mechanism is plausible also for neuronal ensembles, here we analyze the activity of a group of neurons, when they all perceive a weak periodic signal. We find that, as in the case of one or two coupled neurons, the probabilities of the spike patterns, now computed from the spike sequences of all the neurons, depend on the signal's amplitude and period, and thus, the patterns' probabilities encode the information of the signal. We also find that the resonances with the period of the signal or with the noise level are more pronounced when a group of neurons perceive the signal, in comparison with when only one or two coupled neurons perceive it. Neuronal coupling is beneficial for signal encoding as a group of neurons is able to encode a small-amplitude signal, which could not be encoded when it is perceived by just one or two coupled neurons. Interestingly, we find that for a group of neurons, just a few connections with one another can significantly improve the encoding of small-amplitude signals. Our findings indicate that information encoding in preferred and infrequent spike patterns is a plausible mechanism that can be employed by neuronal populations to encode weak periodic inputs, exploiting the presence of neural noise.
1806.05753
Thierry Mora
Andreas Mayer, Vijay Balasubramanian, Aleksandra M. Walczak, Thierry Mora
How a well-adapting immune system remembers
null
Proc Natl Acad Sci 116(18) 8815-8823 (2019)
10.1073/pnas.1812810116
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its memory repertoire by balancing evidence from new pathogen encounters against past experience of infection to predict and prepare for future threats. This framework links the observed initial rapid increase of the memory pool early in life followed by a mid-life plateau to the ease of learning salient features of sparse environments. We also derive a modulated memory pool update rule in agreement with current vaccine response experiments. Our results suggest that pathogenic environments are sparse and that memory repertoires significantly decrease infection costs even with moderate sampling. The predicted optimal update scheme maps onto commonly considered competitive dynamics for antigen receptors.
[ { "created": "Thu, 14 Jun 2018 22:03:55 GMT", "version": "v1" }, { "created": "Tue, 13 Nov 2018 10:58:08 GMT", "version": "v2" } ]
2019-05-14
[ [ "Mayer", "Andreas", "" ], [ "Balasubramanian", "Vijay", "" ], [ "Walczak", "Aleksandra M.", "" ], [ "Mora", "Thierry", "" ] ]
An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its memory repertoire by balancing evidence from new pathogen encounters against past experience of infection to predict and prepare for future threats. This framework links the observed initial rapid increase of the memory pool early in life followed by a mid-life plateau to the ease of learning salient features of sparse environments. We also derive a modulated memory pool update rule in agreement with current vaccine response experiments. Our results suggest that pathogenic environments are sparse and that memory repertoires significantly decrease infection costs even with moderate sampling. The predicted optimal update scheme maps onto commonly considered competitive dynamics for antigen receptors.
2009.05285
Amit Tewari
Amit Tewari
Temporal Analysis of COVID-19 Peak Outbreak
5 pages, 10 figures, 2 tables
null
null
null
q-bio.PE physics.soc-ph
http://creativecommons.org/licenses/by-sa/4.0/
Intent of this research is to explore how mathematical models, specifically Susceptible-Infected-Removed (SIR) model, can be utilized to forecast peak outbreak timeline of COVID-19 epidemic amongst a population of interest starting from the date of first reported case. Till the time of this research, there was no effective and universally accepted vaccine to control transmission and spread of this infection. COVID-19 primarily spreads in population through respiratory droplets from an infected person cough and sneeze which infects people who are in proximity. COVID-19 is spreading contagiously across the world. If health policy makers and medical experts could get early and timely insights into when peak infection rate would occur after first reported case, they could plan and optimize medical personnel, ventilators supply, and other medical resources without over-taxing the infrastructure. The predictions may also help policymakers devise strategies to control the epidemic, potentially saving many lives. Thus, it can aid in critical decision-making process by providing actionable insights into COVID-19 outbreak by leveraging available data.
[ { "created": "Fri, 11 Sep 2020 08:34:28 GMT", "version": "v1" } ]
2020-09-14
[ [ "Tewari", "Amit", "" ] ]
Intent of this research is to explore how mathematical models, specifically Susceptible-Infected-Removed (SIR) model, can be utilized to forecast peak outbreak timeline of COVID-19 epidemic amongst a population of interest starting from the date of first reported case. Till the time of this research, there was no effective and universally accepted vaccine to control transmission and spread of this infection. COVID-19 primarily spreads in population through respiratory droplets from an infected person cough and sneeze which infects people who are in proximity. COVID-19 is spreading contagiously across the world. If health policy makers and medical experts could get early and timely insights into when peak infection rate would occur after first reported case, they could plan and optimize medical personnel, ventilators supply, and other medical resources without over-taxing the infrastructure. The predictions may also help policymakers devise strategies to control the epidemic, potentially saving many lives. Thus, it can aid in critical decision-making process by providing actionable insights into COVID-19 outbreak by leveraging available data.
1104.5458
George Kesidis
Yaman Aksu, David J. Miller, George Kesidis, Don C. Bigler, Qing X. Yang
An MRI-Derived Definition of MCI-to-AD Conversion for Long-Term, Automati c Prognosis of MCI Patients
null
null
10.1371/journal.pone.0025074
null
q-bio.NC physics.med-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Alzheimer's disease (AD) and mild cognitive impairment (MCI), continue to be widely studied. While there is no consensus on whether MCIs actually "convert" to AD, the more important question is not whether MCIs convert, but what is the best such definition. We focus on automatic prognostication, nominally using only a baseline image brain scan, of whether an MCI individual will convert to AD within a multi-year period following the initial clinical visit. This is in fact not a traditional supervised learning problem since, in ADNI, there are no definitive labeled examples of MCI conversion. Prior works have defined MCI subclasses based on whether or not clinical/cognitive scores such as CDR significantly change from baseline. There are concerns with these definitions, however, since e.g. most MCIs (and ADs) do not change from a baseline CDR=0.5, even while physiological changes may be occurring. These works ignore rich phenotypical information in an MCI patient's brain scan and labeled AD and Control examples, in defining conversion. We propose an innovative conversion definition, wherein an MCI patient is declared to be a converter if any of the patient's brain scans (at follow-up visits) are classified "AD" by an (accurately-designed) Control-AD classifier. This novel definition bootstraps the design of a second classifier, specifically trained to predict whether or not MCIs will convert. This second classifier thus predicts whether an AD-Control classifier will predict that a patient has AD. Our results demonstrate this new definition leads not only to much higher prognostic accuracy than by-CDR conversion, but also to subpopulations much more consistent with known AD brain region biomarkers. We also identify key prognostic region biomarkers, essential for accurately discriminating the converter and nonconverter groups.
[ { "created": "Thu, 28 Apr 2011 17:56:32 GMT", "version": "v1" } ]
2015-05-28
[ [ "Aksu", "Yaman", "" ], [ "Miller", "David J.", "" ], [ "Kesidis", "George", "" ], [ "Bigler", "Don C.", "" ], [ "Yang", "Qing X.", "" ] ]
Alzheimer's disease (AD) and mild cognitive impairment (MCI), continue to be widely studied. While there is no consensus on whether MCIs actually "convert" to AD, the more important question is not whether MCIs convert, but what is the best such definition. We focus on automatic prognostication, nominally using only a baseline image brain scan, of whether an MCI individual will convert to AD within a multi-year period following the initial clinical visit. This is in fact not a traditional supervised learning problem since, in ADNI, there are no definitive labeled examples of MCI conversion. Prior works have defined MCI subclasses based on whether or not clinical/cognitive scores such as CDR significantly change from baseline. There are concerns with these definitions, however, since e.g. most MCIs (and ADs) do not change from a baseline CDR=0.5, even while physiological changes may be occurring. These works ignore rich phenotypical information in an MCI patient's brain scan and labeled AD and Control examples, in defining conversion. We propose an innovative conversion definition, wherein an MCI patient is declared to be a converter if any of the patient's brain scans (at follow-up visits) are classified "AD" by an (accurately-designed) Control-AD classifier. This novel definition bootstraps the design of a second classifier, specifically trained to predict whether or not MCIs will convert. This second classifier thus predicts whether an AD-Control classifier will predict that a patient has AD. Our results demonstrate this new definition leads not only to much higher prognostic accuracy than by-CDR conversion, but also to subpopulations much more consistent with known AD brain region biomarkers. We also identify key prognostic region biomarkers, essential for accurately discriminating the converter and nonconverter groups.
1303.3332
Brent Pedersen
Brent S Pedersen, Ivana V Yang, Subhajyoti De
CruzDB: software for annotation of genomic intervals with UCSC genome-browser data
4 pages, 1 figure
null
null
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The biological significance of genomic features is often context-dependent. We present CruzDB, a fast and intuitive programmatic interface to the UCSC genome browser that facilitates integrative analyses of diverse local and remotely hosted datasets. We showcase the syntax of CruzDB using miRNA-binding sites as examples, and further demonstrate its utility with 3 novel biological discoveries. First, we find that while exons replicate early, introns tend to replicate late, suggesting a complex replication pattern in gene regions. Second, variants associated with cognitive functions map to lincRNA transcripts of relevant function. Third, lamina-associated domains are highly enriched in olfaction-related genes. CruzDB is available at https://github.com/brentp/cruzdb
[ { "created": "Thu, 14 Mar 2013 01:41:09 GMT", "version": "v1" }, { "created": "Tue, 9 Jul 2013 22:02:30 GMT", "version": "v2" } ]
2013-07-11
[ [ "Pedersen", "Brent S", "" ], [ "Yang", "Ivana V", "" ], [ "De", "Subhajyoti", "" ] ]
The biological significance of genomic features is often context-dependent. We present CruzDB, a fast and intuitive programmatic interface to the UCSC genome browser that facilitates integrative analyses of diverse local and remotely hosted datasets. We showcase the syntax of CruzDB using miRNA-binding sites as examples, and further demonstrate its utility with 3 novel biological discoveries. First, we find that while exons replicate early, introns tend to replicate late, suggesting a complex replication pattern in gene regions. Second, variants associated with cognitive functions map to lincRNA transcripts of relevant function. Third, lamina-associated domains are highly enriched in olfaction-related genes. CruzDB is available at https://github.com/brentp/cruzdb
1912.05433
Tiberiu Tesileanu
Tiberiu Tesileanu, Mary M. Conte, John J. Briguglio, Ann M. Hermundstad, Jonathan D. Victor, Vijay Balasubramanian
Efficient coding of natural scene statistics predicts discrimination thresholds for grayscale textures
33 pages, 12 figures
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
Previously, in (Hermundstad et al., 2014), we showed that when sampling is limiting, the efficient coding principle leads to a "variance is salience" hypothesis, and that this hypothesis accounts for visual sensitivity to binary image statistics. Here, using extensive new psychophysical data and image analysis, we show that this hypothesis accounts for visual sensitivity to a large set of grayscale image statistics at a striking level of detail, and also identify the limits of the prediction. We define a 66-dimensional space of local grayscale light-intensity correlations, and measure the relevance of each direction to natural scenes. The "variance is salience" hypothesis predicts that two-point correlations are most salient, and predicts their relative salience. We tested these predictions in a texture-segregation task using un-natural, synthetic textures. As predicted, correlations beyond second order are not salient, and predicted thresholds for over 300 second-order correlations match psychophysical thresholds closely (median fractional error <0.13).
[ { "created": "Wed, 11 Dec 2019 16:41:27 GMT", "version": "v1" }, { "created": "Fri, 10 Jul 2020 19:39:24 GMT", "version": "v2" } ]
2020-07-14
[ [ "Tesileanu", "Tiberiu", "" ], [ "Conte", "Mary M.", "" ], [ "Briguglio", "John J.", "" ], [ "Hermundstad", "Ann M.", "" ], [ "Victor", "Jonathan D.", "" ], [ "Balasubramanian", "Vijay", "" ] ]
Previously, in (Hermundstad et al., 2014), we showed that when sampling is limiting, the efficient coding principle leads to a "variance is salience" hypothesis, and that this hypothesis accounts for visual sensitivity to binary image statistics. Here, using extensive new psychophysical data and image analysis, we show that this hypothesis accounts for visual sensitivity to a large set of grayscale image statistics at a striking level of detail, and also identify the limits of the prediction. We define a 66-dimensional space of local grayscale light-intensity correlations, and measure the relevance of each direction to natural scenes. The "variance is salience" hypothesis predicts that two-point correlations are most salient, and predicts their relative salience. We tested these predictions in a texture-segregation task using un-natural, synthetic textures. As predicted, correlations beyond second order are not salient, and predicted thresholds for over 300 second-order correlations match psychophysical thresholds closely (median fractional error <0.13).
2306.11768
Zaixi Zhang
Zaixi Zhang, Jiaxian Yan, Qi Liu, Enhong Chen, and Marinka Zitnik
A Systematic Survey in Geometric Deep Learning for Structure-based Drug Design
20 pages, under review
null
null
null
q-bio.QM cs.CE cs.LG
http://creativecommons.org/licenses/by-nc-sa/4.0/
Structure-based drug design (SBDD) utilizes the three-dimensional geometry of proteins to identify potential drug candidates. Traditional methods, grounded in physicochemical modeling and informed by domain expertise, are resource-intensive. Recent developments in geometric deep learning, focusing on the integration and processing of 3D geometric data, coupled with the availability of accurate protein 3D structure predictions from tools like AlphaFold, have greatly advanced the field of structure-based drug design. This paper systematically reviews the current state of geometric deep learning in SBDD. We first outline foundational tasks in SBDD, detail prevalent 3D protein representations, and highlight representative predictive and generative models. We then offer in-depth reviews of each key task, including binding site prediction, binding pose generation, \emph{de novo} molecule generation, linker design, and binding affinity prediction. We provide formal problem definitions and outline each task's representative methods, datasets, evaluation metrics, and performance benchmarks. Finally, we summarize the current challenges and future opportunities: current challenges in SBDD include oversimplified problem formulations, inadequate out-of-distribution generalization, a lack of reliable evaluation metrics and large-scale benchmarks, and the need for experimental verification and enhanced model understanding; opportunities include leveraging multimodal datasets, integrating domain knowledge, building comprehensive benchmarks, designing criteria based on clinical endpoints, and developing foundation models that broaden the range of design tasks. We also curate \url{https://github.com/zaixizhang/Awesome-SBDD}, reflecting ongoing contributions and new datasets in SBDD.
