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1203.0875
Jing Kang Dr.
Jing Kang, Bing Xu, Ye Yao, Wei Lin, Conor Hennessy, Peter Fraser, Jianfeng Feng
A Dynamical Model Reveals Gene Co-Localizations in Nucleus
16 pages, 7 figures; PloS Computational Biology 2011
null
10.1371/journal.pcbi.1002094
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Co-localization of networks of genes in the nucleus is thought to play an important role in determining gene expression patterns. Based upon experimental data, we built a dynamical model to test whether pure diffusion could account for the observed co-localization of genes within a defined subnuclear region. A simple standard Brownian motion model in two and three dimensions shows that preferential co-localization is possible for co-regulated genes without any direct interaction, and suggests the occurrence may be due to a limitation in the number of available transcription factors. Experimental data of chromatin movements demonstrates that fractional rather than standard Brownian motion is more appropriate to model gene mobilizations, and we tested our dynamical model against recent static experimental data, using a sub-diffusion process by which the genes tend to colocalize more easily. Moreover, in order to compare our model with recently obtained experimental data, we studied the association level between genes and factors, and presented data supporting the validation of this dynamic model. As further applications of our model, we applied it to test against more biological observations. We found that increasing transcription factor number, rather than factory number and nucleus size, might be the reason for decreasing gene co-localization. In the scenario of frequency- or amplitude-modulation of transcription factors, our model predicted that frequency-modulation may increase the co-localization between its targeted genes.
[ { "created": "Mon, 5 Mar 2012 11:57:06 GMT", "version": "v1" } ]
2012-03-06
[ [ "Kang", "Jing", "" ], [ "Xu", "Bing", "" ], [ "Yao", "Ye", "" ], [ "Lin", "Wei", "" ], [ "Hennessy", "Conor", "" ], [ "Fraser", "Peter", "" ], [ "Feng", "Jianfeng", "" ] ]
Co-localization of networks of genes in the nucleus is thought to play an important role in determining gene expression patterns. Based upon experimental data, we built a dynamical model to test whether pure diffusion could account for the observed co-localization of genes within a defined subnuclear region. A simple standard Brownian motion model in two and three dimensions shows that preferential co-localization is possible for co-regulated genes without any direct interaction, and suggests the occurrence may be due to a limitation in the number of available transcription factors. Experimental data of chromatin movements demonstrates that fractional rather than standard Brownian motion is more appropriate to model gene mobilizations, and we tested our dynamical model against recent static experimental data, using a sub-diffusion process by which the genes tend to colocalize more easily. Moreover, in order to compare our model with recently obtained experimental data, we studied the association level between genes and factors, and presented data supporting the validation of this dynamic model. As further applications of our model, we applied it to test against more biological observations. We found that increasing transcription factor number, rather than factory number and nucleus size, might be the reason for decreasing gene co-localization. In the scenario of frequency- or amplitude-modulation of transcription factors, our model predicted that frequency-modulation may increase the co-localization between its targeted genes.
0709.3606
Baruch Meerson
Michael Assaf, Baruch Meerson
Noise enhanced persistence in a biochemical regulatory network with feedback control
4 pages, 4 figures, submitted for publication
Phys. Rev. Lett. 100, 058105 (2008)
10.1103/PhysRevLett.100.058105
null
q-bio.MN cond-mat.stat-mech
null
We find that discrete noise of inhibiting (signal) molecules can greatly delay the extinction of plasmids in a plasmid replication system: a prototypical biochemical regulatory network. We calculate the probability distribution of the metastable state of the plasmids and show on this example that the reaction rate equations may fail in predicting the average number of regulated molecules even when this number is large, and the time is much shorter than the mean extinction time.
[ { "created": "Sat, 22 Sep 2007 21:03:56 GMT", "version": "v1" }, { "created": "Sun, 2 Dec 2007 21:04:52 GMT", "version": "v2" } ]
2016-10-06
[ [ "Assaf", "Michael", "" ], [ "Meerson", "Baruch", "" ] ]
We find that discrete noise of inhibiting (signal) molecules can greatly delay the extinction of plasmids in a plasmid replication system: a prototypical biochemical regulatory network. We calculate the probability distribution of the metastable state of the plasmids and show on this example that the reaction rate equations may fail in predicting the average number of regulated molecules even when this number is large, and the time is much shorter than the mean extinction time.
1510.07810
Caterina La Porta AM
Alessandro L. Sellerio, Emilio Ciusani, Noa Bossel Ben-Moshe, Stefania Coco, Andrea Piccinini, Christopher R. Myers, James P. Sethna, Costanza Giampietro, Stefano Zapperi, Caterina A. M. La Porta
Overshoot during phenotypic switching of cancer cell populations
null
Sci. Rep. 5, 15464, (2015)
10.1038/srep15464
null
q-bio.CB physics.bio-ph
http://creativecommons.org/licenses/by/4.0/
The dynamics of tumor cell populations is hotly debated: do populations derive hierarchically from a subpopulation of cancer stem cells (CSCs), or are stochastic transitions that mutate differentiated cancer cells to CSCs important? Here we argue that regulation must also be important. We sort human melanoma cells using three distinct cancer stem cell (CSC) markers - CXCR6, CD271 and ABCG2 - and observe that the fraction of non-CSC-marked cells first overshoots to a higher level and then returns to the level of unsorted cells. This clearly indicates that the CSC population is homeostatically regulated. Combining experimental measurements with theoretical modeling and numerical simulations, we show that the population dynamics of cancer cells is associated with a complex miRNA network regulating the Wnt and PI3K pathways. Hence phenotypic switching is not stochastic, but is tightly regulated by the balance between positive and negative cells in the population. Reducing the fraction of CSCs below a threshold triggers massive phenotypic switching, suggesting that a therapeutic strategy based on CSC eradication is unlikely to succeed.
[ { "created": "Tue, 27 Oct 2015 08:40:46 GMT", "version": "v1" } ]
2015-10-28
[ [ "Sellerio", "Alessandro L.", "" ], [ "Ciusani", "Emilio", "" ], [ "Ben-Moshe", "Noa Bossel", "" ], [ "Coco", "Stefania", "" ], [ "Piccinini", "Andrea", "" ], [ "Myers", "Christopher R.", "" ], [ "Sethna", "Jame...
The dynamics of tumor cell populations is hotly debated: do populations derive hierarchically from a subpopulation of cancer stem cells (CSCs), or are stochastic transitions that mutate differentiated cancer cells to CSCs important? Here we argue that regulation must also be important. We sort human melanoma cells using three distinct cancer stem cell (CSC) markers - CXCR6, CD271 and ABCG2 - and observe that the fraction of non-CSC-marked cells first overshoots to a higher level and then returns to the level of unsorted cells. This clearly indicates that the CSC population is homeostatically regulated. Combining experimental measurements with theoretical modeling and numerical simulations, we show that the population dynamics of cancer cells is associated with a complex miRNA network regulating the Wnt and PI3K pathways. Hence phenotypic switching is not stochastic, but is tightly regulated by the balance between positive and negative cells in the population. Reducing the fraction of CSCs below a threshold triggers massive phenotypic switching, suggesting that a therapeutic strategy based on CSC eradication is unlikely to succeed.
2204.08608
Shiqiu Yin
Zaiyun Lin (Beijing Stonewise Technology) and Shiqiu Yin (Beijing Stonewise Technology) and Lei Shi (Beijing Stonewise Technology) and Wenbiao Zhou (Beijing Stonewise Technology) and YingSheng Zhang (Beijing Stonewise Technology)
G2GT: Retrosynthesis Prediction with Graph to Graph Attention Neural Network and Self-Training
number of pages:12 and number of figures:5
null
null
null
q-bio.QM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Retrosynthesis prediction is one of the fundamental challenges in organic chemistry and related fields. The goal is to find reactants molecules that can synthesize product molecules. To solve this task, we propose a new graph-to-graph transformation model, G2GT, in which the graph encoder and graph decoder are built upon the standard transformer structure. We also show that self-training, a powerful data augmentation method that utilizes unlabeled molecule data, can significantly improve the model's performance. Inspired by the reaction type label and ensemble learning, we proposed a novel weak ensemble method to enhance diversity. We combined beam search, nucleus, and top-k sampling methods to further improve inference diversity and proposed a simple ranking algorithm to retrieve the final top-10 results. We achieved new state-of-the-art results on both the USPTO-50K dataset, with top1 accuracy of 54%, and the larger data set USPTO-full, with top1 accuracy of 50%, and competitive top-10 results.
[ { "created": "Tue, 19 Apr 2022 01:55:52 GMT", "version": "v1" } ]
2022-04-20
[ [ "Lin", "Zaiyun", "", "Beijing Stonewise Technology" ], [ "Yin", "Shiqiu", "", "Beijing\n Stonewise Technology" ], [ "Shi", "Lei", "", "Beijing Stonewise Technology" ], [ "Zhou", "Wenbiao", "", "Beijing Stonewise Technology" ], [ ...
Retrosynthesis prediction is one of the fundamental challenges in organic chemistry and related fields. The goal is to find reactants molecules that can synthesize product molecules. To solve this task, we propose a new graph-to-graph transformation model, G2GT, in which the graph encoder and graph decoder are built upon the standard transformer structure. We also show that self-training, a powerful data augmentation method that utilizes unlabeled molecule data, can significantly improve the model's performance. Inspired by the reaction type label and ensemble learning, we proposed a novel weak ensemble method to enhance diversity. We combined beam search, nucleus, and top-k sampling methods to further improve inference diversity and proposed a simple ranking algorithm to retrieve the final top-10 results. We achieved new state-of-the-art results on both the USPTO-50K dataset, with top1 accuracy of 54%, and the larger data set USPTO-full, with top1 accuracy of 50%, and competitive top-10 results.
1610.01493
Gabriel Alvarez
G. Alvarez, L. Fernandez, R. Salinas
Construction of hazard maps of Hantavirus contagion using Remote Sensing, logistic regression and Artificial Neural Networks: case Araucan\'ia Region, Chile
13 pages, 14 figures
null
null
null
q-bio.PE physics.bio-ph stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this research, methods and computational results based on statistical analysis and mathematical modelling, data collection in situ in order to make a hazard map of Hanta Virus infection in the region of Araucania, Chile are presented. The development of this work involves several elements such as Landsat satellite images, biological information regarding seropositivity of Hanta Virus and information concerning positive cases of infection detected in the region. All this information has been processed to find a function that models the danger of contagion in the region, through logistic regression analysis and Artificial Neural Networks
[ { "created": "Wed, 5 Oct 2016 15:58:20 GMT", "version": "v1" } ]
2016-10-06
[ [ "Alvarez", "G.", "" ], [ "Fernandez", "L.", "" ], [ "Salinas", "R.", "" ] ]
In this research, methods and computational results based on statistical analysis and mathematical modelling, data collection in situ in order to make a hazard map of Hanta Virus infection in the region of Araucania, Chile are presented. The development of this work involves several elements such as Landsat satellite images, biological information regarding seropositivity of Hanta Virus and information concerning positive cases of infection detected in the region. All this information has been processed to find a function that models the danger of contagion in the region, through logistic regression analysis and Artificial Neural Networks
2104.09307
Yong Li
Zhenfeng Shao, Yong Li, Xiao Huang, Bowen Cai, Lin Ding, Wenkang Pan, Ya Zhang
Monitoring urban ecosystem service value using dynamic multi-level grids
null
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
Ecosystem services are the direct and indirect contributions of an ecosystem to human well-being and survival. Ecosystem valuation is a method of assigning a monetary value to an ecosystem with its goods and services,often referred to as ecosystem service value (ESV). With the rapid expansion of cities, a mismatch occurs between urban development and ecological development, and it is increasingly urgent to establish a valid ecological assessment method. In this study, we propose an ecological evaluation standard framework by designing an ESV monitoring workflow based on the establishment of multi-level grids. The proposed method is able to capture multi-scale features, facilitates multi-level spatial expression, and can effectively reveal the spatial heterogeneity of ESV. Taking Haian city in the Jiangsu province as the study case, we implemented the proposed dynamic multi-level grids-based (DMLG) to calculate its urban ESV in 2016 and 2019. We found that the ESV of Haian city showed considerable growth (increased by 24.54 million RMB). Negative ESVs are concentrated in the central city, which presented a rapid trend of outward expansion. The results illustrated that the ongoing urban expanse does not reduce the ecological value in the study area. The proposed unified grid framework can be applied to other geographical regions and is expected to benefit future studies in ecosystem service evaluation in terms of capture multi-level spatial heterogeneity.
[ { "created": "Thu, 15 Apr 2021 10:57:43 GMT", "version": "v1" } ]
2021-04-20
[ [ "Shao", "Zhenfeng", "" ], [ "Li", "Yong", "" ], [ "Huang", "Xiao", "" ], [ "Cai", "Bowen", "" ], [ "Ding", "Lin", "" ], [ "Pan", "Wenkang", "" ], [ "Zhang", "Ya", "" ] ]
Ecosystem services are the direct and indirect contributions of an ecosystem to human well-being and survival. Ecosystem valuation is a method of assigning a monetary value to an ecosystem with its goods and services,often referred to as ecosystem service value (ESV). With the rapid expansion of cities, a mismatch occurs between urban development and ecological development, and it is increasingly urgent to establish a valid ecological assessment method. In this study, we propose an ecological evaluation standard framework by designing an ESV monitoring workflow based on the establishment of multi-level grids. The proposed method is able to capture multi-scale features, facilitates multi-level spatial expression, and can effectively reveal the spatial heterogeneity of ESV. Taking Haian city in the Jiangsu province as the study case, we implemented the proposed dynamic multi-level grids-based (DMLG) to calculate its urban ESV in 2016 and 2019. We found that the ESV of Haian city showed considerable growth (increased by 24.54 million RMB). Negative ESVs are concentrated in the central city, which presented a rapid trend of outward expansion. The results illustrated that the ongoing urban expanse does not reduce the ecological value in the study area. The proposed unified grid framework can be applied to other geographical regions and is expected to benefit future studies in ecosystem service evaluation in terms of capture multi-level spatial heterogeneity.
1508.03492
Satoru Morita
Satoru Morita
Evolutionary game on networks with high clustering coefficient
12 pages, 3 figures
Nonlinear Theory and Its Applications IEICE 7, 110-117 (2016)
10.1587/nolta.7.110
null
q-bio.PE nlin.AO physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This study investigates the influence of lattice structure in evolutionary games. The snowdrift games is considered in networks with high clustering coefficients, that use four different strategy-updating. Analytical conjectures using pair approximation were compared with the numerical results. Results indicate that general statements asserting that the lattice structure enhances cooperation are misleading.
[ { "created": "Fri, 14 Aug 2015 13:26:15 GMT", "version": "v1" } ]
2021-11-05
[ [ "Morita", "Satoru", "" ] ]
This study investigates the influence of lattice structure in evolutionary games. The snowdrift games is considered in networks with high clustering coefficients, that use four different strategy-updating. Analytical conjectures using pair approximation were compared with the numerical results. Results indicate that general statements asserting that the lattice structure enhances cooperation are misleading.
2107.00578
Rodrigo M\'endez Rojano
Rodrigo M\'endez Rojano, Mansur Zhussupbekov, James F. Antaki, Didier Lucor
Uncertainty quantification of a thrombosis model considering the clotting assay PFA-100
17 pages, 10 figures, 3 tables, original research article
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Mathematical models of thrombosis are currently used to study clinical scenarios of pathological thrombus formation. Most of these models involve inherent uncertainties that must be assessed to increase the confidence in model predictions and identify avenues of improvement for both thrombosis modeling and anti-platelet therapies. In this work, an uncertainty quantification analysis of a multi-constituent thrombosis model is performed considering a common assay for platelet function (PFA-100). The analysis is performed using a polynomial chaos expansion as a parametric surrogate for the thrombosis model. The polynomial approximation is validated and used to perform a global sensitivity analysis via computation of Sobol' coefficients. Six out of fifteen parameters were found to be influential in the simulation variability considering only individual effects. Nonetheless, parameter interactions are highlighted when considering the total Sobol' indices. In addition to the sensitivity analysis, the surrogate model was used to compute the PFA-100 closure times of 300,000 virtual cases that align well with clinical data. The current methodology could be used including common anti-platelet therapies to identify scenarios that preserve the hematological balance.
[ { "created": "Tue, 29 Jun 2021 14:33:49 GMT", "version": "v1" } ]
2021-07-02
[ [ "Rojano", "Rodrigo Méndez", "" ], [ "Zhussupbekov", "Mansur", "" ], [ "Antaki", "James F.", "" ], [ "Lucor", "Didier", "" ] ]
Mathematical models of thrombosis are currently used to study clinical scenarios of pathological thrombus formation. Most of these models involve inherent uncertainties that must be assessed to increase the confidence in model predictions and identify avenues of improvement for both thrombosis modeling and anti-platelet therapies. In this work, an uncertainty quantification analysis of a multi-constituent thrombosis model is performed considering a common assay for platelet function (PFA-100). The analysis is performed using a polynomial chaos expansion as a parametric surrogate for the thrombosis model. The polynomial approximation is validated and used to perform a global sensitivity analysis via computation of Sobol' coefficients. Six out of fifteen parameters were found to be influential in the simulation variability considering only individual effects. Nonetheless, parameter interactions are highlighted when considering the total Sobol' indices. In addition to the sensitivity analysis, the surrogate model was used to compute the PFA-100 closure times of 300,000 virtual cases that align well with clinical data. The current methodology could be used including common anti-platelet therapies to identify scenarios that preserve the hematological balance.
2404.07390
Brian Camley
Pedrom Zadeh and Brian A. Camley
Nonlinear dynamics of confined cell migration -- modeling and inference
null
null
null
null
q-bio.CB cond-mat.soft physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The motility of eukaryotic cells is strongly influenced by their environment, with confined cells often developing qualitatively different motility patterns from those migrating on simple two-dimensional substrates. Recent experiments, coupled with data-driven methods to extract a cell's equation of motion, showed that cancerous MDA-MB-231 cells persistently hop in a limit cycle when placed on two-state adhesive micropatterns (two large squares connected by a narrow bridge), while they remain stationary on average in rectangular confinements. In contrast, healthy MCF10A cells migrating on the two-state micropattern are bistable, i.e., they settle into either basin on average with only noise-induced hops between the two states. We can capture all these behaviors with a single computational phase field model of a crawling cell, under the assumption that contact with non-adhesive substrate inhibits the cell front. Our model predicts that larger and softer cells are more likely to persistently hop, while smaller and stiffer cells are more likely to be bistable. Other key factors controlling cell migration are the frequency of protrusions and their magnitude of noise. Our results show that relatively simple assumptions about how cells sense their geometry can explain a wide variety of different cell behaviors, and show the power of data-driven approaches to characterize both experiment and simulation.
[ { "created": "Wed, 10 Apr 2024 23:32:47 GMT", "version": "v1" } ]
2024-04-12
[ [ "Zadeh", "Pedrom", "" ], [ "Camley", "Brian A.", "" ] ]
The motility of eukaryotic cells is strongly influenced by their environment, with confined cells often developing qualitatively different motility patterns from those migrating on simple two-dimensional substrates. Recent experiments, coupled with data-driven methods to extract a cell's equation of motion, showed that cancerous MDA-MB-231 cells persistently hop in a limit cycle when placed on two-state adhesive micropatterns (two large squares connected by a narrow bridge), while they remain stationary on average in rectangular confinements. In contrast, healthy MCF10A cells migrating on the two-state micropattern are bistable, i.e., they settle into either basin on average with only noise-induced hops between the two states. We can capture all these behaviors with a single computational phase field model of a crawling cell, under the assumption that contact with non-adhesive substrate inhibits the cell front. Our model predicts that larger and softer cells are more likely to persistently hop, while smaller and stiffer cells are more likely to be bistable. Other key factors controlling cell migration are the frequency of protrusions and their magnitude of noise. Our results show that relatively simple assumptions about how cells sense their geometry can explain a wide variety of different cell behaviors, and show the power of data-driven approaches to characterize both experiment and simulation.
1307.7844
Aaron Darling
Micha{\l} Modzelewski and Norbert Dojer
MSARC: Multiple Sequence Alignment by Residue Clustering
Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013)
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Progressive methods offer efficient and reasonably good solutions to the multiple sequence alignment problem. However, resulting alignments are biased by guide-trees, especially for relatively distant sequences. We propose MSARC, a new graph-clustering based algorithm that aligns sequence sets without guide-trees. Experiments on the BAliBASE dataset show that MSARC achieves alignment quality similar to best progressive methods and substantially higher than the quality of other non-progressive algorithms. Furthermore, MSARC outperforms all other methods on sequence sets with the similarity structure hardly represented by a phylogenetic tree. Furthermore, MSARC outperforms all other methods on sequence sets whose evolutionary distances are hardly representable by a phylogenetic tree. These datasets are most exposed to the guide-tree bias of alignments. MSARC is available at http://bioputer.mimuw.edu.pl/msarc
[ { "created": "Tue, 30 Jul 2013 07:05:01 GMT", "version": "v1" } ]
2013-07-31
[ [ "Modzelewski", "Michał", "" ], [ "Dojer", "Norbert", "" ] ]
Progressive methods offer efficient and reasonably good solutions to the multiple sequence alignment problem. However, resulting alignments are biased by guide-trees, especially for relatively distant sequences. We propose MSARC, a new graph-clustering based algorithm that aligns sequence sets without guide-trees. Experiments on the BAliBASE dataset show that MSARC achieves alignment quality similar to best progressive methods and substantially higher than the quality of other non-progressive algorithms. Furthermore, MSARC outperforms all other methods on sequence sets with the similarity structure hardly represented by a phylogenetic tree. Furthermore, MSARC outperforms all other methods on sequence sets whose evolutionary distances are hardly representable by a phylogenetic tree. These datasets are most exposed to the guide-tree bias of alignments. MSARC is available at http://bioputer.mimuw.edu.pl/msarc
1508.05929
Matthew Fisher
Matthew P. A. Fisher
Quantum Cognition: The possibility of processing with nuclear spins in the brain
8 pages, 3 figures
Annals of Physics 362, 593-602 (2015)
null
null
q-bio.NC physics.bio-ph quant-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The possibility that quantum processing with nuclear spins might be operative in the brain is proposed and then explored. Phosphorus is identified as the unique biological element with a nuclear spin that can serve as a qubit for such putative quantum processing - a neural qubit - while the phosphate ion is the only possible qubit-transporter. We identify the "Posner molecule", $\text{Ca}_9 (\text{PO}_4)_6$, as the unique molecule that can protect the neural qubits on very long times and thereby serve as a (working) quantum-memory. A central requirement for quantum-processing is quantum entanglement. It is argued that the enzyme catalyzed chemical reaction which breaks a pyrophosphate ion into two phosphate ions can quantum entangle pairs of qubits. Posner molecules, formed by binding such phosphate pairs with extracellular calcium ions, will inherit the nuclear spin entanglement. A mechanism for transporting Posner molecules into presynaptic neurons during a "kiss and run" exocytosis, which releases neurotransmitters into the synaptic cleft, is proposed. Quantum measurements can occur when a pair of Posner molecules chemically bind and subsequently melt, releasing a shower of intra-cellular calcium ions that can trigger further neurotransmitter release and enhance the probability of post-synaptic neuron firing. Multiple entangled Posner molecules, triggering non-local quantum correlations of neuron firing rates, would provide the key mechanism for neural quantum processing. Implications, both in vitro and in vivo, are briefly mentioned.
[ { "created": "Wed, 19 Aug 2015 18:23:38 GMT", "version": "v1" }, { "created": "Sat, 29 Aug 2015 00:00:42 GMT", "version": "v2" } ]
2015-11-10
[ [ "Fisher", "Matthew P. A.", "" ] ]
The possibility that quantum processing with nuclear spins might be operative in the brain is proposed and then explored. Phosphorus is identified as the unique biological element with a nuclear spin that can serve as a qubit for such putative quantum processing - a neural qubit - while the phosphate ion is the only possible qubit-transporter. We identify the "Posner molecule", $\text{Ca}_9 (\text{PO}_4)_6$, as the unique molecule that can protect the neural qubits on very long times and thereby serve as a (working) quantum-memory. A central requirement for quantum-processing is quantum entanglement. It is argued that the enzyme catalyzed chemical reaction which breaks a pyrophosphate ion into two phosphate ions can quantum entangle pairs of qubits. Posner molecules, formed by binding such phosphate pairs with extracellular calcium ions, will inherit the nuclear spin entanglement. A mechanism for transporting Posner molecules into presynaptic neurons during a "kiss and run" exocytosis, which releases neurotransmitters into the synaptic cleft, is proposed. Quantum measurements can occur when a pair of Posner molecules chemically bind and subsequently melt, releasing a shower of intra-cellular calcium ions that can trigger further neurotransmitter release and enhance the probability of post-synaptic neuron firing. Multiple entangled Posner molecules, triggering non-local quantum correlations of neuron firing rates, would provide the key mechanism for neural quantum processing. Implications, both in vitro and in vivo, are briefly mentioned.
1010.1714
Randall Beer
Randall D. Beer and Bryan Daniels
Saturation Probabilities of Continuous-Time Sigmoidal Networks
53 pages, 9 Figures
null
null
null
q-bio.NC math.CO math.DS nlin.AO q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
From genetic regulatory networks to nervous systems, the interactions between elements in biological networks often take a sigmoidal or S-shaped form. This paper develops a probabilistic characterization of the parameter space of continuous-time sigmoidal networks (CTSNs), a simple but dynamically-universal model of such interactions. We describe an efficient and accurate method for calculating the probability of observing effectively M-dimensional dynamics in an N-element CTSN, as well as a closed-form but approximate method. We then study the dependence of this probability on N, M, and the parameter ranges over which sampling occurs. This analysis provides insight into the overall structure of CTSN parameter space.
[ { "created": "Fri, 8 Oct 2010 15:10:38 GMT", "version": "v1" } ]
2010-10-11
[ [ "Beer", "Randall D.", "" ], [ "Daniels", "Bryan", "" ] ]
From genetic regulatory networks to nervous systems, the interactions between elements in biological networks often take a sigmoidal or S-shaped form. This paper develops a probabilistic characterization of the parameter space of continuous-time sigmoidal networks (CTSNs), a simple but dynamically-universal model of such interactions. We describe an efficient and accurate method for calculating the probability of observing effectively M-dimensional dynamics in an N-element CTSN, as well as a closed-form but approximate method. We then study the dependence of this probability on N, M, and the parameter ranges over which sampling occurs. This analysis provides insight into the overall structure of CTSN parameter space.
q-bio/0508028
Darren E. Segall
Darren E. Segall, Phillip C. Nelson and Rob Phillips
Excluded-Volume Effects in Tethered-Particle Experiments: Bead Size Matters
4 pages, 3 figures
Phys. Rev. Lett. Vol 96, no. 088306 (2006)
10.1103/PhysRevLett.96.088306
null
q-bio.BM
null
The tethered-particle method is a single-molecule technique that has been used to explore the dynamics of a variety of macromolecules of biological interest. We give a theoretical analysis of the particle motions in such experiments. Our analysis reveals that the proximity of the tethered bead to a nearby surface (the microscope slide) gives rise to a volume-exclusion effect, resulting in an entropic force on the molecule. This force stretches the molecule, changing its statistical properties. In particular, the proximity of bead and surface brings about intriguing scaling relations between key observables (statistical moments of the bead) and parameters such as the bead size and contour length of the molecule. We present both approximate analytic solutions and numerical results for these effects in both flexible and semiflexible tethers. Finally, our results give a precise, experimentally-testable prediction for the probability distribution of the distance between the polymer attachment point and the center of the mobile bead.
[ { "created": "Sat, 20 Aug 2005 17:58:10 GMT", "version": "v1" }, { "created": "Wed, 31 Aug 2005 01:27:56 GMT", "version": "v2" } ]
2009-11-11
[ [ "Segall", "Darren E.", "" ], [ "Nelson", "Phillip C.", "" ], [ "Phillips", "Rob", "" ] ]
The tethered-particle method is a single-molecule technique that has been used to explore the dynamics of a variety of macromolecules of biological interest. We give a theoretical analysis of the particle motions in such experiments. Our analysis reveals that the proximity of the tethered bead to a nearby surface (the microscope slide) gives rise to a volume-exclusion effect, resulting in an entropic force on the molecule. This force stretches the molecule, changing its statistical properties. In particular, the proximity of bead and surface brings about intriguing scaling relations between key observables (statistical moments of the bead) and parameters such as the bead size and contour length of the molecule. We present both approximate analytic solutions and numerical results for these effects in both flexible and semiflexible tethers. Finally, our results give a precise, experimentally-testable prediction for the probability distribution of the distance between the polymer attachment point and the center of the mobile bead.
1203.0180
Ovidiu Radulescu
S.A. Vakulenko, O. Radulescu
Flexible and robust networks
Journal of Bioinformatics and Computational Biology, in press
null
null
null
q-bio.MN
http://creativecommons.org/licenses/publicdomain/
We consider networks with two types of nodes. The v-nodes, called centers, are hyper- connected and interact one to another via many u-nodes, called satellites. This central- ized architecture, widespread in gene networks, possesses two fundamental properties. Namely, this organization creates feedback loops that are capable to generate practically any prescribed patterning dynamics, chaotic or periodic, or having a number of equilib- rium states. Moreover, this organization is robust with respect to random perturbations of the system.
[ { "created": "Thu, 1 Mar 2012 13:33:39 GMT", "version": "v1" } ]
2012-03-02
[ [ "Vakulenko", "S. A.", "" ], [ "Radulescu", "O.", "" ] ]
We consider networks with two types of nodes. The v-nodes, called centers, are hyper- connected and interact one to another via many u-nodes, called satellites. This central- ized architecture, widespread in gene networks, possesses two fundamental properties. Namely, this organization creates feedback loops that are capable to generate practically any prescribed patterning dynamics, chaotic or periodic, or having a number of equilib- rium states. Moreover, this organization is robust with respect to random perturbations of the system.
q-bio/0411019
Boris Shklovskii
B. I. Shklovskii
A simple derivation of the Gompertz law for human mortality
2 pages, typos corrected
Theory in Biosciences, 123, 431 (2005)
null
null
q-bio.CB cond-mat.dis-nn cond-mat.other q-bio.OT
null
The Gompertz law of dependence of human mortality rate on age is derived from a simple model of death as a result of the exponentially rare escape of abnormal cells from immunological response.
