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1111.6495
Taiki Takahashi
Taiki Takahashi
A neuroeconomic theory of bidirectional synaptic plasticity and addiction
null
null
null
null
q-bio.NC q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Neuronal mechanisms underlying addiction have been attracting attention in neurobiology, economics, neuropsychiatry, and neuroeconomics. This paper proposes a possible link between economic theory of addiction (Becker and Murphy, 1988) and neurobiological theory of bidirectional synaptic plasticity (Bienenstock, Cooper, Munro, 1982) based on recent findings in neuroeconomics and neurobiology of addiction. Furthermore, it is suggested that several neurobiological substrates such as cortisol (a stress hormone), NMDA and AMPA receptors/subunits and intracellular calcium in the postsynaptic neurons are critical factors determining parameters in Becker and Murphy's economic theory of addiction. Future directions in the application of the theory to studies in neuroeconomics and neuropsychiatry of addiction and its relation to stress at the molecular level are discussed.
[ { "created": "Tue, 22 Nov 2011 22:45:23 GMT", "version": "v1" } ]
2011-11-29
[ [ "Takahashi", "Taiki", "" ] ]
Neuronal mechanisms underlying addiction have been attracting attention in neurobiology, economics, neuropsychiatry, and neuroeconomics. This paper proposes a possible link between economic theory of addiction (Becker and Murphy, 1988) and neurobiological theory of bidirectional synaptic plasticity (Bienenstock, Cooper, Munro, 1982) based on recent findings in neuroeconomics and neurobiology of addiction. Furthermore, it is suggested that several neurobiological substrates such as cortisol (a stress hormone), NMDA and AMPA receptors/subunits and intracellular calcium in the postsynaptic neurons are critical factors determining parameters in Becker and Murphy's economic theory of addiction. Future directions in the application of the theory to studies in neuroeconomics and neuropsychiatry of addiction and its relation to stress at the molecular level are discussed.
q-bio/0504008
Ulrich S. Schwarz
Ulrich S. Schwarz (1) and Ronen Alon (2) ((1) MPI Colloids and Interfaces, (2) Weizmann Institute)
L-selectin mediated leukocyte tethering in shear flow is controlled by multiple contacts and cytoskeletal anchorage facilitating fast rebinding events
9 pages, Revtex, 4 Postscript figures included
PNAS 101: 6940-6945 (2004)
10.1073/pnas.0305822101
null
q-bio.SC
null
L-selectin mediated tethers result in leukocyte rolling only above a threshold in shear. Here we present biophysical modeling based on recently published data from flow chamber experiments (Dwir et al., J. Cell Biol. 163: 649-659, 2003) which supports the interpretation that L-selectin mediated tethers below the shear threshold correspond to single L-selectin carbohydrate bonds dissociating on the time scale of milliseconds, whereas L-selectin mediated tethers above the shear threshold are stabilized by multiple bonds and fast rebinding of broken bonds, resulting in tether lifetimes on the timescale of $10^{-1}$ seconds. Our calculations for cluster dissociation suggest that the single molecule rebinding rate is of the order of $10^4$ Hz. A similar estimate results if increased tether dissociation for tail-truncated L-selectin mutants above the shear threshold is modeled as diffusive escape of single receptors from the rebinding region due to increased mobility. Using computer simulations, we show that our model yields first order dissociation kinetics and exponential dependence of tether dissociation rates on shear stress. Our results suggest that multiple contacts, cytoskeletal anchorage of L-selectin and local rebinding of ligand play important roles in L-selectin tether stabilization and progression of tethers into persistent rolling on endothelial surfaces.
[ { "created": "Wed, 6 Apr 2005 02:13:15 GMT", "version": "v1" } ]
2009-11-11
[ [ "Schwarz", "Ulrich S.", "" ], [ "Alon", "Ronen", "" ] ]
L-selectin mediated tethers result in leukocyte rolling only above a threshold in shear. Here we present biophysical modeling based on recently published data from flow chamber experiments (Dwir et al., J. Cell Biol. 163: 649-659, 2003) which supports the interpretation that L-selectin mediated tethers below the shear threshold correspond to single L-selectin carbohydrate bonds dissociating on the time scale of milliseconds, whereas L-selectin mediated tethers above the shear threshold are stabilized by multiple bonds and fast rebinding of broken bonds, resulting in tether lifetimes on the timescale of $10^{-1}$ seconds. Our calculations for cluster dissociation suggest that the single molecule rebinding rate is of the order of $10^4$ Hz. A similar estimate results if increased tether dissociation for tail-truncated L-selectin mutants above the shear threshold is modeled as diffusive escape of single receptors from the rebinding region due to increased mobility. Using computer simulations, we show that our model yields first order dissociation kinetics and exponential dependence of tether dissociation rates on shear stress. Our results suggest that multiple contacts, cytoskeletal anchorage of L-selectin and local rebinding of ligand play important roles in L-selectin tether stabilization and progression of tethers into persistent rolling on endothelial surfaces.
2202.01516
Shu Guo
Tao Liu, Shu Guo, Hao Liu, Rui Kang, Mingyang Bai, Jiyang Jiang, Wei Wen, Xing Pan, Jun Tai, Jianxin Li, Jian Cheng, Jing Jing, Zhenzhou Wu, Haijun Niu, Haogang Zhu, Zixiao Li, Yongjun Wang, Henry Brodaty, Perminder Sachdev, Daqing Li
Network resilience in the aging brain
24 pages, 6 figures
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
Degeneration and adaptation are two competing sides of the same coin called resilience in the progressive processes of brain aging or diseases. Degeneration accumulates during brain aging and other cerebral activities, causing structural atrophy and dysfunction. At the same time, adaptation allows brain network reorganize to compensate for structural loss to maintain cognition function. Although hidden resilience mechanism is critical and fundamental to uncover the brain aging law, due to the lack of datasets and appropriate methodology, it remains essentially unknown how these two processes interact dynamically across brain networks. To quantitatively investigate this complex process, we analyze aging brains based on 6-year follow-up multimodal neuroimaging database from 63 persons. We reveal the critical mechanism of network resilience that various perturbation may cause fast brain structural atrophy, and then brain can reorganize its functional layout to lower its operational efficiency, which helps to slow down the structural atrophy and finally recover its functional efficiency equilibrium. This empirical finding could be explained by our theoretical model, suggesting one universal resilience dynamical function. This resilience is achieved in the brain functional network with evolving percolation and rich-club features. Our findings can help to understand the brain aging process and design possible mitigation methods to adjust interaction between degeneration and adaptation from resilience viewpoint.
[ { "created": "Thu, 3 Feb 2022 10:53:00 GMT", "version": "v1" } ]
2022-02-04
[ [ "Liu", "Tao", "" ], [ "Guo", "Shu", "" ], [ "Liu", "Hao", "" ], [ "Kang", "Rui", "" ], [ "Bai", "Mingyang", "" ], [ "Jiang", "Jiyang", "" ], [ "Wen", "Wei", "" ], [ "Pan", "Xing", "" ], [ "Tai", "Jun", "" ], [ "Li", "Jianxin", "" ], [ "Cheng", "Jian", "" ], [ "Jing", "Jing", "" ], [ "Wu", "Zhenzhou", "" ], [ "Niu", "Haijun", "" ], [ "Zhu", "Haogang", "" ], [ "Li", "Zixiao", "" ], [ "Wang", "Yongjun", "" ], [ "Brodaty", "Henry", "" ], [ "Sachdev", "Perminder", "" ], [ "Li", "Daqing", "" ] ]
Degeneration and adaptation are two competing sides of the same coin called resilience in the progressive processes of brain aging or diseases. Degeneration accumulates during brain aging and other cerebral activities, causing structural atrophy and dysfunction. At the same time, adaptation allows brain network reorganize to compensate for structural loss to maintain cognition function. Although hidden resilience mechanism is critical and fundamental to uncover the brain aging law, due to the lack of datasets and appropriate methodology, it remains essentially unknown how these two processes interact dynamically across brain networks. To quantitatively investigate this complex process, we analyze aging brains based on 6-year follow-up multimodal neuroimaging database from 63 persons. We reveal the critical mechanism of network resilience that various perturbation may cause fast brain structural atrophy, and then brain can reorganize its functional layout to lower its operational efficiency, which helps to slow down the structural atrophy and finally recover its functional efficiency equilibrium. This empirical finding could be explained by our theoretical model, suggesting one universal resilience dynamical function. This resilience is achieved in the brain functional network with evolving percolation and rich-club features. Our findings can help to understand the brain aging process and design possible mitigation methods to adjust interaction between degeneration and adaptation from resilience viewpoint.