[ { "created": "Tue, 20 Jun 2023 14:21:58 GMT", "version": "v1" }, { "created": "Thu, 22 Jun 2023 03:05:21 GMT", "version": "v2" }, { "created": "Mon, 3 Jul 2023 14:38:17 GMT", "version": "v3" }, { "created": "Sat, 14 Oct 2023 20:54:09 GMT", "version": "v4" }, { "created": "Tue, 24 Oct 2023 14:22:59 GMT", "version": "v5" } ]
2023-10-25
[ [ "Zhang", "Zaixi", "" ], [ "Yan", "Jiaxian", "" ], [ "Liu", "Qi", "" ], [ "Chen", "Enhong", "" ], [ "Zitnik", "Marinka", "" ] ]
Structure-based drug design (SBDD) utilizes the three-dimensional geometry of proteins to identify potential drug candidates. Traditional methods, grounded in physicochemical modeling and informed by domain expertise, are resource-intensive. Recent developments in geometric deep learning, focusing on the integration and processing of 3D geometric data, coupled with the availability of accurate protein 3D structure predictions from tools like AlphaFold, have greatly advanced the field of structure-based drug design. This paper systematically reviews the current state of geometric deep learning in SBDD. We first outline foundational tasks in SBDD, detail prevalent 3D protein representations, and highlight representative predictive and generative models. We then offer in-depth reviews of each key task, including binding site prediction, binding pose generation, \emph{de novo} molecule generation, linker design, and binding affinity prediction. We provide formal problem definitions and outline each task's representative methods, datasets, evaluation metrics, and performance benchmarks. Finally, we summarize the current challenges and future opportunities: current challenges in SBDD include oversimplified problem formulations, inadequate out-of-distribution generalization, a lack of reliable evaluation metrics and large-scale benchmarks, and the need for experimental verification and enhanced model understanding; opportunities include leveraging multimodal datasets, integrating domain knowledge, building comprehensive benchmarks, designing criteria based on clinical endpoints, and developing foundation models that broaden the range of design tasks. We also curate \url{https://github.com/zaixizhang/Awesome-SBDD}, reflecting ongoing contributions and new datasets in SBDD.
2407.18329
Shuqiang Wang
Yongcheng Zong, Shuqiang Wang
A New Brain Network Construction Paradigm for Brain Disorder via Diffusion-based Graph Contrastive Learning
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Brain network analysis plays an increasingly important role in studying brain function and the exploring of disease mechanisms. However, existing brain network construction tools have some limitations, including dependency on empirical users, weak consistency in repeated experiments and time-consuming processes. In this work, a diffusion-based brain network pipeline, DGCL is designed for end-to-end construction of brain networks. Initially, the brain region-aware module (BRAM) precisely determines the spatial locations of brain regions by the diffusion process, avoiding subjective parameter selection. Subsequently, DGCL employs graph contrastive learning to optimize brain connections by eliminating individual differences in redundant connections unrelated to diseases, thereby enhancing the consistency of brain networks within the same group. Finally, the node-graph contrastive loss and classification loss jointly constrain the learning process of the model to obtain the reconstructed brain network, which is then used to analyze important brain connections. Validation on two datasets, ADNI and ABIDE, demonstrates that DGCL surpasses traditional methods and other deep learning models in predicting disease development stages. Significantly, the proposed model improves the efficiency and generalization of brain network construction. In summary, the proposed DGCL can be served as a universal brain network construction scheme, which can effectively identify important brain connections through generative paradigms and has the potential to provide disease interpretability support for neuroscience research.
[ { "created": "Sat, 6 Jul 2024 02:47:48 GMT", "version": "v1" } ]
2024-07-29
[ [ "Zong", "Yongcheng", "" ], [ "Wang", "Shuqiang", "" ] ]
Brain network analysis plays an increasingly important role in studying brain function and the exploring of disease mechanisms. However, existing brain network construction tools have some limitations, including dependency on empirical users, weak consistency in repeated experiments and time-consuming processes. In this work, a diffusion-based brain network pipeline, DGCL is designed for end-to-end construction of brain networks. Initially, the brain region-aware module (BRAM) precisely determines the spatial locations of brain regions by the diffusion process, avoiding subjective parameter selection. Subsequently, DGCL employs graph contrastive learning to optimize brain connections by eliminating individual differences in redundant connections unrelated to diseases, thereby enhancing the consistency of brain networks within the same group. Finally, the node-graph contrastive loss and classification loss jointly constrain the learning process of the model to obtain the reconstructed brain network, which is then used to analyze important brain connections. Validation on two datasets, ADNI and ABIDE, demonstrates that DGCL surpasses traditional methods and other deep learning models in predicting disease development stages. Significantly, the proposed model improves the efficiency and generalization of brain network construction. In summary, the proposed DGCL can be served as a universal brain network construction scheme, which can effectively identify important brain connections through generative paradigms and has the potential to provide disease interpretability support for neuroscience research.
q-bio/0310031
Paul Higgs
P.G.Higgs, D.Jameson, H.Jow, M.Rattray
The Evolution of tRNA-Leu Genes in Animal Mitochondrial Genomes
20 pages, 6 figures. J. Mol. Evol. (in press)
null
null
null
q-bio.PE
null
Animal mitochondrial genomes usually have two transfer RNAs for Leucine: one, with anticodon UAG, translates the four-codon family CUN, whilst the other, with anticodon UAA, translates the two-codon family UUR. These two genes must differ at the third anticodon position, but in some species the genes differ at many additional sites, indicating that these genes have been independent for a long time. Duplication and deletion of genes in mitochondrial genomes occurs frequently during the evolution of the Metazoa. If a tRNA-Leu gene were duplicated and a substitution occurred in the anticodon, this would effectively turn one type of tRNA into the other. The original copy of the second tRNA type might then be lost by a deletion elsewhere in the genome. There are several groups of species in which the two tRNA-Leu genes occur next to one another (or very close) on the genome, which suggests that tandem duplication has occurred. Here we use RNA-specific phylogenetic methods to determine evolutionary trees for both genes. We present evidence that the process of duplication, anticodon mutation and deletion of tRNA-Leu genes has occurred at least five times during the evolution of the Metazoa - once in the common ancestor of all Protostomes, once in the common ancestor of Echinoderms and Hemichordates, once in the hermit crab, and twice independently in Molluscs.
[ { "created": "Thu, 23 Oct 2003 22:11:13 GMT", "version": "v1" } ]
2007-05-23
[ [ "Higgs", "P. G.", "" ], [ "Jameson", "D.", "" ], [ "Jow", "H.", "" ], [ "Rattray", "M.", "" ] ]
Animal mitochondrial genomes usually have two transfer RNAs for Leucine: one, with anticodon UAG, translates the four-codon family CUN, whilst the other, with anticodon UAA, translates the two-codon family UUR. These two genes must differ at the third anticodon position, but in some species the genes differ at many additional sites, indicating that these genes have been independent for a long time. Duplication and deletion of genes in mitochondrial genomes occurs frequently during the evolution of the Metazoa. If a tRNA-Leu gene were duplicated and a substitution occurred in the anticodon, this would effectively turn one type of tRNA into the other. The original copy of the second tRNA type might then be lost by a deletion elsewhere in the genome. There are several groups of species in which the two tRNA-Leu genes occur next to one another (or very close) on the genome, which suggests that tandem duplication has occurred. Here we use RNA-specific phylogenetic methods to determine evolutionary trees for both genes. We present evidence that the process of duplication, anticodon mutation and deletion of tRNA-Leu genes has occurred at least five times during the evolution of the Metazoa - once in the common ancestor of all Protostomes, once in the common ancestor of Echinoderms and Hemichordates, once in the hermit crab, and twice independently in Molluscs.
1702.01568
Volker Pernice
Volker Pernice, Rava Azeredo da Silveira
Interpretation of Correlated Neural Variability from Models of Feed-Forward and Recurrent Circuits
41 pages, 10 figures
null
10.1371/journal.pcbi.1005979
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The correlated variability in the responses of a neural population to the repeated presentation of a sensory stimulus is a universally observed phenomenon. Such correlations have been studied in much detail, both with respect to their mechanistic origin and to their influence on stimulus discrimination and on the performance of population codes. In particular, recurrent neural network models have been used to understand the origin (or lack) of correlations in neural activity. Here, we apply a model of recurrently connected stochastic neurons to interpret correlations found in a population of neurons recorded from mouse auditory cortex. We study the consequences of recurrent connections on the stimulus dependence of correlations, and we compare them to those from alternative sources of correlated variability, like correlated gain fluctuations and common input in feed-forward architectures. We find that a recurrent network model with random effective connections reproduces observed statistics, like the relation between noise and signal correlations in the data, in a natural way. In the model, we can analyze directly the relation between network parameters, correlations, and how well pairs of stimuli can be discriminated based on population activity. In this way, we can relate circuit parameters to information processing.
[ { "created": "Mon, 6 Feb 2017 11:13:15 GMT", "version": "v1" } ]
2018-07-04
[ [ "Pernice", "Volker", "" ], [ "da Silveira", "Rava Azeredo", "" ] ]
The correlated variability in the responses of a neural population to the repeated presentation of a sensory stimulus is a universally observed phenomenon. Such correlations have been studied in much detail, both with respect to their mechanistic origin and to their influence on stimulus discrimination and on the performance of population codes. In particular, recurrent neural network models have been used to understand the origin (or lack) of correlations in neural activity. Here, we apply a model of recurrently connected stochastic neurons to interpret correlations found in a population of neurons recorded from mouse auditory cortex. We study the consequences of recurrent connections on the stimulus dependence of correlations, and we compare them to those from alternative sources of correlated variability, like correlated gain fluctuations and common input in feed-forward architectures. We find that a recurrent network model with random effective connections reproduces observed statistics, like the relation between noise and signal correlations in the data, in a natural way. In the model, we can analyze directly the relation between network parameters, correlations, and how well pairs of stimuli can be discriminated based on population activity. In this way, we can relate circuit parameters to information processing.
2308.08898
Sitabhra Sinha
Anand Pathak, Shakti N. Menon and Sitabhra Sinha
A hierarchy index for networks in the brain reveals a complex entangled organizational structure
16 pages, 5 figures + 10 pages Supplementary Information
PNAS 121, e2314291121 (2024)
10.1073/pnas.2314291121
null
q-bio.NC physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Networks involved in information processing often have their nodes arranged hierarchically, with the majority of connections occurring in adjacent levels. However, despite being an intuitively appealing concept, the hierarchical organization of large networks, such as those in the brain, are difficult to identify, especially in absence of additional information beyond that provided by the connectome. In this paper, we propose a framework to uncover the hierarchical structure of a given network, that identifies the nodes occupying each level as well as the sequential order of the levels. It involves optimizing a metric that we use to quantify the extent of hierarchy present in a network. Applying this measure to various brain networks, ranging from the nervous system of the nematode Caenorhabditis elegans to the human connectome, we unexpectedly find that they exhibit a common network architectural motif intertwining hierarchy and modularity. This suggests that brain networks may have evolved to simultaneously exploit the functional advantages of these two types of organizations, viz., relatively independent modules performing distributed processing in parallel and a hierarchical structure that allows sequential pooling of these multiple processing streams. An intriguing possibility is that this property we report may be common to information processing networks in general.
[ { "created": "Thu, 17 Aug 2023 10:15:36 GMT", "version": "v1" } ]
2024-07-02
[ [ "Pathak", "Anand", "" ], [ "Menon", "Shakti N.", "" ], [ "Sinha", "Sitabhra", "" ] ]
Networks involved in information processing often have their nodes arranged hierarchically, with the majority of connections occurring in adjacent levels. However, despite being an intuitively appealing concept, the hierarchical organization of large networks, such as those in the brain, are difficult to identify, especially in absence of additional information beyond that provided by the connectome. In this paper, we propose a framework to uncover the hierarchical structure of a given network, that identifies the nodes occupying each level as well as the sequential order of the levels. It involves optimizing a metric that we use to quantify the extent of hierarchy present in a network. Applying this measure to various brain networks, ranging from the nervous system of the nematode Caenorhabditis elegans to the human connectome, we unexpectedly find that they exhibit a common network architectural motif intertwining hierarchy and modularity. This suggests that brain networks may have evolved to simultaneously exploit the functional advantages of these two types of organizations, viz., relatively independent modules performing distributed processing in parallel and a hierarchical structure that allows sequential pooling of these multiple processing streams. An intriguing possibility is that this property we report may be common to information processing networks in general.
1102.4039
Andrew Gray Mr
Andrew R. Gray
Notes on Hybridization in Leaf frogs of the Genus Agalychnis (Anura, Hylidae, Phyllomedusinae)
null
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Two species of Endangered Leaf frogs, Agalychnis moreletii and Agalychnis annae, belonging to the tree frog Subfamily Phyllomedusinae, Genus Agalychnis, were hybridized for the first time whilst being maintained in captivity. Previous to this, these allopatric Central American species were considered as being distinctly separate. Crossbreeding following genetic analysis reveals that the two species are extremely closely related, and the hybrid of A. moreletii and A. annae is presented for the first time. The importance of identifying degrees of genetic variation between species and different populations of the same species, for conservation purposes, is highlighted and discussed.
[ { "created": "Sun, 20 Feb 2011 02:37:59 GMT", "version": "v1" } ]
2011-02-22
[ [ "Gray", "Andrew R.", "" ] ]
Two species of Endangered Leaf frogs, Agalychnis moreletii and Agalychnis annae, belonging to the tree frog Subfamily Phyllomedusinae, Genus Agalychnis, were hybridized for the first time whilst being maintained in captivity. Previous to this, these allopatric Central American species were considered as being distinctly separate. Crossbreeding following genetic analysis reveals that the two species are extremely closely related, and the hybrid of A. moreletii and A. annae is presented for the first time. The importance of identifying degrees of genetic variation between species and different populations of the same species, for conservation purposes, is highlighted and discussed.
q-bio/0609005
Horacio Ceva
E. Burgos, H. Ceva, R. Perazzo, M. Devoto, D. Medan, M. Zimmermann, A. M. Delbue
Why Nestedness in Mutualistic Networks?
Journal of Theoretical Biology (Accepted, 2007)
null
10.1016/j.jtbi.2007.07.030
null
q-bio.PE
null
We investigate the relationship between the nested organization of mutualistic systems and their robustness against the extinction of species. We establish that a nested pattern of contacts is the best possible one as far as robustness is concerned, but only when the least linked species have the greater probability of becoming extinct. We introduce a coefficient that provides a quantitative measure of the robustness of a mutualistic system.
[ { "created": "Tue, 5 Sep 2006 14:00:56 GMT", "version": "v1" }, { "created": "Thu, 20 Sep 2007 16:53:20 GMT", "version": "v2" } ]
2007-09-20
[ [ "Burgos", "E.", "" ], [ "Ceva", "H.", "" ], [ "Perazzo", "R.", "" ], [ "Devoto", "M.", "" ], [ "Medan", "D.", "" ], [ "Zimmermann", "M.", "" ], [ "Delbue", "A. M.", "" ] ]
We investigate the relationship between the nested organization of mutualistic systems and their robustness against the extinction of species. We establish that a nested pattern of contacts is the best possible one as far as robustness is concerned, but only when the least linked species have the greater probability of becoming extinct. We introduce a coefficient that provides a quantitative measure of the robustness of a mutualistic system.