[ { "created": "Thu, 4 Nov 2004 21:38:29 GMT", "version": "v1" }, { "created": "Mon, 8 Nov 2004 15:33:13 GMT", "version": "v2" }, { "created": "Wed, 10 Nov 2004 20:55:21 GMT", "version": "v3" } ]
2007-05-23
[ [ "Shklovskii", "B. I.", "" ] ]
The Gompertz law of dependence of human mortality rate on age is derived from a simple model of death as a result of the exponentially rare escape of abnormal cells from immunological response.
1503.03550
Yunxin Zhang
Jingwei Li, Yunxin Zhang
Correlations between promoter activity and its nucleotide positions in spacing region
null
null
null
null
q-bio.GN physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Transcription is one of the essential processes for cells to read genetic information encoded in genes, which is initiated by the binding of RNA polymerase to related promoter. Experiments have found that the nucleotide sequence of promoter has great influence on gene expression strength, or promoter activity. In synthetic biology, one interesting question is how we can synthesize a promoter with given activity, and which positions of promoter sequence are important for determining its activity. In this study, based on recent experimental data, correlations between promoter activity and its sequence positions are analyzed by various methods. Our results show that, except nucleotides in the two highly conserved regions, $-35$ box and $-10$ box, influences of nucleotides in other positions are also not neglectable. For example, modifications of nucleotides around position $-19$ in spacing region may change promoter activity in a large scale. The results of this study might be helpful to our understanding of biophysical mechanism of gene transcription, and may also be helpful to the design of synthetic cell factory.
[ { "created": "Thu, 12 Mar 2015 01:32:20 GMT", "version": "v1" } ]
2015-03-13
[ [ "Li", "Jingwei", "" ], [ "Zhang", "Yunxin", "" ] ]
Transcription is one of the essential processes for cells to read genetic information encoded in genes, which is initiated by the binding of RNA polymerase to related promoter. Experiments have found that the nucleotide sequence of promoter has great influence on gene expression strength, or promoter activity. In synthetic biology, one interesting question is how we can synthesize a promoter with given activity, and which positions of promoter sequence are important for determining its activity. In this study, based on recent experimental data, correlations between promoter activity and its sequence positions are analyzed by various methods. Our results show that, except nucleotides in the two highly conserved regions, $-35$ box and $-10$ box, influences of nucleotides in other positions are also not neglectable. For example, modifications of nucleotides around position $-19$ in spacing region may change promoter activity in a large scale. The results of this study might be helpful to our understanding of biophysical mechanism of gene transcription, and may also be helpful to the design of synthetic cell factory.
2405.12897
James Holehouse
James Holehouse
Principles of bursty mRNA expression and irreversibility in single cells and extrinsically varying populations
15 pages, 6 figures
null
null
null
q-bio.SC cond-mat.stat-mech q-bio.PE
http://creativecommons.org/licenses/by/4.0/
The canonical model of mRNA expression is the telegraph model, describing a gene that switches on and off, subject to transcription and decay. It describes steady-state mRNA distributions that subscribe to transcription in bursts with first-order decay, referred to as super-Poissonian expression. Using a telegraph-like model, I propose an answer to the question of why gene expression is bursty in the first place, and what benefits it confers. Using analytics for the entropy production rate, I find that entropy production is maximal when the on and off switching rates between the gene states are approximately equal. This is related to a lower bound on the free energy necessary to keep the system out of equilibrium, meaning that bursty gene expression may have evolved in part due to free energy efficiency. It is shown that there are trade-offs between having slow nuclear export, which can reduce cytoplasmic mRNA noise, and the energy required to keep the system out of equilibrium -- nuclear compartmentalization comes with an associated free energy cost. At the population level, I find that extrinsic variation, manifested in cell-to-cell differences in kinetic parameters, can make the system more or less reversible -- and potentially energy efficient -- depending on where the noise is located. This highlights that there evolutionary constraints on the suppression of extrinsic noise, whose origin is in cellular heterogeneity, in addition to intrinsic randomness arising from molecular collisions. Finally, I investigate the partially observed nature of most mRNA expression data which seems to obey detailed balance, yet remains unavoidably out-of-equilibrium.
[ { "created": "Tue, 21 May 2024 16:07:48 GMT", "version": "v1" } ]
2024-05-22
[ [ "Holehouse", "James", "" ] ]
The canonical model of mRNA expression is the telegraph model, describing a gene that switches on and off, subject to transcription and decay. It describes steady-state mRNA distributions that subscribe to transcription in bursts with first-order decay, referred to as super-Poissonian expression. Using a telegraph-like model, I propose an answer to the question of why gene expression is bursty in the first place, and what benefits it confers. Using analytics for the entropy production rate, I find that entropy production is maximal when the on and off switching rates between the gene states are approximately equal. This is related to a lower bound on the free energy necessary to keep the system out of equilibrium, meaning that bursty gene expression may have evolved in part due to free energy efficiency. It is shown that there are trade-offs between having slow nuclear export, which can reduce cytoplasmic mRNA noise, and the energy required to keep the system out of equilibrium -- nuclear compartmentalization comes with an associated free energy cost. At the population level, I find that extrinsic variation, manifested in cell-to-cell differences in kinetic parameters, can make the system more or less reversible -- and potentially energy efficient -- depending on where the noise is located. This highlights that there evolutionary constraints on the suppression of extrinsic noise, whose origin is in cellular heterogeneity, in addition to intrinsic randomness arising from molecular collisions. Finally, I investigate the partially observed nature of most mRNA expression data which seems to obey detailed balance, yet remains unavoidably out-of-equilibrium.
2210.02913
Hideaki Yamamoto
Takuma Sumi, Hideaki Yamamoto, Yuichi Katori, Satoshi Moriya, Tomohiro Konno, Shigeo Sato, Ayumi Hirano-Iwata
Biological neurons act as generalization filters in reservoir computing
31 pages, 5 figures, 3 supplementary figures
Proc. Natl. Acad. Sci., U.S.A. 120, e2217008120 (2023)
10.1073/pnas.2217008120
null
q-bio.NC stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Reservoir computing is a machine learning paradigm that transforms the transient dynamics of high-dimensional nonlinear systems for processing time-series data. Although reservoir computing was initially proposed to model information processing in the mammalian cortex, it remains unclear how the non-random network architecture, such as the modular architecture, in the cortex integrates with the biophysics of living neurons to characterize the function of biological neuronal networks (BNNs). Here, we used optogenetics and fluorescent calcium imaging to record the multicellular responses of cultured BNNs and employed the reservoir computing framework to decode their computational capabilities. Micropatterned substrates were used to embed the modular architecture in the BNNs. We first show that modular BNNs can be used to classify static input patterns with a linear decoder and that the modularity of the BNNs positively correlates with the classification accuracy. We then used a timer task to verify that BNNs possess a short-term memory of ~1 s and finally show that this property can be exploited for spoken digit classification. Interestingly, BNN-based reservoirs allow transfer learning, wherein a network trained on one dataset can be used to classify separate datasets of the same category. Such classification was not possible when the input patterns were directly decoded by a linear decoder, suggesting that BNNs act as a generalization filter to improve reservoir computing performance. Our findings pave the way toward a mechanistic understanding of information processing within BNNs and, simultaneously, build future expectations toward the realization of physical reservoir computing systems based on BNNs.
[ { "created": "Thu, 6 Oct 2022 13:32:26 GMT", "version": "v1" } ]
2023-06-14
[ [ "Sumi", "Takuma", "" ], [ "Yamamoto", "Hideaki", "" ], [ "Katori", "Yuichi", "" ], [ "Moriya", "Satoshi", "" ], [ "Konno", "Tomohiro", "" ], [ "Sato", "Shigeo", "" ], [ "Hirano-Iwata", "Ayumi", "" ] ]
Reservoir computing is a machine learning paradigm that transforms the transient dynamics of high-dimensional nonlinear systems for processing time-series data. Although reservoir computing was initially proposed to model information processing in the mammalian cortex, it remains unclear how the non-random network architecture, such as the modular architecture, in the cortex integrates with the biophysics of living neurons to characterize the function of biological neuronal networks (BNNs). Here, we used optogenetics and fluorescent calcium imaging to record the multicellular responses of cultured BNNs and employed the reservoir computing framework to decode their computational capabilities. Micropatterned substrates were used to embed the modular architecture in the BNNs. We first show that modular BNNs can be used to classify static input patterns with a linear decoder and that the modularity of the BNNs positively correlates with the classification accuracy. We then used a timer task to verify that BNNs possess a short-term memory of ~1 s and finally show that this property can be exploited for spoken digit classification. Interestingly, BNN-based reservoirs allow transfer learning, wherein a network trained on one dataset can be used to classify separate datasets of the same category. Such classification was not possible when the input patterns were directly decoded by a linear decoder, suggesting that BNNs act as a generalization filter to improve reservoir computing performance. Our findings pave the way toward a mechanistic understanding of information processing within BNNs and, simultaneously, build future expectations toward the realization of physical reservoir computing systems based on BNNs.
1702.05620
Juan Biondi
Gerardo Fern\'andez, Juan Biondi, Silvia Castro, Osvaldo Agamennoni
Pupil size behavior during on line processing of sentences
Journal of Integrative Neuroscience 2017
null
10.1142/S0219635216500266
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In the present work we analyzed the pupil size behavior of forty subjects while they read well defined sentences with different contextual predictability (i.e., regular sentences and proverbs). In general, pupil size increased when reading regular sentences, but when readers realized that they were reading proverbs their pupils strongly increase until finishing proverbs' reading. Our results suggest that an increased pupil size is not limited to cognitive load (i.e., relative difficulty in processing) because when participants accurately recognized words during reading proverbs, theirs pupil size increased too. Our results show that pupil size dynamics may be a reliable measure to investigate the cognitive processes involved in sentence processing and memory functioning.
[ { "created": "Sat, 18 Feb 2017 15:03:58 GMT", "version": "v1" } ]
2017-02-21
[ [ "Fernández", "Gerardo", "" ], [ "Biondi", "Juan", "" ], [ "Castro", "Silvia", "" ], [ "Agamennoni", "Osvaldo", "" ] ]
In the present work we analyzed the pupil size behavior of forty subjects while they read well defined sentences with different contextual predictability (i.e., regular sentences and proverbs). In general, pupil size increased when reading regular sentences, but when readers realized that they were reading proverbs their pupils strongly increase until finishing proverbs' reading. Our results suggest that an increased pupil size is not limited to cognitive load (i.e., relative difficulty in processing) because when participants accurately recognized words during reading proverbs, theirs pupil size increased too. Our results show that pupil size dynamics may be a reliable measure to investigate the cognitive processes involved in sentence processing and memory functioning.
1608.08828
Richard Betzel
Richard F. Betzel, Danielle S. Bassett
Multi-scale brain networks
12 pages, 3 figures, review article
null
null
null
q-bio.NC physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The network architecture of the human brain has become a feature of increasing interest to the neuroscientific community, largely because of its potential to illuminate human cognition, its variation over development and aging, and its alteration in disease or injury. Traditional tools and approaches to study this architecture have largely focused on single scales -- of topology, time, and space. Expanding beyond this narrow view, we focus this review on pertinent questions and novel methodological advances for the multi-scale brain. We separate our exposition into content related to multi-scale topological structure, multi-scale temporal structure, and multi-scale spatial structure. In each case, we recount empirical evidence for such structures, survey network-based methodological approaches to reveal these structures, and outline current frontiers and open questions. Although predominantly peppered with examples from human neuroimaging, we hope that this account will offer an accessible guide to any neuroscientist aiming to measure, characterize, and understand the full richness of the brain's multiscale network structure -- irrespective of species, imaging modality, or spatial resolution.
[ { "created": "Wed, 31 Aug 2016 12:43:05 GMT", "version": "v1" }, { "created": "Fri, 4 Nov 2016 15:33:27 GMT", "version": "v2" } ]
2016-11-07
[ [ "Betzel", "Richard F.", "" ], [ "Bassett", "Danielle S.", "" ] ]
The network architecture of the human brain has become a feature of increasing interest to the neuroscientific community, largely because of its potential to illuminate human cognition, its variation over development and aging, and its alteration in disease or injury. Traditional tools and approaches to study this architecture have largely focused on single scales -- of topology, time, and space. Expanding beyond this narrow view, we focus this review on pertinent questions and novel methodological advances for the multi-scale brain. We separate our exposition into content related to multi-scale topological structure, multi-scale temporal structure, and multi-scale spatial structure. In each case, we recount empirical evidence for such structures, survey network-based methodological approaches to reveal these structures, and outline current frontiers and open questions. Although predominantly peppered with examples from human neuroimaging, we hope that this account will offer an accessible guide to any neuroscientist aiming to measure, characterize, and understand the full richness of the brain's multiscale network structure -- irrespective of species, imaging modality, or spatial resolution.
2404.17605
Roy Kishony
Tal Ifargan, Lukas Hafner, Maor Kern, Ori Alcalay, Roy Kishony
Autonomous LLM-driven research from data to human-verifiable research papers
null
null
null
null
q-bio.OT cs.AI
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
As AI promises to accelerate scientific discovery, it remains unclear whether fully AI-driven research is possible and whether it can adhere to key scientific values, such as transparency, traceability and verifiability. Mimicking human scientific practices, we built data-to-paper, an automation platform that guides interacting LLM agents through a complete stepwise research process, while programmatically back-tracing information flow and allowing human oversight and interactions. In autopilot mode, provided with annotated data alone, data-to-paper raised hypotheses, designed research plans, wrote and debugged analysis codes, generated and interpreted results, and created complete and information-traceable research papers. Even though research novelty was relatively limited, the process demonstrated autonomous generation of de novo quantitative insights from data. For simple research goals, a fully-autonomous cycle can create manuscripts which recapitulate peer-reviewed publications without major errors in about 80-90%, yet as goal complexity increases, human co-piloting becomes critical for assuring accuracy. Beyond the process itself, created manuscripts too are inherently verifiable, as information-tracing allows to programmatically chain results, methods and data. Our work thereby demonstrates a potential for AI-driven acceleration of scientific discovery while enhancing, rather than jeopardizing, traceability, transparency and verifiability.
[ { "created": "Wed, 24 Apr 2024 23:15:49 GMT", "version": "v1" } ]
2024-04-30
[ [ "Ifargan", "Tal", "" ], [ "Hafner", "Lukas", "" ], [ "Kern", "Maor", "" ], [ "Alcalay", "Ori", "" ], [ "Kishony", "Roy", "" ] ]
As AI promises to accelerate scientific discovery, it remains unclear whether fully AI-driven research is possible and whether it can adhere to key scientific values, such as transparency, traceability and verifiability. Mimicking human scientific practices, we built data-to-paper, an automation platform that guides interacting LLM agents through a complete stepwise research process, while programmatically back-tracing information flow and allowing human oversight and interactions. In autopilot mode, provided with annotated data alone, data-to-paper raised hypotheses, designed research plans, wrote and debugged analysis codes, generated and interpreted results, and created complete and information-traceable research papers. Even though research novelty was relatively limited, the process demonstrated autonomous generation of de novo quantitative insights from data. For simple research goals, a fully-autonomous cycle can create manuscripts which recapitulate peer-reviewed publications without major errors in about 80-90%, yet as goal complexity increases, human co-piloting becomes critical for assuring accuracy. Beyond the process itself, created manuscripts too are inherently verifiable, as information-tracing allows to programmatically chain results, methods and data. Our work thereby demonstrates a potential for AI-driven acceleration of scientific discovery while enhancing, rather than jeopardizing, traceability, transparency and verifiability.
2203.11299
Willy Wong
Willy Wong
A Fundamental Inequality Governing the Rate Coding Response of Sensory Neurons
null
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
A fundamental inequality governing the spike activity of peripheral neurons is derived and tested against auditory data. This inequality states that the steady-state firing rate must lie between the arithmetic and geometric means of the spontaneous and peak activities during adaptation. Implications towards the development of auditory mechanistic models are explored.
[ { "created": "Mon, 21 Mar 2022 19:15:29 GMT", "version": "v1" }, { "created": "Thu, 9 Feb 2023 02:10:46 GMT", "version": "v2" }, { "created": "Wed, 2 Aug 2023 00:52:21 GMT", "version": "v3" } ]
2023-08-03
[ [ "Wong", "Willy", "" ] ]
A fundamental inequality governing the spike activity of peripheral neurons is derived and tested against auditory data. This inequality states that the steady-state firing rate must lie between the arithmetic and geometric means of the spontaneous and peak activities during adaptation. Implications towards the development of auditory mechanistic models are explored.
2305.13338
Marcin Joachimiak
Marcin P. Joachimiak, J. Harry Caufield, Nomi L. Harris, Hyeongsik Kim, Christopher J. Mungall
Gene Set Summarization using Large Language Models
null
null
null
null
q-bio.GN cs.AI cs.CL q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Molecular biologists frequently interpret gene lists derived from high-throughput experiments and computational analysis. This is typically done as a statistical enrichment analysis that measures the over- or under-representation of biological function terms associated with genes or their properties, based on curated assertions from a knowledge base (KB) such as the Gene Ontology (GO). Interpreting gene lists can also be framed as a textual summarization task, enabling the use of Large Language Models (LLMs), potentially utilizing scientific texts directly and avoiding reliance on a KB. We developed SPINDOCTOR (Structured Prompt Interpolation of Natural Language Descriptions of Controlled Terms for Ontology Reporting), a method that uses GPT models to perform gene set function summarization as a complement to standard enrichment analysis. This method can use different sources of gene functional information: (1) structured text derived from curated ontological KB annotations, (2) ontology-free narrative gene summaries, or (3) direct model retrieval. We demonstrate that these methods are able to generate plausible and biologically valid summary GO term lists for gene sets. However, GPT-based approaches are unable to deliver reliable scores or p-values and often return terms that are not statistically significant. Crucially, these methods were rarely able to recapitulate the most precise and informative term from standard enrichment, likely due to an inability to generalize and reason using an ontology. Results are highly nondeterministic, with minor variations in prompt resulting in radically different term lists. Our results show that at this point, LLM-based methods are unsuitable as a replacement for standard term enrichment analysis and that manual curation of ontological assertions remains necessary.
[ { "created": "Sun, 21 May 2023 02:06:33 GMT", "version": "v1" }, { "created": "Thu, 25 May 2023 19:10:13 GMT", "version": "v2" }, { "created": "Thu, 4 Jul 2024 02:16:11 GMT", "version": "v3" } ]
2024-07-08
[ [ "Joachimiak", "Marcin P.", "" ], [ "Caufield", "J. Harry", "" ], [ "Harris", "Nomi L.", "" ], [ "Kim", "Hyeongsik", "" ], [ "Mungall", "Christopher J.", "" ] ]
Molecular biologists frequently interpret gene lists derived from high-throughput experiments and computational analysis. This is typically done as a statistical enrichment analysis that measures the over- or under-representation of biological function terms associated with genes or their properties, based on curated assertions from a knowledge base (KB) such as the Gene Ontology (GO). Interpreting gene lists can also be framed as a textual summarization task, enabling the use of Large Language Models (LLMs), potentially utilizing scientific texts directly and avoiding reliance on a KB. We developed SPINDOCTOR (Structured Prompt Interpolation of Natural Language Descriptions of Controlled Terms for Ontology Reporting), a method that uses GPT models to perform gene set function summarization as a complement to standard enrichment analysis. This method can use different sources of gene functional information: (1) structured text derived from curated ontological KB annotations, (2) ontology-free narrative gene summaries, or (3) direct model retrieval. We demonstrate that these methods are able to generate plausible and biologically valid summary GO term lists for gene sets. However, GPT-based approaches are unable to deliver reliable scores or p-values and often return terms that are not statistically significant. Crucially, these methods were rarely able to recapitulate the most precise and informative term from standard enrichment, likely due to an inability to generalize and reason using an ontology. Results are highly nondeterministic, with minor variations in prompt resulting in radically different term lists. Our results show that at this point, LLM-based methods are unsuitable as a replacement for standard term enrichment analysis and that manual curation of ontological assertions remains necessary.
1407.6125
Nicolo Colombo
Nicol\`o Colombo and Nikos Vlassis
Spectral Sequence Motif Discovery
20 pages, 3 figures, 1 table
null
null
null
q-bio.QM cs.CE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Sequence discovery tools play a central role in several fields of computational biology. In the framework of Transcription Factor binding studies, motif finding algorithms of increasingly high performance are required to process the big datasets produced by new high-throughput sequencing technologies. Most existing algorithms are computationally demanding and often cannot support the large size of new experimental data. We present a new motif discovery algorithm that is built on a recent machine learning technique, referred to as Method of Moments. Based on spectral decompositions, this method is robust under model misspecification and is not prone to locally optimal solutions. We obtain an algorithm that is extremely fast and designed for the analysis of big sequencing data. In a few minutes, we can process datasets of hundreds of thousand sequences and extract motif profiles that match those computed by various state-of-the-art algorithms.
[ { "created": "Wed, 23 Jul 2014 08:07:50 GMT", "version": "v1" }, { "created": "Tue, 26 Aug 2014 18:33:45 GMT", "version": "v2" } ]
2014-08-27
[ [ "Colombo", "Nicolò", "" ], [ "Vlassis", "Nikos", "" ] ]
Sequence discovery tools play a central role in several fields of computational biology. In the framework of Transcription Factor binding studies, motif finding algorithms of increasingly high performance are required to process the big datasets produced by new high-throughput sequencing technologies. Most existing algorithms are computationally demanding and often cannot support the large size of new experimental data. We present a new motif discovery algorithm that is built on a recent machine learning technique, referred to as Method of Moments. Based on spectral decompositions, this method is robust under model misspecification and is not prone to locally optimal solutions. We obtain an algorithm that is extremely fast and designed for the analysis of big sequencing data. In a few minutes, we can process datasets of hundreds of thousand sequences and extract motif profiles that match those computed by various state-of-the-art algorithms.
1610.07426
Nicholas Parker
L. E. Wadkin, L. F. Elliot, I. Neganova, N. G. Parker, V. Chichagova, G. Swan, A. Laude, M. Lako, A. Shukurov
Dynamics of single human embryonic stem cells and their pairs: a quantitative analysis
29 pages, including 9 pages of Supplemental Information
Scientific Reports 7, 570 (2017)
10.1038/s41598-017-00648-0
null
q-bio.QM physics.bio-ph q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Numerous biological approaches are available to characterise the mechanisms which govern the formation of human embryonic stem cell (hESC) colonies. To understand how the kinematics of single and pairs of hESCs impact colony formation, we study their mobility characteristics using time-lapse imaging. We perform a detailed statistical analysis of their speed, survival, directionality, distance travelled and diffusivity. We confirm that single and pairs of cells migrate as a diffusive random walk. Moreover, we show that the presence of Cell Tracer significantly reduces hESC mobility. Our results open the path to employ the theoretical framework of the diffusive random walk for the prognostic modelling and optimisation of the growth of hESC colonies. Indeed, we employ this random walk model to estimate the seeding density required to minimise the occurrence of hESC colonies arising from more than one founder cell and the minimal cell number needed for successful colony formation. We believe that our prognostic model can be extended to investigate the kinematic behaviour of somatic cells emerging from hESC differentiation and to enable its wide application in phenotyping of pluripotent stem cells for large scale stem cell culture expansion and differentiation platforms.
[ { "created": "Mon, 24 Oct 2016 14:26:06 GMT", "version": "v1" }, { "created": "Wed, 1 Mar 2017 19:08:50 GMT", "version": "v2" } ]
2018-01-08
[ [ "Wadkin", "L. E.", "" ], [ "Elliot", "L. F.", "" ], [ "Neganova", "I.", "" ], [ "Parker", "N. G.", "" ], [ "Chichagova", "V.", "" ], [ "Swan", "G.", "" ], [ "Laude", "A.", "" ], [ "Lako", "M.", ...
Numerous biological approaches are available to characterise the mechanisms which govern the formation of human embryonic stem cell (hESC) colonies. To understand how the kinematics of single and pairs of hESCs impact colony formation, we study their mobility characteristics using time-lapse imaging. We perform a detailed statistical analysis of their speed, survival, directionality, distance travelled and diffusivity. We confirm that single and pairs of cells migrate as a diffusive random walk. Moreover, we show that the presence of Cell Tracer significantly reduces hESC mobility. Our results open the path to employ the theoretical framework of the diffusive random walk for the prognostic modelling and optimisation of the growth of hESC colonies. Indeed, we employ this random walk model to estimate the seeding density required to minimise the occurrence of hESC colonies arising from more than one founder cell and the minimal cell number needed for successful colony formation. We believe that our prognostic model can be extended to investigate the kinematic behaviour of somatic cells emerging from hESC differentiation and to enable its wide application in phenotyping of pluripotent stem cells for large scale stem cell culture expansion and differentiation platforms.
0910.1178
Alfredo Iorio
Alfredo Iorio
On (Schr\"oedinger's) quest for new physics for life
9 pages, 5 pages, Fourth International Workshop DICE2008
Journal of Physics: Conference Series 174 (2009) 012036
10.1088/1742-6596/174/1/012036
null
q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Two recent investigations are reviewed: quantum effects for DNA aggregates and scars formation on virus capsids. The possibility that scars could explain certain data recently obtained by Sundquist's group in electron cryotomography of immature HIV-1 virions is also briefly addressed. Furthermore, a bottom-up reflection is presented on the need to invent new physics to pave the way to a rigorous physical theory of biological phenomena. Our experience in the two researches presented here and our personal interpretation of Schroedinger's vision are behind the latter request.
[ { "created": "Wed, 7 Oct 2009 08:00:12 GMT", "version": "v1" } ]
2009-10-08
[ [ "Iorio", "Alfredo", "" ] ]
Two recent investigations are reviewed: quantum effects for DNA aggregates and scars formation on virus capsids. The possibility that scars could explain certain data recently obtained by Sundquist's group in electron cryotomography of immature HIV-1 virions is also briefly addressed. Furthermore, a bottom-up reflection is presented on the need to invent new physics to pave the way to a rigorous physical theory of biological phenomena. Our experience in the two researches presented here and our personal interpretation of Schroedinger's vision are behind the latter request.
1507.05368
Gennadi Glinsky
Gennadi Glinsky
Rapidly evolving in humans topologically associating domains
null
null
null
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Genome-wide proximity placement analysis of 10,598 HSGRL within the context of the principal regulatory structures of the interphase chromatin, namely topologically-associating domains (TADs) and specific sub-TAD structures termed super-enhancer domains (SEDs) revealed that 0.8%-10.3% of TADs contain more than half of HSGRL. Of the 3,127 TADs in the hESC genome, 24 (0.8%); 53 (1.7%); 259 (8.3%); and 322 (10.3%) harbor 1,110 (52.4%); 1,936 (50.9%); 1,151 (59.6%); and 1,601 (58.3%) HSGRL sequences from four distinct families, respectively. TADs that are enriched for HSGRL and termed rapidly-evolving in humans TADs (revTADs) manifest distinct correlation patterns between HSGRL placements and recombination rates. There are significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (p < 0.0001 in all instances). In hESC genome, 331 of 504 (66%) of SE-harboring TADs contain HSGRL and 68% of SEs co-localize with HSGRL, suggesting that HSGRL rewired SE-driven GRNs within revTADs by inserting novel and/or erasing existing regulatory sequences. Consequently, markedly distinct features of chromatin structures evolved in hESC compared to mouse: the SE quantity is 3-fold higher and the median SE size is significantly larger; concomitantly, the TAD number is increased by 42% while the median TAD size is decreased (p=9.11E-37). Present analyses revealed a global role for HSGRL in increasing both quantity and size of SEs and increasing the number and size reduction of TADs, which may facilitate a convergence of TAD and SED architectures of interphase chromatin and define a trend of increasing regulatory complexity during evolution of GRNs.
[ { "created": "Mon, 20 Jul 2015 02:21:37 GMT", "version": "v1" } ]
2015-07-21
[ [ "Glinsky", "Gennadi", "" ] ]
Genome-wide proximity placement analysis of 10,598 HSGRL within the context of the principal regulatory structures of the interphase chromatin, namely topologically-associating domains (TADs) and specific sub-TAD structures termed super-enhancer domains (SEDs) revealed that 0.8%-10.3% of TADs contain more than half of HSGRL. Of the 3,127 TADs in the hESC genome, 24 (0.8%); 53 (1.7%); 259 (8.3%); and 322 (10.3%) harbor 1,110 (52.4%); 1,936 (50.9%); 1,151 (59.6%); and 1,601 (58.3%) HSGRL sequences from four distinct families, respectively. TADs that are enriched for HSGRL and termed rapidly-evolving in humans TADs (revTADs) manifest distinct correlation patterns between HSGRL placements and recombination rates. There are significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (p < 0.0001 in all instances). In hESC genome, 331 of 504 (66%) of SE-harboring TADs contain HSGRL and 68% of SEs co-localize with HSGRL, suggesting that HSGRL rewired SE-driven GRNs within revTADs by inserting novel and/or erasing existing regulatory sequences. Consequently, markedly distinct features of chromatin structures evolved in hESC compared to mouse: the SE quantity is 3-fold higher and the median SE size is significantly larger; concomitantly, the TAD number is increased by 42% while the median TAD size is decreased (p=9.11E-37). Present analyses revealed a global role for HSGRL in increasing both quantity and size of SEs and increasing the number and size reduction of TADs, which may facilitate a convergence of TAD and SED architectures of interphase chromatin and define a trend of increasing regulatory complexity during evolution of GRNs.
1203.5835
Mike Steel Prof.