0907.1127
Shuhei Mano
Shuhei Mano
Ancestral Graph with Bias in Gene Conversion
29 pages, 2 figures
J. Appl. Probab. 50 (2013) 239-255
null
null
q-bio.PE math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Gene conversion is a mechanism by which a double-strand break in a DNA molecule is repaired using a homologous DNA molecule as a template. As a result, one gene is 'copied and pasted' onto the other gene. It was recently reported that the direction of gene conversion appears to be biased towards G and C nucleotides. In this paper a stochastic model of the dynamics of the bias in gene conversion is developed for a finite population of members in a multigene family. The dual process is the biased voter model, which generates an ancestral random graph for a given sample. An importance-sampling algorithm for computing the likelihood of the sample is also given.
[ { "created": "Tue, 7 Jul 2009 01:43:24 GMT", "version": "v1" }, { "created": "Fri, 20 Jan 2012 08:58:42 GMT", "version": "v2" } ]
2013-04-08
[ [ "Mano", "Shuhei", "" ] ]
Gene conversion is a mechanism by which a double-strand break in a DNA molecule is repaired using a homologous DNA molecule as a template. As a result, one gene is 'copied and pasted' onto the other gene. It was recently reported that the direction of gene conversion appears to be biased towards G and C nucleotides. In this paper a stochastic model of the dynamics of the bias in gene conversion is developed for a finite population of members in a multigene family. The dual process is the biased voter model, which generates an ancestral random graph for a given sample. An importance-sampling algorithm for computing the likelihood of the sample is also given.
2110.01339
{\L}ukasz Struski
Dawid Warszycki, {\L}ukasz Struski, Marek \'Smieja, Rafa{\l} Kafel, Rafa{\l} Kurczab
Pharmacoprint -- a combination of pharmacophore fingerprint and artificial intelligence as a tool for computer-aided drug design
Journal of Chemical Information and Modeling (2021)
null
10.1021/acs.jcim.1c00589
null
q-bio.QM cs.LG
http://creativecommons.org/licenses/by/4.0/
Structural fingerprints and pharmacophore modeling are methodologies that have been used for at least two decades in various fields of cheminformatics: from similarity searching to machine learning (ML). Advances in silico techniques consequently led to combining both these methodologies into a new approach known as pharmacophore fingerprint. Herein, we propose a high-resolution, pharmacophore fingerprint called Pharmacoprint that encodes the presence, types, and relationships between pharmacophore features of a molecule. Pharmacoprint was evaluated in classification experiments by using ML algorithms (logistic regression, support vector machines, linear support vector machines, and neural networks) and outperformed other popular molecular fingerprints (i.e., Estate, MACCS, PubChem, Substructure, Klekotha-Roth, CDK, Extended, and GraphOnly) and ChemAxon Pharmacophoric Features fingerprint. Pharmacoprint consisted of 39973 bits; several methods were applied for dimensionality reduction, and the best algorithm not only reduced the length of bit string but also improved the efficiency of ML tests. Further optimization allowed us to define the best parameter settings for using Pharmacoprint in discrimination tests and for maximizing statistical parameters. Finally, Pharmacoprint generated for 3D structures with defined hydrogens as input data was applied to neural networks with a supervised autoencoder for selecting the most important bits and allowed to maximize Matthews Correlation Coefficient up to 0.962. The results show the potential of Pharmacoprint as a new, perspective tool for computer-aided drug design.
[ { "created": "Mon, 4 Oct 2021 11:36:39 GMT", "version": "v1" }, { "created": "Tue, 31 Oct 2023 09:30:08 GMT", "version": "v2" } ]
2023-11-01
[ [ "Warszycki", "Dawid", "" ], [ "Struski", "Łukasz", "" ], [ "Śmieja", "Marek", "" ], [ "Kafel", "Rafał", "" ], [ "Kurczab", "Rafał", "" ] ]
Structural fingerprints and pharmacophore modeling are methodologies that have been used for at least two decades in various fields of cheminformatics: from similarity searching to machine learning (ML). Advances in silico techniques consequently led to combining both these methodologies into a new approach known as pharmacophore fingerprint. Herein, we propose a high-resolution, pharmacophore fingerprint called Pharmacoprint that encodes the presence, types, and relationships between pharmacophore features of a molecule. Pharmacoprint was evaluated in classification experiments by using ML algorithms (logistic regression, support vector machines, linear support vector machines, and neural networks) and outperformed other popular molecular fingerprints (i.e., Estate, MACCS, PubChem, Substructure, Klekotha-Roth, CDK, Extended, and GraphOnly) and ChemAxon Pharmacophoric Features fingerprint. Pharmacoprint consisted of 39973 bits; several methods were applied for dimensionality reduction, and the best algorithm not only reduced the length of bit string but also improved the efficiency of ML tests. Further optimization allowed us to define the best parameter settings for using Pharmacoprint in discrimination tests and for maximizing statistical parameters. Finally, Pharmacoprint generated for 3D structures with defined hydrogens as input data was applied to neural networks with a supervised autoencoder for selecting the most important bits and allowed to maximize Matthews Correlation Coefficient up to 0.962. The results show the potential of Pharmacoprint as a new, perspective tool for computer-aided drug design.
1404.0568
Samuela Pasquali
Tristan Cragnolini, Yoann Laurin, Philippe Derreumaux, Samuela Pasquali
The coarse-grained HiRE-RNA model for de novo calculations of RNA free energy surfaces, folding pathways and complex structure prediction
null
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
HiRE-RNA is a simplified, coarse-grained RNA model for the prediction of equilibrium configurations, dynamics and thermodynamics. Using a reduced set of particles and detailed interactions accounting for base-pairing and stacking we show that non-canonical and multiple base interactions are necessary to capture the full physical behavior of complex RNAs. In this paper we give a full account of the model and we present results on the folding, stability and free energy surfaces of 16 systems with 12 to 76 nucleotides of increasingly complex architectures, ranging from monomers to dimers, using a total of 850$\mu$s simulation time.
[ { "created": "Wed, 2 Apr 2014 14:27:09 GMT", "version": "v1" }, { "created": "Mon, 9 Mar 2015 08:17:53 GMT", "version": "v2" } ]
2015-03-10
[ [ "Cragnolini", "Tristan", "" ], [ "Laurin", "Yoann", "" ], [ "Derreumaux", "Philippe", "" ], [ "Pasquali", "Samuela", "" ] ]
HiRE-RNA is a simplified, coarse-grained RNA model for the prediction of equilibrium configurations, dynamics and thermodynamics. Using a reduced set of particles and detailed interactions accounting for base-pairing and stacking we show that non-canonical and multiple base interactions are necessary to capture the full physical behavior of complex RNAs. In this paper we give a full account of the model and we present results on the folding, stability and free energy surfaces of 16 systems with 12 to 76 nucleotides of increasingly complex architectures, ranging from monomers to dimers, using a total of 850$\mu$s simulation time.
1005.0361
Michael Denker
Michael Denker and S\'ebastien Roux and Henrik Lind\'en and Markus Diesmann and Alexa Riehle and Sonja Gr\"un
The Local Field Potential Reflects Surplus Spike Synchrony
45 pages, 8 figures, 3 supplemental figures
Cereb. Cortex (2011) 21(12): 2681-2695
10.1093/cercor/bhr040
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The oscillatory nature of the cortical local field potential (LFP) is commonly interpreted as a reflection of synchronized network activity, but its relationship to observed transient coincident firing of neurons on the millisecond time-scale remains unclear. Here we present experimental evidence to reconcile the notions of synchrony at the level of neuronal spiking and at the mesoscopic scale. We demonstrate that only in time intervals of excess spike synchrony, coincident spikes are better entrained to the LFP than predicted by the locking of the individual spikes. This effect is enhanced in periods of large LFP amplitudes. A quantitative model explains the LFP dynamics by the orchestrated spiking activity in neuronal groups that contribute the observed surplus synchrony. From the correlation analysis, we infer that neurons participate in different constellations but contribute only a fraction of their spikes to temporally precise spike configurations, suggesting a dual coding scheme of rate and synchrony. This finding provides direct evidence for the hypothesized relation that precise spike synchrony constitutes a major temporally and spatially organized component of the LFP. Revealing that transient spike synchronization correlates not only with behavior, but with a mesoscopic brain signal corroborates its relevance in cortical processing.