1511.03965
Paul Fran\c{c}ois
Paul Fran\c{c}ois, Mathieu Hemery, Kyle A. Johnson, Laura N. Saunders
Phenotypic spandrel: absolute discrimination and ligand antagonism
null
null
10.1088/1478-3975/13/6/066011
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We consider the general problem of sensitive and specific discrimination between biochemical species. An important instance is immune discrimination between self and not-self, where it is also observed experimentally that ligands just below discrimination threshold negatively impact response, a phenomenon called antagonism. We characterize mathematically the generic properties of such discrimination, first relating it to biochemical adaptation. Then, based on basic biochemical rules, we establish that, surprisingly, antagonism is a generic consequence of any strictly specific discrimination made independently from ligand concentration. Thus antagonism constitutes a "phenotypic spandrel": a phenotype existing as a necessary by-product of another phenotype. We exhibit a simple analytic model of discrimination displaying antagonism, where antagonism strength is linear in distance from detection threshold. This contrasts with traditional proofreading based models where antagonism vanishes far from threshold and thus displays an inverted hierarchy of antagonism compared to simpler models. The phenotypic spandrel studied here is expected to structure many decision pathways such as immune detection mediated by TCRs and FC$\epsilon$RIs, as well as endocrine signalling/disruption.
[ { "created": "Thu, 12 Nov 2015 16:59:31 GMT", "version": "v1" }, { "created": "Fri, 8 Jan 2016 15:49:29 GMT", "version": "v2" }, { "created": "Fri, 7 Oct 2016 15:52:09 GMT", "version": "v3" } ]
2016-12-21
[ [ "François", "Paul", "" ], [ "Hemery", "Mathieu", "" ], [ "Johnson", "Kyle A.", "" ], [ "Saunders", "Laura N.", "" ] ]
We consider the general problem of sensitive and specific discrimination between biochemical species. An important instance is immune discrimination between self and not-self, where it is also observed experimentally that ligands just below discrimination threshold negatively impact response, a phenomenon called antagonism. We characterize mathematically the generic properties of such discrimination, first relating it to biochemical adaptation. Then, based on basic biochemical rules, we establish that, surprisingly, antagonism is a generic consequence of any strictly specific discrimination made independently from ligand concentration. Thus antagonism constitutes a "phenotypic spandrel": a phenotype existing as a necessary by-product of another phenotype. We exhibit a simple analytic model of discrimination displaying antagonism, where antagonism strength is linear in distance from detection threshold. This contrasts with traditional proofreading based models where antagonism vanishes far from threshold and thus displays an inverted hierarchy of antagonism compared to simpler models. The phenotypic spandrel studied here is expected to structure many decision pathways such as immune detection mediated by TCRs and FC$\epsilon$RIs, as well as endocrine signalling/disruption.
1410.8087
Gabriele Micali
Diana Clausznitzer, Gabriele Micali, Silke Neumann, Victor Sourjik and Robert G. Endres
Predicting chemical environments of bacteria from receptor signaling
DG and GM contributed equally to this work
PLoS Comput Biol 10(10): e1003870 (2014)
10.1371/journal.pcbi.1003870
null
q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Sensory systems have evolved to respond to input stimuli of certain statistical properties, and to reliably transmit this information through biochemical pathways. Hence, for an experimentally well-characterized sensory system, one ought to be able to extract valuable information about the statistics of the stimuli. Based on dose-response curves from in vivo fluorescence resonance energy transfer (FRET) experiments of the bacterial chemotaxis sensory system, we predict the chemical gradients chemotactic Escherichia coli cells typically encounter in their natural environment. To predict average gradients cells experience, we revaluate the phenomenological Weber's law and its generalizations to the Weber-Fechner law and fold-change detection. To obtain full distributions of gradients we use information theory and simulations, considering limitations of information transmission from both cell-external and internal noise. We identify broad distributions of exponential gradients, which lead to log-normal stimuli and maximal drift velocity. Our results thus provide a first step towards deciphering the chemical nature of complex, experimentally inaccessible cellular microenvironments, such as the human intestine.
[ { "created": "Mon, 27 Oct 2014 11:38:09 GMT", "version": "v1" } ]
2014-10-30
[ [ "Clausznitzer", "Diana", "" ], [ "Micali", "Gabriele", "" ], [ "Neumann", "Silke", "" ], [ "Sourjik", "Victor", "" ], [ "Endres", "Robert G.", "" ] ]
Sensory systems have evolved to respond to input stimuli of certain statistical properties, and to reliably transmit this information through biochemical pathways. Hence, for an experimentally well-characterized sensory system, one ought to be able to extract valuable information about the statistics of the stimuli. Based on dose-response curves from in vivo fluorescence resonance energy transfer (FRET) experiments of the bacterial chemotaxis sensory system, we predict the chemical gradients chemotactic Escherichia coli cells typically encounter in their natural environment. To predict average gradients cells experience, we revaluate the phenomenological Weber's law and its generalizations to the Weber-Fechner law and fold-change detection. To obtain full distributions of gradients we use information theory and simulations, considering limitations of information transmission from both cell-external and internal noise. We identify broad distributions of exponential gradients, which lead to log-normal stimuli and maximal drift velocity. Our results thus provide a first step towards deciphering the chemical nature of complex, experimentally inaccessible cellular microenvironments, such as the human intestine.
1304.6661
Carsten Conradi
Katharina Holstein and Dietrich Flockerzi and Carsten Conradi
Multistationarity in sequential distributed multisite phosphorylation networks
null
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Multisite phosphorylation networks are encountered in many intracellular processes like signal transduction, cell-cycle control or nuclear signal integration. In this contribution networks describing the phosphorylation and dephosphorylation of a protein at $n$ sites in a sequential distributive mechanism are considered. Multistationarity (i.e.\ the existence of at least two positive steady state solutions of the associated polynomial dynamical system) has been analyzed and established in several contributions. It is, for example, known that there exist values for he rate constants where multistationarity occurs. However, nothing else is known about these rate constants. Here we present a sign condition that is necessary and sufficient for multistationarity in $n$-site sequential, distributive phosphorylation. We express this sign condition in terms of linear systems and show that solutions of these systems define rate constants where multistationarity is possible. We then present, for $n\geq 2$, a collection of {\em feasible} linear systems and hence give a new and independent proof that multistationarity is possible for $n\geq 2$. Moreover, our results allow to explicitly obtain values for the rate constants where multistationarity is possible. Hence we believe that, for the first time, a systematic exploration of the region in parameter space where multistationarity occurs has become possible.One consequence of our work is that, for any pair of steady states, the ratio of the steady state concentrations of kinase-substrate complexes equals that of phosphatase-substrate complexes.
[ { "created": "Wed, 24 Apr 2013 16:39:38 GMT", "version": "v1" }, { "created": "Tue, 7 May 2013 13:34:12 GMT", "version": "v2" }, { "created": "Tue, 2 Jul 2013 16:02:06 GMT", "version": "v3" } ]
2013-07-03
[ [ "Holstein", "Katharina", "" ], [ "Flockerzi", "Dietrich", "" ], [ "Conradi", "Carsten", "" ] ]
Multisite phosphorylation networks are encountered in many intracellular processes like signal transduction, cell-cycle control or nuclear signal integration. In this contribution networks describing the phosphorylation and dephosphorylation of a protein at $n$ sites in a sequential distributive mechanism are considered. Multistationarity (i.e.\ the existence of at least two positive steady state solutions of the associated polynomial dynamical system) has been analyzed and established in several contributions. It is, for example, known that there exist values for he rate constants where multistationarity occurs. However, nothing else is known about these rate constants. Here we present a sign condition that is necessary and sufficient for multistationarity in $n$-site sequential, distributive phosphorylation. We express this sign condition in terms of linear systems and show that solutions of these systems define rate constants where multistationarity is possible. We then present, for $n\geq 2$, a collection of {\em feasible} linear systems and hence give a new and independent proof that multistationarity is possible for $n\geq 2$. Moreover, our results allow to explicitly obtain values for the rate constants where multistationarity is possible. Hence we believe that, for the first time, a systematic exploration of the region in parameter space where multistationarity occurs has become possible.One consequence of our work is that, for any pair of steady states, the ratio of the steady state concentrations of kinase-substrate complexes equals that of phosphatase-substrate complexes.
q-bio/0612027
Michael Deem
Jeong-Man Park and Michael W. Deem
Phase Diagrams of Quasispecies Theory with Recombination and Horizontal Gene Transfer
5 pages, 1 figure, to appear in Physics Review Letters
null
10.1103/PhysRevLett.98.058101
null
q-bio.PE
null
We consider how transfer of genetic information between individuals influences the phase diagram and mean fitness of both the Eigen and the parallel, or Crow-Kimura, models of evolution. In the absence of genetic transfer, these physical models of evolution consider the replication and point mutation of the genomes of independent individuals in a large population. A phase transition occurs, such that below a critical mutation rate an identifiable quasispecies forms. We generalize these models of quasispecies evolution to include horizontal gene transfer. We show how transfer of genetic information changes the phase diagram and mean fitness and introduces metastability in quasispecies theory, via an analytic field theoretic mapping.
[ { "created": "Thu, 14 Dec 2006 21:33:05 GMT", "version": "v1" } ]
2009-11-13
[ [ "Park", "Jeong-Man", "" ], [ "Deem", "Michael W.", "" ] ]
We consider how transfer of genetic information between individuals influences the phase diagram and mean fitness of both the Eigen and the parallel, or Crow-Kimura, models of evolution. In the absence of genetic transfer, these physical models of evolution consider the replication and point mutation of the genomes of independent individuals in a large population. A phase transition occurs, such that below a critical mutation rate an identifiable quasispecies forms. We generalize these models of quasispecies evolution to include horizontal gene transfer. We show how transfer of genetic information changes the phase diagram and mean fitness and introduces metastability in quasispecies theory, via an analytic field theoretic mapping.
1203.2883
Serena Bradde
Vanni Bucci, Serena Bradde, Giulio Biroli and Joao B. Xavier
Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota
20 pages, 5 figures accepted for publication in Plos Comp Bio. Supplementary video and information available
null
10.1371/journal.pcbi.1002497
null
q-bio.QM cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically. Antibiotic cessation does not necessarily restore pre-treatment conditions and disturbed microbiota are often susceptible to pathogen invasion. Here we propose a mathematical model to explain how antibiotic-mediated switches in the microbiota composition can result from simple social interactions between antibiotic-tolerant and antibiotic-sensitive bacterial groups. We build a two-species (e.g. two functional-groups) model and identify regions of domination by antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of multistability where domination by either group is possible. Using a new framework that we derived from statistical physics, we calculate the duration of each microbiota composition state. This is shown to depend on the balance between random fluctuations in the bacterial densities and the strength of microbial interactions. The singular value decomposition of recent metagenomic data confirms our assumption of grouping microbes as antibiotic-tolerant or antibiotic-sensitive in response to a single antibiotic. Our methodology can be extended to multiple bacterial groups and thus it provides an ecological formalism to help interpret the present surge in microbiome data.
[ { "created": "Tue, 13 Mar 2012 18:05:39 GMT", "version": "v1" } ]
2015-06-04
[ [ "Bucci", "Vanni", "" ], [ "Bradde", "Serena", "" ], [ "Biroli", "Giulio", "" ], [ "Xavier", "Joao B.", "" ] ]
The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically. Antibiotic cessation does not necessarily restore pre-treatment conditions and disturbed microbiota are often susceptible to pathogen invasion. Here we propose a mathematical model to explain how antibiotic-mediated switches in the microbiota composition can result from simple social interactions between antibiotic-tolerant and antibiotic-sensitive bacterial groups. We build a two-species (e.g. two functional-groups) model and identify regions of domination by antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of multistability where domination by either group is possible. Using a new framework that we derived from statistical physics, we calculate the duration of each microbiota composition state. This is shown to depend on the balance between random fluctuations in the bacterial densities and the strength of microbial interactions. The singular value decomposition of recent metagenomic data confirms our assumption of grouping microbes as antibiotic-tolerant or antibiotic-sensitive in response to a single antibiotic. Our methodology can be extended to multiple bacterial groups and thus it provides an ecological formalism to help interpret the present surge in microbiome data.
1606.02801
Edmund Crampin
Patrick E. McSharry and Edmund J. Crampin
Identifying statistically significant patterns in gene expression data
null
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Motivation: Clustering techniques are routinely applied to identify patterns of co-expression in gene expression data. Co-regulation, and involvement of genes in similar cellular function, is subsequently inferred from the clusters which are obtained. Increasingly sophisticated algorithms have been applied to microarray data, however, less attention has been given to the statistical significance of the results of clustering studies. We present a technique for the analysis of commonly used hierarchical linkage-based clustering called Significance Analysis of Linkage Trees (SALT). Results: The statistical significance of pairwise similarity levels between gene expression profiles, a measure of co-expression, is established using a surrogate data analysis method. We find that a modified version of the standard linkage technique, complete-linkage, must be used to generate hierarchical linkage trees with the appropriate properties. The approach is illustrated using synthetic data generated from a novel model of gene expression profiles and is then applied to previously analysed microarray data on the transcriptional response of human fibroblasts to serum stimulation.
[ { "created": "Thu, 9 Jun 2016 02:20:57 GMT", "version": "v1" } ]
2016-06-10
[ [ "McSharry", "Patrick E.", "" ], [ "Crampin", "Edmund J.", "" ] ]
Motivation: Clustering techniques are routinely applied to identify patterns of co-expression in gene expression data. Co-regulation, and involvement of genes in similar cellular function, is subsequently inferred from the clusters which are obtained. Increasingly sophisticated algorithms have been applied to microarray data, however, less attention has been given to the statistical significance of the results of clustering studies. We present a technique for the analysis of commonly used hierarchical linkage-based clustering called Significance Analysis of Linkage Trees (SALT). Results: The statistical significance of pairwise similarity levels between gene expression profiles, a measure of co-expression, is established using a surrogate data analysis method. We find that a modified version of the standard linkage technique, complete-linkage, must be used to generate hierarchical linkage trees with the appropriate properties. The approach is illustrated using synthetic data generated from a novel model of gene expression profiles and is then applied to previously analysed microarray data on the transcriptional response of human fibroblasts to serum stimulation.
1206.4434
S\'ilvio Duarte Queir\'os M.
Andrea Cavagna, Silvio M. Duarte Queiros, Irene Giardina, Fabio Stefanini, Massimiliano Viale
Diffusion of individual birds in starling flocks
22 pages, 10 figures
Proc. R. Soc. B 280, 20122484 (2013)
10.1098/rspb.2012.2484
null
q-bio.PE physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Flocking is a paradigmatic example of collective animal behaviour, where decentralized interaction rules give rise to a globally ordered state. In the emergence of order out of self-organization we find similarities between biological systems, as bird flocks, and some physical systems, as ferromagnets. In both cases, the tendency of individuals to align to their neighbours gives rise to a polarized state. There is, however, one crucial difference: the interaction network within an animal group is not necessarily fixed in time, as each individual moves and may change its neighbours. Therefore, the dynamical interaction mechanism in biological and physical system can be quite different, not only due to the gross disparity in the complexity of the individual entities, but also because of the potential role of inter-individual motion. To assess the relevance of this mechanism it is necessary to gain quantitative experimental information about how much individuals move with respect to each other within the group. Here, by using data from field observations on starlings, we study the diffusion properties of individual birds within a flock and investigate the effect of diffusion on the dynamics of the interaction network. We find that birds diffuse faster than Brownian particles (superdiffusion) and in a strongly anisotropic way. We also find that neighbours change in time exclusively as a consequence of diffusion, so that no specific mechanism to keep one's neighbours seems to be enforced. Finally, we study the diffusion properties of birds at the border of the flock. We find that these individuals remain on the border significantly longer than what would be expected on the basis of a purely diffusional model, suggesting that there is a sort barrier a bird must cross to make the transition from border to interior of the flock.