Mike Steel
Root location in random trees: A polarity property of all sampling consistent phylogenetic models except one
8 pages, 1 figure
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Neutral macroevolutionary models, such as the Yule model, give rise to a probability distribution on the set of discrete rooted binary trees over a given leaf set. Such models can provide a signal as to the approximate location of the root when only the unrooted phylogenetic tree is known, and this signal becomes relatively more significant as the number of leaves grows. In this short note, we show that among models that treat all taxa equally, and are sampling consistent (i.e. the distribution on trees is not affected by taxa yet to be included), all such models, except one, convey some information as to the location of the ancestral root in an unrooted tree.
[ { "created": "Mon, 26 Mar 2012 22:48:57 GMT", "version": "v1" } ]
2012-03-28
[ [ "Steel", "Mike", "" ] ]
Neutral macroevolutionary models, such as the Yule model, give rise to a probability distribution on the set of discrete rooted binary trees over a given leaf set. Such models can provide a signal as to the approximate location of the root when only the unrooted phylogenetic tree is known, and this signal becomes relatively more significant as the number of leaves grows. In this short note, we show that among models that treat all taxa equally, and are sampling consistent (i.e. the distribution on trees is not affected by taxa yet to be included), all such models, except one, convey some information as to the location of the ancestral root in an unrooted tree.
1506.04461
Tomasz Rutkowski
Daiki Aminaka, Shoji Makino, and Tomasz M. Rutkowski
Chromatic and High-frequency cVEP-based BCI Paradigm
4 pages, 4 figures, accepted for EMBC 2015, IEEE copyright
null
10.1109/EMBC.2015.7318755
null
q-bio.NC cs.HC
http://creativecommons.org/licenses/by-nc-sa/3.0/
We present results of an approach to a code-modulated visual evoked potential (cVEP) based brain-computer interface (BCI) paradigm using four high-frequency flashing stimuli. To generate higher frequency stimulation compared to the state-of-the-art cVEP-based BCIs, we propose to use the light-emitting diodes (LEDs) driven from a small micro-controller board hardware generator designed by our team. The high-frequency and green-blue chromatic flashing stimuli are used in the study in order to minimize a danger of a photosensitive epilepsy (PSE). We compare the the green-blue chromatic cVEP-based BCI accuracies with the conventional white-black flicker based interface.
[ { "created": "Mon, 15 Jun 2015 02:43:39 GMT", "version": "v1" }, { "created": "Mon, 22 Jun 2015 14:21:23 GMT", "version": "v2" } ]
2016-11-17
[ [ "Aminaka", "Daiki", "" ], [ "Makino", "Shoji", "" ], [ "Rutkowski", "Tomasz M.", "" ] ]
We present results of an approach to a code-modulated visual evoked potential (cVEP) based brain-computer interface (BCI) paradigm using four high-frequency flashing stimuli. To generate higher frequency stimulation compared to the state-of-the-art cVEP-based BCIs, we propose to use the light-emitting diodes (LEDs) driven from a small micro-controller board hardware generator designed by our team. The high-frequency and green-blue chromatic flashing stimuli are used in the study in order to minimize a danger of a photosensitive epilepsy (PSE). We compare the the green-blue chromatic cVEP-based BCI accuracies with the conventional white-black flicker based interface.
2008.00687
Gennadi Glinsky
Gennadi Glinsky
Genomics-guided drawing of malignant regulatory signatures revealed a pivotal role of human stem cell-associated retroviral sequences (SCARS) and functionally-active hESC enhancers
6 figues; 6 tables
null
null
null
q-bio.GN q-bio.MN q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
From patients and physicians perspectives, the clinical definition of a tumor malignant phenotype could be restricted to the early diagnosis of sub-types of malignancies with the increased risk of existing therapy failure and high likelihood of death from cancer. It is the viewpoint from which the understanding of malignant regulatory signatures is considered in this contribution. Analyses from this perspective of experimental and clinical observations revealed the pivotal role of human stem cell-associated retroviral sequences (SCARS) in the origin and pathophysiology of clinically-lethal malignancies. SCARS represent evolutionary- and biologically-related family of genomic regulatory sequences, the principal physiological function of which is to create and maintain the stemness phenotype during human preimplantation embryogenesis. SCARS expression must be silenced during cellular differentiation and SCARS activity remains silent in most terminally-differentiated human cells performing specialized functions in the human body. De-repression and sustained activation of SCARS result in differentiation-defective phenotypes, tissue- and organ-specific clinical manifestations of which are diagnosed as pathological conditions defined by a consensus of pathomorphological, molecular, and genetic examinations as the malignant growth. Contemporary evidence are presented that high-fidelity molecular signals of continuing activities of SCARS in association with genomic regulatory networks of thousands functionally-active enhancers triggering engagements of down-stream genetic loci may serve as both reliable diagnostic tools and druggable molecular targets readily amenable for diagnosis and efficient therapeutic management of clinically-lethal malignancies.
[ { "created": "Mon, 3 Aug 2020 07:34:59 GMT", "version": "v1" } ]
2020-08-04
[ [ "Glinsky", "Gennadi", "" ] ]
From patients and physicians perspectives, the clinical definition of a tumor malignant phenotype could be restricted to the early diagnosis of sub-types of malignancies with the increased risk of existing therapy failure and high likelihood of death from cancer. It is the viewpoint from which the understanding of malignant regulatory signatures is considered in this contribution. Analyses from this perspective of experimental and clinical observations revealed the pivotal role of human stem cell-associated retroviral sequences (SCARS) in the origin and pathophysiology of clinically-lethal malignancies. SCARS represent evolutionary- and biologically-related family of genomic regulatory sequences, the principal physiological function of which is to create and maintain the stemness phenotype during human preimplantation embryogenesis. SCARS expression must be silenced during cellular differentiation and SCARS activity remains silent in most terminally-differentiated human cells performing specialized functions in the human body. De-repression and sustained activation of SCARS result in differentiation-defective phenotypes, tissue- and organ-specific clinical manifestations of which are diagnosed as pathological conditions defined by a consensus of pathomorphological, molecular, and genetic examinations as the malignant growth. Contemporary evidence are presented that high-fidelity molecular signals of continuing activities of SCARS in association with genomic regulatory networks of thousands functionally-active enhancers triggering engagements of down-stream genetic loci may serve as both reliable diagnostic tools and druggable molecular targets readily amenable for diagnosis and efficient therapeutic management of clinically-lethal malignancies.
1506.00344
Duo-Fang Li
Duo-Fang Li, Tian-Guang Cao, Jin-Peng Geng, Li-Hua Qiao, Jian-Zhong Gu, Yong Zhan
Error Threshold of Fully Random Eigen Model
6 pages, 3 figures, 1 table
Chin. Phys. Lett., 2015,32(1):018702
10.1088/0256-307X/32/1/018702
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Species evolution is essentially a random process of interaction between biological populations and their environments. As a result, some physical parameters in evolution models are subject to statistical fluctuations. In this paper, two important parameters in the Eigen model, the fitness and mutation rate, are treated as Gaussian distributed random variables simultaneously to examine the property of the error threshold. Numerical simulation results show that the error threshold in the fully random model appears as a crossover region instead of a phase transition point, and as the fluctuation strength increases the crossover region becomes smoother and smoother. Furthermore, it is shown that the randomization of the mutation rate plays a dominant role in changing the error threshold in the fully random model, which is consistent with the existing experimental data. The implication of the threshold change due to the randomization for antiviral strategies is discussed.
[ { "created": "Mon, 1 Jun 2015 04:13:56 GMT", "version": "v1" } ]
2015-06-02
[ [ "Li", "Duo-Fang", "" ], [ "Cao", "Tian-Guang", "" ], [ "Geng", "Jin-Peng", "" ], [ "Qiao", "Li-Hua", "" ], [ "Gu", "Jian-Zhong", "" ], [ "Zhan", "Yong", "" ] ]
Species evolution is essentially a random process of interaction between biological populations and their environments. As a result, some physical parameters in evolution models are subject to statistical fluctuations. In this paper, two important parameters in the Eigen model, the fitness and mutation rate, are treated as Gaussian distributed random variables simultaneously to examine the property of the error threshold. Numerical simulation results show that the error threshold in the fully random model appears as a crossover region instead of a phase transition point, and as the fluctuation strength increases the crossover region becomes smoother and smoother. Furthermore, it is shown that the randomization of the mutation rate plays a dominant role in changing the error threshold in the fully random model, which is consistent with the existing experimental data. The implication of the threshold change due to the randomization for antiviral strategies is discussed.
1401.6602
Daniel Rabosky
Daniel L. Rabosky
Automatic detection of key innovations, rate shifts, and diversity-dependence on phylogenetic trees
null
null
10.1371/journal.pone.0089543
null
q-bio.QM q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A number of methods have been developed to infer differential rates of species diversification through time and among clades using time-calibrated phylogenetic trees. However, we lack a general framework that can delineate and quantify heterogeneous mixtures of dynamic processes within single phylogenies. I developed a method that can identify arbitrary numbers of time-varying diversification processes on phylogenies without specifying their locations in advance. The method uses reversible-jump Markov Chain Monte Carlo to move between model subspaces that vary in the number of distinct diversification regimes. The model assumes that changes in evolutionary regimes occur across the branches of phylogenetic trees under a compound Poisson process and explicitly accounts for rate variation through time and among lineages. Using simulated datasets, I demonstrate that the method can be used to quantify complex mixtures of time-dependent, diversity-dependent, and constant-rate diversification processes. I compared the performance of the method to the MEDUSA model of rate variation among lineages. As an empirical example, I analyzed the history of speciation and extinction during the radiation of modern whales. The method described here will greatly facilitate the exploration of macroevolutionary dynamics across large phylogenetic trees, which may have been shaped by heterogeneous mixtures of distinct evolutionary processes.
[ { "created": "Sun, 26 Jan 2014 01:28:52 GMT", "version": "v1" } ]
2015-06-18
[ [ "Rabosky", "Daniel L.", "" ] ]
A number of methods have been developed to infer differential rates of species diversification through time and among clades using time-calibrated phylogenetic trees. However, we lack a general framework that can delineate and quantify heterogeneous mixtures of dynamic processes within single phylogenies. I developed a method that can identify arbitrary numbers of time-varying diversification processes on phylogenies without specifying their locations in advance. The method uses reversible-jump Markov Chain Monte Carlo to move between model subspaces that vary in the number of distinct diversification regimes. The model assumes that changes in evolutionary regimes occur across the branches of phylogenetic trees under a compound Poisson process and explicitly accounts for rate variation through time and among lineages. Using simulated datasets, I demonstrate that the method can be used to quantify complex mixtures of time-dependent, diversity-dependent, and constant-rate diversification processes. I compared the performance of the method to the MEDUSA model of rate variation among lineages. As an empirical example, I analyzed the history of speciation and extinction during the radiation of modern whales. The method described here will greatly facilitate the exploration of macroevolutionary dynamics across large phylogenetic trees, which may have been shaped by heterogeneous mixtures of distinct evolutionary processes.
2206.13818
Benjamin Walker
Benjamin J. Walker, Giulia L. Celora, Alain Goriely, Derek E. Moulton, Helen M. Byrne
Minimal Morphoelastic Models of Solid Tumour Spheroids: A Tutorial
null
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Tumour spheroids have been the focus of a variety of mathematical models, ranging from Greenspan's classical study of the 1970s through to contemporary agent-based models. Of the many factors that regulate spheroid growth, mechanical effects are perhaps some of the least studied, both theoretically and experimentally, though experimental enquiry has established their significance to tumour growth dynamics. In this tutorial, we formulate a hierarchy of mathematical models of increasing complexity to explore the role of mechanics in spheroid growth, all the while seeking to retain desirable simplicity and analytical tractability. Beginning with the theory of morphoelasticity, which combines solid mechanics and growth, we successively refine our assumptions to develop a somewhat minimal model of mechanically regulated spheroid growth that is free from many unphysical and undesirable behaviours. In doing so, we will see how iterating upon simple models can provide rigorous guarantees of emergent behaviour, which are often precluded by existing, more complex modelling approaches. Perhaps surprisingly, we also demonstrate that the final model considered in this tutorial agrees favourably with classical experimental results, highlighting the potential for simple models to provide mechanistic insight whilst also serving as mathematical examples.
[ { "created": "Tue, 28 Jun 2022 08:23:07 GMT", "version": "v1" }, { "created": "Wed, 21 Dec 2022 13:31:05 GMT", "version": "v2" } ]
2022-12-22
[ [ "Walker", "Benjamin J.", "" ], [ "Celora", "Giulia L.", "" ], [ "Goriely", "Alain", "" ], [ "Moulton", "Derek E.", "" ], [ "Byrne", "Helen M.", "" ] ]
Tumour spheroids have been the focus of a variety of mathematical models, ranging from Greenspan's classical study of the 1970s through to contemporary agent-based models. Of the many factors that regulate spheroid growth, mechanical effects are perhaps some of the least studied, both theoretically and experimentally, though experimental enquiry has established their significance to tumour growth dynamics. In this tutorial, we formulate a hierarchy of mathematical models of increasing complexity to explore the role of mechanics in spheroid growth, all the while seeking to retain desirable simplicity and analytical tractability. Beginning with the theory of morphoelasticity, which combines solid mechanics and growth, we successively refine our assumptions to develop a somewhat minimal model of mechanically regulated spheroid growth that is free from many unphysical and undesirable behaviours. In doing so, we will see how iterating upon simple models can provide rigorous guarantees of emergent behaviour, which are often precluded by existing, more complex modelling approaches. Perhaps surprisingly, we also demonstrate that the final model considered in this tutorial agrees favourably with classical experimental results, highlighting the potential for simple models to provide mechanistic insight whilst also serving as mathematical examples.
2302.02968
Carles Falc\'o
Carles Falc\'o, Daniel J. Cohen, Jos\'e A. Carrillo, Ruth E. Baker
Quantifying tissue growth, shape and collision via continuum models and Bayesian inference
null
null
null
null
q-bio.TO nlin.PS q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Although tissues are usually studied in isolation, this situation rarely occurs in biology, as cells, tissues, and organs, coexist and interact across scales to determine both shape and function. Here, we take a quantitative approach combining data from recent experiments, mathematical modelling, and Bayesian parameter inference, to describe the self-assembly of multiple epithelial sheets by growth and collision. We use two simple and well-studied continuum models, where cells move either randomly or following population pressure gradients. After suitable calibration, both models prove to be practically identifiable, and can reproduce the main features of single tissue expansions. However, our findings reveal that whenever tissue-tissue interactions become relevant, the random motion assumption can lead to unrealistic behaviour. Under this setting, a model accounting for population pressure from different cell populations is more appropriate and shows a better agreement with experimental measurements. Finally, we discuss how tissue shape and pressure affect multi-tissue collisions. Our work thus provides a systematic approach to quantify and predict complex tissue configurations with applications in the design of tissue composites and more generally in tissue engineering.
[ { "created": "Mon, 6 Feb 2023 17:58:18 GMT", "version": "v1" } ]
2023-02-07
[ [ "Falcó", "Carles", "" ], [ "Cohen", "Daniel J.", "" ], [ "Carrillo", "José A.", "" ], [ "Baker", "Ruth E.", "" ] ]
Although tissues are usually studied in isolation, this situation rarely occurs in biology, as cells, tissues, and organs, coexist and interact across scales to determine both shape and function. Here, we take a quantitative approach combining data from recent experiments, mathematical modelling, and Bayesian parameter inference, to describe the self-assembly of multiple epithelial sheets by growth and collision. We use two simple and well-studied continuum models, where cells move either randomly or following population pressure gradients. After suitable calibration, both models prove to be practically identifiable, and can reproduce the main features of single tissue expansions. However, our findings reveal that whenever tissue-tissue interactions become relevant, the random motion assumption can lead to unrealistic behaviour. Under this setting, a model accounting for population pressure from different cell populations is more appropriate and shows a better agreement with experimental measurements. Finally, we discuss how tissue shape and pressure affect multi-tissue collisions. Our work thus provides a systematic approach to quantify and predict complex tissue configurations with applications in the design of tissue composites and more generally in tissue engineering.
1703.02828
Masahiko Ueda
Masahiko Ueda, Nobuto Takeuchi, Kunihiko Kaneko
Stronger selection can slow down evolution driven by recombination on a smooth fitness landscape
12 pages, 2 figures
PLoS ONE 12(8): e0183120 (2017)
10.1371/journal.pone.0183120
null
q-bio.PE cond-mat.stat-mech physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Stronger selection implies faster evolution---that is, the greater the force, the faster the change. This apparently self-evident proposition, however, is derived under the assumption that genetic variation within a population is primarily supplied by mutation (i.e.\ mutation-driven evolution). Here, we show that this proposition does not actually hold for recombination-driven evolution, i.e.\ evolution in which genetic variation is primarily created by recombination rather than mutation. By numerically investigating population genetics models of recombination, migration and selection, we demonstrate that stronger selection can slow down evolution on a perfectly smooth fitness landscape. Through simple analytical calculation, this apparently counter-intuitive result is shown to stem from two opposing effects of natural selection on the rate of evolution. On the one hand, natural selection tends to increase the rate of evolution by increasing the fixation probability of fitter genotypes. On the other hand, natural selection tends to decrease the rate of evolution by decreasing the chance of recombination between immigrants and resident individuals. As a consequence of these opposing effects, there is a finite selection pressure maximizing the rate of evolution. Hence, stronger selection can imply slower evolution if genetic variation is primarily supplied by recombination.
[ { "created": "Wed, 8 Mar 2017 13:19:12 GMT", "version": "v1" }, { "created": "Tue, 27 Jun 2017 06:00:07 GMT", "version": "v2" }, { "created": "Fri, 4 Aug 2017 02:55:48 GMT", "version": "v3" } ]
2017-08-18
[ [ "Ueda", "Masahiko", "" ], [ "Takeuchi", "Nobuto", "" ], [ "Kaneko", "Kunihiko", "" ] ]
Stronger selection implies faster evolution---that is, the greater the force, the faster the change. This apparently self-evident proposition, however, is derived under the assumption that genetic variation within a population is primarily supplied by mutation (i.e.\ mutation-driven evolution). Here, we show that this proposition does not actually hold for recombination-driven evolution, i.e.\ evolution in which genetic variation is primarily created by recombination rather than mutation. By numerically investigating population genetics models of recombination, migration and selection, we demonstrate that stronger selection can slow down evolution on a perfectly smooth fitness landscape. Through simple analytical calculation, this apparently counter-intuitive result is shown to stem from two opposing effects of natural selection on the rate of evolution. On the one hand, natural selection tends to increase the rate of evolution by increasing the fixation probability of fitter genotypes. On the other hand, natural selection tends to decrease the rate of evolution by decreasing the chance of recombination between immigrants and resident individuals. As a consequence of these opposing effects, there is a finite selection pressure maximizing the rate of evolution. Hence, stronger selection can imply slower evolution if genetic variation is primarily supplied by recombination.
2012.15223
Cameron Smith
Cameron A. Smith and Christian A. Yates
Incorporating domain growth into hybrid methods for reaction-diffusion systems
Main text: 22 pages, 6 figures. Supplementary material: 8 pages
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Reaction--diffusion mechanism are a robust paradigm that can be used to represent many biological and physical phenomena over multiple spatial scales. Applications include intracellular dynamics, the migration of cells and the patterns formed by vegetation in semi-arid landscapes. Moreover, domain growth is an important process for embryonic growth and wound healing. There are many numerical modelling frameworks capable of simulating such systems on growing domains, however each of these may be well suited to different spatial scales and particle numbers. Recently, spatially extended hybrid methods on static domains have been produced in order to bridge the gap between these different modelling paradigms in order to represent multiscale phenomena. However, such methods have not been developed with domain growth in mind. In this paper, we develop three hybrid methods on growing domains, extending three of the prominent static domain hybrid methods. We also provide detailed algorithms to allow others to employ them. We demonstrate that the methods are able to accurately model three representative reaction-diffusion systems accurately and without bias.
[ { "created": "Wed, 30 Dec 2020 16:32:54 GMT", "version": "v1" } ]
2021-01-01
[ [ "Smith", "Cameron A.", "" ], [ "Yates", "Christian A.", "" ] ]
Reaction--diffusion mechanism are a robust paradigm that can be used to represent many biological and physical phenomena over multiple spatial scales. Applications include intracellular dynamics, the migration of cells and the patterns formed by vegetation in semi-arid landscapes. Moreover, domain growth is an important process for embryonic growth and wound healing. There are many numerical modelling frameworks capable of simulating such systems on growing domains, however each of these may be well suited to different spatial scales and particle numbers. Recently, spatially extended hybrid methods on static domains have been produced in order to bridge the gap between these different modelling paradigms in order to represent multiscale phenomena. However, such methods have not been developed with domain growth in mind. In this paper, we develop three hybrid methods on growing domains, extending three of the prominent static domain hybrid methods. We also provide detailed algorithms to allow others to employ them. We demonstrate that the methods are able to accurately model three representative reaction-diffusion systems accurately and without bias.
1812.00191
Yuting Fang
Yuting Fang, Adam Noel, Andrew W. Eckford, and Nan Yang
Expected Density of Cooperative Bacteria in a 2D Quorum Sensing Based Molecular Communication System
7 pages, 7 figures; This work has been accepted by IEEE Globecom 2019
null
null
null
q-bio.CB physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The exchange of small molecular signals within microbial populations is generally referred to as quorum sensing (QS). QS is ubiquitous in nature and enables microorganisms to respond to fluctuations in living environments by working together. In this study, a QS-based molecular communication system within a microbial population in a two-dimensional (2D) environment is analytically modeled. Microorganisms are randomly distributed on a 2D circle where each one releases molecules at random times. The number of molecules observed at each randomly-distributed bacterium is first derived by characterizing the diffusion and degradation of signaling molecules within the population. Using the derived result and some approximation, the expected density of cooperative bacteria is derived. Our model captures the basic features of QS. The analytical results for noisy signal propagation agree with simulation results where the Brownian motion of molecules is simulated by a particle-based method. Therefore, we anticipate that our model can be used to predict the density of cooperative bacteria in a variety of QS-coordinated activities, e.g., biofilm formation and antibiotic resistance.
[ { "created": "Sat, 1 Dec 2018 11:38:23 GMT", "version": "v1" }, { "created": "Sat, 4 May 2019 06:21:47 GMT", "version": "v2" }, { "created": "Fri, 13 Sep 2019 04:23:43 GMT", "version": "v3" } ]
2019-09-16
[ [ "Fang", "Yuting", "" ], [ "Noel", "Adam", "" ], [ "Eckford", "Andrew W.", "" ], [ "Yang", "Nan", "" ] ]
The exchange of small molecular signals within microbial populations is generally referred to as quorum sensing (QS). QS is ubiquitous in nature and enables microorganisms to respond to fluctuations in living environments by working together. In this study, a QS-based molecular communication system within a microbial population in a two-dimensional (2D) environment is analytically modeled. Microorganisms are randomly distributed on a 2D circle where each one releases molecules at random times. The number of molecules observed at each randomly-distributed bacterium is first derived by characterizing the diffusion and degradation of signaling molecules within the population. Using the derived result and some approximation, the expected density of cooperative bacteria is derived. Our model captures the basic features of QS. The analytical results for noisy signal propagation agree with simulation results where the Brownian motion of molecules is simulated by a particle-based method. Therefore, we anticipate that our model can be used to predict the density of cooperative bacteria in a variety of QS-coordinated activities, e.g., biofilm formation and antibiotic resistance.
1811.06717
Oksana Gorobets Prof.
Svitlana Gorobets, Oksana Gorobets, Yuri Gorobets, Maryna Bulaievska
Ferrimagnetic organelles in multicellular organisms
16 pages, 15 figures
null
null
null
q-bio.TO cond-mat.soft physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this paper, it was revealed by means of methods of atomic force microscopy and magnetic force microscopy that the biogenic magnetic nanoparticles are localized in the form of chains in the walls of the capillaries of animals and the walls of the conducting tissue of plants and fungi. The biogenic magnetic nanoparticles are part of the transport system in multicellular organisms. In this connection, a new idea of function of biogenic magnetic nanoparticles is discussed in the paper that the chains of biogenic magnetic nanoparticles represent a ferrimagnetic organelles of a specific purpose.
[ { "created": "Fri, 16 Nov 2018 09:18:32 GMT", "version": "v1" } ]
2018-11-19
[ [ "Gorobets", "Svitlana", "" ], [ "Gorobets", "Oksana", "" ], [ "Gorobets", "Yuri", "" ], [ "Bulaievska", "Maryna", "" ] ]
In this paper, it was revealed by means of methods of atomic force microscopy and magnetic force microscopy that the biogenic magnetic nanoparticles are localized in the form of chains in the walls of the capillaries of animals and the walls of the conducting tissue of plants and fungi. The biogenic magnetic nanoparticles are part of the transport system in multicellular organisms. In this connection, a new idea of function of biogenic magnetic nanoparticles is discussed in the paper that the chains of biogenic magnetic nanoparticles represent a ferrimagnetic organelles of a specific purpose.
1104.0543
Vladimir Chechetkin R.
V.R. Chechetkin
Kinetics of binding and geometry of cells on molecular biochips
10 pages, 1 figure
Physics Letters A, 2007, V. 366, N 4-5, pp. 460-465
10.1016/j.physleta.2007.01.079
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We examine how the shape of cells and the geometry of experiment affect the reaction-diffusion kinetics at the binding between target and probe molecules on molecular biochips. In particular, we compare the binding kinetics for the probes immobilized on surface of the semispherical and flat circular cells, the limit of thin slab of analyte solution over probe cell as well as hemispherical gel pads and cells printed in gel slab over a substrate. It is shown that hemispherical geometry provides significantly faster binding kinetics and ensures more spatially homogeneous distribution of local (from a pixel) signals over a cell in the transient regime. The advantage of using thin slabs with small volume of analyte solution may be hampered by the much longer binding kinetics needing the auxiliary mixing devices. Our analysis proves that the shape of cells and the geometry of experiment should be included to the list of essential factors at biochip designing.
[ { "created": "Mon, 4 Apr 2011 12:30:36 GMT", "version": "v1" } ]
2011-04-05
[ [ "Chechetkin", "V. R.", "" ] ]
We examine how the shape of cells and the geometry of experiment affect the reaction-diffusion kinetics at the binding between target and probe molecules on molecular biochips. In particular, we compare the binding kinetics for the probes immobilized on surface of the semispherical and flat circular cells, the limit of thin slab of analyte solution over probe cell as well as hemispherical gel pads and cells printed in gel slab over a substrate. It is shown that hemispherical geometry provides significantly faster binding kinetics and ensures more spatially homogeneous distribution of local (from a pixel) signals over a cell in the transient regime. The advantage of using thin slabs with small volume of analyte solution may be hampered by the much longer binding kinetics needing the auxiliary mixing devices. Our analysis proves that the shape of cells and the geometry of experiment should be included to the list of essential factors at biochip designing.
2111.14489
Yuki Koyanagi
J{\o}rgen Ellegaard Andersen, Jens Ledet Jensen, Yuki Koyanagi, Jakob Toudahl Nielsen and Rasmus Villemoes
Using Topology to Estimate Structural Similarities of Proteins
11 pages, 11 figures
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by/4.0/
An effective model for protein structures is important for the study of protein geometry, which, to a large extent, determine the functions of proteins. There are a number of approaches for modelling; one might focus on the conformation of the backbone or H-bonds, and the model may be based on the geometry or the topology of the structure in focus. We focus on the topology of H-bonds in proteins, and explore the link between the topology and the geometry of protein structures. More specifically, we take inspiration from CASP Evaluation of Model Accuracy and investigate the extent to which structural similarities, via GDT_TS, can be estimated from the topology of H-bonds. We report on two experiments; one where we attempt to mimic the computation of GDT_TS based solely on the topology of H-bonds, and the other where we perform linear regression where the independent variables are various scores computed from the topology of H-bonds. We achieved an average $\Delta\text{GDT}$ of 6.45 with 54.5% of predictions inside 2 $\Delta\mathrm{GDT}$ for the first method, and an average $\Delta\mathrm{GDT}$ of 4.41 with 72.7% of predictions inside 2 $\Delta\mathrm{GDT}$ for the second method.
[ { "created": "Mon, 29 Nov 2021 12:23:42 GMT", "version": "v1" } ]
2021-11-30
[ [ "Andersen", "Jørgen Ellegaard", "" ], [ "Jensen", "Jens Ledet", "" ], [ "Koyanagi", "Yuki", "" ], [ "Nielsen", "Jakob Toudahl", "" ], [ "Villemoes", "Rasmus", "" ] ]
An effective model for protein structures is important for the study of protein geometry, which, to a large extent, determine the functions of proteins. There are a number of approaches for modelling; one might focus on the conformation of the backbone or H-bonds, and the model may be based on the geometry or the topology of the structure in focus. We focus on the topology of H-bonds in proteins, and explore the link between the topology and the geometry of protein structures. More specifically, we take inspiration from CASP Evaluation of Model Accuracy and investigate the extent to which structural similarities, via GDT_TS, can be estimated from the topology of H-bonds. We report on two experiments; one where we attempt to mimic the computation of GDT_TS based solely on the topology of H-bonds, and the other where we perform linear regression where the independent variables are various scores computed from the topology of H-bonds. We achieved an average $\Delta\text{GDT}$ of 6.45 with 54.5% of predictions inside 2 $\Delta\mathrm{GDT}$ for the first method, and an average $\Delta\mathrm{GDT}$ of 4.41 with 72.7% of predictions inside 2 $\Delta\mathrm{GDT}$ for the second method.