[ { "created": "Mon, 3 May 2010 18:10:19 GMT", "version": "v1" } ]
2011-11-24
[ [ "Denker", "Michael", "" ], [ "Roux", "Sébastien", "" ], [ "Lindén", "Henrik", "" ], [ "Diesmann", "Markus", "" ], [ "Riehle", "Alexa", "" ], [ "Grün", "Sonja", "" ] ]
The oscillatory nature of the cortical local field potential (LFP) is commonly interpreted as a reflection of synchronized network activity, but its relationship to observed transient coincident firing of neurons on the millisecond time-scale remains unclear. Here we present experimental evidence to reconcile the notions of synchrony at the level of neuronal spiking and at the mesoscopic scale. We demonstrate that only in time intervals of excess spike synchrony, coincident spikes are better entrained to the LFP than predicted by the locking of the individual spikes. This effect is enhanced in periods of large LFP amplitudes. A quantitative model explains the LFP dynamics by the orchestrated spiking activity in neuronal groups that contribute the observed surplus synchrony. From the correlation analysis, we infer that neurons participate in different constellations but contribute only a fraction of their spikes to temporally precise spike configurations, suggesting a dual coding scheme of rate and synchrony. This finding provides direct evidence for the hypothesized relation that precise spike synchrony constitutes a major temporally and spatially organized component of the LFP. Revealing that transient spike synchronization correlates not only with behavior, but with a mesoscopic brain signal corroborates its relevance in cortical processing.
2212.00735
Yining Wang
Yining Wang, Xumeng Gong, Shaochuan Li, Bing Yang, YiWu Sun, Chuan Shi, Yangang Wang, Cheng Yang, Hui Li, Le Song
xTrimoABFold: De novo Antibody Structure Prediction without MSA
14 pages, 5 figures
null
null
null
q-bio.QM cs.AI cs.CL cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In the field of antibody engineering, an essential task is to design a novel antibody whose paratopes bind to a specific antigen with correct epitopes. Understanding antibody structure and its paratope can facilitate a mechanistic understanding of its function. Therefore, antibody structure prediction from its sequence alone has always been a highly valuable problem for de novo antibody design. AlphaFold2, a breakthrough in the field of structural biology, provides a solution to predict protein structure based on protein sequences and computationally expensive coevolutionary multiple sequence alignments (MSAs). However, the computational efficiency and undesirable prediction accuracy of antibodies, especially on the complementarity-determining regions (CDRs) of antibodies limit their applications in the industrially high-throughput drug design. To learn an informative representation of antibodies, we employed a deep antibody language model (ALM) on curated sequences from the observed antibody space database via a transformer model. We also developed a novel model named xTrimoABFold to predict antibody structure from antibody sequence based on the pretrained ALM as well as efficient evoformers and structural modules. The model was trained end-to-end on the antibody structures in PDB by minimizing the ensemble loss of domain-specific focal loss on CDR and the frame-aligned point loss. xTrimoABFold outperforms AlphaFold2 and other protein language model based SOTAs, e.g., OmegaFold, HelixFold-Single, and IgFold with a large significant margin (30+\% improvement on RMSD) while performing 151 times faster than AlphaFold2. To the best of our knowledge, xTrimoABFold achieved state-of-the-art antibody structure prediction. Its improvement in both accuracy and efficiency makes it a valuable tool for de novo antibody design and could make further improvements in immuno-theory.
[ { "created": "Wed, 30 Nov 2022 09:26:08 GMT", "version": "v1" }, { "created": "Sun, 11 Dec 2022 07:42:49 GMT", "version": "v2" }, { "created": "Fri, 5 May 2023 03:52:01 GMT", "version": "v3" } ]
2023-05-08
[ [ "Wang", "Yining", "" ], [ "Gong", "Xumeng", "" ], [ "Li", "Shaochuan", "" ], [ "Yang", "Bing", "" ], [ "Sun", "YiWu", "" ], [ "Shi", "Chuan", "" ], [ "Wang", "Yangang", "" ], [ "Yang", "Cheng", "" ], [ "Li", "Hui", "" ], [ "Song", "Le", "" ] ]
In the field of antibody engineering, an essential task is to design a novel antibody whose paratopes bind to a specific antigen with correct epitopes. Understanding antibody structure and its paratope can facilitate a mechanistic understanding of its function. Therefore, antibody structure prediction from its sequence alone has always been a highly valuable problem for de novo antibody design. AlphaFold2, a breakthrough in the field of structural biology, provides a solution to predict protein structure based on protein sequences and computationally expensive coevolutionary multiple sequence alignments (MSAs). However, the computational efficiency and undesirable prediction accuracy of antibodies, especially on the complementarity-determining regions (CDRs) of antibodies limit their applications in the industrially high-throughput drug design. To learn an informative representation of antibodies, we employed a deep antibody language model (ALM) on curated sequences from the observed antibody space database via a transformer model. We also developed a novel model named xTrimoABFold to predict antibody structure from antibody sequence based on the pretrained ALM as well as efficient evoformers and structural modules. The model was trained end-to-end on the antibody structures in PDB by minimizing the ensemble loss of domain-specific focal loss on CDR and the frame-aligned point loss. xTrimoABFold outperforms AlphaFold2 and other protein language model based SOTAs, e.g., OmegaFold, HelixFold-Single, and IgFold with a large significant margin (30+\% improvement on RMSD) while performing 151 times faster than AlphaFold2. To the best of our knowledge, xTrimoABFold achieved state-of-the-art antibody structure prediction. Its improvement in both accuracy and efficiency makes it a valuable tool for de novo antibody design and could make further improvements in immuno-theory.
1005.2648
Aleksandra Walczak
Aleksandra M. Walczak, Andrew Mugler and Chris H. WIggins
Analytic methods for modeling stochastic regulatory networks
null
Methods Mol. Biol. (2012) 880, 273-322
10.1007/978-1-61779-833-7_13
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The past decade has seen a revived interest in the unavoidable or intrinsic noise in biochemical and genetic networks arising from the finite copy number of the participating species. That is, rather than modeling regulatory networks in terms of the deterministic dynamics of concentrations, we model the dynamics of the probability of a given copy number of the reactants in single cells. Most of the modeling activity of the last decade has centered on stochastic simulation of individual realizations, i.e., Monte-Carlo methods for generating stochastic time series. Here we review the mathematical description in terms of probability distributions, introducing the relevant derivations and illustrating several cases for which analytic progress can be made either instead of or before turning to numerical computation.
[ { "created": "Sat, 15 May 2010 04:03:31 GMT", "version": "v1" } ]
2015-03-17
[ [ "Walczak", "Aleksandra M.", "" ], [ "Mugler", "Andrew", "" ], [ "WIggins", "Chris H.", "" ] ]
The past decade has seen a revived interest in the unavoidable or intrinsic noise in biochemical and genetic networks arising from the finite copy number of the participating species. That is, rather than modeling regulatory networks in terms of the deterministic dynamics of concentrations, we model the dynamics of the probability of a given copy number of the reactants in single cells. Most of the modeling activity of the last decade has centered on stochastic simulation of individual realizations, i.e., Monte-Carlo methods for generating stochastic time series. Here we review the mathematical description in terms of probability distributions, introducing the relevant derivations and illustrating several cases for which analytic progress can be made either instead of or before turning to numerical computation.
1803.04659
Aaron Tuor
Richard Olney, Aaron Tuor, Filip Jagodzinski, Brian Hutchinson
Protein Mutation Stability Ternary Classification using Neural Networks and Rigidity Analysis
To appear in the Proceedings of 10th International Conference on Bioinformatics and Computational Biology (BICOB 2018)
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Discerning how a mutation affects the stability of a protein is central to the study of a wide range of diseases. Machine learning and statistical analysis techniques can inform how to allocate limited resources to the considerable time and cost associated with wet lab mutagenesis experiments. In this work we explore the effectiveness of using a neural network classifier to predict the change in the stability of a protein due to a mutation. Assessing the accuracy of our approach is dependent on the use of experimental data about the effects of mutations performed in vitro. Because the experimental data is prone to discrepancies when similar experiments have been performed by multiple laboratories, the use of the data near the juncture of stabilizing and destabilizing mutations is questionable. We address this later problem via a systematic approach in which we explore the use of a three-way classification scheme with stabilizing, destabilizing, and inconclusive labels. For a systematic search of potential classification cutoff values our classifier achieved 68 percent accuracy on ternary classification for cutoff values of -0.6 and 0.7 with a low rate of classifying stabilizing as destabilizing and vice versa.