[ { "created": "Wed, 20 Jun 2012 09:52:31 GMT", "version": "v1" }, { "created": "Wed, 13 Feb 2013 20:34:18 GMT", "version": "v2" } ]
2013-02-14
[ [ "Cavagna", "Andrea", "" ], [ "Queiros", "Silvio M. Duarte", "" ], [ "Giardina", "Irene", "" ], [ "Stefanini", "Fabio", "" ], [ "Viale", "Massimiliano", "" ] ]
Flocking is a paradigmatic example of collective animal behaviour, where decentralized interaction rules give rise to a globally ordered state. In the emergence of order out of self-organization we find similarities between biological systems, as bird flocks, and some physical systems, as ferromagnets. In both cases, the tendency of individuals to align to their neighbours gives rise to a polarized state. There is, however, one crucial difference: the interaction network within an animal group is not necessarily fixed in time, as each individual moves and may change its neighbours. Therefore, the dynamical interaction mechanism in biological and physical system can be quite different, not only due to the gross disparity in the complexity of the individual entities, but also because of the potential role of inter-individual motion. To assess the relevance of this mechanism it is necessary to gain quantitative experimental information about how much individuals move with respect to each other within the group. Here, by using data from field observations on starlings, we study the diffusion properties of individual birds within a flock and investigate the effect of diffusion on the dynamics of the interaction network. We find that birds diffuse faster than Brownian particles (superdiffusion) and in a strongly anisotropic way. We also find that neighbours change in time exclusively as a consequence of diffusion, so that no specific mechanism to keep one's neighbours seems to be enforced. Finally, we study the diffusion properties of birds at the border of the flock. We find that these individuals remain on the border significantly longer than what would be expected on the basis of a purely diffusional model, suggesting that there is a sort barrier a bird must cross to make the transition from border to interior of the flock.
1806.07469
Xiaochang Leng
Xiaochang Leng, Yingchao Yang, Xiaomin Deng, Susan M. Lessner, Michael A. Sutton, Tarek Shazly
Micromechanical Experimental and Numerical Studies of Collagen Fibers Failure in Arterial Tissue
33 pages, 11 figures
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Arterial tissue failures lead to a number of clinical conditions that develop rapidly and unpredictably in vivo. Structural components and their interfacial mechanical strength of arterial tissue play a critical role in the process of arterail delamination. Therefore, there is a pressing need to understand the micromechanical mechanisms of arterial delamination. The objective of this study was to investigate various failure mechanisms (e.g. failure of collagen fibers) responsible for arterial interfacial delamination. In-situ tensile tests of fibers were performed on a micro-tester in the scanning electron microscope. A 3D unit cell model containing an individual fiber bridging two arterial tissue layers was constructed. An exponential cohesive zone model (CZM) was used to assess the stiffening and softening mechanical behaviors of collagen fiber bundles between the two arterial layers. An anisotropic constitutive model was implemented for characterizing the mechanical properties of the amorphous matrix which includes the fibrous cap and the underlying plaque tissue and a nonlinear elastic model was adopted for characterizing the mechanical properties of the fibers. The CZM and elastic parameter values of fibers were identified through an inverse boundary value approach that matches the load-displacement curves from simulation predictions of tensile test of collagen fibers with experimental measurements. The identified parameter values were then used as input in the 3D unit cell model, through which micromechanical factors affecting the resultant traction-separation relation for the unit cell were investigated via a parametric analysis. Results of the parametric analysis showed the applicability of the 3D unit cell model approach for evaluating the micromechanical mechanisms of arterial tissue failure processes.
[ { "created": "Tue, 19 Jun 2018 21:11:39 GMT", "version": "v1" } ]
2018-06-21
[ [ "Leng", "Xiaochang", "" ], [ "Yang", "Yingchao", "" ], [ "Deng", "Xiaomin", "" ], [ "Lessner", "Susan M.", "" ], [ "Sutton", "Michael A.", "" ], [ "Shazly", "Tarek", "" ] ]
Arterial tissue failures lead to a number of clinical conditions that develop rapidly and unpredictably in vivo. Structural components and their interfacial mechanical strength of arterial tissue play a critical role in the process of arterail delamination. Therefore, there is a pressing need to understand the micromechanical mechanisms of arterial delamination. The objective of this study was to investigate various failure mechanisms (e.g. failure of collagen fibers) responsible for arterial interfacial delamination. In-situ tensile tests of fibers were performed on a micro-tester in the scanning electron microscope. A 3D unit cell model containing an individual fiber bridging two arterial tissue layers was constructed. An exponential cohesive zone model (CZM) was used to assess the stiffening and softening mechanical behaviors of collagen fiber bundles between the two arterial layers. An anisotropic constitutive model was implemented for characterizing the mechanical properties of the amorphous matrix which includes the fibrous cap and the underlying plaque tissue and a nonlinear elastic model was adopted for characterizing the mechanical properties of the fibers. The CZM and elastic parameter values of fibers were identified through an inverse boundary value approach that matches the load-displacement curves from simulation predictions of tensile test of collagen fibers with experimental measurements. The identified parameter values were then used as input in the 3D unit cell model, through which micromechanical factors affecting the resultant traction-separation relation for the unit cell were investigated via a parametric analysis. Results of the parametric analysis showed the applicability of the 3D unit cell model approach for evaluating the micromechanical mechanisms of arterial tissue failure processes.
2105.13288
Soumyajyoti Biswas
Anvesh Reddy, Hanesh Koganti, Sai Krishna, Suhas Reddy, Soumyajyoti Biswas
Machine learning predictions of COVID-19 second wave end-times in Indian states
8 pages, 6 figures, 1 table
Indian Journal of Physics (2021)
10.1007/s12648-021-02195-x
null
q-bio.PE physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The estimate of the remaining time of an ongoing wave of epidemic spreading is a critical issue. Due to the variations of a wide range of parameters in an epidemic, for simple models such as Susceptible-Infected-Removed (SIR) model, it is difficult to estimate such a time scale. On the other hand, multidimensional data with a large set attributes are precisely what one can use in statistical learning algorithms to make predictions. Here we show, how the predictability of the SIR model changes with various parameters using a supervised learning algorithm. We then estimate the condition in which the model gives the least error in predicting the duration of the first wave of the COVID-19 pandemic in different states in India. Finally, we use the SIR model with the above mentioned optimal conditions to generate a training data set and use it in the supervised learning algorithm to estimate the end-time of the ongoing second wave of the pandemic in different states in India.
[ { "created": "Wed, 26 May 2021 14:19:22 GMT", "version": "v1" } ]
2021-10-12
[ [ "Reddy", "Anvesh", "" ], [ "Koganti", "Hanesh", "" ], [ "Krishna", "Sai", "" ], [ "Reddy", "Suhas", "" ], [ "Biswas", "Soumyajyoti", "" ] ]
The estimate of the remaining time of an ongoing wave of epidemic spreading is a critical issue. Due to the variations of a wide range of parameters in an epidemic, for simple models such as Susceptible-Infected-Removed (SIR) model, it is difficult to estimate such a time scale. On the other hand, multidimensional data with a large set attributes are precisely what one can use in statistical learning algorithms to make predictions. Here we show, how the predictability of the SIR model changes with various parameters using a supervised learning algorithm. We then estimate the condition in which the model gives the least error in predicting the duration of the first wave of the COVID-19 pandemic in different states in India. Finally, we use the SIR model with the above mentioned optimal conditions to generate a training data set and use it in the supervised learning algorithm to estimate the end-time of the ongoing second wave of the pandemic in different states in India.
2308.05115
Ziyang Xu
Ziyang Xu, Haitian Zhong, Bingrui He, Xueying Wang and Tianchi Lu
PTransIPs: Identification of phosphorylation sites enhanced by protein PLM embeddings
null
null
10.1109/JBHI.2024.3377362
null
q-bio.QM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Phosphorylation is pivotal in numerous fundamental cellular processes and plays a significant role in the onset and progression of various diseases. The accurate identification of these phosphorylation sites is crucial for unraveling the molecular mechanisms within cells and during viral infections, potentially leading to the discovery of novel therapeutic targets. In this study, we develop PTransIPs, a new deep learning framework for the identification of phosphorylation sites. Independent testing results demonstrate that PTransIPs outperforms existing state-of-the-art (SOTA) methods, achieving AUCs of 0.9232 and 0.9660 for the identification of phosphorylated S/T and Y sites, respectively. PTransIPs contributes from three aspects. 1) PTransIPs is the first to apply protein pre-trained language model (PLM) embeddings to this task. It utilizes ProtTrans and EMBER2 to extract sequence and structure embeddings, respectively, as additional inputs into the model, effectively addressing issues of dataset size and overfitting, thus enhancing model performance; 2) PTransIPs is based on Transformer architecture, optimized through the integration of convolutional neural networks and TIM loss function, providing practical insights for model design and training; 3) The encoding of amino acids in PTransIPs enables it to serve as a universal framework for other peptide bioactivity tasks, with its excellent performance shown in extended experiments of this paper. Our code, data and models are publicly available at https://github.com/StatXzy7/PTransIPs.
[ { "created": "Tue, 8 Aug 2023 07:50:38 GMT", "version": "v1" }, { "created": "Fri, 18 Aug 2023 06:35:50 GMT", "version": "v2" }, { "created": "Wed, 13 Mar 2024 05:02:32 GMT", "version": "v3" } ]
2024-03-27
[ [ "Xu", "Ziyang", "" ], [ "Zhong", "Haitian", "" ], [ "He", "Bingrui", "" ], [ "Wang", "Xueying", "" ], [ "Lu", "Tianchi", "" ] ]
Phosphorylation is pivotal in numerous fundamental cellular processes and plays a significant role in the onset and progression of various diseases. The accurate identification of these phosphorylation sites is crucial for unraveling the molecular mechanisms within cells and during viral infections, potentially leading to the discovery of novel therapeutic targets. In this study, we develop PTransIPs, a new deep learning framework for the identification of phosphorylation sites. Independent testing results demonstrate that PTransIPs outperforms existing state-of-the-art (SOTA) methods, achieving AUCs of 0.9232 and 0.9660 for the identification of phosphorylated S/T and Y sites, respectively. PTransIPs contributes from three aspects. 1) PTransIPs is the first to apply protein pre-trained language model (PLM) embeddings to this task. It utilizes ProtTrans and EMBER2 to extract sequence and structure embeddings, respectively, as additional inputs into the model, effectively addressing issues of dataset size and overfitting, thus enhancing model performance; 2) PTransIPs is based on Transformer architecture, optimized through the integration of convolutional neural networks and TIM loss function, providing practical insights for model design and training; 3) The encoding of amino acids in PTransIPs enables it to serve as a universal framework for other peptide bioactivity tasks, with its excellent performance shown in extended experiments of this paper. Our code, data and models are publicly available at https://github.com/StatXzy7/PTransIPs.
2302.06842
Gerry Gralton
S. Gerry Gralton, Farah Alkhatib, Ben Zwick, George Bourantas, Adam Wittek, Karol Miller
Random boundaries: quantifying segmentation uncertainty in solutions to boundary-value problems
null
null
null
null
q-bio.TO
http://creativecommons.org/licenses/by-nc-nd/4.0/
Engineering simulations using boundary-value partial differential equations often implicitly assume that the uncertainty in the location of the boundary has a negligible impact on the output of the simulation. In this work, we develop a novel method for describing the geometric uncertainty in image-derived models and use a naive method for subsequently quantifying a simulation's sensitivity to that uncertainty. A Gaussian random field is constructed to represent the space of possible geometries, based on image-derived quantities such as pixel size, which can then be used to probe the simulation's output space. The algorithm is demonstrated with examples from biomechanics where patient-specific geometries are often segmented from low-resolution, three-dimensional images. These examples show the method's wide applicability with examples using linear elasticity and fluid dynamics. We show that important biomechanical outputs of these example simulations, namely maximum principal stress and wall shear stress, can be highly sensitive to realistic uncertainties in geometry.
[ { "created": "Tue, 14 Feb 2023 05:33:06 GMT", "version": "v1" }, { "created": "Sun, 28 Jan 2024 12:53:23 GMT", "version": "v2" }, { "created": "Mon, 10 Jun 2024 02:56:39 GMT", "version": "v3" } ]
2024-06-11
[ [ "Gralton", "S. Gerry", "" ], [ "Alkhatib", "Farah", "" ], [ "Zwick", "Ben", "" ], [ "Bourantas", "George", "" ], [ "Wittek", "Adam", "" ], [ "Miller", "Karol", "" ] ]
Engineering simulations using boundary-value partial differential equations often implicitly assume that the uncertainty in the location of the boundary has a negligible impact on the output of the simulation. In this work, we develop a novel method for describing the geometric uncertainty in image-derived models and use a naive method for subsequently quantifying a simulation's sensitivity to that uncertainty. A Gaussian random field is constructed to represent the space of possible geometries, based on image-derived quantities such as pixel size, which can then be used to probe the simulation's output space. The algorithm is demonstrated with examples from biomechanics where patient-specific geometries are often segmented from low-resolution, three-dimensional images. These examples show the method's wide applicability with examples using linear elasticity and fluid dynamics. We show that important biomechanical outputs of these example simulations, namely maximum principal stress and wall shear stress, can be highly sensitive to realistic uncertainties in geometry.
1907.09151
Luca Ciandrini
Pascal S. Rogalla, Timothy J. Rudge and Luca Ciandrini
An equilibrium model for ribosome competition
null
null
10.1088/1478-3975/ab4fbc
null
q-bio.SC cond-mat.stat-mech physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The number of ribosomes in a cell is considered as limiting, and gene expression is thus largely determined by their cellular concentration. In this work we develop a toy model to study the trade-off between the ribosomal supply and the demand of the translation machinery, dictated by the composition of the transcript pool. Our equilibrium framework is useful to highlight qualitative behaviours and new means of gene expression regulation determined by the fine balance of this trade-off. We also speculate on the possible impact of these mechanisms on cellular physiology.