1406.7250
Shankar Vembu
Amit G. Deshwar, Shankar Vembu, Christina K. Yung, Gun Ho Jang, Lincoln Stein, Quaid Morris
Reconstructing subclonal composition and evolution from whole genome sequencing of tumors
null
null
null
null
q-bio.PE cs.LG stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Tumors often contain multiple subpopulations of cancerous cells defined by distinct somatic mutations. We describe a new method, PhyloWGS, that can be applied to WGS data from one or more tumor samples to reconstruct complete genotypes of these subpopulations based on variant allele frequencies (VAFs) of point mutations and population frequencies of structural variations. We introduce a principled phylogenic correction for VAFs in loci affected by copy number alterations and we show that this correction greatly improves subclonal reconstruction compared to existing methods.
[ { "created": "Fri, 27 Jun 2014 18:01:20 GMT", "version": "v1" }, { "created": "Mon, 27 Oct 2014 19:24:52 GMT", "version": "v2" }, { "created": "Tue, 6 Jan 2015 22:05:57 GMT", "version": "v3" } ]
2015-01-08
[ [ "Deshwar", "Amit G.", "" ], [ "Vembu", "Shankar", "" ], [ "Yung", "Christina K.", "" ], [ "Jang", "Gun Ho", "" ], [ "Stein", "Lincoln", "" ], [ "Morris", "Quaid", "" ] ]
Tumors often contain multiple subpopulations of cancerous cells defined by distinct somatic mutations. We describe a new method, PhyloWGS, that can be applied to WGS data from one or more tumor samples to reconstruct complete genotypes of these subpopulations based on variant allele frequencies (VAFs) of point mutations and population frequencies of structural variations. We introduce a principled phylogenic correction for VAFs in loci affected by copy number alterations and we show that this correction greatly improves subclonal reconstruction compared to existing methods.
q-bio/0605008
Enrico Carlon
T. Heim, L.-C. Tranchevent, E. Carlon and G. T. Barkema
Physics-based analysis of Affymetrix microarray data
11 pages, 10 figures
J. Phys. Chem. B 110, 22786 (2006)
10.1021/jp062889x
null
q-bio.BM cond-mat.stat-mech physics.chem-ph
null
We analyze publicly available data on Affymetrix microarrays spike-in experiments on the human HGU133 chipset in which sequences are added in solution at known concentrations. The spike-in set contains sequences of bacterial, human and artificial origin. Our analysis is based on a recently introduced molecular-based model [E. Carlon and T. Heim, Physica A 362, 433 (2006)] which takes into account both probe-target hybridization and target-target partial hybridization in solution. The hybridization free energies are obtained from the nearest-neighbor model with experimentally determined parameters. The molecular-based model suggests a rescaling that should result in a "collapse" of the data at different concentrations into a single universal curve. We indeed find such a collapse, with the same parameters as obtained before for the older HGU95 chip set. The quality of the collapse varies according to the probe set considered. Artificial sequences, chosen by Affymetrix to be as different as possible from any other human genome sequence, generally show a much better collapse and thus a better agreement with the model than all other sequences. This suggests that the observed deviations from the predicted collapse are related to the choice of probes or have a biological origin, rather than being a problem with the proposed model.
[ { "created": "Fri, 5 May 2006 09:11:56 GMT", "version": "v1" } ]
2011-11-10
[ [ "Heim", "T.", "" ], [ "Tranchevent", "L. -C.", "" ], [ "Carlon", "E.", "" ], [ "Barkema", "G. T.", "" ] ]
We analyze publicly available data on Affymetrix microarrays spike-in experiments on the human HGU133 chipset in which sequences are added in solution at known concentrations. The spike-in set contains sequences of bacterial, human and artificial origin. Our analysis is based on a recently introduced molecular-based model [E. Carlon and T. Heim, Physica A 362, 433 (2006)] which takes into account both probe-target hybridization and target-target partial hybridization in solution. The hybridization free energies are obtained from the nearest-neighbor model with experimentally determined parameters. The molecular-based model suggests a rescaling that should result in a "collapse" of the data at different concentrations into a single universal curve. We indeed find such a collapse, with the same parameters as obtained before for the older HGU95 chip set. The quality of the collapse varies according to the probe set considered. Artificial sequences, chosen by Affymetrix to be as different as possible from any other human genome sequence, generally show a much better collapse and thus a better agreement with the model than all other sequences. This suggests that the observed deviations from the predicted collapse are related to the choice of probes or have a biological origin, rather than being a problem with the proposed model.
1212.3120
Evgenii Levites
Evgenii Vladimirovich Levites and Svetlana Sergeevna Kirikovich
Zygotic combinatorial process in plants
14 pages, 1 table
null
null
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Experimental data that prove the existence of the zygotic combinatorial process occurring in an embryogenesis-entering zygote are presented in the paper. The zygotic combinatorial process is found when analyzing F1 hybrid plants obtained from crossing homozygous forms different, minimum, in two marker enzymes, and it is found in that hybrid plant which, with one marker enzyme heterozygous spectrum, has a homozygous spectrum of the other. The zygotic combinatorial process leads to F1 hybrids uniformity aberration. The zygotic combinatory process revealed in the study is supposed to be conditioned by chromosome polyteny in mother plant cells and diminution of chromatin excess from the embryogenesis-entering zygote. An obligatory condition for combinatorial process is the presence of free exchange of cromatides among homological chromosomes in an embryogenesis-entering cell, i.e. the presence of crossing-over analogous to the one proceeding at meiosis. The found combinatorial process and the earlier-obtained data confirm the hypothesis on multi-dimensionality of inherited information coding. Differential polyteny of certain chromosome regions can lead to differences among homozygous plants having the same alleles in genes located in polytenized regions and controlling morpho-physiological traits.
[ { "created": "Thu, 13 Dec 2012 10:50:18 GMT", "version": "v1" } ]
2012-12-14
[ [ "Levites", "Evgenii Vladimirovich", "" ], [ "Kirikovich", "Svetlana Sergeevna", "" ] ]
Experimental data that prove the existence of the zygotic combinatorial process occurring in an embryogenesis-entering zygote are presented in the paper. The zygotic combinatorial process is found when analyzing F1 hybrid plants obtained from crossing homozygous forms different, minimum, in two marker enzymes, and it is found in that hybrid plant which, with one marker enzyme heterozygous spectrum, has a homozygous spectrum of the other. The zygotic combinatorial process leads to F1 hybrids uniformity aberration. The zygotic combinatory process revealed in the study is supposed to be conditioned by chromosome polyteny in mother plant cells and diminution of chromatin excess from the embryogenesis-entering zygote. An obligatory condition for combinatorial process is the presence of free exchange of cromatides among homological chromosomes in an embryogenesis-entering cell, i.e. the presence of crossing-over analogous to the one proceeding at meiosis. The found combinatorial process and the earlier-obtained data confirm the hypothesis on multi-dimensionality of inherited information coding. Differential polyteny of certain chromosome regions can lead to differences among homozygous plants having the same alleles in genes located in polytenized regions and controlling morpho-physiological traits.
1908.07570
Ryota Takaki
Ryota Takaki, Mauro L. Mugnai, Yonathan Goldtzvik, D. Thirumalai
How kinesin waits for ATP affects the nucleotide and load dependence of the stepping kinetics
null
null
10.1073/pnas.1913650116
null
q-bio.SC cond-mat.soft physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Dimeric molecular motors walk on polar tracks by binding and hydrolyzing one ATP per step. Despite tremendous progress, the waiting state for ATP binding in the well-studied kinesin that walks on microtubule (MT), remains controversial. One experiment suggests that in the waiting state both heads are bound to the MT, while the other shows that ATP binds to the leading head after the partner head detaches. To discriminate between these two scenarios, we developed a theory to calculate accurately several experimentally measurable quantities as a function of ATP concentration and resistive force. In particular, we predict that measurement of the randomness parameter could discriminate between the two scenarios for the waiting state of kinesin, thereby resolving this standing controversy.
[ { "created": "Tue, 20 Aug 2019 19:06:39 GMT", "version": "v1" } ]
2022-06-08
[ [ "Takaki", "Ryota", "" ], [ "Mugnai", "Mauro L.", "" ], [ "Goldtzvik", "Yonathan", "" ], [ "Thirumalai", "D.", "" ] ]
Dimeric molecular motors walk on polar tracks by binding and hydrolyzing one ATP per step. Despite tremendous progress, the waiting state for ATP binding in the well-studied kinesin that walks on microtubule (MT), remains controversial. One experiment suggests that in the waiting state both heads are bound to the MT, while the other shows that ATP binds to the leading head after the partner head detaches. To discriminate between these two scenarios, we developed a theory to calculate accurately several experimentally measurable quantities as a function of ATP concentration and resistive force. In particular, we predict that measurement of the randomness parameter could discriminate between the two scenarios for the waiting state of kinesin, thereby resolving this standing controversy.
2204.12598
Halie Rando
Halie M. Rando, Christian Brueffer, Ronan Lordan, Anna Ada Dattoli, David Manheim, Jesse G. Meyer, Ariel I. Mundo, Dimitri Perrin, David Mai, Nils Wellhausen, COVID-19 Review Consortium, Anthony Gitter, Casey S. Greene
Molecular and Serologic Diagnostic Technologies for SARS-CoV-2
null
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by/4.0/
The COVID-19 pandemic has presented many challenges that have spurred biotechnological research to address specific problems. Diagnostics is one area where biotechnology has been critical. Diagnostic tests play a vital role in managing a viral threat by facilitating the detection of infected and/or recovered individuals. From the perspective of what information is provided, these tests fall into two major categories, molecular and serological. Molecular diagnostic techniques assay whether a virus is present in a biological sample, thus making it possible to identify individuals who are currently infected. Additionally, when the immune system is exposed to a virus, it responds by producing antibodies specific to the virus. Serological tests make it possible to identify individuals who have mounted an immune response to a virus of interest and therefore facilitate the identification of individuals who have previously encountered the virus. These two categories of tests provide different perspectives valuable to understanding the spread of SARS-CoV-2. Within these categories, different biotechnological approaches offer specific advantages and disadvantages. Here we review the categories of tests developed for the detection of the SARS-CoV-2 virus or antibodies against SARS-CoV-2 and discuss the role of diagnostics in the COVID-19 pandemic.
[ { "created": "Tue, 26 Apr 2022 21:22:40 GMT", "version": "v1" }, { "created": "Thu, 28 Apr 2022 17:59:08 GMT", "version": "v2" } ]
2022-04-29
[ [ "Rando", "Halie M.", "" ], [ "Brueffer", "Christian", "" ], [ "Lordan", "Ronan", "" ], [ "Dattoli", "Anna Ada", "" ], [ "Manheim", "David", "" ], [ "Meyer", "Jesse G.", "" ], [ "Mundo", "Ariel I.", "" ], ...
The COVID-19 pandemic has presented many challenges that have spurred biotechnological research to address specific problems. Diagnostics is one area where biotechnology has been critical. Diagnostic tests play a vital role in managing a viral threat by facilitating the detection of infected and/or recovered individuals. From the perspective of what information is provided, these tests fall into two major categories, molecular and serological. Molecular diagnostic techniques assay whether a virus is present in a biological sample, thus making it possible to identify individuals who are currently infected. Additionally, when the immune system is exposed to a virus, it responds by producing antibodies specific to the virus. Serological tests make it possible to identify individuals who have mounted an immune response to a virus of interest and therefore facilitate the identification of individuals who have previously encountered the virus. These two categories of tests provide different perspectives valuable to understanding the spread of SARS-CoV-2. Within these categories, different biotechnological approaches offer specific advantages and disadvantages. Here we review the categories of tests developed for the detection of the SARS-CoV-2 virus or antibodies against SARS-CoV-2 and discuss the role of diagnostics in the COVID-19 pandemic.
1502.03481
Leonardo Barbosa
Leonardo S. Barbosa and Nestor Caticha
Backward Renormalization Priors and the Cortical Source Localization Problem with EEG or MEG
null
null
null
null
q-bio.QM q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We study source localization from high dimensional M/EEG data by extending a multiscale method based on Entropic inference devised to increase the spatial resolution of inverse problems. This method is used to construct informative prior distributions in a manner inspired in the context of fMRI (Amaral et al 2004). We construct a set of renormalized lattices that approximate the cortex region where the source activity is located and address the related problem of defining the relevant variables in a coarser scale representation of the cortex. The priors can be used in conjunction with other Bayesian methods such as the Variational Bayes method (VB, Sato et al 2004). The central point of the algorithm is that it uses a posterior obtained at a coarse scale to induce a prior at the next finer scale stage of the problem. We present results which suggest, on simulated data, that this way of including prior information is a useful aid for the source location problem. This is judged by the rate and magnitude of errors in source localization. Better convergence times are also achieved. We also present results on public data collected during a face recognition task.
[ { "created": "Wed, 11 Feb 2015 23:09:59 GMT", "version": "v1" } ]
2015-02-13
[ [ "Barbosa", "Leonardo S.", "" ], [ "Caticha", "Nestor", "" ] ]
We study source localization from high dimensional M/EEG data by extending a multiscale method based on Entropic inference devised to increase the spatial resolution of inverse problems. This method is used to construct informative prior distributions in a manner inspired in the context of fMRI (Amaral et al 2004). We construct a set of renormalized lattices that approximate the cortex region where the source activity is located and address the related problem of defining the relevant variables in a coarser scale representation of the cortex. The priors can be used in conjunction with other Bayesian methods such as the Variational Bayes method (VB, Sato et al 2004). The central point of the algorithm is that it uses a posterior obtained at a coarse scale to induce a prior at the next finer scale stage of the problem. We present results which suggest, on simulated data, that this way of including prior information is a useful aid for the source location problem. This is judged by the rate and magnitude of errors in source localization. Better convergence times are also achieved. We also present results on public data collected during a face recognition task.
1709.06720
Vladimir Privman
Sergii Domanskyi, Justin W. Nicholatos, Joshua E. Schilling, Vladimir Privman, Sergiy Libert
SIRT6 Knockout Cells Resist Apoptosis Initiation but Not Progression: A Computational Method to Evaluate the Progression of Apoptosis
null
Apoptosis 22 (11), 1336-1343 (2017)
10.1007/s10495-017-1412-0
VP-280
q-bio.QM cond-mat.stat-mech q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Apoptosis is essential for numerous processes, such as development, resistance to infections, and suppression of tumorigenesis. Here, we investigate the influence of the nutrient sensing and longevity-assuring enzyme SIRT6 on the dynamics of apoptosis triggered by serum starvation. Specifically, we characterize the progression of apoptosis in wild type and SIRT6 deficient mouse embryonic fibroblasts using time-lapse flow cytometry and computational modelling based on rate-equations and cell distribution analysis. We find that SIRT6 deficient cells resist apoptosis by delaying its initiation. Interestingly, once apoptosis is initiated, the rate of its progression is higher in SIRT6 null cells compared to identically cultured wild type cells. However, SIRT6 null cells succumb to apoptosis more slowly, not only in response to nutrient deprivation but also in response to other stresses. Our data suggest that SIRT6 plays a role in several distinct steps of apoptosis. Overall, we demonstrate the utility of our computational model to describe stages of apoptosis progression and the integrity of the cellular membrane. Such measurements will be useful in a broad range of biological applications. We describe a computational method to evaluate the progression of apoptosis through different stages. Using this method, we describe how cells devoid of SIRT6 longevity gene respond to apoptosis stimuli, specifically, how they respond to starvation. We find that SIRT6 cells resist apoptosis initiation; however, once initiated, they progress through the apoptosis at a faster rate. These data are first of the kind and suggest that SIRT6 activities might play different roles at different stages of apoptosis. The model that we propose can be used to quantitatively evaluate progression of apoptosis and will be useful in studies of cancer treatments and other areas where apoptosis is involved.
[ { "created": "Wed, 20 Sep 2017 04:31:26 GMT", "version": "v1" } ]
2017-11-22
[ [ "Domanskyi", "Sergii", "" ], [ "Nicholatos", "Justin W.", "" ], [ "Schilling", "Joshua E.", "" ], [ "Privman", "Vladimir", "" ], [ "Libert", "Sergiy", "" ] ]
Apoptosis is essential for numerous processes, such as development, resistance to infections, and suppression of tumorigenesis. Here, we investigate the influence of the nutrient sensing and longevity-assuring enzyme SIRT6 on the dynamics of apoptosis triggered by serum starvation. Specifically, we characterize the progression of apoptosis in wild type and SIRT6 deficient mouse embryonic fibroblasts using time-lapse flow cytometry and computational modelling based on rate-equations and cell distribution analysis. We find that SIRT6 deficient cells resist apoptosis by delaying its initiation. Interestingly, once apoptosis is initiated, the rate of its progression is higher in SIRT6 null cells compared to identically cultured wild type cells. However, SIRT6 null cells succumb to apoptosis more slowly, not only in response to nutrient deprivation but also in response to other stresses. Our data suggest that SIRT6 plays a role in several distinct steps of apoptosis. Overall, we demonstrate the utility of our computational model to describe stages of apoptosis progression and the integrity of the cellular membrane. Such measurements will be useful in a broad range of biological applications. We describe a computational method to evaluate the progression of apoptosis through different stages. Using this method, we describe how cells devoid of SIRT6 longevity gene respond to apoptosis stimuli, specifically, how they respond to starvation. We find that SIRT6 cells resist apoptosis initiation; however, once initiated, they progress through the apoptosis at a faster rate. These data are first of the kind and suggest that SIRT6 activities might play different roles at different stages of apoptosis. The model that we propose can be used to quantitatively evaluate progression of apoptosis and will be useful in studies of cancer treatments and other areas where apoptosis is involved.
q-bio/0601027
Jie Liang
Ronald Jackups, Jr. and Jie Liang
Interstrand pairing patterns in $\beta$-barrel membrane proteins: the positive-outside rule, aromatic rescue, and strand registration prediction
26 pages, 4 figures, and 4 tables
J. Mol. Biol. (2005) 354:979--993
10.1016/j.jmb.2005.09.094
null
q-bio.BM
null
$\beta$-barrel membrane proteins are found in the outer membrane of gram-negative bacteria, mitochondria, and chloroplasts. We have developed probabilistic models to quantify propensities of residues for different spatial locations and for interstrand pairwise contact interactions involving strong H-bonds, side-chain interactions, and weak H-bonds. The propensity values and p-values measuring statistical significance are calculated exactly by analytical formulae we have developed. Contrary to the ``positive-inside'' rule for helical membrane proteins, $\beta$-barrel membrane proteins follow a significant albeit weaker ``positive-outside'' rule, in that the basic residues Arg and Lys are disproportionately favored in the extracellular cap region and disfavored in the periplasmic cap region. Different residue pairs prefer strong backbone H-bonded interstrand pairings (e.g. Gly-Aromatic) or non-H-bonded pairings (e.g. Aromatic-Aromatic). In addition, Tyr and Phe participate in aromatic rescue by shielding Gly from polar environments. These propensities can be used to predict the registration of strand pairs, an important task for the structure prediction of $\beta$-barrel membrane proteins. Our accuracy of 44% is considerably better than random (7%) and other studies. Our results imply several experiments that can help to elucidate the mechanisms of in vitro and in vivo folding of $\beta$-barrel membrane proteins. See supplementary material after the bibliography for detailed techniques.
[ { "created": "Thu, 19 Jan 2006 06:33:05 GMT", "version": "v1" } ]
2012-08-27
[ [ "Jackups,", "Ronald", "Jr." ], [ "Liang", "Jie", "" ] ]
$\beta$-barrel membrane proteins are found in the outer membrane of gram-negative bacteria, mitochondria, and chloroplasts. We have developed probabilistic models to quantify propensities of residues for different spatial locations and for interstrand pairwise contact interactions involving strong H-bonds, side-chain interactions, and weak H-bonds. The propensity values and p-values measuring statistical significance are calculated exactly by analytical formulae we have developed. Contrary to the ``positive-inside'' rule for helical membrane proteins, $\beta$-barrel membrane proteins follow a significant albeit weaker ``positive-outside'' rule, in that the basic residues Arg and Lys are disproportionately favored in the extracellular cap region and disfavored in the periplasmic cap region. Different residue pairs prefer strong backbone H-bonded interstrand pairings (e.g. Gly-Aromatic) or non-H-bonded pairings (e.g. Aromatic-Aromatic). In addition, Tyr and Phe participate in aromatic rescue by shielding Gly from polar environments. These propensities can be used to predict the registration of strand pairs, an important task for the structure prediction of $\beta$-barrel membrane proteins. Our accuracy of 44% is considerably better than random (7%) and other studies. Our results imply several experiments that can help to elucidate the mechanisms of in vitro and in vivo folding of $\beta$-barrel membrane proteins. See supplementary material after the bibliography for detailed techniques.
1704.05534
Dennis Thomas
Dennis G. Thomas and Nathan A. Baker
GIBS: A grand-canonical Monte Carlo simulation program for simulating ion-biomolecule interactions
null
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The ionic environment of biomolecules strongly influences their structure, conformational stability, and inter-molecular interactions.This paper introduces GIBS, a grand-canonical Monte Carlo (GCMC) simulation program for computing the thermodynamic properties of ion solutions and their distributions around biomolecules. This software implements algorithms that automate the excess chemical potential calculations for a given target salt concentration. GIBS uses a cavity-bias algorithm to achieve high sampling acceptance rates for inserting ions and solvent hard spheres in simulating dense ionic systems. In the current version, ion-ion interactions are described using Coulomb, hard-sphere, or Lennard-Jones (L-J) potentials; solvent-ion interactions are described using hard-sphere, L-J and attractive square-well potentials; and, solvent-solvent interactions are described using hard-sphere repulsions. This paper and the software package includes examples of using GIBS to compute the ion excess chemical potentials and mean activity coefficients of sodium chloride as well as to compute the cylindrical radial distribution functions of monovalent (Na$^+$, Rb$^+$), divalent (Sr$^{2+}$), and trivalent (CoHex$^{3+}$) around fixed all-atom models of 25 base-pair nucleic acid duplexes. GIBS is written in C++ and is freely available community use; it can be downloaded at https://github.com/Electrostatics/GIBS.
[ { "created": "Tue, 18 Apr 2017 21:18:11 GMT", "version": "v1" }, { "created": "Thu, 3 Aug 2017 22:35:57 GMT", "version": "v2" } ]
2017-08-07
[ [ "Thomas", "Dennis G.", "" ], [ "Baker", "Nathan A.", "" ] ]
The ionic environment of biomolecules strongly influences their structure, conformational stability, and inter-molecular interactions.This paper introduces GIBS, a grand-canonical Monte Carlo (GCMC) simulation program for computing the thermodynamic properties of ion solutions and their distributions around biomolecules. This software implements algorithms that automate the excess chemical potential calculations for a given target salt concentration. GIBS uses a cavity-bias algorithm to achieve high sampling acceptance rates for inserting ions and solvent hard spheres in simulating dense ionic systems. In the current version, ion-ion interactions are described using Coulomb, hard-sphere, or Lennard-Jones (L-J) potentials; solvent-ion interactions are described using hard-sphere, L-J and attractive square-well potentials; and, solvent-solvent interactions are described using hard-sphere repulsions. This paper and the software package includes examples of using GIBS to compute the ion excess chemical potentials and mean activity coefficients of sodium chloride as well as to compute the cylindrical radial distribution functions of monovalent (Na$^+$, Rb$^+$), divalent (Sr$^{2+}$), and trivalent (CoHex$^{3+}$) around fixed all-atom models of 25 base-pair nucleic acid duplexes. GIBS is written in C++ and is freely available community use; it can be downloaded at https://github.com/Electrostatics/GIBS.
1804.11310
Hao Wang
Hao Wang, Jiahui Wang, Xin Yuan Thow, Sanghoon Lee, Wendy Yen Xian Peh, Kian Ann Ng, Tianyiyi He, Nitish V. Thakor and Chengkuo Lee
Unveiling Stimulation Secrets of Electrical Excitation of Neural Tissue Using a Circuit Probability Theory
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A new theory, named the Circuit-Probability theory, is proposed to unveil the secret of electrical nerve stimulation, essentially explain the nonlinear and resonant phenomena observed when neural and non-neural tissues are electrically stimulated. For the explanation of frequency dependent response, an inductor is involved in the neural circuit model. Furthermore, predicted response to varied stimulation strength is calculated stochastically. Based on this theory, many empirical models, such as strength-duration relationship and LNP model, can be theoretically explained, derived, and amended. This theory can explain the complex nonlinear interactions in electrical stimulation and fit in vivo experiment data on stimulation-responses of many experiments. As such, the C-P theory should be able to guide novel experiments and more importantly, offer an in-depth physical understanding of the neural tissue. As a promising neural model, we can even further explore the more accurate circuit configuration and probability equation to better describe the electrical stimulation of neural tissues in the future.
[ { "created": "Mon, 30 Apr 2018 16:34:08 GMT", "version": "v1" }, { "created": "Thu, 14 Jun 2018 06:01:29 GMT", "version": "v2" } ]
2018-06-15
[ [ "Wang", "Hao", "" ], [ "Wang", "Jiahui", "" ], [ "Thow", "Xin Yuan", "" ], [ "Lee", "Sanghoon", "" ], [ "Peh", "Wendy Yen Xian", "" ], [ "Ng", "Kian Ann", "" ], [ "He", "Tianyiyi", "" ], [ "Thakor",...
A new theory, named the Circuit-Probability theory, is proposed to unveil the secret of electrical nerve stimulation, essentially explain the nonlinear and resonant phenomena observed when neural and non-neural tissues are electrically stimulated. For the explanation of frequency dependent response, an inductor is involved in the neural circuit model. Furthermore, predicted response to varied stimulation strength is calculated stochastically. Based on this theory, many empirical models, such as strength-duration relationship and LNP model, can be theoretically explained, derived, and amended. This theory can explain the complex nonlinear interactions in electrical stimulation and fit in vivo experiment data on stimulation-responses of many experiments. As such, the C-P theory should be able to guide novel experiments and more importantly, offer an in-depth physical understanding of the neural tissue. As a promising neural model, we can even further explore the more accurate circuit configuration and probability equation to better describe the electrical stimulation of neural tissues in the future.
2302.05378
Simone Saitta
Simone Saitta, Francesco Sturla, Riccardo Gorla, Omar A. Oliva, Emiliano Votta, Francesco Bedogni, Alberto Redaelli
A CT-based deep learning system for automatic assessment of aortic root morphology for TAVI planning
null
null
null
null
q-bio.QM eess.IV
http://creativecommons.org/licenses/by/4.0/
Accurate planning of transcatheter aortic implantation (TAVI) is important to minimize complications, and it requires anatomic evaluation of the aortic root (AR), commonly done through 3D computed tomography (CT) image analysis. Currently, there is no standard automated solution for this process. Two convolutional neural networks (CNNs) with 3D U-Net architectures (model 1 and model 2) were trained on 310 CT scans for AR analysis. Model 1 performed AR segmentation and model 2 identified the aortic annulus and sinotubular junction (STJ) contours. Results were validated against manual measurements of 178 TAVI candidates. After training, the two models were integrated into a fully automated pipeline for geometric analysis of the AR. The trained CNNs effectively segmented the AR, annulus and STJ, resulting in mean Dice scores of 0.93 for the AR, and mean surface distances of 1.16 mm and 1.30 mm for the annulus and STJ, respectively. Automatic measurements were in good agreement with manual annotations, yielding annulus diameters that differed by 0.52 [-2.96, 4.00] mm (bias and 95% limits of agreement for manual minus algorithm). Evaluating the area-derived diameter, bias and limits of agreement were 0.07 [-0.25, 0.39] mm. STJ and sinuses diameters computed by the automatic method yielded differences of 0.16 [-2.03, 2.34] and 0.1 [-2.93, 3.13] mm, respectively. The proposed tool is a fully automatic solution to quantify morphological biomarkers for pre-TAVI planning. The method was validated against manual annotation from clinical experts and showed to be quick and effective in assessing AR anatomy, with potential for time and cost savings.
[ { "created": "Fri, 10 Feb 2023 16:58:54 GMT", "version": "v1" } ]
2023-02-13
[ [ "Saitta", "Simone", "" ], [ "Sturla", "Francesco", "" ], [ "Gorla", "Riccardo", "" ], [ "Oliva", "Omar A.", "" ], [ "Votta", "Emiliano", "" ], [ "Bedogni", "Francesco", "" ], [ "Redaelli", "Alberto", "" ]...
Accurate planning of transcatheter aortic implantation (TAVI) is important to minimize complications, and it requires anatomic evaluation of the aortic root (AR), commonly done through 3D computed tomography (CT) image analysis. Currently, there is no standard automated solution for this process. Two convolutional neural networks (CNNs) with 3D U-Net architectures (model 1 and model 2) were trained on 310 CT scans for AR analysis. Model 1 performed AR segmentation and model 2 identified the aortic annulus and sinotubular junction (STJ) contours. Results were validated against manual measurements of 178 TAVI candidates. After training, the two models were integrated into a fully automated pipeline for geometric analysis of the AR. The trained CNNs effectively segmented the AR, annulus and STJ, resulting in mean Dice scores of 0.93 for the AR, and mean surface distances of 1.16 mm and 1.30 mm for the annulus and STJ, respectively. Automatic measurements were in good agreement with manual annotations, yielding annulus diameters that differed by 0.52 [-2.96, 4.00] mm (bias and 95% limits of agreement for manual minus algorithm). Evaluating the area-derived diameter, bias and limits of agreement were 0.07 [-0.25, 0.39] mm. STJ and sinuses diameters computed by the automatic method yielded differences of 0.16 [-2.03, 2.34] and 0.1 [-2.93, 3.13] mm, respectively. The proposed tool is a fully automatic solution to quantify morphological biomarkers for pre-TAVI planning. The method was validated against manual annotation from clinical experts and showed to be quick and effective in assessing AR anatomy, with potential for time and cost savings.