[ { "created": "Tue, 13 Mar 2018 07:11:29 GMT", "version": "v1" } ]
2018-03-14
[ [ "Olney", "Richard", "" ], [ "Tuor", "Aaron", "" ], [ "Jagodzinski", "Filip", "" ], [ "Hutchinson", "Brian", "" ] ]
Discerning how a mutation affects the stability of a protein is central to the study of a wide range of diseases. Machine learning and statistical analysis techniques can inform how to allocate limited resources to the considerable time and cost associated with wet lab mutagenesis experiments. In this work we explore the effectiveness of using a neural network classifier to predict the change in the stability of a protein due to a mutation. Assessing the accuracy of our approach is dependent on the use of experimental data about the effects of mutations performed in vitro. Because the experimental data is prone to discrepancies when similar experiments have been performed by multiple laboratories, the use of the data near the juncture of stabilizing and destabilizing mutations is questionable. We address this later problem via a systematic approach in which we explore the use of a three-way classification scheme with stabilizing, destabilizing, and inconclusive labels. For a systematic search of potential classification cutoff values our classifier achieved 68 percent accuracy on ternary classification for cutoff values of -0.6 and 0.7 with a low rate of classifying stabilizing as destabilizing and vice versa.
2006.15626
Bjorn Johansson
Bjorn Johansson
Masking the general population might attenuate COVID-19 outbreaks
null
null
null
null
q-bio.PE physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The effect of masking the general population on a COVID-19 epidemic is estimated by computer simulation using two separate state-of-the-art web-based softwares, one of them calibrated for the SARS-CoV-2 virus. The questions addressed are these: 1. Can mask use by the general population limit the spread of SARS-CoV-2 in a country? 2. What types of masks exist, and how elaborate must a mask be to be effective against COVID-19? 3. Does the mask have to be applied early in an epidemic? 4. A brief general discussion of masks and some possible future research questions regarding masks and SARS-CoV-2. Results are as follows: (1) The results indicate that any type of mask, even simple home-made ones, may be effective. Masks use seems to have an effect in lowering new patients even the protective effect of each mask (here dubbed "one-mask protection") is low. Strict adherence to mask use does not appear to be critical. However, increasing the one-mask protection to > 50% was found to be advantageous. Masks seemed able to reduce overflow of capacity, e.g. of intensive care. As the default parameters of the software included another intervention, it seems possible to combine mask and other interventions. (2) Masks do seem to reduce the number of new cases even if introduced at a late stage in an epidemic. However, early implementation helps reduce the cumulative and total number of cases. (3) The simulations suggest that it might be possible to eliminate a COVID-19 outbreak by widespread mask use during a limited period. The results from these simulations are encouraging, but do not necessarily represent the real-life situation, so it is suggested that clinical trials of masks are now carried out while continuously monitoring effects and side-effects.
[ { "created": "Sun, 28 Jun 2020 14:57:44 GMT", "version": "v1" } ]
2020-06-30
[ [ "Johansson", "Bjorn", "" ] ]
The effect of masking the general population on a COVID-19 epidemic is estimated by computer simulation using two separate state-of-the-art web-based softwares, one of them calibrated for the SARS-CoV-2 virus. The questions addressed are these: 1. Can mask use by the general population limit the spread of SARS-CoV-2 in a country? 2. What types of masks exist, and how elaborate must a mask be to be effective against COVID-19? 3. Does the mask have to be applied early in an epidemic? 4. A brief general discussion of masks and some possible future research questions regarding masks and SARS-CoV-2. Results are as follows: (1) The results indicate that any type of mask, even simple home-made ones, may be effective. Masks use seems to have an effect in lowering new patients even the protective effect of each mask (here dubbed "one-mask protection") is low. Strict adherence to mask use does not appear to be critical. However, increasing the one-mask protection to > 50% was found to be advantageous. Masks seemed able to reduce overflow of capacity, e.g. of intensive care. As the default parameters of the software included another intervention, it seems possible to combine mask and other interventions. (2) Masks do seem to reduce the number of new cases even if introduced at a late stage in an epidemic. However, early implementation helps reduce the cumulative and total number of cases. (3) The simulations suggest that it might be possible to eliminate a COVID-19 outbreak by widespread mask use during a limited period. The results from these simulations are encouraging, but do not necessarily represent the real-life situation, so it is suggested that clinical trials of masks are now carried out while continuously monitoring effects and side-effects.
1111.1496
Ekaterina Nikitina G.
E. Nikitina, L. Urazova, O. Churuksaeva
Dinamics of HPV Infection among Women with Cervical Lesions
null
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A total of 293 women treated at Tomsk Cancer Research Institute were examined. HPV type 16 had the highest incidence rate (45.0%) followed by HPV 31-17,0%, HPV 56/33-15,0%, HPV 51/18/52-13,0%, HPV 58/35/39/45-7,0%, HPV 59-5,0%. Persistent infection was detected in 35.7% of primarily HPV-positive cases (10 out of 28 patients), mainly in cervical cancer patients. Total number of primarily HPV-positive and HPV-negative patients with cervical cancer was 95.0% and 5.0%, respectively. The corresponding values after the complex treatment were 35.0% and 65.0%, respectively, pointing to the treatment efficiency.
[ { "created": "Mon, 7 Nov 2011 06:45:46 GMT", "version": "v1" } ]
2011-11-08
[ [ "Nikitina", "E.", "" ], [ "Urazova", "L.", "" ], [ "Churuksaeva", "O.", "" ] ]
A total of 293 women treated at Tomsk Cancer Research Institute were examined. HPV type 16 had the highest incidence rate (45.0%) followed by HPV 31-17,0%, HPV 56/33-15,0%, HPV 51/18/52-13,0%, HPV 58/35/39/45-7,0%, HPV 59-5,0%. Persistent infection was detected in 35.7% of primarily HPV-positive cases (10 out of 28 patients), mainly in cervical cancer patients. Total number of primarily HPV-positive and HPV-negative patients with cervical cancer was 95.0% and 5.0%, respectively. The corresponding values after the complex treatment were 35.0% and 65.0%, respectively, pointing to the treatment efficiency.
2112.14134
Luka Ribar
Tai Miyazaki Kirby, Luka Ribar, Rodolphe Sepulchre
Reliability of Event Timing in Silicon Neurons
null
null
null
null
q-bio.NC cs.NE cs.SY eess.SY
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Analog, low-voltage electronics show great promise in producing silicon neurons (SiNs) with unprecedented levels of energy efficiency. Yet, their inherently high susceptibility to process, voltage and temperature (PVT) variations, and noise has long been recognised as a major bottleneck in developing effective neuromorphic solutions. Inspired by spike transmission studies in biophysical, neocortical neurons, we demonstrate that the inherent noise and variability can coexist with reliable spike transmission in analog SiNs, similarly to biological neurons. We illustrate this property on a recent neuromorphic model of a bursting neuron by showcasing three different relevant types of reliable event transmission: single spike transmission, burst transmission, and the on-off control of a half-centre oscillator (HCO) network.
[ { "created": "Tue, 28 Dec 2021 13:24:23 GMT", "version": "v1" } ]
2021-12-30
[ [ "Kirby", "Tai Miyazaki", "" ], [ "Ribar", "Luka", "" ], [ "Sepulchre", "Rodolphe", "" ] ]
Analog, low-voltage electronics show great promise in producing silicon neurons (SiNs) with unprecedented levels of energy efficiency. Yet, their inherently high susceptibility to process, voltage and temperature (PVT) variations, and noise has long been recognised as a major bottleneck in developing effective neuromorphic solutions. Inspired by spike transmission studies in biophysical, neocortical neurons, we demonstrate that the inherent noise and variability can coexist with reliable spike transmission in analog SiNs, similarly to biological neurons. We illustrate this property on a recent neuromorphic model of a bursting neuron by showcasing three different relevant types of reliable event transmission: single spike transmission, burst transmission, and the on-off control of a half-centre oscillator (HCO) network.