[ { "created": "Mon, 22 Jul 2019 06:35:29 GMT", "version": "v1" }, { "created": "Mon, 14 Oct 2019 20:42:24 GMT", "version": "v2" } ]
2020-02-19
[ [ "Rogalla", "Pascal S.", "" ], [ "Rudge", "Timothy J.", "" ], [ "Ciandrini", "Luca", "" ] ]
The number of ribosomes in a cell is considered as limiting, and gene expression is thus largely determined by their cellular concentration. In this work we develop a toy model to study the trade-off between the ribosomal supply and the demand of the translation machinery, dictated by the composition of the transcript pool. Our equilibrium framework is useful to highlight qualitative behaviours and new means of gene expression regulation determined by the fine balance of this trade-off. We also speculate on the possible impact of these mechanisms on cellular physiology.
1806.01467
Susan Cheng
Jeramie D. Watrous, Teemu Niiranen, Kim A. Lagerborg, Mir Henglin, Yong-Jian Xu, Sonia Sharma, Ramachandran S. Vasan, Martin G. Larson, Aaron Armando, Oswald Quehenberger, Edward A. Dennis, Susan Cheng, Mohit Jain
Directed Non-Targeted Mass Spectrometry and Chemical Networking for Discovery of Eicosanoids
null
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by-nc-sa/4.0/
Eicosanoids and related species are critical, small bioactive mediators of human physiology and inflammation. While ~1100 distinct eicosanoids have been predicted to exist, to date, less than 150 of these molecules have been measured in humans, limiting our understanding of eicosanoids and their role in human biology. Using a directed non-targeted mass spectrometry approach in conjunction with computational chemical networking of spectral fragmentation patterns, we find over 500 discrete chemical signals highly consistent with known and putative eicosanoids in human plasma, including 46 putative novel molecules not previously described, thereby greatly expanding the breath of prior analytical strategies. In plasma samples from 1500 individuals, we find members of this expanded eicosanoid library hold close association with markers of inflammation, as well as clinical characteristics linked with inflammation, including advancing age and obesity. These experimental and computational approaches enable discovery of new chemical entities and will shed important insight into the role of bioactive molecules in human disease.
[ { "created": "Tue, 5 Jun 2018 02:24:59 GMT", "version": "v1" } ]
2018-06-06
[ [ "Watrous", "Jeramie D.", "" ], [ "Niiranen", "Teemu", "" ], [ "Lagerborg", "Kim A.", "" ], [ "Henglin", "Mir", "" ], [ "Xu", "Yong-Jian", "" ], [ "Sharma", "Sonia", "" ], [ "Vasan", "Ramachandran S.", "" ], [ "Larson", "Martin G.", "" ], [ "Armando", "Aaron", "" ], [ "Quehenberger", "Oswald", "" ], [ "Dennis", "Edward A.", "" ], [ "Cheng", "Susan", "" ], [ "Jain", "Mohit", "" ] ]
Eicosanoids and related species are critical, small bioactive mediators of human physiology and inflammation. While ~1100 distinct eicosanoids have been predicted to exist, to date, less than 150 of these molecules have been measured in humans, limiting our understanding of eicosanoids and their role in human biology. Using a directed non-targeted mass spectrometry approach in conjunction with computational chemical networking of spectral fragmentation patterns, we find over 500 discrete chemical signals highly consistent with known and putative eicosanoids in human plasma, including 46 putative novel molecules not previously described, thereby greatly expanding the breath of prior analytical strategies. In plasma samples from 1500 individuals, we find members of this expanded eicosanoid library hold close association with markers of inflammation, as well as clinical characteristics linked with inflammation, including advancing age and obesity. These experimental and computational approaches enable discovery of new chemical entities and will shed important insight into the role of bioactive molecules in human disease.
1208.1560
Jiang Zhang
Jiang Zhang and Yuanjing Feng
Common Patterns of Energy Flow and Biomass Distribution on Weighted Food Webs
26 pages, 7 figures
null
null
null
q-bio.PE physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Weights of edges and nodes on food webs which are available from the empirical data hide much information about energy flows and biomass distributions in ecosystem. We define a set of variables related to weights for each species $i$, including the throughflow $T_i$, the total biomass $X_i$, and the dissipated flow $D_i$ (output to the environment) to uncover the following common patterns in 19 empirical weighted food webs: (1) DGBD distributions (Discrete version of a Generalized Beta Distribution), a kind of deformed Zipf's law, of energy flow and storage biomass; (2) The allometric scaling law $T_i\propto X_i^{\alpha}$, which can be viewed as the counterpart of the Kleiber's 3/4 law at the population level; (3) The dissipation law $D_i\propto T_i^{\beta}$; and (4) The gravity law, including univariate version $f_{ij}\propto (T_iT_j)^{\gamma}$ and bivariate approvement $f_{ij}\propto T_i^{\gamma_1}T_j^{\gamma_2}$. These patterns are very common and significant in all collected webs, as a result, some remarkable regularities are hidden in weights.
[ { "created": "Wed, 8 Aug 2012 01:25:39 GMT", "version": "v1" } ]
2012-08-09
[ [ "Zhang", "Jiang", "" ], [ "Feng", "Yuanjing", "" ] ]
Weights of edges and nodes on food webs which are available from the empirical data hide much information about energy flows and biomass distributions in ecosystem. We define a set of variables related to weights for each species $i$, including the throughflow $T_i$, the total biomass $X_i$, and the dissipated flow $D_i$ (output to the environment) to uncover the following common patterns in 19 empirical weighted food webs: (1) DGBD distributions (Discrete version of a Generalized Beta Distribution), a kind of deformed Zipf's law, of energy flow and storage biomass; (2) The allometric scaling law $T_i\propto X_i^{\alpha}$, which can be viewed as the counterpart of the Kleiber's 3/4 law at the population level; (3) The dissipation law $D_i\propto T_i^{\beta}$; and (4) The gravity law, including univariate version $f_{ij}\propto (T_iT_j)^{\gamma}$ and bivariate approvement $f_{ij}\propto T_i^{\gamma_1}T_j^{\gamma_2}$. These patterns are very common and significant in all collected webs, as a result, some remarkable regularities are hidden in weights.
2102.04720
Brian Mathias
Brian Mathias, Christian Andrae, Anika Schwager, Manuela Macedonia, Katharina von Kriegstein
Twelve- and fourteen-year-old school children differentially benefit from sensorimotor- and multisensory-enriched vocabulary training
null
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by-nc-nd/4.0/
Both children and adults have been shown to benefit from the integration of multisensory and sensorimotor enrichment into pedagogy. For example, integrating pictures or gestures into foreign language (L2) vocabulary learning can improve learning outcomes relative to unisensory learning. However, whereas adults seem to benefit to a greater extent from sensorimotor enrichment such as the performance of gestures in contrast to multisensory enrichment with pictures, this is not the case in elementary school children. Here, we compared multisensory- and sensorimotor-enriched learning in an intermediate age group that falls between the age groups tested in previous studies (elementary school children and young adults), in an attempt to determine the developmental time point at which children's responses to enrichment mature from a child-like pattern into an adult-like pattern. Twelve-year-old and fourteen-year-old German children were trained over 5 consecutive days on auditorily-presented, concrete and abstract, Spanish vocabulary. The vocabulary was learned under picture-enriched, gesture-enriched, and non-enriched (auditory-only) conditions. The children performed vocabulary recall and translation tests at 3 days, 2 months, and 6 months post-learning. Both picture and gesture enrichment interventions were found to benefit children's L2 learning relative to non-enriched learning up to 6 months post-training. Interestingly, gesture-enriched learning was even more beneficial than picture-enriched learning for the fourteen-year-olds, while the twelve-year-olds benefitted equivalently from learning enriched with pictures and gestures. These findings provide evidence for opting to integrate gestures rather than pictures into L2 pedagogy starting at fourteen years of age.
[ { "created": "Tue, 9 Feb 2021 09:32:12 GMT", "version": "v1" } ]
2021-02-10
[ [ "Mathias", "Brian", "" ], [ "Andrae", "Christian", "" ], [ "Schwager", "Anika", "" ], [ "Macedonia", "Manuela", "" ], [ "von Kriegstein", "Katharina", "" ] ]
Both children and adults have been shown to benefit from the integration of multisensory and sensorimotor enrichment into pedagogy. For example, integrating pictures or gestures into foreign language (L2) vocabulary learning can improve learning outcomes relative to unisensory learning. However, whereas adults seem to benefit to a greater extent from sensorimotor enrichment such as the performance of gestures in contrast to multisensory enrichment with pictures, this is not the case in elementary school children. Here, we compared multisensory- and sensorimotor-enriched learning in an intermediate age group that falls between the age groups tested in previous studies (elementary school children and young adults), in an attempt to determine the developmental time point at which children's responses to enrichment mature from a child-like pattern into an adult-like pattern. Twelve-year-old and fourteen-year-old German children were trained over 5 consecutive days on auditorily-presented, concrete and abstract, Spanish vocabulary. The vocabulary was learned under picture-enriched, gesture-enriched, and non-enriched (auditory-only) conditions. The children performed vocabulary recall and translation tests at 3 days, 2 months, and 6 months post-learning. Both picture and gesture enrichment interventions were found to benefit children's L2 learning relative to non-enriched learning up to 6 months post-training. Interestingly, gesture-enriched learning was even more beneficial than picture-enriched learning for the fourteen-year-olds, while the twelve-year-olds benefitted equivalently from learning enriched with pictures and gestures. These findings provide evidence for opting to integrate gestures rather than pictures into L2 pedagogy starting at fourteen years of age.
q-bio/0407023
Steven Samuel Plotkin
C. Clementi and S. S. Plotkin
The effects of non-native interactions on protein folding rates: Theory and simulation
35 pages, 12 figures, 1 table
Protein Science 2004 13: 1750-1766
null
null
q-bio.BM
null
Proteins are minimally frustrated polymers. However, for realistic protein models non-native interactions must be taken into account. In this paper we analyze the effect of non-native interactions on the folding rate and on the folding free energy barrier. We present an analytic theory to account for the modification on the free energy landscape upon introduction of non-native contacts, added as a perturbation to the strong native interactions driving folding. Our theory predicts a rate-enhancement regime at fixed temperature, under the introduction of weak, non-native interactions. We have thoroughly tested this theoretical prediction with simulations of a coarse-grained protein model, by employing an off-lattice $C_\alpha$ model of the src-SH3 domain. The strong agreement between results from simulations and theory confirm the non trivial result that a relatively small amount of non-native interaction energy can actually assist the folding to the native structure.
[ { "created": "Thu, 15 Jul 2004 01:44:42 GMT", "version": "v1" } ]
2007-05-23
[ [ "Clementi", "C.", "" ], [ "Plotkin", "S. S.", "" ] ]
Proteins are minimally frustrated polymers. However, for realistic protein models non-native interactions must be taken into account. In this paper we analyze the effect of non-native interactions on the folding rate and on the folding free energy barrier. We present an analytic theory to account for the modification on the free energy landscape upon introduction of non-native contacts, added as a perturbation to the strong native interactions driving folding. Our theory predicts a rate-enhancement regime at fixed temperature, under the introduction of weak, non-native interactions. We have thoroughly tested this theoretical prediction with simulations of a coarse-grained protein model, by employing an off-lattice $C_\alpha$ model of the src-SH3 domain. The strong agreement between results from simulations and theory confirm the non trivial result that a relatively small amount of non-native interaction energy can actually assist the folding to the native structure.
1907.06909
Kevin Woods
Kevin J P Woods, Adam Hewett, Andrea Spencer, Benjamin Morillon, Psyche Loui
Modulation in background music influences sustained attention
20 pages, 5 figures. Behavioral portion of larger planned manuscript to include neuroimaging. Comments welcome (kevin@brain.fm)
null
null
null
q-bio.NC q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Background music is known to affect performance on cognitive tasks, possibly due to temporal modulations in the acoustic signal, but little is known about how music should be designed to aid performance. Since acoustic modulation has been shown to shape neural activity in known networks, we chose to test the effects of acoustic modulation on sustained attention, which requires activity in these networks and is a common ingredient for success across many tasks. To understand how specific aspects of background music influence sustained attention, we manipulated the rate and depth of amplitude modulations imposed on otherwise identical music. This produced stimuli that were musically and acoustically identical except for a peak in the modulation spectrum that could change intensity or shift location under manipulations of depth or rate respectively. These controlled musical backgrounds were presented to participants (total N = 677) during the sustained attention to response (SART) task. In two experiments, we show performance benefits due to added modulation, with best performance at 16 Hz (beta band) rate and higher modulation depths; neighboring parameter settings did not produce this benefit. Further examination of individual differences within our overall sample showed that those with a high level of self-reported ADHD symptomaticity tended to perform better with more intense beta modulation. These results suggest optimal parameters for adding modulation to background music, which are consistent with theories of oscillatory dynamics that relate auditory stimulation to behavior, yet demonstrate the need for a personalized approach in creating functional music for everyday use.
[ { "created": "Tue, 16 Jul 2019 09:33:39 GMT", "version": "v1" } ]
2019-07-17
[ [ "Woods", "Kevin J P", "" ], [ "Hewett", "Adam", "" ], [ "Spencer", "Andrea", "" ], [ "Morillon", "Benjamin", "" ], [ "Loui", "Psyche", "" ] ]
Background music is known to affect performance on cognitive tasks, possibly due to temporal modulations in the acoustic signal, but little is known about how music should be designed to aid performance. Since acoustic modulation has been shown to shape neural activity in known networks, we chose to test the effects of acoustic modulation on sustained attention, which requires activity in these networks and is a common ingredient for success across many tasks. To understand how specific aspects of background music influence sustained attention, we manipulated the rate and depth of amplitude modulations imposed on otherwise identical music. This produced stimuli that were musically and acoustically identical except for a peak in the modulation spectrum that could change intensity or shift location under manipulations of depth or rate respectively. These controlled musical backgrounds were presented to participants (total N = 677) during the sustained attention to response (SART) task. In two experiments, we show performance benefits due to added modulation, with best performance at 16 Hz (beta band) rate and higher modulation depths; neighboring parameter settings did not produce this benefit. Further examination of individual differences within our overall sample showed that those with a high level of self-reported ADHD symptomaticity tended to perform better with more intense beta modulation. These results suggest optimal parameters for adding modulation to background music, which are consistent with theories of oscillatory dynamics that relate auditory stimulation to behavior, yet demonstrate the need for a personalized approach in creating functional music for everyday use.
1810.08362
Gerardo F. Goya
V. Raffa, F. Falcone, M.P. Calatayud, G.F. Goya and A. Cuschieri
Pico-Newton mechanical forces promote neurite growth
16 pages, 3 figures
null
10.1016/j.bpj.2018.10.009
null
q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Investigations over half a century have indicated that mechanical forces induce neurite growth - with neurites elongating at a rate of 0.1-0.3{\mu}mh^{-1} per pico-Newton (pN) of applied force - when mechanical tension exceeds a threshold, with this being identified as 400-1000 pN for neurites of PC12 cells. Here we demonstrate that there is no threshold for neurite elongation of PC12 cells in response to applied mechanical forces. Instead, this proceeds at the same previously identified rate, on the application of tensions with intensity below 1pN. This supports the idea of mechanical tension as an endogenous signal used by neurons for promoting neurite elongation.