1605.07675
David Holcman
C. Guerrier D. Holcman
Hybrid Markov-mass action law for cell activation by rare binding events
4 pages (submitted)
null
null
null
q-bio.SC physics.bio-ph physics.data-an
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The binding of molecules, ions or proteins to specific target sites is a generic step for cell activation. However, this step relies on rare events where stochastic particles located in a large bulk are searching for small and often hidden targets and thus remains difficult to study. We present here a hybrid discrete-continuum model where the large ensemble of particles is described by mass-action laws. The rare discrete binding events are modeled by a Markov chain for the encounter of a finite number of small targets by few Brownian particles, for which the arrival time is Poissonian. This model is applied for predicting the time distribution of vesicular release at neuronal synapses that remains elusive. This release is triggered by the binding of few calcium ions that can originate either from the synaptic bulk or from the transient entry through calcium channels. We report that the distribution of release time is bimodal although triggered by a single fast action potential: while the first peak follows a stimulation, the second corresponds to the random arrival over much longer time of ions located in the bulk to small binding targets. To conclude, the present multiscale stochastic chemical reaction modeling allows studying cellular events based on integrating discrete molecular events over various time scales.
[ { "created": "Tue, 24 May 2016 22:34:43 GMT", "version": "v1" } ]
2016-05-26
[ [ "Holcman", "C. Guerrier D.", "" ] ]
The binding of molecules, ions or proteins to specific target sites is a generic step for cell activation. However, this step relies on rare events where stochastic particles located in a large bulk are searching for small and often hidden targets and thus remains difficult to study. We present here a hybrid discrete-continuum model where the large ensemble of particles is described by mass-action laws. The rare discrete binding events are modeled by a Markov chain for the encounter of a finite number of small targets by few Brownian particles, for which the arrival time is Poissonian. This model is applied for predicting the time distribution of vesicular release at neuronal synapses that remains elusive. This release is triggered by the binding of few calcium ions that can originate either from the synaptic bulk or from the transient entry through calcium channels. We report that the distribution of release time is bimodal although triggered by a single fast action potential: while the first peak follows a stimulation, the second corresponds to the random arrival over much longer time of ions located in the bulk to small binding targets. To conclude, the present multiscale stochastic chemical reaction modeling allows studying cellular events based on integrating discrete molecular events over various time scales.
1605.04825
Graziano Vernizzi
Graziano Vernizzi, Henri Orland, A. Zee
Improved RNA pseudoknots prediction and classification using a new topological invariant
9 pages, 6 figures
Phys. Rev. E 94, 042410 (2016)
10.1103/PhysRevE.94.042410
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We propose a new topological characterization of RNA secondary structures with pseudoknots based on two topological invariants. Starting from the classic arc-representation of RNA secondary structures, we consider a model that couples both I) the topological genus of the graph and II) the number of crossing arcs of the corresponding primitive graph. We add a term proportional to these topological invariants to the standard free energy of the RNA molecule, thus obtaining a novel free energy parametrization which takes into account the abundance of topologies of RNA pseudoknots observed in RNA databases.
[ { "created": "Mon, 16 May 2016 16:18:45 GMT", "version": "v1" } ]
2016-10-19
[ [ "Vernizzi", "Graziano", "" ], [ "Orland", "Henri", "" ], [ "Zee", "A.", "" ] ]
We propose a new topological characterization of RNA secondary structures with pseudoknots based on two topological invariants. Starting from the classic arc-representation of RNA secondary structures, we consider a model that couples both I) the topological genus of the graph and II) the number of crossing arcs of the corresponding primitive graph. We add a term proportional to these topological invariants to the standard free energy of the RNA molecule, thus obtaining a novel free energy parametrization which takes into account the abundance of topologies of RNA pseudoknots observed in RNA databases.
2006.12322
Gregor Corbin
G. Corbin, C. Engwer, A. Klar, J. Nieto, J. Soler, C. Surulescu, M. Wenske
Modeling glioma invasion with anisotropy- and hypoxia-triggered motility enhancement: from subcellular dynamics to macroscopic PDEs with multiple taxis
null
null
null
null
q-bio.TO cs.NA math.NA
http://creativecommons.org/licenses/by-nc-sa/4.0/
We deduce a model for glioma invasion making use of DTI data and accounting for the dynamics of brain tissue being actively degraded by tumor cells via excessive acidity production, but also according to the local orientation of tissue fibers. Our approach has a multiscale character: we start with a microscopic description of single cell dynamics including biochemical and/or biophysical effects of the tumor microenvironment, translated on the one hand into cell stress and corresponding forces and on the other hand into receptor binding dynamics; these lead on the mesoscopic level to kinetic equations involving transport terms w.r.t. all kinetic variables and eventually, by appropriate upscaling, to a macroscopic reaction-diffusion equation for glioma density with multiple taxis, coupled to (integro-)differential equations characterizing the evolution of acidity and macro- and mesoscopic tissue. Our approach also allows for a switch between fast and slower moving regimes, %diffusion- and drift-dominated regimes, according to the local tissue anisotropy. We perform numerical simulations to investigate the behavior of solutions w.r.t. various scenarios of tissue dynamics and the dominance of each of the tactic terms, also suggesting how the model can be used to perform a numerical necrosis-based tumor grading or support radiotherapy planning by dose painting. We also provide a discussion about alternative ways of including cell level environmental influences in such multiscale modeling approach, ultimately leading in the macroscopic limit to (multiple) taxis.
[ { "created": "Mon, 22 Jun 2020 15:07:04 GMT", "version": "v1" } ]
2020-06-23
[ [ "Corbin", "G.", "" ], [ "Engwer", "C.", "" ], [ "Klar", "A.", "" ], [ "Nieto", "J.", "" ], [ "Soler", "J.", "" ], [ "Surulescu", "C.", "" ], [ "Wenske", "M.", "" ] ]
We deduce a model for glioma invasion making use of DTI data and accounting for the dynamics of brain tissue being actively degraded by tumor cells via excessive acidity production, but also according to the local orientation of tissue fibers. Our approach has a multiscale character: we start with a microscopic description of single cell dynamics including biochemical and/or biophysical effects of the tumor microenvironment, translated on the one hand into cell stress and corresponding forces and on the other hand into receptor binding dynamics; these lead on the mesoscopic level to kinetic equations involving transport terms w.r.t. all kinetic variables and eventually, by appropriate upscaling, to a macroscopic reaction-diffusion equation for glioma density with multiple taxis, coupled to (integro-)differential equations characterizing the evolution of acidity and macro- and mesoscopic tissue. Our approach also allows for a switch between fast and slower moving regimes, %diffusion- and drift-dominated regimes, according to the local tissue anisotropy. We perform numerical simulations to investigate the behavior of solutions w.r.t. various scenarios of tissue dynamics and the dominance of each of the tactic terms, also suggesting how the model can be used to perform a numerical necrosis-based tumor grading or support radiotherapy planning by dose painting. We also provide a discussion about alternative ways of including cell level environmental influences in such multiscale modeling approach, ultimately leading in the macroscopic limit to (multiple) taxis.
2208.06362
Imra Aqeel
Imra Aqeel and Abdul Majid
Hybrid Approach to Identify Druglikeness Leading Compounds against COVID-19 3CL Protease
28 pages
null
10.3390/ph15111333
null
q-bio.BM cs.LG
http://creativecommons.org/licenses/by/4.0/
SARS-COV-2 is a positive single-strand RNA-based macromolecule that has caused the death of more than 6.3 million people since June 2022. Moreover, by disturbing global supply chains through lockdown, the virus has indirectly caused devastating damage to the global economy. It is vital to design and develop drugs for this virus and its various variants. In this paper, we developed an in-silico study-based hybrid framework to repurpose existing therapeutic agents in finding drug-like bioactive molecules that would cure Covid-19. We employed the Lipinski rules on the retrieved molecules from the ChEMBL database and found 133 drug-likeness bioactive molecules against SARS coronavirus 3CL Protease. Based on standard IC50, the dataset was divided into three classes active, inactive, and intermediate. Our comparative analysis demonstrated that the proposed Extra Tree Regressor (ETR) based QSAR model has improved prediction results related to the bioactivity of chemical compounds as compared to Gradient Boosting, XGBoost, Support Vector, Decision Tree, and Random Forest based regressor models. ADMET analysis is carried out to identify thirteen bioactive molecules with ChEMBL IDs 187460, 190743, 222234, 222628, 222735, 222769, 222840, 222893, 225515, 358279, 363535, 365134 and 426898. These molecules are highly suitable drug candidates for SARS-COV-2 3CL Protease. In the next step, the efficacy of bioactive molecules is computed in terms of binding affinity using molecular docking and then shortlisted six bioactive molecules with ChEMBL IDs 187460, 222769, 225515, 358279, 363535, and 365134. These molecules can be suitable drug candidates for SARS-COV-2. It is anticipated that the pharmacologist/drug manufacturer would further investigate these six molecules to find suitable drug candidates for SARS-COV-2. They can adopt these promising compounds for their downstream drug development stages.
[ { "created": "Wed, 3 Aug 2022 22:17:22 GMT", "version": "v1" }, { "created": "Mon, 15 Aug 2022 20:56:35 GMT", "version": "v2" }, { "created": "Wed, 24 Aug 2022 09:25:25 GMT", "version": "v3" } ]
2022-11-01
[ [ "Aqeel", "Imra", "" ], [ "Majid", "Abdul", "" ] ]
SARS-COV-2 is a positive single-strand RNA-based macromolecule that has caused the death of more than 6.3 million people since June 2022. Moreover, by disturbing global supply chains through lockdown, the virus has indirectly caused devastating damage to the global economy. It is vital to design and develop drugs for this virus and its various variants. In this paper, we developed an in-silico study-based hybrid framework to repurpose existing therapeutic agents in finding drug-like bioactive molecules that would cure Covid-19. We employed the Lipinski rules on the retrieved molecules from the ChEMBL database and found 133 drug-likeness bioactive molecules against SARS coronavirus 3CL Protease. Based on standard IC50, the dataset was divided into three classes active, inactive, and intermediate. Our comparative analysis demonstrated that the proposed Extra Tree Regressor (ETR) based QSAR model has improved prediction results related to the bioactivity of chemical compounds as compared to Gradient Boosting, XGBoost, Support Vector, Decision Tree, and Random Forest based regressor models. ADMET analysis is carried out to identify thirteen bioactive molecules with ChEMBL IDs 187460, 190743, 222234, 222628, 222735, 222769, 222840, 222893, 225515, 358279, 363535, 365134 and 426898. These molecules are highly suitable drug candidates for SARS-COV-2 3CL Protease. In the next step, the efficacy of bioactive molecules is computed in terms of binding affinity using molecular docking and then shortlisted six bioactive molecules with ChEMBL IDs 187460, 222769, 225515, 358279, 363535, and 365134. These molecules can be suitable drug candidates for SARS-COV-2. It is anticipated that the pharmacologist/drug manufacturer would further investigate these six molecules to find suitable drug candidates for SARS-COV-2. They can adopt these promising compounds for their downstream drug development stages.
2306.14902
Kong Deqian
Deqian Kong, Bo Pang, Tian Han and Ying Nian Wu
Molecule Design by Latent Space Energy-Based Modeling and Gradual Distribution Shifting
null
39th Conference on Uncertainty in Artificial Intelligence 2023
null
null
q-bio.BM cs.LG stat.ML
http://creativecommons.org/licenses/by/4.0/
Generation of molecules with desired chemical and biological properties such as high drug-likeness, high binding affinity to target proteins, is critical for drug discovery. In this paper, we propose a probabilistic generative model to capture the joint distribution of molecules and their properties. Our model assumes an energy-based model (EBM) in the latent space. Conditional on the latent vector, the molecule and its properties are modeled by a molecule generation model and a property regression model respectively. To search for molecules with desired properties, we propose a sampling with gradual distribution shifting (SGDS) algorithm, so that after learning the model initially on the training data of existing molecules and their properties, the proposed algorithm gradually shifts the model distribution towards the region supported by molecules with desired values of properties. Our experiments show that our method achieves very strong performances on various molecule design tasks.
[ { "created": "Fri, 9 Jun 2023 03:04:21 GMT", "version": "v1" } ]
2023-07-12
[ [ "Kong", "Deqian", "" ], [ "Pang", "Bo", "" ], [ "Han", "Tian", "" ], [ "Wu", "Ying Nian", "" ] ]
Generation of molecules with desired chemical and biological properties such as high drug-likeness, high binding affinity to target proteins, is critical for drug discovery. In this paper, we propose a probabilistic generative model to capture the joint distribution of molecules and their properties. Our model assumes an energy-based model (EBM) in the latent space. Conditional on the latent vector, the molecule and its properties are modeled by a molecule generation model and a property regression model respectively. To search for molecules with desired properties, we propose a sampling with gradual distribution shifting (SGDS) algorithm, so that after learning the model initially on the training data of existing molecules and their properties, the proposed algorithm gradually shifts the model distribution towards the region supported by molecules with desired values of properties. Our experiments show that our method achieves very strong performances on various molecule design tasks.
0711.2723
Ganesh Bagler Dr
Ganesh Bagler and Somdatta Sinha
Assortative mixing in Protein Contact Networks and protein folding kinetics
Published in Bioinformatics
Bioinformatics, vol. 23, no. 14, 1760--1767 (2007)
10.1093/bioinformatics/btm257
null
q-bio.MN q-bio.BM
null
Starting from linear chains of amino acids, the spontaneous folding of proteins into their elaborate three-dimensional structures is one of the remarkable examples of biological self-organization. We investigated native state structures of 30 single-domain, two-state proteins, from complex networks perspective, to understand the role of topological parameters in proteins' folding kinetics, at two length scales-- as ``Protein Contact Networks (PCNs)'' and their corresponding ``Long-range Interaction Networks (LINs)'' constructed by ignoring the short-range interactions. Our results show that, both PCNs and LINs exhibit the exceptional topological property of ``assortative mixing'' that is absent in all other biological and technological networks studied so far. We show that the degree distribution of these contact networks is partly responsible for the observed assortativity. The coefficient of assortativity also shows a positive correlation with the rate of protein folding at both short and long contact scale, whereas, the clustering coefficients of only the LINs exhibit a negative correlation. The results indicate that the general topological parameters of these naturally-evolved protein networks can effectively represent the structural and functional properties required for fast information transfer among the residues facilitating biochemical/kinetic functions, such as, allostery, stability, and the rate of folding.
[ { "created": "Sat, 17 Nov 2007 08:45:23 GMT", "version": "v1" } ]
2007-11-20
[ [ "Bagler", "Ganesh", "" ], [ "Sinha", "Somdatta", "" ] ]
Starting from linear chains of amino acids, the spontaneous folding of proteins into their elaborate three-dimensional structures is one of the remarkable examples of biological self-organization. We investigated native state structures of 30 single-domain, two-state proteins, from complex networks perspective, to understand the role of topological parameters in proteins' folding kinetics, at two length scales-- as ``Protein Contact Networks (PCNs)'' and their corresponding ``Long-range Interaction Networks (LINs)'' constructed by ignoring the short-range interactions. Our results show that, both PCNs and LINs exhibit the exceptional topological property of ``assortative mixing'' that is absent in all other biological and technological networks studied so far. We show that the degree distribution of these contact networks is partly responsible for the observed assortativity. The coefficient of assortativity also shows a positive correlation with the rate of protein folding at both short and long contact scale, whereas, the clustering coefficients of only the LINs exhibit a negative correlation. The results indicate that the general topological parameters of these naturally-evolved protein networks can effectively represent the structural and functional properties required for fast information transfer among the residues facilitating biochemical/kinetic functions, such as, allostery, stability, and the rate of folding.
q-bio/0609001
Philippe Veber
Nicola Yanev (IRISA / INRIA Rennes), Rumen Andonov (IRISA / INRIA Rennes), Philippe Veber (IRISA / INRIA Rennes), Stefan Balev (LIH EA3219)
Lagrangian Approaches for a class of Matching Problems in Computational Biology
null
null
null
null
q-bio.QM
null
This paper presents efficient algorithms for solving the problem of aligning a protein structure template to a query amino-acid sequence, known as protein threading problem. We consider the problem as a special case of graph matching problem. We give formal graph and integer programming models of the problem. After studying the properties of these models, we propose two kinds of Lagrangian relaxation for solving them. We present experimental results on real life instances showing the efficiency of our approaches.
[ { "created": "Fri, 1 Sep 2006 13:41:43 GMT", "version": "v1" } ]
2007-05-23
[ [ "Yanev", "Nicola", "", "IRISA / INRIA Rennes" ], [ "Andonov", "Rumen", "", "IRISA / INRIA\n Rennes" ], [ "Veber", "Philippe", "", "IRISA / INRIA Rennes" ], [ "Balev", "Stefan", "", "LIH EA3219" ] ]
This paper presents efficient algorithms for solving the problem of aligning a protein structure template to a query amino-acid sequence, known as protein threading problem. We consider the problem as a special case of graph matching problem. We give formal graph and integer programming models of the problem. After studying the properties of these models, we propose two kinds of Lagrangian relaxation for solving them. We present experimental results on real life instances showing the efficiency of our approaches.
2210.16414
Navid Shervani-Tabar
Navid Shervani-Tabar and Robert Rosenbaum
Meta-Learning Biologically Plausible Plasticity Rules with Random Feedback Pathways
null
null
null
null
q-bio.NC cs.LG cs.NE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Backpropagation is widely used to train artificial neural networks, but its relationship to synaptic plasticity in the brain is unknown. Some biological models of backpropagation rely on feedback projections that are symmetric with feedforward connections, but experiments do not corroborate the existence of such symmetric backward connectivity. Random feedback alignment offers an alternative model in which errors are propagated backward through fixed, random backward connections. This approach successfully trains shallow models, but learns slowly and does not perform well with deeper models or online learning. In this study, we develop a meta-learning approach to discover interpretable, biologically plausible plasticity rules that improve online learning performance with fixed random feedback connections. The resulting plasticity rules show improved online training of deep models in the low data regime. Our results highlight the potential of meta-learning to discover effective, interpretable learning rules satisfying biological constraints.
[ { "created": "Fri, 28 Oct 2022 21:40:56 GMT", "version": "v1" }, { "created": "Tue, 1 Nov 2022 23:23:15 GMT", "version": "v2" }, { "created": "Mon, 7 Nov 2022 13:29:28 GMT", "version": "v3" }, { "created": "Thu, 1 Dec 2022 14:31:10 GMT", "version": "v4" }, { "crea...
2023-02-08
[ [ "Shervani-Tabar", "Navid", "" ], [ "Rosenbaum", "Robert", "" ] ]
Backpropagation is widely used to train artificial neural networks, but its relationship to synaptic plasticity in the brain is unknown. Some biological models of backpropagation rely on feedback projections that are symmetric with feedforward connections, but experiments do not corroborate the existence of such symmetric backward connectivity. Random feedback alignment offers an alternative model in which errors are propagated backward through fixed, random backward connections. This approach successfully trains shallow models, but learns slowly and does not perform well with deeper models or online learning. In this study, we develop a meta-learning approach to discover interpretable, biologically plausible plasticity rules that improve online learning performance with fixed random feedback connections. The resulting plasticity rules show improved online training of deep models in the low data regime. Our results highlight the potential of meta-learning to discover effective, interpretable learning rules satisfying biological constraints.
q-bio/0406047
I. C. Baianu Dr.
I.C. Baianu, P.R. Lozano, V.I. Prisecaru and H.C. Lin
Applications of Novel Techniques to Health Foods, Medical and Agricultural Biotechnology
39 pages and 9 figures
null
null
HMAT04
q-bio.OT
null
Selected applications of novel techniques in Agricultural Biotechnology, Health Food formulations and Medical Biotechnology are being reviewed with the aim of unraveling future developments and policy changes that are likely to open new niches for Biotechnology and prevent the shrinking or closing the existing ones. Amongst the selected novel techniques with applications to both Agricultural and Medical Biotechnology are: immobilized bacterial cells and enzymes, microencapsulation and liposome production, genetic manipulation of microorganisms, development of novel vaccines from plants, epigenomics of mammalian cells and organisms, as well as biocomputational tools for molecular modeling related to disease and Bioinformatics. Both fundamental and applied aspects of the emerging new techniques are being discussed in relation to their anticipated impact on future biotechnology applications together with policy changes that are needed for continued success in both Agricultural and Medical Biotechnology. Several novel techniques are illustrated in an attempt to convey the most representative and powerful tools that are currently being developed for both immediate and long term applications in Agriculture, Health Food formulation and production, pharmaceuticals and Medicine. The research aspects are naturally emphasized in our review as they are key to further developments in Medical and Agricultural Biotechnology.
[ { "created": "Thu, 24 Jun 2004 03:40:08 GMT", "version": "v1" } ]
2007-05-23
[ [ "Baianu", "I. C.", "" ], [ "Lozano", "P. R.", "" ], [ "Prisecaru", "V. I.", "" ], [ "Lin", "H. C.", "" ] ]
Selected applications of novel techniques in Agricultural Biotechnology, Health Food formulations and Medical Biotechnology are being reviewed with the aim of unraveling future developments and policy changes that are likely to open new niches for Biotechnology and prevent the shrinking or closing the existing ones. Amongst the selected novel techniques with applications to both Agricultural and Medical Biotechnology are: immobilized bacterial cells and enzymes, microencapsulation and liposome production, genetic manipulation of microorganisms, development of novel vaccines from plants, epigenomics of mammalian cells and organisms, as well as biocomputational tools for molecular modeling related to disease and Bioinformatics. Both fundamental and applied aspects of the emerging new techniques are being discussed in relation to their anticipated impact on future biotechnology applications together with policy changes that are needed for continued success in both Agricultural and Medical Biotechnology. Several novel techniques are illustrated in an attempt to convey the most representative and powerful tools that are currently being developed for both immediate and long term applications in Agriculture, Health Food formulation and production, pharmaceuticals and Medicine. The research aspects are naturally emphasized in our review as they are key to further developments in Medical and Agricultural Biotechnology.
1603.00958
Elecia Johnston
Elecia B Johnston, Sandip D Kamath, Andreas L Lopata, Patrick M Schaeffer
Tus-Ter-lock immuno-PCR assays for the sensitive detection of tropomyosin-specific IgE antibodies
Author's final version, 5 figures
Bioanalysis, 2014, Vol. 6, No. 4, Pages 465-476
10.4155/bio.13.315
null
q-bio.BM q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Background: The increasing prevalence of food allergies requires development of specific and sensitive tests capable of identifying the allergen responsible for the disease. The development of serologic tests that can detect specific IgE antibodies to allergenic proteins would therefore be highly received. Results: Here we present two new quantitative immuno-PCR assays for the sensitive detection of antibodies specific to the shrimp allergen tropomyosin. Both assays are based on the self-assembling Tus-Ter-lock protein-DNA conjugation system. Significantly elevated levels of tropomyosin-specific IgE were detected in sera from patients allergic to shrimp. Conclusions: This is the first time an allergenic protein has been fused with Tus to enable specific IgE antibody detection in human sera by quantitative immuno-PCR.
[ { "created": "Thu, 3 Mar 2016 03:22:22 GMT", "version": "v1" } ]
2016-03-04
[ [ "Johnston", "Elecia B", "" ], [ "Kamath", "Sandip D", "" ], [ "Lopata", "Andreas L", "" ], [ "Schaeffer", "Patrick M", "" ] ]
Background: The increasing prevalence of food allergies requires development of specific and sensitive tests capable of identifying the allergen responsible for the disease. The development of serologic tests that can detect specific IgE antibodies to allergenic proteins would therefore be highly received. Results: Here we present two new quantitative immuno-PCR assays for the sensitive detection of antibodies specific to the shrimp allergen tropomyosin. Both assays are based on the self-assembling Tus-Ter-lock protein-DNA conjugation system. Significantly elevated levels of tropomyosin-specific IgE were detected in sera from patients allergic to shrimp. Conclusions: This is the first time an allergenic protein has been fused with Tus to enable specific IgE antibody detection in human sera by quantitative immuno-PCR.
2001.03119
Simona Arrighi
Simona Arrighi, Adriana Moroni, Laura Tassoni, Francesco Boschin, Federica Badino, Eugenio Bortolini, Paolo Boscato, Jacopo Crezzini, Carla Figus, Manuela Forte, Federico Lugli, Giulia Marciani, Gregorio Oxilia, Fabio Negrino, Julien Riel-Salvatore, Matteo Romandini, Enza Elena Spinapolice, Marco Peresani, Annamaria Ronchitelli, Stefano Benazzi
Bone tools, ornaments and other unusual objects during the Middle to Upper Palaeolithic transition in Italy
null
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The arrival of Modern Humans (MHs) in Europe between 50 ka and 36 ka coincides with significant changes in human behaviour, regarding the production of tools, the exploitation of resources and the systematic use of ornaments and colouring substances. The emergence of the so-called modern behaviours is usually associated with MHs, although in these last decades findings relating to symbolic thinking of pre-Sapiens groups have been claimed. In this paper we present a synthesis of the Italian evidence concerning bone manufacturing and the use of ornaments and pigments in the time span encompassing the demise of Neandertals and their replacement by MHs. Current data show that Mousterian bone tools are mostly obtained from bone fragments used as is. Conversely an organized production of fine shaped bone tools is characteristic of the Uluzzian and the Protoaurignacian, when the complexity inherent in the manufacturing processes suggests that bone artefacts are not to be considered as expedient resources. Some traces of symbolic activities are associated to Neandertals in Northern Italy. Ornaments (mostly tusk shells) and pigments used for decorative purposes are well recorded during the Uluzzian. Their features and distribution witness to an intriguing cultural homogeneity within this technocomplex. The Protoaurignacian is characterized by a wider archaeological evidence, consisting of personal ornaments (mostly pierced gastropods), pigments and artistic items.
[ { "created": "Wed, 4 Dec 2019 13:29:30 GMT", "version": "v1" } ]
2020-01-10
[ [ "Arrighi", "Simona", "" ], [ "Moroni", "Adriana", "" ], [ "Tassoni", "Laura", "" ], [ "Boschin", "Francesco", "" ], [ "Badino", "Federica", "" ], [ "Bortolini", "Eugenio", "" ], [ "Boscato", "Paolo", "" ]...
The arrival of Modern Humans (MHs) in Europe between 50 ka and 36 ka coincides with significant changes in human behaviour, regarding the production of tools, the exploitation of resources and the systematic use of ornaments and colouring substances. The emergence of the so-called modern behaviours is usually associated with MHs, although in these last decades findings relating to symbolic thinking of pre-Sapiens groups have been claimed. In this paper we present a synthesis of the Italian evidence concerning bone manufacturing and the use of ornaments and pigments in the time span encompassing the demise of Neandertals and their replacement by MHs. Current data show that Mousterian bone tools are mostly obtained from bone fragments used as is. Conversely an organized production of fine shaped bone tools is characteristic of the Uluzzian and the Protoaurignacian, when the complexity inherent in the manufacturing processes suggests that bone artefacts are not to be considered as expedient resources. Some traces of symbolic activities are associated to Neandertals in Northern Italy. Ornaments (mostly tusk shells) and pigments used for decorative purposes are well recorded during the Uluzzian. Their features and distribution witness to an intriguing cultural homogeneity within this technocomplex. The Protoaurignacian is characterized by a wider archaeological evidence, consisting of personal ornaments (mostly pierced gastropods), pigments and artistic items.
2002.05114
Nam Lyong Kang
Nam. Lyong Kang
New method for evaluating fitness using the waist-to-height ratio among Korean adults
null
null
null
null
q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Objectives: This paper introduces a new method for evaluating fitness and determining effective exercises for reducing abdominal obesity in Korean adults using the new kind of waist-to-height ratio (WHT2R). Materials and Methods: The body mass index (BMI), body shape index (ABSI), and two other waist-to-height ratios (WHT.5R, WHTR) were considered as possible contenders for the WHT2R. The correlation coefficients were calculated by correlation analyses between the indices and four fitness tests for comparison. The LMV (lump mean value) and FSPW (fitness sensitivity percentage to WHT2R) were introduced to find the association between fitness and abdominal obesity using a linear regression method and to use as an indicator for the effective control of abdominal obesity. Results: The WHT2R is more suitable for assessing fitness than the other indices and can be controlled effectively by decreasing the 10-m shuttle run score for both males and females. Conclusions: The WHT2R can be used as a possible contender for evaluating fitness and is an effective indicator for the reduction of abdominal obesity. The LMV and FSPW can be used to establish personal exercise aims.
[ { "created": "Tue, 11 Feb 2020 01:19:17 GMT", "version": "v1" } ]
2020-02-13
[ [ "Kang", "Nam. Lyong", "" ] ]
Objectives: This paper introduces a new method for evaluating fitness and determining effective exercises for reducing abdominal obesity in Korean adults using the new kind of waist-to-height ratio (WHT2R). Materials and Methods: The body mass index (BMI), body shape index (ABSI), and two other waist-to-height ratios (WHT.5R, WHTR) were considered as possible contenders for the WHT2R. The correlation coefficients were calculated by correlation analyses between the indices and four fitness tests for comparison. The LMV (lump mean value) and FSPW (fitness sensitivity percentage to WHT2R) were introduced to find the association between fitness and abdominal obesity using a linear regression method and to use as an indicator for the effective control of abdominal obesity. Results: The WHT2R is more suitable for assessing fitness than the other indices and can be controlled effectively by decreasing the 10-m shuttle run score for both males and females. Conclusions: The WHT2R can be used as a possible contender for evaluating fitness and is an effective indicator for the reduction of abdominal obesity. The LMV and FSPW can be used to establish personal exercise aims.
0811.3124
David Hochberg
Josep M. Ribo and David Hochberg
Stability of racemic and chiral steady states in open and closed chemical systems
25 pages, 1 figure. To appear in Physics Letters A (2008)
null
10.1016/j.physleta.2008.10.079
null
q-bio.PE q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The stability properties of models of spontaneous mirror symmetry breaking in chemistry are characterized algebraically. The models considered here all derive either from the Frank model or from autocatalysis with limited enantioselectivity. Emphasis is given to identifying the critical parameter controlling the chiral symmetry breaking transition from racemic to chiral steady-state solutions. This parameter is identified in each case, and the constraints on the chemical rate constants determined from dynamic stability are derived.