1606.02349
Marius C\u{a}t\u{a}lin Iordan
Marius C\u{a}t\u{a}lin Iordan, Armand Joulin, Diane M. Beck, Li Fei-Fei
Locally-Optimized Inter-Subject Alignment of Functional Cortical Regions
Presented at MLINI-2015 workshop, 2015 (arXiv:cs/0101200)
null
null
MLINI/2015/04
q-bio.NC stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Inter-subject registration of cortical areas is necessary in functional imaging (fMRI) studies for making inferences about equivalent brain function across a population. However, many high-level visual brain areas are defined as peaks of functional contrasts whose cortical position is highly variable. As such, most alignment methods fail to accurately map functional regions of interest (ROIs) across participants. To address this problem, we propose a locally optimized registration method that directly predicts the location of a seed ROI on a separate target cortical sheet by maximizing the functional correlation between their time courses, while simultaneously allowing for non-smooth local deformations in region topology. Our method outperforms the two most commonly used alternatives (anatomical landmark-based AFNI alignment and cortical convexity-based FreeSurfer alignment) in overlap between predicted region and functionally-defined LOC. Furthermore, the maps obtained using our method are more consistent across subjects than both baseline measures. Critically, our method represents an important step forward towards predicting brain regions without explicit localizer scans and deciphering the poorly understood relationship between the location of functional regions, their anatomical extent, and the consistency of computations those regions perform across people.
[ { "created": "Tue, 7 Jun 2016 22:40:30 GMT", "version": "v1" } ]
2016-06-09
[ [ "Iordan", "Marius Cătălin", "" ], [ "Joulin", "Armand", "" ], [ "Beck", "Diane M.", "" ], [ "Fei-Fei", "Li", "" ] ]
Inter-subject registration of cortical areas is necessary in functional imaging (fMRI) studies for making inferences about equivalent brain function across a population. However, many high-level visual brain areas are defined as peaks of functional contrasts whose cortical position is highly variable. As such, most alignment methods fail to accurately map functional regions of interest (ROIs) across participants. To address this problem, we propose a locally optimized registration method that directly predicts the location of a seed ROI on a separate target cortical sheet by maximizing the functional correlation between their time courses, while simultaneously allowing for non-smooth local deformations in region topology. Our method outperforms the two most commonly used alternatives (anatomical landmark-based AFNI alignment and cortical convexity-based FreeSurfer alignment) in overlap between predicted region and functionally-defined LOC. Furthermore, the maps obtained using our method are more consistent across subjects than both baseline measures. Critically, our method represents an important step forward towards predicting brain regions without explicit localizer scans and deciphering the poorly understood relationship between the location of functional regions, their anatomical extent, and the consistency of computations those regions perform across people.
2302.08024
Hui Wang
Xi Chen, Hui Wang and Jinqiao Duan
The most probable dynamics of receptor-ligand binding on cell membrane
12 figures
null
null
null
q-bio.MN
http://creativecommons.org/licenses/by/4.0/
We devise a method for predicting certain receptor-ligand binding behaviors, based on stochastic dynamical modelling. We consider the dynamics of a receptor binding to a ligand on the cell membrane, where the receptor and ligand perform different motions and are thus modeled by stochastic differential equations with Gaussian noise or non-Gaussian noise. We use neural networks based on Onsager-Machlup function to compute the probability $P_1$ of the unbounded receptor diffusing to the cell membrane. Meanwhile, we compute the probability $P_2$ of extracellular ligand arriving at the cell membrane by solving the associated Fokker-Planck equation. Then, we could predict the most probable binding probability by combining $P_1$ and $P_2$. In this way, we conclude with some indication about where the ligand will most probably encounter the receptor, contributing to better understanding of cell's response to external stimuli and communication with other cells.
[ { "created": "Thu, 16 Feb 2023 01:55:19 GMT", "version": "v1" } ]
2023-02-17
[ [ "Chen", "Xi", "" ], [ "Wang", "Hui", "" ], [ "Duan", "Jinqiao", "" ] ]
We devise a method for predicting certain receptor-ligand binding behaviors, based on stochastic dynamical modelling. We consider the dynamics of a receptor binding to a ligand on the cell membrane, where the receptor and ligand perform different motions and are thus modeled by stochastic differential equations with Gaussian noise or non-Gaussian noise. We use neural networks based on Onsager-Machlup function to compute the probability $P_1$ of the unbounded receptor diffusing to the cell membrane. Meanwhile, we compute the probability $P_2$ of extracellular ligand arriving at the cell membrane by solving the associated Fokker-Planck equation. Then, we could predict the most probable binding probability by combining $P_1$ and $P_2$. In this way, we conclude with some indication about where the ligand will most probably encounter the receptor, contributing to better understanding of cell's response to external stimuli and communication with other cells.
1809.06917
Glenn Young
Glenn Young and Andrew Belmonte
Fixation in the stochastic Lotka-Volterra model with small fitness trade-offs
null
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We study the probability of fixation in a stochastic two-species competition model. By identifying a naturally occurring fast timescale, we derive an approximation to the associated backward Kolmogorov equation that allows us to obtain an explicit closed form solution for the probability of fixation of either species. We use our result to study fitness tradeoff strategies and show that, despite some tradeoffs having nearly negligible effects on the corresponding deterministic dynamics, they can have large implications for the outcome of the stochastic system.
[ { "created": "Tue, 18 Sep 2018 20:19:24 GMT", "version": "v1" }, { "created": "Mon, 8 Oct 2018 18:57:12 GMT", "version": "v2" }, { "created": "Wed, 2 Sep 2020 20:13:58 GMT", "version": "v3" } ]
2020-09-04
[ [ "Young", "Glenn", "" ], [ "Belmonte", "Andrew", "" ] ]
We study the probability of fixation in a stochastic two-species competition model. By identifying a naturally occurring fast timescale, we derive an approximation to the associated backward Kolmogorov equation that allows us to obtain an explicit closed form solution for the probability of fixation of either species. We use our result to study fitness tradeoff strategies and show that, despite some tradeoffs having nearly negligible effects on the corresponding deterministic dynamics, they can have large implications for the outcome of the stochastic system.
1010.3775
Danielle Bassett
Danielle S. Bassett, Nicholas F. Wymbs, Mason A. Porter, Peter J. Mucha, Jean M. Carlson, Scott T. Grafton
Dynamic reconfiguration of human brain networks during learning
Main Text: 19 pages, 4 figures Supplementary Materials: 34 pages, 4 figures, 3 tables
PNAS 2011, vol. 108, no. 18, 7641-7646
10.1073/pnas.1018985108
null
q-bio.NC cond-mat.dis-nn math-ph math.MP nlin.AO physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Human learning is a complex phenomenon requiring flexibility to adapt existing brain function and precision in selecting new neurophysiological activities to drive desired behavior. These two attributes -- flexibility and selection -- must operate over multiple temporal scales as performance of a skill changes from being slow and challenging to being fast and automatic. Such selective adaptability is naturally provided by modular structure, which plays a critical role in evolution, development, and optimal network function. Using functional connectivity measurements of brain activity acquired from initial training through mastery of a simple motor skill, we explore the role of modularity in human learning by identifying dynamic changes of modular organization spanning multiple temporal scales. Our results indicate that flexibility, which we measure by the allegiance of nodes to modules, in one experimental session predicts the relative amount of learning in a future session. We also develop a general statistical framework for the identification of modular architectures in evolving systems, which is broadly applicable to disciplines where network adaptability is crucial to the understanding of system performance.
[ { "created": "Tue, 19 Oct 2010 01:30:23 GMT", "version": "v1" }, { "created": "Mon, 24 Oct 2011 03:51:53 GMT", "version": "v2" } ]
2013-06-28
[ [ "Bassett", "Danielle S.", "" ], [ "Wymbs", "Nicholas F.", "" ], [ "Porter", "Mason A.", "" ], [ "Mucha", "Peter J.", "" ], [ "Carlson", "Jean M.", "" ], [ "Grafton", "Scott T.", "" ] ]
Human learning is a complex phenomenon requiring flexibility to adapt existing brain function and precision in selecting new neurophysiological activities to drive desired behavior. These two attributes -- flexibility and selection -- must operate over multiple temporal scales as performance of a skill changes from being slow and challenging to being fast and automatic. Such selective adaptability is naturally provided by modular structure, which plays a critical role in evolution, development, and optimal network function. Using functional connectivity measurements of brain activity acquired from initial training through mastery of a simple motor skill, we explore the role of modularity in human learning by identifying dynamic changes of modular organization spanning multiple temporal scales. Our results indicate that flexibility, which we measure by the allegiance of nodes to modules, in one experimental session predicts the relative amount of learning in a future session. We also develop a general statistical framework for the identification of modular architectures in evolving systems, which is broadly applicable to disciplines where network adaptability is crucial to the understanding of system performance.