[ { "created": "Fri, 19 Oct 2018 06:20:53 GMT", "version": "v1" } ]
2018-10-22
[ [ "Raffa", "V.", "" ], [ "Falcone", "F.", "" ], [ "Calatayud", "M. P.", "" ], [ "Goya", "G. F.", "" ], [ "Cuschieri", "A.", "" ] ]
Investigations over half a century have indicated that mechanical forces induce neurite growth - with neurites elongating at a rate of 0.1-0.3{\mu}mh^{-1} per pico-Newton (pN) of applied force - when mechanical tension exceeds a threshold, with this being identified as 400-1000 pN for neurites of PC12 cells. Here we demonstrate that there is no threshold for neurite elongation of PC12 cells in response to applied mechanical forces. Instead, this proceeds at the same previously identified rate, on the application of tensions with intensity below 1pN. This supports the idea of mechanical tension as an endogenous signal used by neurons for promoting neurite elongation.
0912.5450
Piotr Su{\l}kowski
Joanna I. Su{\l}kowska, Piotr Su{\l}kowski, Jos\'e N. Onuchic
Dodging the crisis of folding proteins with knots
29 pages, 11 figures, 1 table
PNAS 106 (2009) 3119-3124
10.1073/pnas.0811147106
null
q-bio.BM cond-mat.soft
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Proteins with nontrivial topology, containing knots and slipknots, have the ability to fold to their native states without any additional external forces invoked. A mechanism is suggested for folding of these proteins, such as YibK and YbeA, which involves an intermediate configuration with a slipknot. It elucidates the role of topological barriers and backtracking during the folding event. It also illustrates that native contacts are sufficient to guarantee folding in around 1-2% of the simulations, and how slipknot intermediates are needed to reduce the topological bottlenecks. As expected, simulations of proteins with similar structure but with knot removed fold much more efficiently, clearly demonstrating the origin of these topological barriers. Although these studies are based on a simple coarse-grained model, they are already able to extract some of the underlying principles governing folding in such complex topologies.
[ { "created": "Wed, 30 Dec 2009 20:55:10 GMT", "version": "v1" } ]
2010-01-06
[ [ "Sułkowska", "Joanna I.", "" ], [ "Sułkowski", "Piotr", "" ], [ "Onuchic", "José N.", "" ] ]
Proteins with nontrivial topology, containing knots and slipknots, have the ability to fold to their native states without any additional external forces invoked. A mechanism is suggested for folding of these proteins, such as YibK and YbeA, which involves an intermediate configuration with a slipknot. It elucidates the role of topological barriers and backtracking during the folding event. It also illustrates that native contacts are sufficient to guarantee folding in around 1-2% of the simulations, and how slipknot intermediates are needed to reduce the topological bottlenecks. As expected, simulations of proteins with similar structure but with knot removed fold much more efficiently, clearly demonstrating the origin of these topological barriers. Although these studies are based on a simple coarse-grained model, they are already able to extract some of the underlying principles governing folding in such complex topologies.
1702.06665
Michael Beyeler
Michael Beyeler and Nikil Dutt and Jeffrey L. Krichmar
Visual response properties of MSTd emerge from a sparse population code
null
null
10.1523/JNEUROSCI.0396-16.2016
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Neurons in the dorsal subregion of the medial superior temporal (MSTd) area respond to large, complex patterns of retinal flow, implying a role in the analysis of self-motion. Some neurons are selective for the expanding radial motion that occurs as an observer moves through the environment ("heading"), and computational models can account for this finding. However, ample evidence suggests that MSTd neurons may exhibit a continuum of visual response selectivity to large-field motion stimuli, but the underlying computational principles by which these response properties are derived remain poorly understood. Here we describe a computational model of MSTd based on the hypothesis that neurons in MSTd efficiently encode the continuum of large-field retinal flow patterns on the basis of inputs received from neurons in MT, with receptive fields that resemble basis vectors recovered with nonnegative matrix factorization (NMF). These assumptions are sufficient to quantitatively simulate neurophysiological response properties of MSTd cells such as radial, circular, and spiral motion tuning, suggesting that these properties might simply be a by-product of MSTd neurons performing dimensionality reduction on their inputs. At the population level, model MSTd accurately predicts heading using a sparse distributed code, consistent with the idea that biological MSTd might operate in a sparseness regime well-suited to efficiently encode a number of self-motion variables. The present work provides an alternative to the template-model view of MSTd, and offers a biologically plausible account of the receptive field structure across a wide range of visual response properties in MSTd.
[ { "created": "Wed, 22 Feb 2017 03:41:02 GMT", "version": "v1" } ]
2017-02-24
[ [ "Beyeler", "Michael", "" ], [ "Dutt", "Nikil", "" ], [ "Krichmar", "Jeffrey L.", "" ] ]
Neurons in the dorsal subregion of the medial superior temporal (MSTd) area respond to large, complex patterns of retinal flow, implying a role in the analysis of self-motion. Some neurons are selective for the expanding radial motion that occurs as an observer moves through the environment ("heading"), and computational models can account for this finding. However, ample evidence suggests that MSTd neurons may exhibit a continuum of visual response selectivity to large-field motion stimuli, but the underlying computational principles by which these response properties are derived remain poorly understood. Here we describe a computational model of MSTd based on the hypothesis that neurons in MSTd efficiently encode the continuum of large-field retinal flow patterns on the basis of inputs received from neurons in MT, with receptive fields that resemble basis vectors recovered with nonnegative matrix factorization (NMF). These assumptions are sufficient to quantitatively simulate neurophysiological response properties of MSTd cells such as radial, circular, and spiral motion tuning, suggesting that these properties might simply be a by-product of MSTd neurons performing dimensionality reduction on their inputs. At the population level, model MSTd accurately predicts heading using a sparse distributed code, consistent with the idea that biological MSTd might operate in a sparseness regime well-suited to efficiently encode a number of self-motion variables. The present work provides an alternative to the template-model view of MSTd, and offers a biologically plausible account of the receptive field structure across a wide range of visual response properties in MSTd.
1510.06748
Luca Ferretti
Luca Ferretti, Alice Ledda, Guillaume Achaz, Thomas Wiehe and Sebastian E. Ramos-Onsins
Decomposing the site frequency spectrum: the impact of tree topology on neutrality tests
23 pages, 8 figures
null
null
null
q-bio.PE q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We investigate the dependence of the site frequency spectrum (SFS) on the topological structure of genealogical trees. We show that basic population genetic statistics - for instance estimators of $\theta$ or neutrality tests such as Tajima's $D$ - can be decomposed into components of waiting times between coalescent events and of tree topology. Our results clarify the relative impact of the two components on these statistics. We provide a rigorous interpretation of positive or negative values of an important class of neutrality tests in terms of the underlying tree shape. In particular, we show that values of Tajima's $D$ and Fay and Wu's $H$ depend in a direct way on a peculiar measure of tree balance which is mostly determined by the root balance of the tree. We present a new test for selection in the same class as Fay and Wu's $H$ and discuss its interpretation and power. Finally, we determine the trees corresponding to extreme expected values of these neutrality tests and present formulae for these extreme values as a function of sample size and number of segregating sites.
[ { "created": "Thu, 22 Oct 2015 20:10:48 GMT", "version": "v1" }, { "created": "Thu, 12 Jan 2017 23:50:59 GMT", "version": "v2" } ]
2017-01-16
[ [ "Ferretti", "Luca", "" ], [ "Ledda", "Alice", "" ], [ "Achaz", "Guillaume", "" ], [ "Wiehe", "Thomas", "" ], [ "Ramos-Onsins", "Sebastian E.", "" ] ]
We investigate the dependence of the site frequency spectrum (SFS) on the topological structure of genealogical trees. We show that basic population genetic statistics - for instance estimators of $\theta$ or neutrality tests such as Tajima's $D$ - can be decomposed into components of waiting times between coalescent events and of tree topology. Our results clarify the relative impact of the two components on these statistics. We provide a rigorous interpretation of positive or negative values of an important class of neutrality tests in terms of the underlying tree shape. In particular, we show that values of Tajima's $D$ and Fay and Wu's $H$ depend in a direct way on a peculiar measure of tree balance which is mostly determined by the root balance of the tree. We present a new test for selection in the same class as Fay and Wu's $H$ and discuss its interpretation and power. Finally, we determine the trees corresponding to extreme expected values of these neutrality tests and present formulae for these extreme values as a function of sample size and number of segregating sites.
0711.1010
Akira Kinjo
Akira R. Kinjo and Haruki Nakamura
Nature of protein family signatures: Insights from singular value analysis of position-specific scoring matrices
22 pages, 7 figures, 4 tables
PLoS ONE, 3:e1963 (2008)
10.1371/journal.pone.0001963
null
q-bio.BM
null
Position-specific scoring matrices (PSSMs) are useful for detecting weak homology in protein sequence analysis, and they are thought to contain some essential signatures of the protein families. In order to elucidate what kind of ingredients constitute such family-specific signatures, we apply singular value decomposition to a set of PSSMs and examine the properties of dominant right and left singular vectors. The first right singular vectors were correlated with various amino acid indices including relative mutability, amino acid composition in protein interior, hydropathy, or turn propensity, depending on proteins. A significant correlation between the first left singular vector and a measure of site conservation was observed. It is shown that the contribution of the first singular component to the PSSMs act to disfavor potentially but falsely functionally important residues at conserved sites. The second right singular vectors were highly correlated with hydrophobicity scales, and the corresponding left singular vectors with contact numbers of protein structures. It is suggested that sequence alignment with a PSSM is essentially equivalent to threading supplemented with functional information. The presented method may be used to separate functionally important sites from structurally important ones, and thus it may be a useful tool for predicting protein functions.
[ { "created": "Wed, 7 Nov 2007 05:20:40 GMT", "version": "v1" } ]
2008-04-14
[ [ "Kinjo", "Akira R.", "" ], [ "Nakamura", "Haruki", "" ] ]
Position-specific scoring matrices (PSSMs) are useful for detecting weak homology in protein sequence analysis, and they are thought to contain some essential signatures of the protein families. In order to elucidate what kind of ingredients constitute such family-specific signatures, we apply singular value decomposition to a set of PSSMs and examine the properties of dominant right and left singular vectors. The first right singular vectors were correlated with various amino acid indices including relative mutability, amino acid composition in protein interior, hydropathy, or turn propensity, depending on proteins. A significant correlation between the first left singular vector and a measure of site conservation was observed. It is shown that the contribution of the first singular component to the PSSMs act to disfavor potentially but falsely functionally important residues at conserved sites. The second right singular vectors were highly correlated with hydrophobicity scales, and the corresponding left singular vectors with contact numbers of protein structures. It is suggested that sequence alignment with a PSSM is essentially equivalent to threading supplemented with functional information. The presented method may be used to separate functionally important sites from structurally important ones, and thus it may be a useful tool for predicting protein functions.
2305.02223
Maryam Al Yahyai
Maryam Al-Yahyai (1), Fatma Al-Musalhi (1), Nasser Al-Salti (2) and Ibrahim Elmojtaba (1) ((1) Department of Mathematics, College of Science, Sultan Qaboos University, Muscat, Oman, (2) Department of Applied Mathematics and Science, National University of Science and Technology, Muscat, Oman)
The Role of Quarantine and Isolation in Controlling COVID-19 Hospitalization in Oman
34 pages
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this paper, we build a mathematical model for the dynamics of COVID-19 to assess the impact of placing healthy individuals in quarantine and isolating infected ones on the number of hospitalization and intensive care unit cases. The proposed model is fully analyzed in order to prove the positivity of solutions, to study the local and global stability of the disease-free equilibria and to drive the basic and control reproduction numbers of the model. Oman COVID-19 data is used to calibrate the model and estimate the parameters. In particular, the published data for the year 2020 is used, when two waves of the disease hit the country. Moreover, this period of time is chosen when no vaccine had been introduced, but only the non-pharmaceutical intervention (NPI) strategies were the only effective methods to control the spread and, consequently, control the hospitalization cases to avoid pressuring the health system. Based on the estimated parameters, the reproduction number and contribution of different transmission routes are approximated numerically. Sensitivity analysis is performed to identify the significant parameters in spreading the disease. Numerical simulation is carried out to demonstrate the effects of quarantine and isolation on the number of hospitalized cases.
[ { "created": "Wed, 3 May 2023 16:03:27 GMT", "version": "v1" } ]
2023-05-04
[ [ "Al-Yahyai", "Maryam", "" ], [ "Al-Musalhi", "Fatma", "" ], [ "Al-Salti", "Nasser", "" ], [ "Elmojtaba", "Ibrahim", "" ] ]
In this paper, we build a mathematical model for the dynamics of COVID-19 to assess the impact of placing healthy individuals in quarantine and isolating infected ones on the number of hospitalization and intensive care unit cases. The proposed model is fully analyzed in order to prove the positivity of solutions, to study the local and global stability of the disease-free equilibria and to drive the basic and control reproduction numbers of the model. Oman COVID-19 data is used to calibrate the model and estimate the parameters. In particular, the published data for the year 2020 is used, when two waves of the disease hit the country. Moreover, this period of time is chosen when no vaccine had been introduced, but only the non-pharmaceutical intervention (NPI) strategies were the only effective methods to control the spread and, consequently, control the hospitalization cases to avoid pressuring the health system. Based on the estimated parameters, the reproduction number and contribution of different transmission routes are approximated numerically. Sensitivity analysis is performed to identify the significant parameters in spreading the disease. Numerical simulation is carried out to demonstrate the effects of quarantine and isolation on the number of hospitalized cases.
2102.03676
Xavier Michalet
Xavier Michalet
An overview of continuous and discrete phasor analysis of binned or time-gated periodic decays
12 pages, 4 figures, submitted as a Proceedings of SPIE (BiOS Conference 11648, March 6-11, 2021)
Proc. SPIE 11648 (2021) 116480E
10.1063/5.0027834
null
q-bio.QM
http://creativecommons.org/licenses/by-nc-nd/4.0/
Time-resolved analysis of periodically excited luminescence decays by the phasor method in the presence of time-gating or binning is revisited. Analytical expressions for discrete configurations of square gates are derived and the locus of the phasors of such modified periodic single-exponential decays is compared to the canonical universal semicircle. The effects of IRF offset, decay truncation and gate shape are also discussed. Finally, modified expressions for the phase and modulus lifetimes are provided for some simple cases. A discussion of a modified phasor calibration approach is presented.
[ { "created": "Sat, 6 Feb 2021 22:00:55 GMT", "version": "v1" }, { "created": "Thu, 11 Feb 2021 21:49:10 GMT", "version": "v2" } ]
2024-06-12
[ [ "Michalet", "Xavier", "" ] ]
Time-resolved analysis of periodically excited luminescence decays by the phasor method in the presence of time-gating or binning is revisited. Analytical expressions for discrete configurations of square gates are derived and the locus of the phasors of such modified periodic single-exponential decays is compared to the canonical universal semicircle. The effects of IRF offset, decay truncation and gate shape are also discussed. Finally, modified expressions for the phase and modulus lifetimes are provided for some simple cases. A discussion of a modified phasor calibration approach is presented.