[ { "created": "Wed, 19 Nov 2008 14:21:31 GMT", "version": "v1" } ]
2008-11-20
[ [ "Ribo", "Josep M.", "" ], [ "Hochberg", "David", "" ] ]
The stability properties of models of spontaneous mirror symmetry breaking in chemistry are characterized algebraically. The models considered here all derive either from the Frank model or from autocatalysis with limited enantioselectivity. Emphasis is given to identifying the critical parameter controlling the chiral symmetry breaking transition from racemic to chiral steady-state solutions. This parameter is identified in each case, and the constraints on the chemical rate constants determined from dynamic stability are derived.
2304.06353
Alexandra Blenkinsop
Alexandra Blenkinsop, Lysandros Sofocleous, Francesco di Lauro, Evangelia Georgia Kostaki, Ard van Sighem, Daniela Bezemer, Thijs van de Laar, Peter Reiss, Godelieve de Bree, Nikos Pantazis, and Oliver Ratmann
Bayesian mixture models for phylogenetic source attribution from consensus sequences and time since infection estimates
null
null
null
null
q-bio.PE stat.ME
http://creativecommons.org/licenses/by/4.0/
In stopping the spread of infectious diseases, pathogen genomic data can be used to reconstruct transmission events and characterize population-level sources of infection. Most approaches for identifying transmission pairs do not account for the time that passed since divergence of pathogen variants in individuals, which is problematic in viruses with high within-host evolutionary rates. This is prompting us to consider possible transmission pairs in terms of phylogenetic data and additional estimates of time since infection derived from clinical biomarkers. We develop Bayesian mixture models with an evolutionary clock as signal component and additional mixed effects or covariate random functions describing the mixing weights to classify potential pairs into likely and unlikely transmission pairs. We demonstrate that although sources cannot be identified at the individual level with certainty, even with the additional data on time elapsed, inferences into the population-level sources of transmission are possible, and more accurate than using only phylogenetic data without time since infection estimates. We apply the approach to estimate age-specific sources of HIV infection in Amsterdam MSM transmission networks between 2010-2021. This study demonstrates that infection time estimates provide informative data to characterize transmission sources, and shows how phylogenetic source attribution can then be done with multi-dimensional mixture models.
[ { "created": "Thu, 13 Apr 2023 09:19:35 GMT", "version": "v1" } ]
2023-04-14
[ [ "Blenkinsop", "Alexandra", "" ], [ "Sofocleous", "Lysandros", "" ], [ "di Lauro", "Francesco", "" ], [ "Kostaki", "Evangelia Georgia", "" ], [ "van Sighem", "Ard", "" ], [ "Bezemer", "Daniela", "" ], [ "van de Laar...
In stopping the spread of infectious diseases, pathogen genomic data can be used to reconstruct transmission events and characterize population-level sources of infection. Most approaches for identifying transmission pairs do not account for the time that passed since divergence of pathogen variants in individuals, which is problematic in viruses with high within-host evolutionary rates. This is prompting us to consider possible transmission pairs in terms of phylogenetic data and additional estimates of time since infection derived from clinical biomarkers. We develop Bayesian mixture models with an evolutionary clock as signal component and additional mixed effects or covariate random functions describing the mixing weights to classify potential pairs into likely and unlikely transmission pairs. We demonstrate that although sources cannot be identified at the individual level with certainty, even with the additional data on time elapsed, inferences into the population-level sources of transmission are possible, and more accurate than using only phylogenetic data without time since infection estimates. We apply the approach to estimate age-specific sources of HIV infection in Amsterdam MSM transmission networks between 2010-2021. This study demonstrates that infection time estimates provide informative data to characterize transmission sources, and shows how phylogenetic source attribution can then be done with multi-dimensional mixture models.
1507.04487
Henrik Ronellenfitsch
Henrik Ronellenfitsch, Jana Lasser, Douglas C. Daly, Eleni Katifori
Topological phenotypes constitute a new dimension in the phenotypic space of leaf venation networks
null
PLoS Comput Biol. 2015 Dec 23;11(12):e1004680
10.1371/journal.pcbi.1004680
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The leaves of angiosperms contain highly complex venation networks consisting of recursively nested, hierarchically organized loops. We describe a new phenotypic trait of reticulate vascular networks based on the topology of the nested loops. This phenotypic trait encodes information orthogonal to widely used geometric phenotypic traits, and thus constitutes a new dimension in the leaf venation phenotypic space. We apply our metric to a database of 186 leaves and leaflets representing 137 species, predominantly from the Burseraceae family, revealing diverse topological network traits even within this single family. We show that topological information significantly improves identification of leaves from fragments by calculating a "leaf venation fingerprint" from topology and geometry. Further, we present a phenomenological model suggesting that the topological traits can be explained by noise effects unique to specimen during development of each leaf which leave their imprint on the final network. This work opens the path to new quantitative identification techniques for leaves which go beyond simple geometric traits such as vein density and is directly applicable to other planar or sub-planar networks such as blood vessels in the brain.
[ { "created": "Thu, 16 Jul 2015 08:49:34 GMT", "version": "v1" }, { "created": "Wed, 22 Jul 2015 11:17:16 GMT", "version": "v2" }, { "created": "Tue, 1 Dec 2015 18:58:47 GMT", "version": "v3" } ]
2016-06-23
[ [ "Ronellenfitsch", "Henrik", "" ], [ "Lasser", "Jana", "" ], [ "Daly", "Douglas C.", "" ], [ "Katifori", "Eleni", "" ] ]
The leaves of angiosperms contain highly complex venation networks consisting of recursively nested, hierarchically organized loops. We describe a new phenotypic trait of reticulate vascular networks based on the topology of the nested loops. This phenotypic trait encodes information orthogonal to widely used geometric phenotypic traits, and thus constitutes a new dimension in the leaf venation phenotypic space. We apply our metric to a database of 186 leaves and leaflets representing 137 species, predominantly from the Burseraceae family, revealing diverse topological network traits even within this single family. We show that topological information significantly improves identification of leaves from fragments by calculating a "leaf venation fingerprint" from topology and geometry. Further, we present a phenomenological model suggesting that the topological traits can be explained by noise effects unique to specimen during development of each leaf which leave their imprint on the final network. This work opens the path to new quantitative identification techniques for leaves which go beyond simple geometric traits such as vein density and is directly applicable to other planar or sub-planar networks such as blood vessels in the brain.
2010.11124
Paul Smolen
Paul Smolen, Douglas A Baxter, John H Byrne
Modeling Suggests Combined-Drug Treatments for Disorders Impairing Synaptic Plasticity via Shared Signaling Pathways
Accepted to Journal of Computational Neuroscience
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Genetic disorders such as Rubinstein-Taybi syndrome (RTS) and Coffin-Lowry syndrome (CLS) cause lifelong cognitive disability, including deficits in learning and memory. Can pharmacological therapies be suggested to improve learning and memory in these disorders? To address this question, we simulated drug effects within a computational model describing induction of late long-term potentiation (L-LTP). Biochemical pathways impaired in these and other disorders converge on a common target, histone acetylation by acetyltransferases such as CREB binding protein (CBP), which facilitates gene induction necessary for L-LTP. We focused on four drug classes: tropomyosin receptor kinase B (TrkB) agonists, cAMP phosphodiesterase inhibitors, histone deacetylase inhibitors, and ampakines. Simulations suggested each drug type alone may rescue deficits in L-LTP. A potential disadvantage, however, was the necessity of simulating strong drug effects (high doses), which could produce adverse side effects. Thus, we investigated the effects of six drug pairs among the four classes described above. These combination treatments normalized impaired L-LTP with substantially smaller drug doses. In addition three of these combinations, a TrkB agonist paired with an ampakine and a cAMP phosphodiesterase inhibitor paired with a TrkB agonist or an ampakine, exhibited strong synergism in L-LTP rescue. Therefore, we suggest these drug combinations are promising candidates for further empirical studies in animal models of genetic disorders that impair acetylation, L-LTP, and learning.
[ { "created": "Wed, 21 Oct 2020 16:33:31 GMT", "version": "v1" } ]
2020-10-22
[ [ "Smolen", "Paul", "" ], [ "Baxter", "Douglas A", "" ], [ "Byrne", "John H", "" ] ]
Genetic disorders such as Rubinstein-Taybi syndrome (RTS) and Coffin-Lowry syndrome (CLS) cause lifelong cognitive disability, including deficits in learning and memory. Can pharmacological therapies be suggested to improve learning and memory in these disorders? To address this question, we simulated drug effects within a computational model describing induction of late long-term potentiation (L-LTP). Biochemical pathways impaired in these and other disorders converge on a common target, histone acetylation by acetyltransferases such as CREB binding protein (CBP), which facilitates gene induction necessary for L-LTP. We focused on four drug classes: tropomyosin receptor kinase B (TrkB) agonists, cAMP phosphodiesterase inhibitors, histone deacetylase inhibitors, and ampakines. Simulations suggested each drug type alone may rescue deficits in L-LTP. A potential disadvantage, however, was the necessity of simulating strong drug effects (high doses), which could produce adverse side effects. Thus, we investigated the effects of six drug pairs among the four classes described above. These combination treatments normalized impaired L-LTP with substantially smaller drug doses. In addition three of these combinations, a TrkB agonist paired with an ampakine and a cAMP phosphodiesterase inhibitor paired with a TrkB agonist or an ampakine, exhibited strong synergism in L-LTP rescue. Therefore, we suggest these drug combinations are promising candidates for further empirical studies in animal models of genetic disorders that impair acetylation, L-LTP, and learning.
2210.14522
Zhihao Cao
Zhihao Cao, Hongchun Qu
Simulation-based Modelling of Growth and Pollination of Greenhouse Strawberry
null
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
The cultivated strawberry Fragaria ananassa Duch. is widely planted in greenhouses in China. Its production heavily depends on pollination services. Compared with artificial pollination, bee pollination can significantly improve fruit quality and save considerable labor requirement. Multiple factors such as bee foraging behavior, planting pattern and the spatial complexity of the greenhouse environment interacting over time and space are major obstacles to understanding of bee pollination dynamics. We propose a spatially-explicit agent-based simulation model which allows users to explore how various factors including bee foraging behavior and strawberry phenology conditions as well as the greenhouse environment influence pollination efficiency and fruit quality. Simulation experiments allowed us to compare pollination efficiencies in different conditions. Especially, the cause of bee pollination advantage, optimal bee density and bee hive location were discussed based on sensitivity analysis. In addition, simulation results provide some insights for strawberry planting in a greenhouse. The firmly validated open-source model is a useful tool for hypothesis testing and theory development for strawberry pollination research.
[ { "created": "Wed, 26 Oct 2022 07:21:56 GMT", "version": "v1" } ]
2022-10-27
[ [ "Cao", "Zhihao", "" ], [ "Qu", "Hongchun", "" ] ]
The cultivated strawberry Fragaria ananassa Duch. is widely planted in greenhouses in China. Its production heavily depends on pollination services. Compared with artificial pollination, bee pollination can significantly improve fruit quality and save considerable labor requirement. Multiple factors such as bee foraging behavior, planting pattern and the spatial complexity of the greenhouse environment interacting over time and space are major obstacles to understanding of bee pollination dynamics. We propose a spatially-explicit agent-based simulation model which allows users to explore how various factors including bee foraging behavior and strawberry phenology conditions as well as the greenhouse environment influence pollination efficiency and fruit quality. Simulation experiments allowed us to compare pollination efficiencies in different conditions. Especially, the cause of bee pollination advantage, optimal bee density and bee hive location were discussed based on sensitivity analysis. In addition, simulation results provide some insights for strawberry planting in a greenhouse. The firmly validated open-source model is a useful tool for hypothesis testing and theory development for strawberry pollination research.
0904.1215
Jerome Vanclay
Jerome K Vanclay
Tree diameter, height and stocking in even-aged forests
15 pages, 8 figures. Annals of Forest Science, in press
Annals of Forest Science 66 (2009) 702
10.1051/forest/2009063
null
q-bio.QM q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Empirical observations suggest that in pure even-aged forests, the mean diameter of forest trees (D, diameter at breast height, 1.3 m above ground) tends to remain a constant proportion of stand height (H, average height of the largest trees in a stand) divided by the logarithm of stand density (N, number of trees per hectare): D = beta (H-1.3)/Ln(N). Thinning causes a relatively small and temporary change in the slope beta, the magnitude and duration of which depends on the nature of the thinning. This relationship may provide a robust predictor of growth in situations where scarce data and resources preclude more sophisticated modelling approaches.
[ { "created": "Tue, 7 Apr 2009 20:28:55 GMT", "version": "v1" } ]
2009-08-23
[ [ "Vanclay", "Jerome K", "" ] ]
Empirical observations suggest that in pure even-aged forests, the mean diameter of forest trees (D, diameter at breast height, 1.3 m above ground) tends to remain a constant proportion of stand height (H, average height of the largest trees in a stand) divided by the logarithm of stand density (N, number of trees per hectare): D = beta (H-1.3)/Ln(N). Thinning causes a relatively small and temporary change in the slope beta, the magnitude and duration of which depends on the nature of the thinning. This relationship may provide a robust predictor of growth in situations where scarce data and resources preclude more sophisticated modelling approaches.
2306.06138
Yule Wang
Yule Wang, Zijing Wu, Chengrui Li, Anqi Wu
Extraction and Recovery of Spatio-Temporal Structure in Latent Dynamics Alignment with Diffusion Models
null
null
null
null
q-bio.NC cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In the field of behavior-related brain computation, it is necessary to align raw neural signals against the drastic domain shift among them. A foundational framework within neuroscience research posits that trial-based neural population activities rely on low-dimensional latent dynamics, thus focusing on the latter greatly facilitates the alignment procedure. Despite this field's progress, existing methods ignore the intrinsic spatio-temporal structure during the alignment phase. Hence, their solutions usually lead to poor quality in latent dynamics structures and overall performance. To tackle this problem, we propose an alignment method ERDiff, which leverages the expressivity of the diffusion model to preserve the spatio-temporal structure of latent dynamics. Specifically, the latent dynamics structures of the source domain are first extracted by a diffusion model. Then, under the guidance of this diffusion model, such structures are well-recovered through a maximum likelihood alignment procedure in the target domain. We first demonstrate the effectiveness of our proposed method on a synthetic dataset. Then, when applied to neural recordings from the non-human primate motor cortex, under both cross-day and inter-subject settings, our method consistently manifests its capability of preserving the spatiotemporal structure of latent dynamics and outperforms existing approaches in alignment goodness-of-fit and neural decoding performance.
[ { "created": "Fri, 9 Jun 2023 05:53:11 GMT", "version": "v1" }, { "created": "Fri, 8 Mar 2024 20:11:55 GMT", "version": "v2" } ]
2024-03-12
[ [ "Wang", "Yule", "" ], [ "Wu", "Zijing", "" ], [ "Li", "Chengrui", "" ], [ "Wu", "Anqi", "" ] ]
In the field of behavior-related brain computation, it is necessary to align raw neural signals against the drastic domain shift among them. A foundational framework within neuroscience research posits that trial-based neural population activities rely on low-dimensional latent dynamics, thus focusing on the latter greatly facilitates the alignment procedure. Despite this field's progress, existing methods ignore the intrinsic spatio-temporal structure during the alignment phase. Hence, their solutions usually lead to poor quality in latent dynamics structures and overall performance. To tackle this problem, we propose an alignment method ERDiff, which leverages the expressivity of the diffusion model to preserve the spatio-temporal structure of latent dynamics. Specifically, the latent dynamics structures of the source domain are first extracted by a diffusion model. Then, under the guidance of this diffusion model, such structures are well-recovered through a maximum likelihood alignment procedure in the target domain. We first demonstrate the effectiveness of our proposed method on a synthetic dataset. Then, when applied to neural recordings from the non-human primate motor cortex, under both cross-day and inter-subject settings, our method consistently manifests its capability of preserving the spatiotemporal structure of latent dynamics and outperforms existing approaches in alignment goodness-of-fit and neural decoding performance.
2307.14360
Ludwig A. Hoffmann
Ludwig A. Hoffmann, Luca Giomi
Theory of cellular homochirality and trait evolution in flocking systems
10 pages, 7 figures
null
null
null
q-bio.CB cond-mat.soft physics.bio-ph
http://creativecommons.org/licenses/by/4.0/
Chirality is a feature of many biological systems and much research has been focused on understanding the origin and implications of this property. Famously, sugars and amino acids found in nature are homochiral, i.e., chiral symmetry is broken and only one of the two possible chiral states is ever observed. Certain types of cells show chiral behavior, too. Understanding the origin of cellular chirality and its effect on tissues and cellular dynamics is still an open problem and subject to much (recent) research, e.g., in the context of drosophila morphogenesis. Here, we develop a simple model to describe the possible origin of homochirality in cells. Combining the Vicsek model for collective behavior with the model of Jafarpour et al., developed to describe the emergence of molecular homochirality, we investigate how a homochiral state might have evolved in cells from an initially symmetric state without any mechanisms that explicitly break chiral symmetry. We investigate the transition to homochirality and show how the "openness" of the system as well as noise determine if and when a globally homochiral state is reached. We discuss how our model can be applied to the evolution of traits in flocking systems in general, or to study systems consisting of multiple interacting species.
[ { "created": "Mon, 24 Jul 2023 17:33:12 GMT", "version": "v1" } ]
2023-07-28
[ [ "Hoffmann", "Ludwig A.", "" ], [ "Giomi", "Luca", "" ] ]
Chirality is a feature of many biological systems and much research has been focused on understanding the origin and implications of this property. Famously, sugars and amino acids found in nature are homochiral, i.e., chiral symmetry is broken and only one of the two possible chiral states is ever observed. Certain types of cells show chiral behavior, too. Understanding the origin of cellular chirality and its effect on tissues and cellular dynamics is still an open problem and subject to much (recent) research, e.g., in the context of drosophila morphogenesis. Here, we develop a simple model to describe the possible origin of homochirality in cells. Combining the Vicsek model for collective behavior with the model of Jafarpour et al., developed to describe the emergence of molecular homochirality, we investigate how a homochiral state might have evolved in cells from an initially symmetric state without any mechanisms that explicitly break chiral symmetry. We investigate the transition to homochirality and show how the "openness" of the system as well as noise determine if and when a globally homochiral state is reached. We discuss how our model can be applied to the evolution of traits in flocking systems in general, or to study systems consisting of multiple interacting species.
0708.2038
Julius Lucks
Julius B. Lucks, David R. Nelson, Grzegorz Kudla, Joshua B. Plotkin
Genome landscapes and bacteriophage codon usage
9 Color Figures, 5 Tables, 53 References
Lucks JB, Nelson DR, Kudla GR, Plotkin JB (2008) Genome Landscapes and Bacteriophage Codon Usage. PLoS Computational Biology 4(2): e1000001
10.1371/journal.pcbi.1000001
null
q-bio.GN
null
Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonmous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa and L. lactis as their primary host. We introduce the concept of a `genome landscape,' which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such a GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.
[ { "created": "Tue, 14 Aug 2007 22:44:18 GMT", "version": "v1" } ]
2008-03-04
[ [ "Lucks", "Julius B.", "" ], [ "Nelson", "David R.", "" ], [ "Kudla", "Grzegorz", "" ], [ "Plotkin", "Joshua B.", "" ] ]
Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonmous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa and L. lactis as their primary host. We introduce the concept of a `genome landscape,' which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such a GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.
2005.12879
Nicholas Randolph
E. Benjamin Randall, Nicholas Z. Randolph, Alen Alexanderian, Mette S. Olufsen
Global sensitivity analysis informed model reduction and selection applied to a Valsalva maneuver model
null
null
10.1016/j.jtbi.2021.110759
null
q-bio.QM stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this study, we develop a methodology for model reduction and selection informed by global sensitivity analysis (GSA) methods. We apply these techniques to a control model that takes systolic blood pressure and thoracic tissue pressure data as inputs and predicts heart rate in response to the Valsalva maneuver (VM). The study compares four GSA methods based on Sobol' indices (SIs) quantifying the parameter influence on the difference between the model output and the heart rate data. The GSA methods include standard scalar SIs determining the average parameter influence over the time interval studied and three time-varying methods analyzing how parameter influence changes over time. The time-varying methods include a new technique, termed limited-memory SIs, predicting parameter influence using a moving window approach. Using the limited-memory SIs, we perform model reduction and selection to analyze the necessity of modeling both the aortic and carotid baroreceptor regions in response to the VM. We compare the original model to three systematically reduced models including (i) the aortic and carotid regions, (ii) the aortic region only, and (iii) the carotid region only. Model selection is done quantitatively using the Akaike and Bayesian Information Criteria and qualitatively by comparing the neurological predictions. Results show that it is necessary to incorporate both the aortic and carotid regions to model the VM.
[ { "created": "Tue, 26 May 2020 17:18:34 GMT", "version": "v1" }, { "created": "Fri, 26 Feb 2021 21:47:40 GMT", "version": "v2" }, { "created": "Fri, 14 May 2021 15:48:22 GMT", "version": "v3" } ]
2021-05-17
[ [ "Randall", "E. Benjamin", "" ], [ "Randolph", "Nicholas Z.", "" ], [ "Alexanderian", "Alen", "" ], [ "Olufsen", "Mette S.", "" ] ]
In this study, we develop a methodology for model reduction and selection informed by global sensitivity analysis (GSA) methods. We apply these techniques to a control model that takes systolic blood pressure and thoracic tissue pressure data as inputs and predicts heart rate in response to the Valsalva maneuver (VM). The study compares four GSA methods based on Sobol' indices (SIs) quantifying the parameter influence on the difference between the model output and the heart rate data. The GSA methods include standard scalar SIs determining the average parameter influence over the time interval studied and three time-varying methods analyzing how parameter influence changes over time. The time-varying methods include a new technique, termed limited-memory SIs, predicting parameter influence using a moving window approach. Using the limited-memory SIs, we perform model reduction and selection to analyze the necessity of modeling both the aortic and carotid baroreceptor regions in response to the VM. We compare the original model to three systematically reduced models including (i) the aortic and carotid regions, (ii) the aortic region only, and (iii) the carotid region only. Model selection is done quantitatively using the Akaike and Bayesian Information Criteria and qualitatively by comparing the neurological predictions. Results show that it is necessary to incorporate both the aortic and carotid regions to model the VM.
1310.4010
Marcus Kaiser
Marcus Kaiser
The Potential of the Human Connectome as a Biomarker of Brain Disease
Perspective Article for special issue on Magnetic Resonance Imaging of Healthy and Diseased Brain Networks
Frontiers in Human Neuroscience 7:484, 2013
10.3389/fnhum.2013.00484
null
q-bio.NC physics.med-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The human connectome at the level of fiber tracts between brain regions has been shown to differ in patients with brain disorders compared to healthy control groups. Nonetheless, there is a potentially large number of different network organizations for individual patients that could lead to cognitive deficits prohibiting correct diagnosis. Therefore changes that can distinguish groups might not be sufficient to diagnose the disease that an individual patient suffers from and to indicate the best treatment option for that patient. We describe the challenges introduced by the large variability of connectomes within healthy subjects and patients and outline three common strategies to use connectomes as biomarkers of brain diseases. Finally, we propose a fourth option in using models of simulated brain activity (the dynamic connectome) based on structural connectivity rather than the structure (connectome) itself as a biomarker of disease. Dynamic connectomes, in addition to currently used structural, functional, or effective connectivity, could be an important future biomarker for clinical applications.
[ { "created": "Tue, 15 Oct 2013 11:18:16 GMT", "version": "v1" } ]
2013-10-16
[ [ "Kaiser", "Marcus", "" ] ]
The human connectome at the level of fiber tracts between brain regions has been shown to differ in patients with brain disorders compared to healthy control groups. Nonetheless, there is a potentially large number of different network organizations for individual patients that could lead to cognitive deficits prohibiting correct diagnosis. Therefore changes that can distinguish groups might not be sufficient to diagnose the disease that an individual patient suffers from and to indicate the best treatment option for that patient. We describe the challenges introduced by the large variability of connectomes within healthy subjects and patients and outline three common strategies to use connectomes as biomarkers of brain diseases. Finally, we propose a fourth option in using models of simulated brain activity (the dynamic connectome) based on structural connectivity rather than the structure (connectome) itself as a biomarker of disease. Dynamic connectomes, in addition to currently used structural, functional, or effective connectivity, could be an important future biomarker for clinical applications.
1611.00693
Osman Kahraman
Osman Kahraman, William S. Klug, Christoph A. Haselwandter
Signatures of protein structure in the cooperative gating of mechanosensitive ion channels
null
EPL, 107 (2014), 48004
10.1209/0295-5075/107/48004
null
q-bio.BM cond-mat.soft physics.bio-ph q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Membrane proteins deform the surrounding lipid bilayer, which can lead to membrane-mediated interactions between neighboring proteins. Using the mechanosensitive channel of large conductance (MscL) as a model system, we demonstrate how the observed differences in protein structure can affect membrane-mediated interactions and cooperativity among membrane proteins. We find that distinct oligomeric states of MscL lead to distinct gateway states for the clustering of MscL, and predict signatures of MscL structure and spatial organization in the cooperative gating of MscL. Our modeling approach establishes a quantitative relation between the observed shapes and cooperative function of membrane~proteins.
[ { "created": "Wed, 2 Nov 2016 17:37:01 GMT", "version": "v1" } ]
2016-11-03
[ [ "Kahraman", "Osman", "" ], [ "Klug", "William S.", "" ], [ "Haselwandter", "Christoph A.", "" ] ]
Membrane proteins deform the surrounding lipid bilayer, which can lead to membrane-mediated interactions between neighboring proteins. Using the mechanosensitive channel of large conductance (MscL) as a model system, we demonstrate how the observed differences in protein structure can affect membrane-mediated interactions and cooperativity among membrane proteins. We find that distinct oligomeric states of MscL lead to distinct gateway states for the clustering of MscL, and predict signatures of MscL structure and spatial organization in the cooperative gating of MscL. Our modeling approach establishes a quantitative relation between the observed shapes and cooperative function of membrane~proteins.
2108.03465
Imdadullah Khan
Sarwan Ali, Bikram Sahoo, Naimat Ullah, Alexander Zelikovskiy, Murray Patterson, Imdadullah Khan
A k-mer Based Approach for SARS-CoV-2 Variant Identification
Accepted for Publication at "International Symposium on Bioinformatics Research and Applications (ISBRA), 2021
null
null
null
q-bio.QM cs.LG
http://creativecommons.org/publicdomain/zero/1.0/
With the rapid spread of the novel coronavirus (COVID-19) across the globe and its continuous mutation, it is of pivotal importance to design a system to identify different known (and unknown) variants of SARS-CoV-2. Identifying particular variants helps to understand and model their spread patterns, design effective mitigation strategies, and prevent future outbreaks. It also plays a crucial role in studying the efficacy of known vaccines against each variant and modeling the likelihood of breakthrough infections. It is well known that the spike protein contains most of the information/variation pertaining to coronavirus variants. In this paper, we use spike sequences to classify different variants of the coronavirus in humans. We show that preserving the order of the amino acids helps the underlying classifiers to achieve better performance. We also show that we can train our model to outperform the baseline algorithms using only a small number of training samples ($1\%$ of the data). Finally, we show the importance of the different amino acids which play a key role in identifying variants and how they coincide with those reported by the USA's Centers for Disease Control and Prevention (CDC).
[ { "created": "Sat, 7 Aug 2021 15:08:15 GMT", "version": "v1" }, { "created": "Wed, 18 Aug 2021 19:46:41 GMT", "version": "v2" }, { "created": "Wed, 25 Aug 2021 07:42:57 GMT", "version": "v3" }, { "created": "Sat, 25 Sep 2021 19:50:09 GMT", "version": "v4" }, { "cr...
2021-10-13
[ [ "Ali", "Sarwan", "" ], [ "Sahoo", "Bikram", "" ], [ "Ullah", "Naimat", "" ], [ "Zelikovskiy", "Alexander", "" ], [ "Patterson", "Murray", "" ], [ "Khan", "Imdadullah", "" ] ]
With the rapid spread of the novel coronavirus (COVID-19) across the globe and its continuous mutation, it is of pivotal importance to design a system to identify different known (and unknown) variants of SARS-CoV-2. Identifying particular variants helps to understand and model their spread patterns, design effective mitigation strategies, and prevent future outbreaks. It also plays a crucial role in studying the efficacy of known vaccines against each variant and modeling the likelihood of breakthrough infections. It is well known that the spike protein contains most of the information/variation pertaining to coronavirus variants. In this paper, we use spike sequences to classify different variants of the coronavirus in humans. We show that preserving the order of the amino acids helps the underlying classifiers to achieve better performance. We also show that we can train our model to outperform the baseline algorithms using only a small number of training samples ($1\%$ of the data). Finally, we show the importance of the different amino acids which play a key role in identifying variants and how they coincide with those reported by the USA's Centers for Disease Control and Prevention (CDC).
1502.05772
Alistair Perry
Alistair Perry, Wei Wen, Anton Lord, Anbupalam Thalamuthu, Perminder Sachdev, Michael Breakspear
The Organisation of the Elderly Connectome
35 pages, 6 figures
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Investigations of the human connectome have elucidated core features of adult structural networks, particularly the crucial role of hub-regions. However, little is known regarding network organisation of the healthy elderly connectome, a crucial prelude to the systematic study of neurodegenerative disorders. Here, whole-brain probabilistic tractography was performed on high-angular diffusion-weighted images acquired from 115 healthy elderly subjects, whom were 76 to 94 years old. Structural networks were reconstructed between 512 cortical and subcortical brain regions. We sought to investigate the architectural features of hub-regions, as well as left-right asymmetries, and sexual dimorphisms. We observed that the topology of hub-regions is consistent with adult connectomic data, and more importantly, their architectural features reflect their ongoing vital role in network communication. We also found substantial sexual dimorphisms, with females exhibiting stronger inter-hemispheric connections between cingulate and prefrontal cortices. Lastly, we demonstrate intriguing left-lateralized subnetworks consistent with the neural circuitry specialised for language and executive functions, while rightward subnetworks were dominant in visual and visuospatial streams. These findings provide insights into healthy brain ageing and provide a benchmark for the study of neurodegenerative disorders such as Alzheimers disease and Frontotemporal Dementia.