1306.1685
Roland Schwarz
Roland F Schwarz, Anne Trinh, Botond Sipos, James D Brenton, Nick Goldman and Florian Markowetz
Phylogenetic quantification of intra-tumour heterogeneity
null
null
10.1371/journal.pcbi.1003535
null
q-bio.QM q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Background: Intra-tumour heterogeneity (ITH) is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance and if so would have prognostic and predictive utility. However, methods for objectively quantifying ITH have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements. Results: To address these challenges we present MEDICC, a method for phylogenetic reconstruction and ITH quantification based on a Minimum Event Distance for Intra-tumour Copynumber Comparisons. Using a transducer-based pairwise comparison function we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes. Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy and additionally allows unbiased numerical quantification of ITH. Conclusions: Accurate quantification and evolutionary inference are essential to understand the functional consequences of ITH. The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data.
[ { "created": "Fri, 7 Jun 2013 10:50:44 GMT", "version": "v1" } ]
2015-06-16
[ [ "Schwarz", "Roland F", "" ], [ "Trinh", "Anne", "" ], [ "Sipos", "Botond", "" ], [ "Brenton", "James D", "" ], [ "Goldman", "Nick", "" ], [ "Markowetz", "Florian", "" ] ]
Background: Intra-tumour heterogeneity (ITH) is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance and if so would have prognostic and predictive utility. However, methods for objectively quantifying ITH have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements. Results: To address these challenges we present MEDICC, a method for phylogenetic reconstruction and ITH quantification based on a Minimum Event Distance for Intra-tumour Copynumber Comparisons. Using a transducer-based pairwise comparison function we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes. Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy and additionally allows unbiased numerical quantification of ITH. Conclusions: Accurate quantification and evolutionary inference are essential to understand the functional consequences of ITH. The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data.
1908.02913
Fabio Sanchez PhD
Fabio Sanchez, Jorge Arroyo-Esquivel, Paola Vasquez
Hospitalization in the transmission of dengue dynamics: The impact on public health policies
19 pages, 7 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Dengue virus has caused major problems for public health officials for decades in tropical and subtropical countries. We construct a compartmental model that includes the risk of hospitalization and its impact on public health policies. The basic reproductive number, $\mathcal{R}_0$, is computed, as well as a sensitivity analysis on $\mathcal{R}_0$ parameters and discuss the relevance in public health policies. The local and global stability of the disease-free equilibrium is established. Numerical simulations are performed to better determine future prevention/control strategies.
[ { "created": "Thu, 8 Aug 2019 03:21:53 GMT", "version": "v1" } ]
2019-08-09
[ [ "Sanchez", "Fabio", "" ], [ "Arroyo-Esquivel", "Jorge", "" ], [ "Vasquez", "Paola", "" ] ]
Dengue virus has caused major problems for public health officials for decades in tropical and subtropical countries. We construct a compartmental model that includes the risk of hospitalization and its impact on public health policies. The basic reproductive number, $\mathcal{R}_0$, is computed, as well as a sensitivity analysis on $\mathcal{R}_0$ parameters and discuss the relevance in public health policies. The local and global stability of the disease-free equilibrium is established. Numerical simulations are performed to better determine future prevention/control strategies.
2309.06447
Malgorzata O'Reilly
Albert C. Soewongsono and Jiahao Diao and Tristan Stark and Amanda E. Wilson and David A. Liberles and Barbara R. Holland and Malgorzata M. O'Reilly
Matrix-analytic methods for the evolution of species trees, gene trees, and their reconciliation
Corrected names of two authors (Liberles, Holland). Added further details of the contributions in the Acknowledgements
null
null
null
q-bio.PE math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We consider the reconciliation problem, in which the task is to find a mapping of a gene tree into a species tree, so as to maximize the likelihood of such fitting, given the available data. We describe a model for the evolution of the species tree, a subfunctionalisation model for the evolution of the gene tree, and provide an algorithm to compute the likelihood of the reconciliation. We derive our results using the theory of matrix-analytic methods and describe efficient algorithms for the computation of a range of useful metrics. We illustrate the theory with examples and provide the physical interpretations of the discussed quantities, with a focus on the practical applications of the theory to incomplete data.
[ { "created": "Tue, 12 Sep 2023 01:26:11 GMT", "version": "v1" }, { "created": "Wed, 8 Nov 2023 06:18:12 GMT", "version": "v2" } ]
2023-11-09
[ [ "Soewongsono", "Albert C.", "" ], [ "Diao", "Jiahao", "" ], [ "Stark", "Tristan", "" ], [ "Wilson", "Amanda E.", "" ], [ "Liberles", "David A.", "" ], [ "Holland", "Barbara R.", "" ], [ "O'Reilly", "Malgorzata M.", "" ] ]
We consider the reconciliation problem, in which the task is to find a mapping of a gene tree into a species tree, so as to maximize the likelihood of such fitting, given the available data. We describe a model for the evolution of the species tree, a subfunctionalisation model for the evolution of the gene tree, and provide an algorithm to compute the likelihood of the reconciliation. We derive our results using the theory of matrix-analytic methods and describe efficient algorithms for the computation of a range of useful metrics. We illustrate the theory with examples and provide the physical interpretations of the discussed quantities, with a focus on the practical applications of the theory to incomplete data.
1605.08228
Angelo Valleriani
Marco Rusconi, Angelo Valleriani
Predict or classify: The deceptive role of time-locking in brain signal classification
23 pages, 5 figures
Scientific Reports 6, 28236 (2016)
10.1038/srep28236
null
q-bio.NC physics.bio-ph stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Several experimental studies claim to be able to predict the outcome of simple decisions from brain signals measured before subjects are aware of their decision. Often, these studies use multivariate pattern recognition methods with the underlying assumption that the ability to classify the brain signal is equivalent to predict the decision itself. Here we show instead that it is possible to correctly classify a signal even if it does not contain any predictive information about the decision. We first define a simple stochastic model that mimics the random decision process between two equivalent alternatives, and generate a large number of independent trials that contain no choice-predictive information. The trials are first time-locked to the time point of the final event and then classified using standard machine-learning techniques. The resulting classification accuracy is above chance level long before the time point of time-locking. We then analyze the same trials using information theory. We demonstrate that the high classification accuracy is a consequence of time-locking and that its time behavior is simply related to the large relaxation time of the process. We conclude that when time-locking is a crucial step in the analysis of neural activity patterns, both the emergence and the timing of the classification accuracy are affected by structural properties of the network that generates the signal.
[ { "created": "Thu, 26 May 2016 11:17:41 GMT", "version": "v1" }, { "created": "Fri, 10 Jun 2016 12:23:34 GMT", "version": "v2" } ]
2016-06-21
[ [ "Rusconi", "Marco", "" ], [ "Valleriani", "Angelo", "" ] ]
Several experimental studies claim to be able to predict the outcome of simple decisions from brain signals measured before subjects are aware of their decision. Often, these studies use multivariate pattern recognition methods with the underlying assumption that the ability to classify the brain signal is equivalent to predict the decision itself. Here we show instead that it is possible to correctly classify a signal even if it does not contain any predictive information about the decision. We first define a simple stochastic model that mimics the random decision process between two equivalent alternatives, and generate a large number of independent trials that contain no choice-predictive information. The trials are first time-locked to the time point of the final event and then classified using standard machine-learning techniques. The resulting classification accuracy is above chance level long before the time point of time-locking. We then analyze the same trials using information theory. We demonstrate that the high classification accuracy is a consequence of time-locking and that its time behavior is simply related to the large relaxation time of the process. We conclude that when time-locking is a crucial step in the analysis of neural activity patterns, both the emergence and the timing of the classification accuracy are affected by structural properties of the network that generates the signal.