2004.02398
Siyu Liu
Jiwei Jia, Siyu Liu, Jing Ding, Guidong Liao, Lihua Zhang, Ran Zhang
The impact of multilateral imported cases of COVID-19 on the epidemic control in China
null
null
null
null
q-bio.PE math.DS
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Nowadays, the epidemic of COVID-19 in China is under control. However, the epidemic are developing rapidly around the world. Due to the normal migration of population, China is facing high risk from imported cases. The potential specific medicine and vaccine is still in the process of clinical trials. Currently, controlling the impact of imported cases is the key to prevent new outbreak of COVID-19 in China. In this paper, we propose two impulsive systems to describe the impact of multilateral imported cases of COVID-19. Based on the published data, we simulate and discussed the epidemic trends under different control strategies. We compare four different scenarios and show the corresponding medical burden. The results help to design appropriate control strategy for imported cases in practice.
[ { "created": "Mon, 6 Apr 2020 04:31:52 GMT", "version": "v1" } ]
2020-04-07
[ [ "Jia", "Jiwei", "" ], [ "Liu", "Siyu", "" ], [ "Ding", "Jing", "" ], [ "Liao", "Guidong", "" ], [ "Zhang", "Lihua", "" ], [ "Zhang", "Ran", "" ] ]
Nowadays, the epidemic of COVID-19 in China is under control. However, the epidemic are developing rapidly around the world. Due to the normal migration of population, China is facing high risk from imported cases. The potential specific medicine and vaccine is still in the process of clinical trials. Currently, controlling the impact of imported cases is the key to prevent new outbreak of COVID-19 in China. In this paper, we propose two impulsive systems to describe the impact of multilateral imported cases of COVID-19. Based on the published data, we simulate and discussed the epidemic trends under different control strategies. We compare four different scenarios and show the corresponding medical burden. The results help to design appropriate control strategy for imported cases in practice.
1202.4691
Teresa Ruiz Herrero
Teresa Ruiz-Herrero, Enrique Velasco, Michael F. Hagan
Mechanisms of budding of nanoscale particles through lipid bilayers
null
null
null
null
q-bio.SC cond-mat.soft
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We examine the budding of a nanoscale particle through a lipid bilayer using molecular dynamics simulations, free energy calculations, and an elastic theory, with the aim of determining the extent to which equilibrium elasticity theory can describe the factors that control the mechanism and efficiency of budding. The particle is a smooth sphere which experiences attractive interactions to the lipid head groups. Depending on the parameters, we observe four classes of dynamical trajectories: particle adhesion to the membrane, stalled partially wrapped states, budding followed by scission, and membrane rupture. In most regions of parameter space we find that the elastic theory agrees nearly quantitatively with the simulated phase behavior as a function of adhesion strength, membrane bending rigidity, and particle radius. However, at parameter values near the transition between particle adhesion and budding, we observe long-lived partially wrapped states which are not captured by existing elastic theories. These states could constrain the accessible system parameters for those enveloped viruses or drug delivery vehicles which rely on exo- or endocytosis for membrane transport.
[ { "created": "Tue, 21 Feb 2012 16:19:48 GMT", "version": "v1" } ]
2012-02-22
[ [ "Ruiz-Herrero", "Teresa", "" ], [ "Velasco", "Enrique", "" ], [ "Hagan", "Michael F.", "" ] ]
We examine the budding of a nanoscale particle through a lipid bilayer using molecular dynamics simulations, free energy calculations, and an elastic theory, with the aim of determining the extent to which equilibrium elasticity theory can describe the factors that control the mechanism and efficiency of budding. The particle is a smooth sphere which experiences attractive interactions to the lipid head groups. Depending on the parameters, we observe four classes of dynamical trajectories: particle adhesion to the membrane, stalled partially wrapped states, budding followed by scission, and membrane rupture. In most regions of parameter space we find that the elastic theory agrees nearly quantitatively with the simulated phase behavior as a function of adhesion strength, membrane bending rigidity, and particle radius. However, at parameter values near the transition between particle adhesion and budding, we observe long-lived partially wrapped states which are not captured by existing elastic theories. These states could constrain the accessible system parameters for those enveloped viruses or drug delivery vehicles which rely on exo- or endocytosis for membrane transport.
1806.05017
Jordi Sol\'e-Casals
Jordi Sole-Casals, Cesar F. Caiafa, Qibin Zhao and Adrzej Cichocki
Brain-Computer Interface with Corrupted EEG Data: A Tensor Completion Approach
21 pages, 3 tables, 4 figures
Sole-Casals, J., Caiafa, C.F., Zhao, Q. et al. Cogn Comput (2018). https://doi.org/10.1007/s12559-018-9574-9
10.1007/s12559-018-9574-9
null
q-bio.QM eess.SP stat.ML
http://creativecommons.org/licenses/by/4.0/
One of the current issues in Brain-Computer Interface is how to deal with noisy Electroencephalography measurements organized as multidimensional datasets. On the other hand, recently, significant advances have been made in multidimensional signal completion algorithms that exploit tensor decomposition models to capture the intricate relationship among entries in a multidimensional signal. We propose to use tensor completion applied to EEG data for improving the classification performance in a motor imagery BCI system with corrupted measurements. Noisy measurements are considered as unknowns that are inferred from a tensor decomposition model. We evaluate the performance of four recently proposed tensor completion algorithms plus a simple interpolation strategy, first with random missing entries and then with missing samples constrained to have a specific structure (random missing channels), which is a more realistic assumption in BCI Applications. We measured the ability of these algorithms to reconstruct the tensor from observed data. Then, we tested the classification accuracy of imagined movement in a BCI experiment with missing samples. We show that for random missing entries, all tensor completion algorithms can recover missing samples increasing the classification performance compared to a simple interpolation approach. For the random missing channels case, we show that tensor completion algorithms help to reconstruct missing channels, significantly improving the accuracy in the classification of motor imagery, however, not at the same level as clean data. Tensor completion algorithms are useful in real BCI applications. The proposed strategy could allow using motor imagery BCI systems even when EEG data is highly affected by missing channels and/or samples, avoiding the need of new acquisitions in the calibration stage.
[ { "created": "Wed, 13 Jun 2018 13:16:28 GMT", "version": "v1" }, { "created": "Thu, 26 Jul 2018 15:53:29 GMT", "version": "v2" } ]
2018-07-27
[ [ "Sole-Casals", "Jordi", "" ], [ "Caiafa", "Cesar F.", "" ], [ "Zhao", "Qibin", "" ], [ "Cichocki", "Adrzej", "" ] ]
One of the current issues in Brain-Computer Interface is how to deal with noisy Electroencephalography measurements organized as multidimensional datasets. On the other hand, recently, significant advances have been made in multidimensional signal completion algorithms that exploit tensor decomposition models to capture the intricate relationship among entries in a multidimensional signal. We propose to use tensor completion applied to EEG data for improving the classification performance in a motor imagery BCI system with corrupted measurements. Noisy measurements are considered as unknowns that are inferred from a tensor decomposition model. We evaluate the performance of four recently proposed tensor completion algorithms plus a simple interpolation strategy, first with random missing entries and then with missing samples constrained to have a specific structure (random missing channels), which is a more realistic assumption in BCI Applications. We measured the ability of these algorithms to reconstruct the tensor from observed data. Then, we tested the classification accuracy of imagined movement in a BCI experiment with missing samples. We show that for random missing entries, all tensor completion algorithms can recover missing samples increasing the classification performance compared to a simple interpolation approach. For the random missing channels case, we show that tensor completion algorithms help to reconstruct missing channels, significantly improving the accuracy in the classification of motor imagery, however, not at the same level as clean data. Tensor completion algorithms are useful in real BCI applications. The proposed strategy could allow using motor imagery BCI systems even when EEG data is highly affected by missing channels and/or samples, avoiding the need of new acquisitions in the calibration stage.
1909.10139
Alex McAvoy
Alex McAvoy, Benjamin Allen, Martin A. Nowak
Social goods dilemmas in heterogeneous societies
72 pages; final version
Nature Human Behaviour (2020)
10.1038/s41562-020-0881-2
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Prosocial behaviors are encountered in the donation game, the prisoner's dilemma, relaxed social dilemmas, and public goods games. Many studies assume that the population structure is homogeneous, meaning all individuals have the same number of interaction partners, or that the social good is of one particular type. Here, we explore general evolutionary dynamics for arbitrary spatial structures and social goods. We find that heterogeneous networks, wherein some individuals have many more interaction partners than others, can enhance the evolution of prosocial behaviors. However, they often accumulate most of the benefits in the hands of a few highly-connected individuals, while many others receive low or negative payoff. Surprisingly, selection can favor producers of social goods even if the total costs exceed the total benefits. In summary, heterogeneous structures have the ability to strongly promote the emergence of prosocial behaviors, but they also create the possibility of generating large inequality.
[ { "created": "Mon, 23 Sep 2019 03:30:07 GMT", "version": "v1" }, { "created": "Fri, 1 May 2020 03:53:18 GMT", "version": "v2" } ]
2020-05-28
[ [ "McAvoy", "Alex", "" ], [ "Allen", "Benjamin", "" ], [ "Nowak", "Martin A.", "" ] ]
Prosocial behaviors are encountered in the donation game, the prisoner's dilemma, relaxed social dilemmas, and public goods games. Many studies assume that the population structure is homogeneous, meaning all individuals have the same number of interaction partners, or that the social good is of one particular type. Here, we explore general evolutionary dynamics for arbitrary spatial structures and social goods. We find that heterogeneous networks, wherein some individuals have many more interaction partners than others, can enhance the evolution of prosocial behaviors. However, they often accumulate most of the benefits in the hands of a few highly-connected individuals, while many others receive low or negative payoff. Surprisingly, selection can favor producers of social goods even if the total costs exceed the total benefits. In summary, heterogeneous structures have the ability to strongly promote the emergence of prosocial behaviors, but they also create the possibility of generating large inequality.
1605.01905
Carina Curto
Carina Curto
What can topology tell us about the neural code?
16 pages, 9 figures
Bulletin of the AMS, vol. 54, no. 1, pp. 63-78, January 2017
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Neuroscience is undergoing a period of rapid experimental progress and expansion. New mathematical tools, previously unknown in the neuroscience community, are now being used to tackle fundamental questions and analyze emerging data sets. Consistent with this trend, the last decade has seen an uptick in the use of topological ideas and methods in neuroscience. In this talk I will survey recent applications of topology in neuroscience, and explain why topology is an especially natural tool for understanding neural codes. Note: This is a write-up of my talk for the Current Events Bulletin, held at the 2016 Joint Math Meetings in Seattle, WA.
[ { "created": "Fri, 6 May 2016 12:06:15 GMT", "version": "v1" } ]
2016-12-28
[ [ "Curto", "Carina", "" ] ]
Neuroscience is undergoing a period of rapid experimental progress and expansion. New mathematical tools, previously unknown in the neuroscience community, are now being used to tackle fundamental questions and analyze emerging data sets. Consistent with this trend, the last decade has seen an uptick in the use of topological ideas and methods in neuroscience. In this talk I will survey recent applications of topology in neuroscience, and explain why topology is an especially natural tool for understanding neural codes. Note: This is a write-up of my talk for the Current Events Bulletin, held at the 2016 Joint Math Meetings in Seattle, WA.
2009.10049
Ananth V S
Bishal Chhetri, Vijay M. Bhagat, D. K. K. Vamsi, Ananth V S, Bhanu Prakash, Swapna Muthuswamy, Pradeep Deshmukh, Carani B Sanjeevi
Optimal Drug Regimen and Combined Drug Therapy and its Efficacy in the Treatment of COVID-19 : An Within-Host Modeling Study
16 pages, 13 figures
null
10.1007/s10441-022-09440-8
null
q-bio.PE math.DS math.OC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The COVID-19 pandemic has resulted in more than 30.35 million infections and 9, 50, 625 deaths in 212 countries over the last few months. Different drug intervention acting at multiple stages of pathogenesis of COVID-19 can substantially reduce the infection induced mortality. The current within-host mathematical modeling studies deals with the optimal drug regimen and the efficacy of combined therapy in treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Inteferon (INF) and Lopinavir/Ritonavir. It is concluded that these drug interventions when administered individually or in combination reduce the infected cells and viral load. Four scenarios involving administration of single drug intervention, two drug interventions, three drug interventions and all the four have been discussed. In all these scenarios the optimal drug regimen is proposed based on two methods. In the first method these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem is formulated. In this setting the optimal drug regimen is proposed. Later using the the comparative effectiveness method the optimal drug regimen is proposed based on basic reproduction number and viral load. The average infected cell count and viral load decreased the most when all the four interventions were applied together. On the other hand the average susceptible cell count decreased the best when Arbidol alone was administered. The basic reproduction number and viral count decreased the best when all the four interventions were applied together reinstating the fact obtained earlier in the optimal control setting. These findings may help physicians with decision making in treatment of life-threatening COVID-19 pneumonia.
[ { "created": "Mon, 21 Sep 2020 17:43:20 GMT", "version": "v1" } ]
2023-09-01
[ [ "Chhetri", "Bishal", "" ], [ "Bhagat", "Vijay M.", "" ], [ "Vamsi", "D. K. K.", "" ], [ "S", "Ananth V", "" ], [ "Prakash", "Bhanu", "" ], [ "Muthuswamy", "Swapna", "" ], [ "Deshmukh", "Pradeep", "" ], [ "Sanjeevi", "Carani B", "" ] ]
The COVID-19 pandemic has resulted in more than 30.35 million infections and 9, 50, 625 deaths in 212 countries over the last few months. Different drug intervention acting at multiple stages of pathogenesis of COVID-19 can substantially reduce the infection induced mortality. The current within-host mathematical modeling studies deals with the optimal drug regimen and the efficacy of combined therapy in treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Inteferon (INF) and Lopinavir/Ritonavir. It is concluded that these drug interventions when administered individually or in combination reduce the infected cells and viral load. Four scenarios involving administration of single drug intervention, two drug interventions, three drug interventions and all the four have been discussed. In all these scenarios the optimal drug regimen is proposed based on two methods. In the first method these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem is formulated. In this setting the optimal drug regimen is proposed. Later using the the comparative effectiveness method the optimal drug regimen is proposed based on basic reproduction number and viral load. The average infected cell count and viral load decreased the most when all the four interventions were applied together. On the other hand the average susceptible cell count decreased the best when Arbidol alone was administered. The basic reproduction number and viral count decreased the best when all the four interventions were applied together reinstating the fact obtained earlier in the optimal control setting. These findings may help physicians with decision making in treatment of life-threatening COVID-19 pneumonia.