[ { "created": "Fri, 20 Feb 2015 04:57:14 GMT", "version": "v1" }, { "created": "Sun, 13 Dec 2015 06:37:26 GMT", "version": "v2" } ]
2015-12-15
[ [ "Perry", "Alistair", "" ], [ "Wen", "Wei", "" ], [ "Lord", "Anton", "" ], [ "Thalamuthu", "Anbupalam", "" ], [ "Sachdev", "Perminder", "" ], [ "Breakspear", "Michael", "" ] ]
Investigations of the human connectome have elucidated core features of adult structural networks, particularly the crucial role of hub-regions. However, little is known regarding network organisation of the healthy elderly connectome, a crucial prelude to the systematic study of neurodegenerative disorders. Here, whole-brain probabilistic tractography was performed on high-angular diffusion-weighted images acquired from 115 healthy elderly subjects, whom were 76 to 94 years old. Structural networks were reconstructed between 512 cortical and subcortical brain regions. We sought to investigate the architectural features of hub-regions, as well as left-right asymmetries, and sexual dimorphisms. We observed that the topology of hub-regions is consistent with adult connectomic data, and more importantly, their architectural features reflect their ongoing vital role in network communication. We also found substantial sexual dimorphisms, with females exhibiting stronger inter-hemispheric connections between cingulate and prefrontal cortices. Lastly, we demonstrate intriguing left-lateralized subnetworks consistent with the neural circuitry specialised for language and executive functions, while rightward subnetworks were dominant in visual and visuospatial streams. These findings provide insights into healthy brain ageing and provide a benchmark for the study of neurodegenerative disorders such as Alzheimers disease and Frontotemporal Dementia.
2005.03430
Roberto Budzinski
R. C. Budzinski, S. R. Lopes, C. Masoller
Symbolic analysis of bursting dynamical regimes of Rulkov neural networks
null
null
10.1016/j.neucom.2020.05.122
null
q-bio.NC nlin.AO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Neurons modeled by the Rulkov map display a variety of dynamic regimes that include tonic spikes and chaotic bursting. Here we study an ensemble of bursting neurons coupled with the Watts-Strogatz small-world topology. We characterize the sequences of bursts using the symbolic method of time-series analysis known as ordinal analysis, which detects nonlinear temporal correlations. We show that the probabilities of the different symbols distinguish different dynamical regimes, which depend on the coupling strength and the network topology. These regimes have different spatio-temporal properties that can be visualized with raster plots.
[ { "created": "Thu, 7 May 2020 13:01:57 GMT", "version": "v1" } ]
2023-06-13
[ [ "Budzinski", "R. C.", "" ], [ "Lopes", "S. R.", "" ], [ "Masoller", "C.", "" ] ]
Neurons modeled by the Rulkov map display a variety of dynamic regimes that include tonic spikes and chaotic bursting. Here we study an ensemble of bursting neurons coupled with the Watts-Strogatz small-world topology. We characterize the sequences of bursts using the symbolic method of time-series analysis known as ordinal analysis, which detects nonlinear temporal correlations. We show that the probabilities of the different symbols distinguish different dynamical regimes, which depend on the coupling strength and the network topology. These regimes have different spatio-temporal properties that can be visualized with raster plots.
2002.12429
Karunia Putra Wijaya
Ahd Mahmoud Al-Salman, Joseph P\'aez Ch\'avez and Karunia Putra Wijaya
A modeling study of predator--prey interaction propounding honest signals and cues
null
null
null
null
q-bio.PE math.DS
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Honest signals and cues have been observed as part of interspecific and intraspecific communication among animals. Recent theories suggest that existing signaling systems have evolved through natural selection imposed by predators. Honest signaling in the interspecific communication can provide insight into the evolution of anti-predation techniques. In this work, we introduce a deterministic three-stage, two-species predator-prey model, which modulates the impact of honest signals and cues on the interacting populations. The model is built from a set of first principles originated from signaling and social learning theory in which the response of predators to transmitted honest signals or cues is determined. The predators then use the signals to decide whether to pursue the attack or save their energy for an easier catch. Other members from the prey population that are not familiar with signaling their fitness observe and learn the technique. Our numerical bifurcation analysis indicates that increasing the predator's search rate and the corresponding assimilation efficiency gives a journey from predator-prey abundance and scarcity, a stable transient cycle between persistence and near-extinction, a homoclinic orbit pointing towards extinction, and ultimately, a quasi-periodic orbit. A similar discovery is met under the increment of the prey's intrinsic birth rate and carrying capacity. When both parameters are of sufficiently large magnitudes, the separator between honest signal and cue takes the similar journey from a stable equilibrium to a quasi-periodic orbit as it increases. In the context of modeling, we conclude that under prey abundance, transmitting error-free honest signals leads to not only a stable but also more predictable predator-prey dynamics.
[ { "created": "Thu, 27 Feb 2020 20:48:21 GMT", "version": "v1" } ]
2020-03-02
[ [ "Al-Salman", "Ahd Mahmoud", "" ], [ "Chávez", "Joseph Páez", "" ], [ "Wijaya", "Karunia Putra", "" ] ]
Honest signals and cues have been observed as part of interspecific and intraspecific communication among animals. Recent theories suggest that existing signaling systems have evolved through natural selection imposed by predators. Honest signaling in the interspecific communication can provide insight into the evolution of anti-predation techniques. In this work, we introduce a deterministic three-stage, two-species predator-prey model, which modulates the impact of honest signals and cues on the interacting populations. The model is built from a set of first principles originated from signaling and social learning theory in which the response of predators to transmitted honest signals or cues is determined. The predators then use the signals to decide whether to pursue the attack or save their energy for an easier catch. Other members from the prey population that are not familiar with signaling their fitness observe and learn the technique. Our numerical bifurcation analysis indicates that increasing the predator's search rate and the corresponding assimilation efficiency gives a journey from predator-prey abundance and scarcity, a stable transient cycle between persistence and near-extinction, a homoclinic orbit pointing towards extinction, and ultimately, a quasi-periodic orbit. A similar discovery is met under the increment of the prey's intrinsic birth rate and carrying capacity. When both parameters are of sufficiently large magnitudes, the separator between honest signal and cue takes the similar journey from a stable equilibrium to a quasi-periodic orbit as it increases. In the context of modeling, we conclude that under prey abundance, transmitting error-free honest signals leads to not only a stable but also more predictable predator-prey dynamics.
1709.04416
Marcus Aguiar de
Carolina L. N. Costa, Flavia M. D. Marquitti, S. Ivan Perez, David M. Schneider, Marlon F. Ramos, Marcus A.M. de Aguiar
Registering the evolutionary history in individual-based models of speciation
This is a revised version, with a new title and 2 new co-authors. 24 pages, 7 figures
Physica A 510 (2018) 1
10.1016/j.physa.2018.05.150
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Understanding the emergence of biodiversity patterns in nature is a central problem in biology. Theoretical models of speciation have addressed this question in the macroecological scale, but little has been investigated in the macroevolutionary context. Knowledge of the evolutionary history allows the study of patterns underlying the processes considered in these models, revealing their signatures and the role of speciation and extinction in shaping macroevolutionary patterns. In this paper we introduce two algorithms to record the evolutionary history of populations in individual-based models of speciation, from which genealogies and phylogenies can be constructed. The first algorithm relies on saving ancestral-descendant relationships, generating a matrix that contains the times to the most recent common ancestor between all pairs of individuals at every generation (the Most Recent Common Ancestor Time matrix, MRCAT). The second algorithm directly records all speciation and extinction events throughout the evolutionary process, generating a matrix with the true phylogeny of species (the Sequential Speciation and Extinction Events, SSEE). We illustrate the use of these algorithms in a spatially explicit individual-based model of speciation. We compare the trees generated via MRCAT and SSEE algorithms with trees inferred by methods that use only genetic distance among extant species, commonly used in empirical studies and applied here to simulated genetic data. Comparisons between tress are performed with metrics describing the overall topology, branch length distribution and imbalance of trees. We observe that both MRCAT and distance-based trees differ from the true phylogeny, with the first being closer to the true tree than the second.
[ { "created": "Wed, 13 Sep 2017 16:56:05 GMT", "version": "v1" }, { "created": "Tue, 19 Dec 2017 11:33:40 GMT", "version": "v2" } ]
2018-10-09
[ [ "Costa", "Carolina L. N.", "" ], [ "Marquitti", "Flavia M. D.", "" ], [ "Perez", "S. Ivan", "" ], [ "Schneider", "David M.", "" ], [ "Ramos", "Marlon F.", "" ], [ "de Aguiar", "Marcus A. M.", "" ] ]
Understanding the emergence of biodiversity patterns in nature is a central problem in biology. Theoretical models of speciation have addressed this question in the macroecological scale, but little has been investigated in the macroevolutionary context. Knowledge of the evolutionary history allows the study of patterns underlying the processes considered in these models, revealing their signatures and the role of speciation and extinction in shaping macroevolutionary patterns. In this paper we introduce two algorithms to record the evolutionary history of populations in individual-based models of speciation, from which genealogies and phylogenies can be constructed. The first algorithm relies on saving ancestral-descendant relationships, generating a matrix that contains the times to the most recent common ancestor between all pairs of individuals at every generation (the Most Recent Common Ancestor Time matrix, MRCAT). The second algorithm directly records all speciation and extinction events throughout the evolutionary process, generating a matrix with the true phylogeny of species (the Sequential Speciation and Extinction Events, SSEE). We illustrate the use of these algorithms in a spatially explicit individual-based model of speciation. We compare the trees generated via MRCAT and SSEE algorithms with trees inferred by methods that use only genetic distance among extant species, commonly used in empirical studies and applied here to simulated genetic data. Comparisons between tress are performed with metrics describing the overall topology, branch length distribution and imbalance of trees. We observe that both MRCAT and distance-based trees differ from the true phylogeny, with the first being closer to the true tree than the second.
1505.01142
Vicente M. Reyes Ph.D.
Vicente M. Reyes
Two Complementary Methods for Relative Quantification of Ligand Binding Site Burial Depth in Proteins: The "Cutting Plane" and "Tangent Sphere" Methods
11 pages text; 7 figures (all multi-panel); 3 tables; 34 total pages (incl. figures & tables)
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We describe two complementary methods to quantify the degree of burial of ligand and/or ligand binding site (LBS) in a protein-ligand complex, namely, the "cutting plane" (CP) and the "tangent sphere" (TS) methods. To construct the CP and TS, two centroids are required: the protein molecular centroid (global centroid, GC), and the LBS centroid (local centroid, LC). The CP is defined as the plane passing through the LBS centroid (LC) and normal to the line passing through the LC and the protein molecular centroid (GC). The "anterior side" of the CP is the side not containing the GC (which the "posterior" side does). The TS is defined as the sphere with center at GC and tangent to the CP at LC. The percentage of protein atoms (a.) inside the TS, and (b.) on the anterior side of the CP, are two complementary measures of ligand or LBS burial depth since the latter is directly proportional to (b.) and inversely proportional to (a.). We tested the CP and TS methods using a test set of 67 well characterized protein-ligand structures (Laskowski et al., 1996), as well as the theoretical case of an artificial protein in the form of a cubic lattice grid of points in the overall shape of a sphere and in which LBS of any depth can be specified. Results from both the CP and TS methods agree very well with data reported by Laskowski et al., and results from the theoretical case further confirm that that both methods are suitable measures of ligand or LBS burial. Prior to this study, there were no such numerical measures of LBS burial available, and hence no way to directly and objectively compare LBS depths in different proteins. LBS burial depth is an important parameter as it is usually directly related to the amount of conformational change a protein undergoes upon ligand binding, and ability to quantify it could allow meaningful comparison of protein dynamics and flexibility.
[ { "created": "Sat, 7 Feb 2015 04:17:39 GMT", "version": "v1" } ]
2015-05-06
[ [ "Reyes", "Vicente M.", "" ] ]
We describe two complementary methods to quantify the degree of burial of ligand and/or ligand binding site (LBS) in a protein-ligand complex, namely, the "cutting plane" (CP) and the "tangent sphere" (TS) methods. To construct the CP and TS, two centroids are required: the protein molecular centroid (global centroid, GC), and the LBS centroid (local centroid, LC). The CP is defined as the plane passing through the LBS centroid (LC) and normal to the line passing through the LC and the protein molecular centroid (GC). The "anterior side" of the CP is the side not containing the GC (which the "posterior" side does). The TS is defined as the sphere with center at GC and tangent to the CP at LC. The percentage of protein atoms (a.) inside the TS, and (b.) on the anterior side of the CP, are two complementary measures of ligand or LBS burial depth since the latter is directly proportional to (b.) and inversely proportional to (a.). We tested the CP and TS methods using a test set of 67 well characterized protein-ligand structures (Laskowski et al., 1996), as well as the theoretical case of an artificial protein in the form of a cubic lattice grid of points in the overall shape of a sphere and in which LBS of any depth can be specified. Results from both the CP and TS methods agree very well with data reported by Laskowski et al., and results from the theoretical case further confirm that that both methods are suitable measures of ligand or LBS burial. Prior to this study, there were no such numerical measures of LBS burial available, and hence no way to directly and objectively compare LBS depths in different proteins. LBS burial depth is an important parameter as it is usually directly related to the amount of conformational change a protein undergoes upon ligand binding, and ability to quantify it could allow meaningful comparison of protein dynamics and flexibility.
2311.11132
R\'emy Ben Messaoud
Remy Ben Messaoud, Vincent Le Du, Brigitte Charlotte Kaufmann, Baptiste Couvy-Duchesne, Lara Migliaccio, Paolo Bartolomeo, Mario Chavez, Fabrizio De Vico Fallani
Low-dimensional controllability of brain networks
null
null
null
null
q-bio.NC q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Network controllability is a powerful tool to study causal relationships in complex systems and identify the driver nodes for steering the network dynamics into desired states. However, due to ill-posed conditions, results become unreliable when the number of drivers becomes too small compared to the network size. This is a very common situation, particularly in real-world applications, where the possibility to access multiple nodes at the same time is limited by technological constraints, such as in the human brain. Although targeting smaller network parts might improve accuracy, challenges may remain for extremely unbalanced situations, when for example there is one single driver. To address this problem, we developed a mathematical framework that combines concepts from spectral graph theory and modern network science. Instead of controlling the original network dynamics, we aimed to control its low-dimensional embedding into the topological space derived from the network Laplacian. By performing extensive simulations on synthetic networks, we showed that a relatively low number of projected components is enough to improve the overall control accuracy, notably when dealing with very few drivers. Based on these findings, we introduced alternative low-dimensional controllability metrics and used them to identify the main driver areas of the human connectome obtained from N=6134 healthy individuals in the UK-biobank cohort. Results revealed previously unappreciated influential regions compared to standard approaches, enabled to draw control maps between distinct specialized large-scale brain systems, and yielded an anatomically-based understanding of hemispheric functional lateralization. Taken together, our results offered a theoretically-grounded solution to deal with network controllability in real-life applications and provided insights into the causal interactions of the human brain.
[ { "created": "Sat, 18 Nov 2023 17:46:32 GMT", "version": "v1" }, { "created": "Wed, 22 Nov 2023 16:59:59 GMT", "version": "v2" }, { "created": "Tue, 28 Nov 2023 14:48:55 GMT", "version": "v3" } ]
2023-11-29
[ [ "Messaoud", "Remy Ben", "" ], [ "Du", "Vincent Le", "" ], [ "Kaufmann", "Brigitte Charlotte", "" ], [ "Couvy-Duchesne", "Baptiste", "" ], [ "Migliaccio", "Lara", "" ], [ "Bartolomeo", "Paolo", "" ], [ "Chavez", ...
Network controllability is a powerful tool to study causal relationships in complex systems and identify the driver nodes for steering the network dynamics into desired states. However, due to ill-posed conditions, results become unreliable when the number of drivers becomes too small compared to the network size. This is a very common situation, particularly in real-world applications, where the possibility to access multiple nodes at the same time is limited by technological constraints, such as in the human brain. Although targeting smaller network parts might improve accuracy, challenges may remain for extremely unbalanced situations, when for example there is one single driver. To address this problem, we developed a mathematical framework that combines concepts from spectral graph theory and modern network science. Instead of controlling the original network dynamics, we aimed to control its low-dimensional embedding into the topological space derived from the network Laplacian. By performing extensive simulations on synthetic networks, we showed that a relatively low number of projected components is enough to improve the overall control accuracy, notably when dealing with very few drivers. Based on these findings, we introduced alternative low-dimensional controllability metrics and used them to identify the main driver areas of the human connectome obtained from N=6134 healthy individuals in the UK-biobank cohort. Results revealed previously unappreciated influential regions compared to standard approaches, enabled to draw control maps between distinct specialized large-scale brain systems, and yielded an anatomically-based understanding of hemispheric functional lateralization. Taken together, our results offered a theoretically-grounded solution to deal with network controllability in real-life applications and provided insights into the causal interactions of the human brain.
2403.09678
Christophe Pouzat
Christophe Pouzat (IRMA), Morgan Andr\'e
A Quasi-Stationary Approach to Metastability in a System of Spiking Neurons with Synaptic Plasticity
null
null
null
null
q-bio.NC math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
After reviewing the behavioral studies of working memory and of the cellular substrate of the latter, we argue that metastable states constitute candidates for the type of transient information storage required by working memory. We then present a simple neural network model made of stochastic units whose synapses exhibit short-term facilitation. The Markov process dynamics of this model was specifically designed to be analytically tractable, simple to simulate numerically and to exhibit a quasi-stationary distribution (QSD). Since the state space is finite this QSD is also a Yaglom limit, which allows us to bridge the gap between quasi-stationarity and metastability by considering the relative orders of magnitude of the relaxation and absorption times. We present first analytical results: characterization of the absorbing region of the Markov process, irreducibility outside this absorbing region and consequently existence and uniqueness of a QSD. We then apply Perron-Frobenius spectral analysis to obtain any specific QSD, and design an approximate method for the first moments of this QSD when the exact method is intractable. Finally we use these methods to study the relaxation time toward the QSD and establish numerically the memorylessness of the time of extinction.
[ { "created": "Wed, 7 Feb 2024 08:07:50 GMT", "version": "v1" } ]
2024-03-18
[ [ "Pouzat", "Christophe", "", "IRMA" ], [ "André", "Morgan", "" ] ]
After reviewing the behavioral studies of working memory and of the cellular substrate of the latter, we argue that metastable states constitute candidates for the type of transient information storage required by working memory. We then present a simple neural network model made of stochastic units whose synapses exhibit short-term facilitation. The Markov process dynamics of this model was specifically designed to be analytically tractable, simple to simulate numerically and to exhibit a quasi-stationary distribution (QSD). Since the state space is finite this QSD is also a Yaglom limit, which allows us to bridge the gap between quasi-stationarity and metastability by considering the relative orders of magnitude of the relaxation and absorption times. We present first analytical results: characterization of the absorbing region of the Markov process, irreducibility outside this absorbing region and consequently existence and uniqueness of a QSD. We then apply Perron-Frobenius spectral analysis to obtain any specific QSD, and design an approximate method for the first moments of this QSD when the exact method is intractable. Finally we use these methods to study the relaxation time toward the QSD and establish numerically the memorylessness of the time of extinction.
2306.10953
Asuna Gilfoyle
Asuna Gilfoyle, Willow Baird
The Impact of Rising Ocean Acidification Levels on Fish Migration
null
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
Ocean acidification, a direct consequence of increased carbon dioxide (CO2) emissions, has emerged as a critical area of concern within the scientific community. The world's oceans absorb approximately one-third of human-caused CO2 emissions, leading to chemical reactions that reduce seawater pH, carbonate ion concentration, and saturation states of biologically important calcium carbonate minerals. This process, known as ocean acidification, has far-reaching implications for marine ecosystems, particularly for marine organisms such as fish, whose migratory patterns are integral to the health and function of these ecosystems.
[ { "created": "Mon, 19 Jun 2023 14:11:30 GMT", "version": "v1" } ]
2023-06-21
[ [ "Gilfoyle", "Asuna", "" ], [ "Baird", "Willow", "" ] ]
Ocean acidification, a direct consequence of increased carbon dioxide (CO2) emissions, has emerged as a critical area of concern within the scientific community. The world's oceans absorb approximately one-third of human-caused CO2 emissions, leading to chemical reactions that reduce seawater pH, carbonate ion concentration, and saturation states of biologically important calcium carbonate minerals. This process, known as ocean acidification, has far-reaching implications for marine ecosystems, particularly for marine organisms such as fish, whose migratory patterns are integral to the health and function of these ecosystems.
1612.06336
Andrew Murphy
Andrew C. Murphy, Sarah F. Muldoon, David Baker, Adam Lastowka, Brittany Bennett, Muzhi Yang, and Danielle S. Bassett
Structure, Function, and Control of the Musculoskeletal Network
null
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The human body is a complex organism whose gross mechanical properties are enabled by an interconnected musculoskeletal network controlled by the nervous system. The nature of musculoskeletal interconnection facilitates stability, voluntary movement, and robustness to injury. However, a fundamental understanding of this network and its control by neural systems has remained elusive. Here we utilize medical databases and mathematical modeling to reveal the organizational structure, predicted function, and neural control of the musculoskeletal system. We construct a whole-body musculoskeletal network in which single muscles connect to multiple bones via both origin and insertion points. We demonstrate that a muscle's role in this network predicts susceptibility of surrounding components to secondary injury. Finally, we illustrate that sets of muscles cluster into network communities that mimic the organization of motor cortex control modules. This novel formalism for describing interactions between the muscular and skeletal systems serves as a foundation to develop and test therapeutic responses to injury, inspiring future advances in clinical treatments.
[ { "created": "Tue, 13 Dec 2016 21:43:11 GMT", "version": "v1" } ]
2016-12-20
[ [ "Murphy", "Andrew C.", "" ], [ "Muldoon", "Sarah F.", "" ], [ "Baker", "David", "" ], [ "Lastowka", "Adam", "" ], [ "Bennett", "Brittany", "" ], [ "Yang", "Muzhi", "" ], [ "Bassett", "Danielle S.", "" ] ]
The human body is a complex organism whose gross mechanical properties are enabled by an interconnected musculoskeletal network controlled by the nervous system. The nature of musculoskeletal interconnection facilitates stability, voluntary movement, and robustness to injury. However, a fundamental understanding of this network and its control by neural systems has remained elusive. Here we utilize medical databases and mathematical modeling to reveal the organizational structure, predicted function, and neural control of the musculoskeletal system. We construct a whole-body musculoskeletal network in which single muscles connect to multiple bones via both origin and insertion points. We demonstrate that a muscle's role in this network predicts susceptibility of surrounding components to secondary injury. Finally, we illustrate that sets of muscles cluster into network communities that mimic the organization of motor cortex control modules. This novel formalism for describing interactions between the muscular and skeletal systems serves as a foundation to develop and test therapeutic responses to injury, inspiring future advances in clinical treatments.
2203.11687
Martin Marzidovsek
Martin Marzidov\v{s}ek, Vid Podpe\v{c}an, Erminia Conti, Marko Debeljak, Christian Mulder
BEFANA: A Tool for Biodiversity-Ecosystem Functioning Assessment by Network Analysis
null
null
null
null
q-bio.QM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
BEFANA is a free and open-source software tool for ecological network analysis and visualisation. It is adapted to ecologists' needs and allows them to study the topology and dynamics of ecological networks as well as apply selected machine learning algorithms. BEFANA is implemented in Python, and structured as an ordered collection of interactive computational notebooks. It relies on widely used open-source libraries, and aims to achieve simplicity, interactivity, and extensibility. BEFANA provides methods and implementations for data loading and preprocessing, network analysis and interactive visualisation, modelling with experimental data, and predictive modelling with machine learning. We showcase BEFANA through a concrete example of a detrital soil food web of agricultural grasslands, and demonstrate all of its main components and functionalities.
[ { "created": "Mon, 21 Mar 2022 16:51:09 GMT", "version": "v1" }, { "created": "Mon, 28 Mar 2022 14:36:59 GMT", "version": "v2" } ]
2022-03-29
[ [ "Marzidovšek", "Martin", "" ], [ "Podpečan", "Vid", "" ], [ "Conti", "Erminia", "" ], [ "Debeljak", "Marko", "" ], [ "Mulder", "Christian", "" ] ]
BEFANA is a free and open-source software tool for ecological network analysis and visualisation. It is adapted to ecologists' needs and allows them to study the topology and dynamics of ecological networks as well as apply selected machine learning algorithms. BEFANA is implemented in Python, and structured as an ordered collection of interactive computational notebooks. It relies on widely used open-source libraries, and aims to achieve simplicity, interactivity, and extensibility. BEFANA provides methods and implementations for data loading and preprocessing, network analysis and interactive visualisation, modelling with experimental data, and predictive modelling with machine learning. We showcase BEFANA through a concrete example of a detrital soil food web of agricultural grasslands, and demonstrate all of its main components and functionalities.
0704.1912
Adrian Melott
L.C. Natarajan, A.L. Melott, B.M. Rothschild, and L.D. Martin (University of Kansas)
Bone Cancer Rates in Dinosaurs Compared with Modern Vertebrates
As published in Transactions of the Kansas Academy of Science
TKAS 110, 155-158 (2007)
null
null
q-bio.PE astro-ph physics.geo-ph
null
Data on the prevalence of bone cancer in dinosaurs is available from past radiological examination of preserved bones. We statistically test this data for consistency with rates extrapolated from information on bone cancer in modern vertebrates, and find that there is no evidence of a different rate. Thus, this test provides no support for a possible role of ionizing radiation in the K-T extinction event.
[ { "created": "Sun, 15 Apr 2007 19:08:16 GMT", "version": "v1" }, { "created": "Mon, 10 Sep 2007 16:28:09 GMT", "version": "v2" }, { "created": "Tue, 11 Sep 2007 14:19:34 GMT", "version": "v3" }, { "created": "Tue, 16 Oct 2007 18:17:26 GMT", "version": "v4" } ]
2007-10-16
[ [ "Natarajan", "L. C.", "", "University of Kansas" ], [ "Melott", "A. L.", "", "University of Kansas" ], [ "Rothschild", "B. M.", "", "University of Kansas" ], [ "Martin", "L. D.", "", "University of Kansas" ] ]
Data on the prevalence of bone cancer in dinosaurs is available from past radiological examination of preserved bones. We statistically test this data for consistency with rates extrapolated from information on bone cancer in modern vertebrates, and find that there is no evidence of a different rate. Thus, this test provides no support for a possible role of ionizing radiation in the K-T extinction event.
2407.02126
Paul Bilokon
Oleksandr Bilokon and Nataliya Bilokon and Paul Bilokon
AI-driven Alternative Medicine: A Novel Approach to Drug Discovery and Repurposing
null
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by/4.0/
AIAltMed is a cutting-edge platform designed for drug discovery and repurposing. It utilizes Tanimoto similarity to identify structurally similar non-medicinal compounds to known medicinal ones. This preprint introduces AIAltMed, discusses the concept of `AI-driven alternative medicine,' evaluates Tanimoto similarity's advantages and limitations, and details the system's architecture. Furthermore, it explores the benefits of extending the system to include PubChem and outlines a corresponding implementation strategy.
[ { "created": "Tue, 2 Jul 2024 10:17:13 GMT", "version": "v1" } ]
2024-07-03
[ [ "Bilokon", "Oleksandr", "" ], [ "Bilokon", "Nataliya", "" ], [ "Bilokon", "Paul", "" ] ]
AIAltMed is a cutting-edge platform designed for drug discovery and repurposing. It utilizes Tanimoto similarity to identify structurally similar non-medicinal compounds to known medicinal ones. This preprint introduces AIAltMed, discusses the concept of `AI-driven alternative medicine,' evaluates Tanimoto similarity's advantages and limitations, and details the system's architecture. Furthermore, it explores the benefits of extending the system to include PubChem and outlines a corresponding implementation strategy.
2202.10873
Jinjiang Guo Ph.D.
Jinjiang Guo, Qi Liu, Han Guo, Xi Lu
Ligandformer: A Graph Neural Network for Predicting Compound Property with Robust Interpretation
7 pages, 4 figures
null
null
null
q-bio.BM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Robust and efficient interpretation of QSAR methods is quite useful to validate AI prediction rationales with subjective opinion (chemist or biologist expertise), understand sophisticated chemical or biological process mechanisms, and provide heuristic ideas for structure optimization in pharmaceutical industry. For this purpose, we construct a multi-layer self-attention based Graph Neural Network framework, namely Ligandformer, for predicting compound property with interpretation. Ligandformer integrates attention maps on compound structure from different network blocks. The integrated attention map reflects the machine's local interest on compound structure, and indicates the relationship between predicted compound property and its structure. This work mainly contributes to three aspects: 1. Ligandformer directly opens the black-box of deep learning methods, providing local prediction rationales on chemical structures. 2. Ligandformer gives robust prediction in different experimental rounds, overcoming the ubiquitous prediction instability of deep learning methods. 3. Ligandformer can be generalized to predict different chemical or biological properties with high performance. Furthermore, Ligandformer can simultaneously output specific property score and visible attention map on structure, which can support researchers to investigate chemical or biological property and optimize structure efficiently. Our framework outperforms over counterparts in terms of accuracy, robustness and generalization, and can be applied in complex system study.