2305.18841
Annie Adhikary
Annie Adhikary
Identification of Novel Diagnostic Neuroimaging Biomarkers for Autism Spectrum Disorder Through Convolutional Neural Network-Based Analysis of Functional, Structural, and Diffusion Tensor Imaging Data Towards Enhanced Autism Diagnosis
15 pages, 7 figures, 2 tables
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Autism spectrum disorder is one of the leading neurodevelopmental disorders in our world, present in over 1% of the population and rapidly increasing in prevalence, yet the condition lacks a robust, objective, and efficient diagnostic. Clinical diagnostic criteria rely on subjective behavioral assessments, which are prone to misdiagnosis as they face limitations in terms of their heterogeneity, specificity, and biases. This study proposes a novel convolutional neural network-based classification tool that aims to identify the potential of different neuroimaging features as autism biomarkers. The model is constructed using a set of sequential layers specifically designed to extract relevant features from brain imaging data. Trained and tested on over 300,000 distinct features across three imaging types, the model shows promise in classifying individuals with autism from typical controls, outperforming metrics of current gold standard diagnostics by achieving an accuracy of 95.4% on a dataset of 1,111 samples with 521 autistic subjects (260 male and 261 female) and 590 controls (297 male and 293 female). 32 optimal features from the training data were identified and classified as candidate biomarkers using an independent samples t-test, in which functional features such as connectivity and the time series of signal intensity from each voxel exhibited the highest mean value differences between individuals with autism and typical control subjects. The p-values of these biomarkers were < 0.001, proving the statistical significance of the results and indicating that this research could pave the way towards the usage of neuroimaging in conjunction with behavioral criteria in clinics.
[ { "created": "Tue, 30 May 2023 08:34:00 GMT", "version": "v1" }, { "created": "Thu, 29 Feb 2024 21:08:17 GMT", "version": "v2" } ]
2024-03-04
[ [ "Adhikary", "Annie", "" ] ]
Autism spectrum disorder is one of the leading neurodevelopmental disorders in our world, present in over 1% of the population and rapidly increasing in prevalence, yet the condition lacks a robust, objective, and efficient diagnostic. Clinical diagnostic criteria rely on subjective behavioral assessments, which are prone to misdiagnosis as they face limitations in terms of their heterogeneity, specificity, and biases. This study proposes a novel convolutional neural network-based classification tool that aims to identify the potential of different neuroimaging features as autism biomarkers. The model is constructed using a set of sequential layers specifically designed to extract relevant features from brain imaging data. Trained and tested on over 300,000 distinct features across three imaging types, the model shows promise in classifying individuals with autism from typical controls, outperforming metrics of current gold standard diagnostics by achieving an accuracy of 95.4% on a dataset of 1,111 samples with 521 autistic subjects (260 male and 261 female) and 590 controls (297 male and 293 female). 32 optimal features from the training data were identified and classified as candidate biomarkers using an independent samples t-test, in which functional features such as connectivity and the time series of signal intensity from each voxel exhibited the highest mean value differences between individuals with autism and typical control subjects. The p-values of these biomarkers were < 0.001, proving the statistical significance of the results and indicating that this research could pave the way towards the usage of neuroimaging in conjunction with behavioral criteria in clinics.
2305.12386
David Morselli
David Morselli, Marcello Edoardo Delitala, Federico Frascoli
Agent-based and continuum models for spatial dynamics of infection by oncolytic viruses
29 pages, 10 figures. Supplementary material available at https://tinyurl.com/5c5nxss8
Bull Math Biol 85, 92 (2023)
10.1007/s11538-023-01192-x
null
q-bio.PE q-bio.CB
http://creativecommons.org/licenses/by/4.0/
The use of oncolytic viruses as cancer treatment has received considerable attention in recent years, however the spatial dynamics of this viral infection is still poorly understood. We present here a stochastic agent-based model describing infected and uninfected cells for solid tumours, which interact with viruses in the absence of an immune response. Two kinds of movement, namely undirected random and pressure-driven movements, are considered: the continuum limit of the models is derived and a systematic comparison between the systems of partial differential equations and the individual-based model, in one and two dimensions, is carried out. In the case of undirected movement, a good agreement between agent-based simulations and the numerical and well-known analytical results for the continuum model is possible. For pressure-driven motion, instead, we observe a wide parameter range in which the infection of the agents remains confined to the center of the tumour, even though the continuum model shows traveling waves of infection; outcomes appear to be more sensitive to stochasticity and uninfected regions appear harder to invade, giving rise to irregular, unpredictable growth patterns. Our results show that the presence of spatial constraints in tumours' microenvironments limiting free expansion has a very significant impact on virotherapy. Outcomes for these tumours suggest a notable increase in variability. All these aspects can have important effects when designing individually tailored therapies where virotherapy is included.
[ { "created": "Sun, 21 May 2023 07:57:46 GMT", "version": "v1" }, { "created": "Tue, 5 Sep 2023 14:13:14 GMT", "version": "v2" } ]
2023-09-06
[ [ "Morselli", "David", "" ], [ "Delitala", "Marcello Edoardo", "" ], [ "Frascoli", "Federico", "" ] ]
The use of oncolytic viruses as cancer treatment has received considerable attention in recent years, however the spatial dynamics of this viral infection is still poorly understood. We present here a stochastic agent-based model describing infected and uninfected cells for solid tumours, which interact with viruses in the absence of an immune response. Two kinds of movement, namely undirected random and pressure-driven movements, are considered: the continuum limit of the models is derived and a systematic comparison between the systems of partial differential equations and the individual-based model, in one and two dimensions, is carried out. In the case of undirected movement, a good agreement between agent-based simulations and the numerical and well-known analytical results for the continuum model is possible. For pressure-driven motion, instead, we observe a wide parameter range in which the infection of the agents remains confined to the center of the tumour, even though the continuum model shows traveling waves of infection; outcomes appear to be more sensitive to stochasticity and uninfected regions appear harder to invade, giving rise to irregular, unpredictable growth patterns. Our results show that the presence of spatial constraints in tumours' microenvironments limiting free expansion has a very significant impact on virotherapy. Outcomes for these tumours suggest a notable increase in variability. All these aspects can have important effects when designing individually tailored therapies where virotherapy is included.
1609.04902
Momiao Xiong
Nan Lin, Yun Zhu, Ruzong Fan and Momiao Xiong
A Quadratically Regularized Functional Canonical Correlation Analysis for Identifying the Global Structure of Pleiotropy with NGS Data
64 pages including 12 figures
null
10.1371/journal.pcbi.1005788
null
q-bio.GN stat.ME
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Investigating the pleiotropic effects of genetic variants can increase statistical power, provide important information to achieve deep understanding of the complex genetic structures of disease, and offer powerful tools for designing effective treatments with fewer side effects. However, the current multiple phenotype association analysis paradigm lacks breadth (number of phenotypes and genetic variants jointly analyzed at the same time) and depth (hierarchical structure of phenotype and genotypes). A key issue for high dimensional pleiotropic analysis is to effectively extract informative internal representation and features from high dimensional genotype and phenotype data. To explore multiple levels of representations of genetic variants, learn their internal patterns involved in the disease development, and overcome critical barriers in advancing the development of novel statistical methods and computational algorithms for genetic pleiotropic analysis, we proposed a new framework referred to as a quadratically regularized functional CCA (QRFCCA) for association analysis which combines three approaches: (1) quadratically regularized matrix factorization, (2) functional data analysis and (3) canonical correlation analysis (CCA). Large-scale simulations show that the QRFCCA has a much higher power than that of the nine competing statistics while retaining the appropriate type 1 errors. To further evaluate performance, the QRFCCA and nine other statistics are applied to the whole genome sequencing dataset from the TwinsUK study. We identify a total of 79 genes with rare variants and 67 genes with common variants significantly associated with the 46 traits using QRFCCA. The results show that the QRFCCA substantially outperforms the nine other statistics.
[ { "created": "Fri, 16 Sep 2016 03:18:44 GMT", "version": "v1" } ]
2018-02-07
[ [ "Lin", "Nan", "" ], [ "Zhu", "Yun", "" ], [ "Fan", "Ruzong", "" ], [ "Xiong", "Momiao", "" ] ]
Investigating the pleiotropic effects of genetic variants can increase statistical power, provide important information to achieve deep understanding of the complex genetic structures of disease, and offer powerful tools for designing effective treatments with fewer side effects. However, the current multiple phenotype association analysis paradigm lacks breadth (number of phenotypes and genetic variants jointly analyzed at the same time) and depth (hierarchical structure of phenotype and genotypes). A key issue for high dimensional pleiotropic analysis is to effectively extract informative internal representation and features from high dimensional genotype and phenotype data. To explore multiple levels of representations of genetic variants, learn their internal patterns involved in the disease development, and overcome critical barriers in advancing the development of novel statistical methods and computational algorithms for genetic pleiotropic analysis, we proposed a new framework referred to as a quadratically regularized functional CCA (QRFCCA) for association analysis which combines three approaches: (1) quadratically regularized matrix factorization, (2) functional data analysis and (3) canonical correlation analysis (CCA). Large-scale simulations show that the QRFCCA has a much higher power than that of the nine competing statistics while retaining the appropriate type 1 errors. To further evaluate performance, the QRFCCA and nine other statistics are applied to the whole genome sequencing dataset from the TwinsUK study. We identify a total of 79 genes with rare variants and 67 genes with common variants significantly associated with the 46 traits using QRFCCA. The results show that the QRFCCA substantially outperforms the nine other statistics.