1401.0002
Evgenii Levites
Svetlana Sergeevna Kirikovich and Evgenii Vladimirovich Levites
Phenotypic class ratios as marker signs of different types of agamospermy
8 pages, 2 tables, 23 references
null
null
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This article focuses on the development of the method for the genetic classification of agamospermous reproduction types in plants using sugar beet as an example. The classification feasibility is ensured by the use of isozymes as genetic markers allowing the identification of all three phenotypic classes in the progeny of individual heterozygous diploid plant and is based on different phenotypic class ratios in the progenies obtained by meiotic and mitotic agamospermy. The data indicate that for sugar beet meiotic agamospermy is the more typical since 13 of 15 explored progenies were classified as those produced by meiotic agamospermy and only 2 as produced by mitotic agamospermy.
[ { "created": "Sat, 28 Dec 2013 11:39:53 GMT", "version": "v1" } ]
2014-01-03
[ [ "Kirikovich", "Svetlana Sergeevna", "" ], [ "Levites", "Evgenii Vladimirovich", "" ] ]
This article focuses on the development of the method for the genetic classification of agamospermous reproduction types in plants using sugar beet as an example. The classification feasibility is ensured by the use of isozymes as genetic markers allowing the identification of all three phenotypic classes in the progeny of individual heterozygous diploid plant and is based on different phenotypic class ratios in the progenies obtained by meiotic and mitotic agamospermy. The data indicate that for sugar beet meiotic agamospermy is the more typical since 13 of 15 explored progenies were classified as those produced by meiotic agamospermy and only 2 as produced by mitotic agamospermy.
1107.2834
John Burke
John Burke, Mathieu Desroches, Anna M. Barry, Tasso J. Kaper, and Mark A. Kramer
A showcase of torus canards in neuronal bursters
null
null
null
null
q-bio.NC math.DS
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Rapid action potential generation --- spiking --- and alternating intervals of spiking and quiescence --- bursting --- are two dynamic patterns observed in neuronal activity. In computational models of neuronal systems, the transition from spiking to bursting often exhibits complex bifurcation structure. One type of transition involves the torus canard, which was originally observed in a simple biophysical model of a Purkinje cell. In this article, we expand on that original result by showing that torus canards arise in a broad array of well-known computational neuronal models with three different classes of bursting dynamics: sub-Hopf/fold cycle bursting, circle/fold cycle bursting, and fold/fold cycle bursting. The essential features that these models share are multiple time scales leading naturally to decomposition into slow and fast systems, a saddle-node of periodic orbits in the fast system, and a torus bifurcation in the full system. We show that the transition from spiking to bursting in each model system is given by an explosion of torus canards. Based on these examples, as well as on emerging theory, we propose that torus canards are a common dynamic phenomenon separating the regimes of spiking and bursting activity.
[ { "created": "Thu, 14 Jul 2011 14:14:29 GMT", "version": "v1" } ]
2011-07-15
[ [ "Burke", "John", "" ], [ "Desroches", "Mathieu", "" ], [ "Barry", "Anna M.", "" ], [ "Kaper", "Tasso J.", "" ], [ "Kramer", "Mark A.", "" ] ]
Rapid action potential generation --- spiking --- and alternating intervals of spiking and quiescence --- bursting --- are two dynamic patterns observed in neuronal activity. In computational models of neuronal systems, the transition from spiking to bursting often exhibits complex bifurcation structure. One type of transition involves the torus canard, which was originally observed in a simple biophysical model of a Purkinje cell. In this article, we expand on that original result by showing that torus canards arise in a broad array of well-known computational neuronal models with three different classes of bursting dynamics: sub-Hopf/fold cycle bursting, circle/fold cycle bursting, and fold/fold cycle bursting. The essential features that these models share are multiple time scales leading naturally to decomposition into slow and fast systems, a saddle-node of periodic orbits in the fast system, and a torus bifurcation in the full system. We show that the transition from spiking to bursting in each model system is given by an explosion of torus canards. Based on these examples, as well as on emerging theory, we propose that torus canards are a common dynamic phenomenon separating the regimes of spiking and bursting activity.
1909.13327
Christoph Feinauer
Matteo Negri, Davide Bergamini, Carlo Baldassi, Riccardo Zecchina, Christoph Feinauer
Natural representation of composite data with replicated autoencoders
11 pages, 4 figures
null
null
null
q-bio.QM cs.LG stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Generative processes in biology and other fields often produce data that can be regarded as resulting from a composition of basic features. Here we present an unsupervised method based on autoencoders for inferring these basic features of data. The main novelty in our approach is that the training is based on the optimization of the `local entropy' rather than the standard loss, resulting in a more robust inference, and enhancing the performance on this type of data considerably. Algorithmically, this is realized by training an interacting system of replicated autoencoders. We apply this method to synthetic and protein sequence data, and show that it is able to infer a hidden representation that correlates well with the underlying generative process, without requiring any prior knowledge.
[ { "created": "Sun, 29 Sep 2019 17:41:44 GMT", "version": "v1" } ]
2019-10-04
[ [ "Negri", "Matteo", "" ], [ "Bergamini", "Davide", "" ], [ "Baldassi", "Carlo", "" ], [ "Zecchina", "Riccardo", "" ], [ "Feinauer", "Christoph", "" ] ]
Generative processes in biology and other fields often produce data that can be regarded as resulting from a composition of basic features. Here we present an unsupervised method based on autoencoders for inferring these basic features of data. The main novelty in our approach is that the training is based on the optimization of the `local entropy' rather than the standard loss, resulting in a more robust inference, and enhancing the performance on this type of data considerably. Algorithmically, this is realized by training an interacting system of replicated autoencoders. We apply this method to synthetic and protein sequence data, and show that it is able to infer a hidden representation that correlates well with the underlying generative process, without requiring any prior knowledge.
1408.2253
Tatjana Tchumatchenko
T. Tchumatchenko, T. Reichenbach
Cochlear-bone wave can yield a hearing sensation as well as otoacoustic emission
37 pages, 4 figures, Nature Communications 2014
null
10.1038/ncomms5160
null
q-bio.QM q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A hearing sensation arises when the elastic basilar membrane inside the cochlea vibrates. The basilar membrane is typically set into motion through airborne sound that displaces the middle ear and induces a pressure difference across the membrane. A second, alternative pathway exists, however: stimulation of the cochlear bone vibrates the basilar membrane as well. This pathway, referred to as bone conduction, is increasingly used in the construction of headphones that bypass the ear canal and the middle ear. Furthermore, otoacoustic emissions, sounds generated inside the ear and measured in the ear canal, may not involve the usual wave on the basilar membrane, suggesting that additional cochlear structures are involved in their propagation. Here we describe a novel propagation mode that emerges through deformation of the cochlear bone. Through a mathematical and computational approach we demonstrate that this wave can explain bone conduction as well as numerous properties of otoacoustic emissions.
[ { "created": "Sun, 10 Aug 2014 16:55:32 GMT", "version": "v1" } ]
2015-06-22
[ [ "Tchumatchenko", "T.", "" ], [ "Reichenbach", "T.", "" ] ]
A hearing sensation arises when the elastic basilar membrane inside the cochlea vibrates. The basilar membrane is typically set into motion through airborne sound that displaces the middle ear and induces a pressure difference across the membrane. A second, alternative pathway exists, however: stimulation of the cochlear bone vibrates the basilar membrane as well. This pathway, referred to as bone conduction, is increasingly used in the construction of headphones that bypass the ear canal and the middle ear. Furthermore, otoacoustic emissions, sounds generated inside the ear and measured in the ear canal, may not involve the usual wave on the basilar membrane, suggesting that additional cochlear structures are involved in their propagation. Here we describe a novel propagation mode that emerges through deformation of the cochlear bone. Through a mathematical and computational approach we demonstrate that this wave can explain bone conduction as well as numerous properties of otoacoustic emissions.
1005.4393
Adrian Melott
Adrian L. Melott (University of Kansas) and Richard K. Bambach (National Museum of Natural History)
A ubiquitous ~62-Myr periodic fluctuation superimposed on general trends in fossil biodiversity. I. Documentation
56 pages. In press at Paleobiology. Submitted to conform with copyedited version
Paleobiology 37:92,2011
null
null
q-bio.PE astro-ph.EP astro-ph.GA physics.bio-ph physics.geo-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We use Fourier analysis and related techniques to investigate the question of periodicities in fossil biodiversity. These techniques are able to identify cycles superimposed on the long-term trends of the Phanerozoic. We review prior results and analyze data previously reduced and published. Joint time-series analysis of various reductions of the Sepkoski Data, Paleobiology Database, and Fossil Record 2 indicate the same periodicity in biodiversity of marine animals at 62 Myr. We have not found this periodicity in the terrestrial fossil record. We have found that the signal strength decreases with time because of the accumulation of apparently "resistant" long-lived genera. The existence of a 62-Myr periodicity despite very different treatment of systematic error, particularly sampling-strength biases, in all three major databases strongly argues for its reality in the fossil record.
[ { "created": "Mon, 24 May 2010 18:25:31 GMT", "version": "v1" }, { "created": "Wed, 25 Aug 2010 17:05:17 GMT", "version": "v2" } ]
2010-11-26
[ [ "Melott", "Adrian L.", "", "University of Kansas" ], [ "Bambach", "Richard K.", "", "National Museum of Natural History" ] ]
We use Fourier analysis and related techniques to investigate the question of periodicities in fossil biodiversity. These techniques are able to identify cycles superimposed on the long-term trends of the Phanerozoic. We review prior results and analyze data previously reduced and published. Joint time-series analysis of various reductions of the Sepkoski Data, Paleobiology Database, and Fossil Record 2 indicate the same periodicity in biodiversity of marine animals at 62 Myr. We have not found this periodicity in the terrestrial fossil record. We have found that the signal strength decreases with time because of the accumulation of apparently "resistant" long-lived genera. The existence of a 62-Myr periodicity despite very different treatment of systematic error, particularly sampling-strength biases, in all three major databases strongly argues for its reality in the fossil record.
1212.1135
Henry Tuckwell
Henry C. Tuckwell
Biophysical properties and computational modeling of calcium spikes in serotonergic neurons of the dorsal raphe nucleus
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Serotonergic neurons of the dorsal raphe nuclei, with their extensive innervation of nearly the whole brain have important modulatory effects on many cognitive and physiological processes. They play important roles in clinical depression and other psychiatric disorders. In order to quantify the effects of serotonergic transmission on target cells it is desirable to construct computational models and to this end these it is necessary to have details of the biophysical and spike properties of the serotonergic neurons. Here several basic properties are reviewed with data from several studies since the 1960s to the present. The quantities included are input resistance, resting membrane potential, membrane time constant, firing rate, spike duration, spike and afterhyperpolarization (AHP) amplitude, spike threshold, cell capacitance, soma and somadendritic areas. The action potentials of these cells are normally triggered by a combination of sodium and calcium currents which may result in autonomous pacemaker activity. We here analyse the mechanisms of high-threshold calcium spikes which have been demonstrated in these cells the presence of TTX. The parameters for calcium dynamics required to give calcium spikes are quite different from those for regular spiking which suggests the involvement of restricted parts of the soma-dendritic surface as has been found, for example, in hippocampal neurons.
[ { "created": "Wed, 5 Dec 2012 19:33:29 GMT", "version": "v1" } ]
2012-12-06
[ [ "Tuckwell", "Henry C.", "" ] ]
Serotonergic neurons of the dorsal raphe nuclei, with their extensive innervation of nearly the whole brain have important modulatory effects on many cognitive and physiological processes. They play important roles in clinical depression and other psychiatric disorders. In order to quantify the effects of serotonergic transmission on target cells it is desirable to construct computational models and to this end these it is necessary to have details of the biophysical and spike properties of the serotonergic neurons. Here several basic properties are reviewed with data from several studies since the 1960s to the present. The quantities included are input resistance, resting membrane potential, membrane time constant, firing rate, spike duration, spike and afterhyperpolarization (AHP) amplitude, spike threshold, cell capacitance, soma and somadendritic areas. The action potentials of these cells are normally triggered by a combination of sodium and calcium currents which may result in autonomous pacemaker activity. We here analyse the mechanisms of high-threshold calcium spikes which have been demonstrated in these cells the presence of TTX. The parameters for calcium dynamics required to give calcium spikes are quite different from those for regular spiking which suggests the involvement of restricted parts of the soma-dendritic surface as has been found, for example, in hippocampal neurons.
q-bio/0612041
Etay Ziv
Etay Ziv, Ilya Nemenman, and Chris H. Wiggins
Optimal signal processing in small stochastic biochemical networks
41 pages 7 figures, 5 tables
null
10.1371/journal.pone.0001077
LA-UR-06-8411
q-bio.MN q-bio.QM
null
We quantify the influence of the topology of a transcriptional regulatory network on its ability to process environmental signals. By posing the problem in terms of information theory, we may do this without specifying the function performed by the network. Specifically, we study the maximum mutual information between the input (chemical) signal and the output (genetic) response attainable by the network in the context of an analytic model of particle number fluctuations. We perform this analysis for all biochemical circuits, including various feedback loops, that can be built out of 3 chemical species, each under the control of one regulator. We find that a generic network, constrained to low molecule numbers and reasonable response times, can transduce more information than a simple binary switch and, in fact, manages to achieve close to the optimal information transmission fidelity. These high-information solutions are robust to tenfold changes in most of the networks' biochemical parameters; moreover they are easier to achieve in networks containing cycles with an odd number of negative regulators (overall negative feedback) due to their decreased molecular noise (a result which we derive analytically). Finally, we demonstrate that a single circuit can support multiple high-information solutions. These findings suggest a potential resolution of the "cross-talk" dilemma as well as the previously unexplained observation that transcription factors which undergo proteolysis are more likely to be auto-repressive.
[ { "created": "Thu, 21 Dec 2006 20:39:46 GMT", "version": "v1" } ]
2015-06-26
[ [ "Ziv", "Etay", "" ], [ "Nemenman", "Ilya", "" ], [ "Wiggins", "Chris H.", "" ] ]
We quantify the influence of the topology of a transcriptional regulatory network on its ability to process environmental signals. By posing the problem in terms of information theory, we may do this without specifying the function performed by the network. Specifically, we study the maximum mutual information between the input (chemical) signal and the output (genetic) response attainable by the network in the context of an analytic model of particle number fluctuations. We perform this analysis for all biochemical circuits, including various feedback loops, that can be built out of 3 chemical species, each under the control of one regulator. We find that a generic network, constrained to low molecule numbers and reasonable response times, can transduce more information than a simple binary switch and, in fact, manages to achieve close to the optimal information transmission fidelity. These high-information solutions are robust to tenfold changes in most of the networks' biochemical parameters; moreover they are easier to achieve in networks containing cycles with an odd number of negative regulators (overall negative feedback) due to their decreased molecular noise (a result which we derive analytically). Finally, we demonstrate that a single circuit can support multiple high-information solutions. These findings suggest a potential resolution of the "cross-talk" dilemma as well as the previously unexplained observation that transcription factors which undergo proteolysis are more likely to be auto-repressive.