[ { "created": "Mon, 21 Feb 2022 15:46:44 GMT", "version": "v1" }, { "created": "Wed, 23 Feb 2022 02:38:11 GMT", "version": "v2" }, { "created": "Thu, 24 Feb 2022 02:54:52 GMT", "version": "v3" } ]
2022-02-25
[ [ "Guo", "Jinjiang", "" ], [ "Liu", "Qi", "" ], [ "Guo", "Han", "" ], [ "Lu", "Xi", "" ] ]
Robust and efficient interpretation of QSAR methods is quite useful to validate AI prediction rationales with subjective opinion (chemist or biologist expertise), understand sophisticated chemical or biological process mechanisms, and provide heuristic ideas for structure optimization in pharmaceutical industry. For this purpose, we construct a multi-layer self-attention based Graph Neural Network framework, namely Ligandformer, for predicting compound property with interpretation. Ligandformer integrates attention maps on compound structure from different network blocks. The integrated attention map reflects the machine's local interest on compound structure, and indicates the relationship between predicted compound property and its structure. This work mainly contributes to three aspects: 1. Ligandformer directly opens the black-box of deep learning methods, providing local prediction rationales on chemical structures. 2. Ligandformer gives robust prediction in different experimental rounds, overcoming the ubiquitous prediction instability of deep learning methods. 3. Ligandformer can be generalized to predict different chemical or biological properties with high performance. Furthermore, Ligandformer can simultaneously output specific property score and visible attention map on structure, which can support researchers to investigate chemical or biological property and optimize structure efficiently. Our framework outperforms over counterparts in terms of accuracy, robustness and generalization, and can be applied in complex system study.
2301.09576
Prashant S Alegaonkar
Charles Johnstone and Prashant S. Alegaonkar
Understanding Physical Processes in Describing a State of Consciousness: A Review
45, 02
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The way we view the reality of nature, including ourselves, depend on consciousness.It also defines the identity of the person, since we know people in terms of their experiences. In general, consciousness defines human existence in this universe. Furthermore, consciousness is associated with the most debated problems in physics such as the notion of observation, observer,in the measurement problem. However,its nature, occurrence mechanism in the brain and the definite universal locality of the consciousness are not clearly known. Due to this consciousness is considered asan essential unresolved scientific problem of the current era.Here, we review the physical processes which are associated in tackling these challenges. Firstly, we discuss the association of consciousness with transmission of signals in the brain, chain of events, quantum phenomena process and integrated information. We also highlight the roles of structure of matter,field, and the concept of universality towards understanding consciousness. Finally, we propose further studies for achieving better understanding of consciousness.
[ { "created": "Thu, 12 Jan 2023 09:33:06 GMT", "version": "v1" } ]
2023-01-24
[ [ "Johnstone", "Charles", "" ], [ "Alegaonkar", "Prashant S.", "" ] ]
The way we view the reality of nature, including ourselves, depend on consciousness.It also defines the identity of the person, since we know people in terms of their experiences. In general, consciousness defines human existence in this universe. Furthermore, consciousness is associated with the most debated problems in physics such as the notion of observation, observer,in the measurement problem. However,its nature, occurrence mechanism in the brain and the definite universal locality of the consciousness are not clearly known. Due to this consciousness is considered asan essential unresolved scientific problem of the current era.Here, we review the physical processes which are associated in tackling these challenges. Firstly, we discuss the association of consciousness with transmission of signals in the brain, chain of events, quantum phenomena process and integrated information. We also highlight the roles of structure of matter,field, and the concept of universality towards understanding consciousness. Finally, we propose further studies for achieving better understanding of consciousness.
2105.14409
Niharika S. D'Souza
Niharika Shimona D'Souza, Mary Beth Nebel, Deana Crocetti, Nicholas Wymbs, Joshua Robinson, Stewart Mostofsky, Archana Venkataraman
A Matrix Autoencoder Framework to Align the Functional and Structural Connectivity Manifolds as Guided by Behavioral Phenotypes
null
null
null
null
q-bio.NC cs.LG eess.SP
http://creativecommons.org/licenses/by/4.0/
We propose a novel matrix autoencoder to map functional connectomes from resting state fMRI (rs-fMRI) to structural connectomes from Diffusion Tensor Imaging (DTI), as guided by subject-level phenotypic measures. Our specialized autoencoder infers a low dimensional manifold embedding for the rs-fMRI correlation matrices that mimics a canonical outer-product decomposition. The embedding is simultaneously used to reconstruct DTI tractography matrices via a second manifold alignment decoder and to predict inter-subject phenotypic variability via an artificial neural network. We validate our framework on a dataset of 275 healthy individuals from the Human Connectome Project database and on a second clinical dataset consisting of 57 subjects with Autism Spectrum Disorder. We demonstrate that the model reliably recovers structural connectivity patterns across individuals, while robustly extracting predictive and interpretable brain biomarkers in a cross-validated setting. Finally, our framework outperforms several baselines at predicting behavioral phenotypes in both real-world datasets.
[ { "created": "Sun, 30 May 2021 02:06:12 GMT", "version": "v1" }, { "created": "Fri, 9 Jul 2021 21:59:34 GMT", "version": "v2" } ]
2021-07-13
[ [ "D'Souza", "Niharika Shimona", "" ], [ "Nebel", "Mary Beth", "" ], [ "Crocetti", "Deana", "" ], [ "Wymbs", "Nicholas", "" ], [ "Robinson", "Joshua", "" ], [ "Mostofsky", "Stewart", "" ], [ "Venkataraman", "Arch...
We propose a novel matrix autoencoder to map functional connectomes from resting state fMRI (rs-fMRI) to structural connectomes from Diffusion Tensor Imaging (DTI), as guided by subject-level phenotypic measures. Our specialized autoencoder infers a low dimensional manifold embedding for the rs-fMRI correlation matrices that mimics a canonical outer-product decomposition. The embedding is simultaneously used to reconstruct DTI tractography matrices via a second manifold alignment decoder and to predict inter-subject phenotypic variability via an artificial neural network. We validate our framework on a dataset of 275 healthy individuals from the Human Connectome Project database and on a second clinical dataset consisting of 57 subjects with Autism Spectrum Disorder. We demonstrate that the model reliably recovers structural connectivity patterns across individuals, while robustly extracting predictive and interpretable brain biomarkers in a cross-validated setting. Finally, our framework outperforms several baselines at predicting behavioral phenotypes in both real-world datasets.
1712.09206
Priyadarshini Panda
Priyadarshini Panda, and Kaushik Roy
Chaos-guided Input Structuring for Improved Learning in Recurrent Neural Networks
11 pages with 5 figures including supplementary material
null
null
null
q-bio.NC cs.NE physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Anatomical studies demonstrate that brain reformats input information to generate reliable responses for performing computations. However, it remains unclear how neural circuits encode complex spatio-temporal patterns. We show that neural dynamics are strongly influenced by the phase alignment between the input and the spontaneous chaotic activity. Input structuring along the dominant chaotic projections causes the chaotic trajectories to become stable channels (or attractors), hence, improving the computational capability of a recurrent network. Using mean field analysis, we derive the impact of input structuring on the overall stability of attractors formed. Our results indicate that input alignment determines the extent of intrinsic noise suppression and hence, alters the attractor state stability, thereby controlling the network's inference ability.
[ { "created": "Tue, 26 Dec 2017 08:29:32 GMT", "version": "v1" }, { "created": "Wed, 17 Jan 2018 15:53:23 GMT", "version": "v2" }, { "created": "Sun, 18 Feb 2018 18:58:48 GMT", "version": "v3" } ]
2018-02-20
[ [ "Panda", "Priyadarshini", "" ], [ "Roy", "Kaushik", "" ] ]
Anatomical studies demonstrate that brain reformats input information to generate reliable responses for performing computations. However, it remains unclear how neural circuits encode complex spatio-temporal patterns. We show that neural dynamics are strongly influenced by the phase alignment between the input and the spontaneous chaotic activity. Input structuring along the dominant chaotic projections causes the chaotic trajectories to become stable channels (or attractors), hence, improving the computational capability of a recurrent network. Using mean field analysis, we derive the impact of input structuring on the overall stability of attractors formed. Our results indicate that input alignment determines the extent of intrinsic noise suppression and hence, alters the attractor state stability, thereby controlling the network's inference ability.
2109.10675
Gustavo Mockaitis
Mahmood Mahmoodi-Eshkaftakia and Gustavo Mockaitis
Structural optimization of biohydrogen production: Impact of pretreatments on volatile fatty acids and biogas parameters
null
Int J Hydrogen Energ. 47(11): 7072-81, 2022
10.1016/j.ijhydene.2021.12.088
null
q-bio.QM
http://creativecommons.org/licenses/by-nc-sa/4.0/
The present study aims to describe an innovative approach that enables the system to achieve high yielding for biohydrogen (bio-H$_2$) production using xylose as a by-product of lignocellulosic biomass processing. A hybrid optimization technique, structural modelling, desirability analysis, and genetic algorithm could determine the optimum input factors to maximize useful biogas parameters, especially bio-H$_2$ and CH$_4$. As found, the input factors (pretreatment, digestion time and biogas relative pressure) and volatile fatty acids (acetic acid, propionic acid and butyric acid) had indirectly and significantly impacted the bio-H$_2$ and desirability score. The pretreatment factor had the most effect on bio-H$_2$ and CH$_4$ production among the factors, and after that, were propionic acid and digestion time. The optimization method showed that the best pretreatment was acidic pretreatment, digestion time > 20 h, relative pressure in a range of 300-800 mbar, acetic acid in a range of 90-200 mg/L, propionic acid in a range of 20-150 mg/L, and butyric acid in a range of 250-420 mg/L. These values caused to produce H$_2$ > 10.2 mmol/L, CH$_4$ > 3.9 mmol/L, N$_2$ < 15.3 mmol/L, CO$_2$ < 19.5 mmol/L, total biogas > 0.31 L, produced biogas > 0.10 L, and accumulated biogas > 0.41 L.
[ { "created": "Wed, 22 Sep 2021 12:04:58 GMT", "version": "v1" }, { "created": "Tue, 8 Feb 2022 17:59:19 GMT", "version": "v2" } ]
2022-02-09
[ [ "Mahmoodi-Eshkaftakia", "Mahmood", "" ], [ "Mockaitis", "Gustavo", "" ] ]
The present study aims to describe an innovative approach that enables the system to achieve high yielding for biohydrogen (bio-H$_2$) production using xylose as a by-product of lignocellulosic biomass processing. A hybrid optimization technique, structural modelling, desirability analysis, and genetic algorithm could determine the optimum input factors to maximize useful biogas parameters, especially bio-H$_2$ and CH$_4$. As found, the input factors (pretreatment, digestion time and biogas relative pressure) and volatile fatty acids (acetic acid, propionic acid and butyric acid) had indirectly and significantly impacted the bio-H$_2$ and desirability score. The pretreatment factor had the most effect on bio-H$_2$ and CH$_4$ production among the factors, and after that, were propionic acid and digestion time. The optimization method showed that the best pretreatment was acidic pretreatment, digestion time > 20 h, relative pressure in a range of 300-800 mbar, acetic acid in a range of 90-200 mg/L, propionic acid in a range of 20-150 mg/L, and butyric acid in a range of 250-420 mg/L. These values caused to produce H$_2$ > 10.2 mmol/L, CH$_4$ > 3.9 mmol/L, N$_2$ < 15.3 mmol/L, CO$_2$ < 19.5 mmol/L, total biogas > 0.31 L, produced biogas > 0.10 L, and accumulated biogas > 0.41 L.
1207.7228
Matthias Schultze-Kraft
Matthias Schultze-Kraft, Markus Diesmann, Sonja Gr\"un, Moritz Helias
Noise Suppression and Surplus Synchrony by Coincidence Detection
null
Schultze-Kraft M, Diesmann M, Gr\"un S, Helias M (2013) Noise Suppression and Surplus Synchrony by Coincidence Detection. PLoS Comput Biol 9(4): e1002904
10.1371/journal.pcbi.1002904
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The functional significance of correlations between action potentials of neurons is still a matter of vivid debates. In particular it is presently unclear how much synchrony is caused by afferent synchronized events and how much is intrinsic due to the connectivity structure of cortex. The available analytical approaches based on the diffusion approximation do not allow to model spike synchrony, preventing a thorough analysis. Here we theoretically investigate to what extent common synaptic afferents and synchronized inputs each contribute to closely time-locked spiking activity of pairs of neurons. We employ direct simulation and extend earlier analytical methods based on the diffusion approximation to pulse-coupling, allowing us to introduce precisely timed correlations in the spiking activity of the synaptic afferents. We investigate the transmission of correlated synaptic input currents by pairs of integrate-and-fire model neurons, so that the same input covariance can be realized by common inputs or by spiking synchrony. We identify two distinct regimes: In the limit of low correlation linear perturbation theory accurately determines the correlation transmission coefficient, which is typically smaller than unity, but increases sensitively even for weakly synchronous inputs. In the limit of high afferent correlation, in the presence of synchrony a qualitatively new picture arises. As the non-linear neuronal response becomes dominant, the output correlation becomes higher than the total correlation in the input. This transmission coefficient larger unity is a direct consequence of non-linear neural processing in the presence of noise, elucidating how synchrony-coded signals benefit from these generic properties present in cortical networks.
[ { "created": "Tue, 31 Jul 2012 12:51:28 GMT", "version": "v1" }, { "created": "Tue, 7 Aug 2012 12:29:49 GMT", "version": "v2" } ]
2013-04-09
[ [ "Schultze-Kraft", "Matthias", "" ], [ "Diesmann", "Markus", "" ], [ "Grün", "Sonja", "" ], [ "Helias", "Moritz", "" ] ]
The functional significance of correlations between action potentials of neurons is still a matter of vivid debates. In particular it is presently unclear how much synchrony is caused by afferent synchronized events and how much is intrinsic due to the connectivity structure of cortex. The available analytical approaches based on the diffusion approximation do not allow to model spike synchrony, preventing a thorough analysis. Here we theoretically investigate to what extent common synaptic afferents and synchronized inputs each contribute to closely time-locked spiking activity of pairs of neurons. We employ direct simulation and extend earlier analytical methods based on the diffusion approximation to pulse-coupling, allowing us to introduce precisely timed correlations in the spiking activity of the synaptic afferents. We investigate the transmission of correlated synaptic input currents by pairs of integrate-and-fire model neurons, so that the same input covariance can be realized by common inputs or by spiking synchrony. We identify two distinct regimes: In the limit of low correlation linear perturbation theory accurately determines the correlation transmission coefficient, which is typically smaller than unity, but increases sensitively even for weakly synchronous inputs. In the limit of high afferent correlation, in the presence of synchrony a qualitatively new picture arises. As the non-linear neuronal response becomes dominant, the output correlation becomes higher than the total correlation in the input. This transmission coefficient larger unity is a direct consequence of non-linear neural processing in the presence of noise, elucidating how synchrony-coded signals benefit from these generic properties present in cortical networks.
2211.02315
Yiheng Liu
Yiheng Liu, Enjie Ge, Ning Qiang, Tianming Liu, Bao Ge
Spatial-Temporal Convolutional Attention for Mapping Functional Brain Networks
5 pages, 5 figures, submitted to 20th IEEE International Symposium on Biomedical Imaging (ISBI 2023)
null
null
null
q-bio.NC cs.CV stat.ML
http://creativecommons.org/licenses/by/4.0/
Using functional magnetic resonance imaging (fMRI) and deep learning to explore functional brain networks (FBNs) has attracted many researchers. However, most of these studies are still based on the temporal correlation between the sources and voxel signals, and lack of researches on the dynamics of brain function. Due to the widespread local correlations in the volumes, FBNs can be generated directly in the spatial domain in a self-supervised manner by using spatial-wise attention (SA), and the resulting FBNs has a higher spatial similarity with templates compared to the classical method. Therefore, we proposed a novel Spatial-Temporal Convolutional Attention (STCA) model to discover the dynamic FBNs by using the sliding windows. To validate the performance of the proposed method, we evaluate the approach on HCP-rest dataset. The results indicate that STCA can be used to discover FBNs in a dynamic way which provide a novel approach to better understand human brain.
[ { "created": "Fri, 4 Nov 2022 08:36:09 GMT", "version": "v1" } ]
2022-11-07
[ [ "Liu", "Yiheng", "" ], [ "Ge", "Enjie", "" ], [ "Qiang", "Ning", "" ], [ "Liu", "Tianming", "" ], [ "Ge", "Bao", "" ] ]
Using functional magnetic resonance imaging (fMRI) and deep learning to explore functional brain networks (FBNs) has attracted many researchers. However, most of these studies are still based on the temporal correlation between the sources and voxel signals, and lack of researches on the dynamics of brain function. Due to the widespread local correlations in the volumes, FBNs can be generated directly in the spatial domain in a self-supervised manner by using spatial-wise attention (SA), and the resulting FBNs has a higher spatial similarity with templates compared to the classical method. Therefore, we proposed a novel Spatial-Temporal Convolutional Attention (STCA) model to discover the dynamic FBNs by using the sliding windows. To validate the performance of the proposed method, we evaluate the approach on HCP-rest dataset. The results indicate that STCA can be used to discover FBNs in a dynamic way which provide a novel approach to better understand human brain.
2104.02853
Gabriela Savioli
Juan Santos (1, 2 and 3), Jos\'e Carcione (4 and 1), Gabriela Savioli (2) and Patricia Gauzellino (5) ((1) School of Earth Sciences and Engineering, Hohai University, Nanjing, China, (2) Universidad de Buenos Aires, Facultad de Ingenier\'ia, Instituto del Gas y del Petr\'oleo, Buenos Aires, Argentina, (3) Departmet of Mathematics, Purdue University, United States, (4) National Institute of Oceanography and Applied Geophysics, OGS, Trieste, Italy, (5) Facultad de Ciencias Astron\'omicas y Geof\'isicas, Universidad Nacional de La Plata, Argentina)
An SEIR epidemic model of fractional order to analyze the evolution of the COVID-19 epidemic in Argentina
20 pages, 14 figures. To be published as a Chapter in the book "Analysis of Infectious Disease Problems (Covid-19) and Their Global Impact", edited by Praveen Agarwal, Juan J. Nieto, Michael Ruzhansky, Delfim F. M. Torres, Springer Nature
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by-nc-nd/4.0/
A pandemic caused by a new coronavirus (COVID-19) has spread worldwide, inducing an epidemic still active in Argentina. In this chapter, we present a case study using an SEIR (Susceptible-Exposed-Infected-Recovered) diffusion model of fractional order in time to analyze the evolution of the epidemic in Buenos Aires and neighboring areas (Regi\'on Metropolitana de Buenos Aires, (RMBA)) comprising about 15 million inhabitants. In the SEIR model, individuals are divided into four classes, namely, susceptible (S), exposed (E), infected (I) and recovered (R). The SEIR model of fractional order allows for the incorporation of memory, with hereditary properties of the system, being a generalization of the classic SEIR first-order system, where such effects are ignored. Furthermore, the fractional model provides one additional parameter to obtain a better fit of the data. The parameters of the model are calibrated by using as data the number of casualties officially reported. Since infinite solutions honour the data, we show a set of cases with different values of the lockdown parameters, fatality rate, and incubation and infectious periods. The different reproduction ratios R0 and infection fatality rates (IFR) so obtained indicate the results may differ from recent reported values, constituting possible alternative solutions. A comparison with results obtained with the classic SEIR model is also included. The analysis allows us to study how isolation and social distancing measures affect the time evolution of the epidemic.
[ { "created": "Wed, 7 Apr 2021 01:42:15 GMT", "version": "v1" } ]
2021-04-08
[ [ "Santos", "Juan", "", "1, 2 and 3" ], [ "Carcione", "José", "", "4 and 1" ], [ "Savioli", "Gabriela", "" ], [ "Gauzellino", "Patricia", "" ] ]
A pandemic caused by a new coronavirus (COVID-19) has spread worldwide, inducing an epidemic still active in Argentina. In this chapter, we present a case study using an SEIR (Susceptible-Exposed-Infected-Recovered) diffusion model of fractional order in time to analyze the evolution of the epidemic in Buenos Aires and neighboring areas (Regi\'on Metropolitana de Buenos Aires, (RMBA)) comprising about 15 million inhabitants. In the SEIR model, individuals are divided into four classes, namely, susceptible (S), exposed (E), infected (I) and recovered (R). The SEIR model of fractional order allows for the incorporation of memory, with hereditary properties of the system, being a generalization of the classic SEIR first-order system, where such effects are ignored. Furthermore, the fractional model provides one additional parameter to obtain a better fit of the data. The parameters of the model are calibrated by using as data the number of casualties officially reported. Since infinite solutions honour the data, we show a set of cases with different values of the lockdown parameters, fatality rate, and incubation and infectious periods. The different reproduction ratios R0 and infection fatality rates (IFR) so obtained indicate the results may differ from recent reported values, constituting possible alternative solutions. A comparison with results obtained with the classic SEIR model is also included. The analysis allows us to study how isolation and social distancing measures affect the time evolution of the epidemic.
0901.0086
Szymon Niewieczerza{\l}
Marek Cieplak and Szymon Niewieczerza{\l}
Hydrodynamic Interactions in Protein Folding
null
null
10.1063/1.3050103
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We incorporate hydrodynamic interactions (HI) in a coarse-grained and structure-based model of proteins by employing the Rotne-Prager hydrodynamic tensor. We study several small proteins and demonstrate that HI facilitate folding. We also study HIV-1 protease and show that HI make the flap closing dynamics faster. The HI are found to affect time correlation functions in the vicinity of the native state even though they have no impact on same time characteristics of the structure fluctuations around the native state.
[ { "created": "Wed, 31 Dec 2008 10:54:26 GMT", "version": "v1" } ]
2009-11-13
[ [ "Cieplak", "Marek", "" ], [ "Niewieczerzał", "Szymon", "" ] ]
We incorporate hydrodynamic interactions (HI) in a coarse-grained and structure-based model of proteins by employing the Rotne-Prager hydrodynamic tensor. We study several small proteins and demonstrate that HI facilitate folding. We also study HIV-1 protease and show that HI make the flap closing dynamics faster. The HI are found to affect time correlation functions in the vicinity of the native state even though they have no impact on same time characteristics of the structure fluctuations around the native state.
q-bio/0602013
Emidio Capriotti
Emidio Capriotti and Rita Casadio
The evaluation of protein folding rate constant is improved by predicting the folding kinetic order with a SVM-based method
The paper will be published on WSEAS Transaction on Biology and Biomedicine
null
null
null
q-bio.BM q-bio.QM
null
Protein folding is a problem of large interest since it concerns the mechanism by which the genetic information is translated into proteins with well defined three-dimensional (3D) structures and functions. Recently theoretical models have been developed to predict the protein folding rate considering the relationships of the process with tolopological parameters derived from the native (atomic-solved) protein structures. Previous works classified proteins in two different groups exhibiting either a single-exponential or a multi-exponential folding kinetics. It is well known that these two classes of proteins are related to different protein structural features. The increasing number of available experimental kinetic data allows the application to the problem of a machine learning approach, in order to predict the kinetic order of the folding process starting from the experimental data so far collected. This information can be used to improve the prediction of the folding rate. In this work first we describe a support vector machine-based method (SVM-KO) to predict for a given protein the kinetic order of the folding process. Using this method we can classify correctly 78% of the folding mechanisms over a set of 63 experimental data. Secondly we focus on the prediction of the logarithm of the folding rate. This value can be obtained as a linear regression task with a SVM-based method. In this paper we show that linear correlation of the predicted with experimental data can improve when the regression task is computed over two different sets, instead of one, each of them composed by the proteins with a correctly predicted two state or multistate kinetic order.
[ { "created": "Mon, 13 Feb 2006 13:26:00 GMT", "version": "v1" } ]
2007-05-23
[ [ "Capriotti", "Emidio", "" ], [ "Casadio", "Rita", "" ] ]
Protein folding is a problem of large interest since it concerns the mechanism by which the genetic information is translated into proteins with well defined three-dimensional (3D) structures and functions. Recently theoretical models have been developed to predict the protein folding rate considering the relationships of the process with tolopological parameters derived from the native (atomic-solved) protein structures. Previous works classified proteins in two different groups exhibiting either a single-exponential or a multi-exponential folding kinetics. It is well known that these two classes of proteins are related to different protein structural features. The increasing number of available experimental kinetic data allows the application to the problem of a machine learning approach, in order to predict the kinetic order of the folding process starting from the experimental data so far collected. This information can be used to improve the prediction of the folding rate. In this work first we describe a support vector machine-based method (SVM-KO) to predict for a given protein the kinetic order of the folding process. Using this method we can classify correctly 78% of the folding mechanisms over a set of 63 experimental data. Secondly we focus on the prediction of the logarithm of the folding rate. This value can be obtained as a linear regression task with a SVM-based method. In this paper we show that linear correlation of the predicted with experimental data can improve when the regression task is computed over two different sets, instead of one, each of them composed by the proteins with a correctly predicted two state or multistate kinetic order.
1412.0603
Alexei Koulakov
Daniel D. Ferrante, Yi Wei, and Alexei A. Koulakov
Statistical model of evolution of brain parcellation
9 pages, plenty of pictures
null
null
null
q-bio.NC cond-mat.dis-nn
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We study the distribution of brain and cortical area sizes [parcellation units (PUs)] obtained for three species: mouse, macaque, and human. We find that the distribution of PU sizes is close to lognormal. We analyze the mathematical model of evolution of brain parcellation based on iterative fragmentation and specialization. In this model, each existing PU has a probability to be split that depends on PU size only. This model shows that the same evolutionary process may have led to brain parcellation in these three species. Our model suggests that region-to-region (macro) connectivity is given by the outer product form. We show that most experimental data on non-vanishing macaque cortex macroconnectivity (62% for area V1) can be explained by the outer product power-law form suggested by our model. We propose a multiplicative Hebbian learning rule for the macroconnectome that could yield the correct scaling of connection strengths between areas. We thus propose a universal evolutionary model that may have contributed to both brain parcellation and mesoscopic level connectivity in mammals.
[ { "created": "Mon, 1 Dec 2014 19:28:10 GMT", "version": "v1" } ]
2014-12-02
[ [ "Ferrante", "Daniel D.", "" ], [ "Wei", "Yi", "" ], [ "Koulakov", "Alexei A.", "" ] ]
We study the distribution of brain and cortical area sizes [parcellation units (PUs)] obtained for three species: mouse, macaque, and human. We find that the distribution of PU sizes is close to lognormal. We analyze the mathematical model of evolution of brain parcellation based on iterative fragmentation and specialization. In this model, each existing PU has a probability to be split that depends on PU size only. This model shows that the same evolutionary process may have led to brain parcellation in these three species. Our model suggests that region-to-region (macro) connectivity is given by the outer product form. We show that most experimental data on non-vanishing macaque cortex macroconnectivity (62% for area V1) can be explained by the outer product power-law form suggested by our model. We propose a multiplicative Hebbian learning rule for the macroconnectome that could yield the correct scaling of connection strengths between areas. We thus propose a universal evolutionary model that may have contributed to both brain parcellation and mesoscopic level connectivity in mammals.
1803.03742
Nir Lahav
Nir Lahav, Baruch Ksherim, Eti Ben-Simon, Adi Maron-Katz, Reuven Cohen and Shlomo Havlin
K-shell decomposition reveals hierarchical cortical organization of the human brain
New Journal of Physics, Volume 18, August 2016
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10.1088/1367-2630/18/8/083013
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q-bio.NC
http://creativecommons.org/licenses/by-nc-sa/4.0/
In recent years numerous attempts to understand the human brain were undertaken from a network point of view. A network framework takes into account the relationships between the different parts of the system and enables to examine how global and complex functions might emerge from network topology. Previous work revealed that the human brain features 'small world' characteristics and that cortical hubs tend to interconnect among themselves. However, in order to fully understand the topological structure of hubs one needs to go beyond the properties of a specific hub and examine the various structural layers of the network. To address this topic further, we applied an analysis known in statistical physics and network theory as k-shell decomposition analysis. The analysis was applied on a human cortical network, derived from MRI\DSI data of six participants. Such analysis enables us to portray a detailed account of cortical connectivity focusing on different neighborhoods of interconnected layers across the cortex. Our findings reveal that the human cortex is highly connected and efficient, and unlike the internet network contains no isolated nodes. The cortical network is comprised of a nucleus alongside shells of increasing connectivity that formed one connected giant component. All these components were further categorized into three hierarchies in accordance with their connectivity profile, with each hierarchy reflecting different functional roles. Such a model may explain an efficient flow of information from the lowest hierarchy to the highest one, with each step enabling increased data integration. At the top, the highest hierarchy (the nucleus) serves as a global interconnected collective and demonstrates high correlation with consciousness related regions, suggesting that the nucleus might serve as a platform for consciousness to emerge.
[ { "created": "Sat, 10 Mar 2018 02:19:09 GMT", "version": "v1" } ]
2018-03-13
[ [ "Lahav", "Nir", "" ], [ "Ksherim", "Baruch", "" ], [ "Ben-Simon", "Eti", "" ], [ "Maron-Katz", "Adi", "" ], [ "Cohen", "Reuven", "" ], [ "Havlin", "Shlomo", "" ] ]
In recent years numerous attempts to understand the human brain were undertaken from a network point of view. A network framework takes into account the relationships between the different parts of the system and enables to examine how global and complex functions might emerge from network topology. Previous work revealed that the human brain features 'small world' characteristics and that cortical hubs tend to interconnect among themselves. However, in order to fully understand the topological structure of hubs one needs to go beyond the properties of a specific hub and examine the various structural layers of the network. To address this topic further, we applied an analysis known in statistical physics and network theory as k-shell decomposition analysis. The analysis was applied on a human cortical network, derived from MRI\DSI data of six participants. Such analysis enables us to portray a detailed account of cortical connectivity focusing on different neighborhoods of interconnected layers across the cortex. Our findings reveal that the human cortex is highly connected and efficient, and unlike the internet network contains no isolated nodes. The cortical network is comprised of a nucleus alongside shells of increasing connectivity that formed one connected giant component. All these components were further categorized into three hierarchies in accordance with their connectivity profile, with each hierarchy reflecting different functional roles. Such a model may explain an efficient flow of information from the lowest hierarchy to the highest one, with each step enabling increased data integration. At the top, the highest hierarchy (the nucleus) serves as a global interconnected collective and demonstrates high correlation with consciousness related regions, suggesting that the nucleus might serve as a platform for consciousness to emerge.