1702.01703
Jens Quedenfeld
Jens Quedenfeld and Sven Rahmann
Variant tolerant read mapping using min-hashing
null
null
null
null
q-bio.GN cs.DS
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
DNA read mapping is a ubiquitous task in bioinformatics, and many tools have been developed to solve the read mapping problem. However, there are two trends that are changing the landscape of readmapping: First, new sequencing technologies provide very long reads with high error rates (up to 15%). Second, many genetic variants in the population are known, so the reference genome is not considered as a single string over ACGT, but as a complex object containing these variants. Most existing read mappers do not handle these new circumstances appropriately. We introduce a new read mapper prototype called VATRAM that considers variants. It is based on Min-Hashing of q-gram sets of reference genome windows. Min-Hashing is one form of locality sensitive hashing. The variants are directly inserted into VATRAMs index which leads to a fast mapping process. Our results show that VATRAM achieves better precision and recall than state-of-the-art read mappers like BWA under certain cirumstances. VATRAM is open source and can be accessed at https://bitbucket.org/Quedenfeld/vatram-src/.
[ { "created": "Mon, 6 Feb 2017 16:52:05 GMT", "version": "v1" }, { "created": "Wed, 8 Feb 2017 10:41:23 GMT", "version": "v2" } ]
2017-02-09
[ [ "Quedenfeld", "Jens", "" ], [ "Rahmann", "Sven", "" ] ]
DNA read mapping is a ubiquitous task in bioinformatics, and many tools have been developed to solve the read mapping problem. However, there are two trends that are changing the landscape of readmapping: First, new sequencing technologies provide very long reads with high error rates (up to 15%). Second, many genetic variants in the population are known, so the reference genome is not considered as a single string over ACGT, but as a complex object containing these variants. Most existing read mappers do not handle these new circumstances appropriately. We introduce a new read mapper prototype called VATRAM that considers variants. It is based on Min-Hashing of q-gram sets of reference genome windows. Min-Hashing is one form of locality sensitive hashing. The variants are directly inserted into VATRAMs index which leads to a fast mapping process. Our results show that VATRAM achieves better precision and recall than state-of-the-art read mappers like BWA under certain cirumstances. VATRAM is open source and can be accessed at https://bitbucket.org/Quedenfeld/vatram-src/.
2105.08288
Shuhan Zheng
Shuhan Zheng, Zhichao Liang, Youzhi Qu, Qingyuan Wu, Haiyan Wu, Quanying Liu
Kuramoto model based analysis reveals oxytocin effects on brain network dynamics
null
null
null
null
q-bio.NC q-bio.QM
http://creativecommons.org/licenses/by-nc-sa/4.0/
The oxytocin effects on large-scale brain networks such as Default Mode Network (DMN) and Frontoparietal Network (FPN) have been largely studied using fMRI data. However, these studies are mainly based on the statistical correlation or Bayesian causality inference, lacking interpretability at physical and neuroscience level. Here, we propose a physics-based framework of Kuramoto model to investigate oxytocin effects on the phase dynamic neural coupling in DMN and FPN. Testing on fMRI data of 59 participants administrated with either oxytocin or placebo, we demonstrate that oxytocin changes the topology of brain communities in DMN and FPN, leading to higher synchronization in the FPN and lower synchronization in the DMN, as well as a higher variance of the coupling strength within the DMN and more flexible coupling patterns across time. These results together indicate that oxytocin may increase the ability to overcome the corresponding internal oscillation dispersion and support the flexibility in neural synchrony in various social contexts, providing new evidence for explaining the oxytocin modulated social behaviors. Our proposed Kuramoto model-based framework can be a potential tool in network neuroscience and offers physical and neural insights into phase dynamics of the brain.
[ { "created": "Tue, 18 May 2021 05:32:07 GMT", "version": "v1" }, { "created": "Wed, 26 May 2021 08:26:21 GMT", "version": "v2" }, { "created": "Sun, 8 Aug 2021 10:55:12 GMT", "version": "v3" }, { "created": "Sat, 9 Oct 2021 05:04:29 GMT", "version": "v4" } ]
2021-10-12
[ [ "Zheng", "Shuhan", "" ], [ "Liang", "Zhichao", "" ], [ "Qu", "Youzhi", "" ], [ "Wu", "Qingyuan", "" ], [ "Wu", "Haiyan", "" ], [ "Liu", "Quanying", "" ] ]
The oxytocin effects on large-scale brain networks such as Default Mode Network (DMN) and Frontoparietal Network (FPN) have been largely studied using fMRI data. However, these studies are mainly based on the statistical correlation or Bayesian causality inference, lacking interpretability at physical and neuroscience level. Here, we propose a physics-based framework of Kuramoto model to investigate oxytocin effects on the phase dynamic neural coupling in DMN and FPN. Testing on fMRI data of 59 participants administrated with either oxytocin or placebo, we demonstrate that oxytocin changes the topology of brain communities in DMN and FPN, leading to higher synchronization in the FPN and lower synchronization in the DMN, as well as a higher variance of the coupling strength within the DMN and more flexible coupling patterns across time. These results together indicate that oxytocin may increase the ability to overcome the corresponding internal oscillation dispersion and support the flexibility in neural synchrony in various social contexts, providing new evidence for explaining the oxytocin modulated social behaviors. Our proposed Kuramoto model-based framework can be a potential tool in network neuroscience and offers physical and neural insights into phase dynamics of the brain.
1201.0339
Ido Kanter
Roni Vardi, Avner Wallach, Evi Kopelowitz, Moshe Abeles, Shimon Marom and Ido Kanter
Synthetic reverberating activity patterns embedded in networks of cortical neurons
8 pages, 5 figures
EPL (Europhysics Letters) 97, 66002 (2012)
10.1209/0295-5075/97/66002
null
q-bio.NC nlin.CD
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Synthetic reverberating activity patterns are experimentally generated by stimulation of a subset of neurons embedded in a spontaneously active network of cortical cells in-vitro. The neurons are artificially connected by means of conditional stimulation matrix, forming a synthetic local circuit with a predefined programmable connectivity and time-delays. Possible uses of this experimental design are demonstrated, analyzing the sensitivity of these deterministic activity patterns to transmission delays and to the nature of ongoing network dynamics.
[ { "created": "Sun, 1 Jan 2012 08:31:23 GMT", "version": "v1" }, { "created": "Mon, 26 Mar 2012 08:28:01 GMT", "version": "v2" } ]
2012-03-27
[ [ "Vardi", "Roni", "" ], [ "Wallach", "Avner", "" ], [ "Kopelowitz", "Evi", "" ], [ "Abeles", "Moshe", "" ], [ "Marom", "Shimon", "" ], [ "Kanter", "Ido", "" ] ]
Synthetic reverberating activity patterns are experimentally generated by stimulation of a subset of neurons embedded in a spontaneously active network of cortical cells in-vitro. The neurons are artificially connected by means of conditional stimulation matrix, forming a synthetic local circuit with a predefined programmable connectivity and time-delays. Possible uses of this experimental design are demonstrated, analyzing the sensitivity of these deterministic activity patterns to transmission delays and to the nature of ongoing network dynamics.
1903.04332
Emmanuel Paradis
Emmanuel Paradis (ISEM)
Interactions between spatial and temporal scales in the evolution of dispersal rate
null
Evolutionary Ecology, Springer Verlag, 1998, 12 (2), pp.235-244
10.1023/A:1006539930788
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The evolution of dispersal rate is studied with a model of several local populations linked by dispersal. Three dispersal strategies are considered where all, half, or none of the offspring disperse. The spatial scale (number of patches) and the temporal scale (probability of local extinction) of the environment are critical in determining the selective advantage of the different dispersal strategies. The results from the simulations suggest that an interaction between group selection and individual selection results in a different outcome in relation to the spatial and temporal scales of the environment. Such an interaction is able to maintain a polymorphism in dispersal strategies. The maintenance of this polymorphism is also scale-dependent. This study suggests a mechanism for the short-term evolution of dispersal, and provides a testable prediction of this hypothesis, namely that loss of dispersal abilities should be more frequent in spatially more continuous environments, or in temporally more stable environments.
[ { "created": "Mon, 11 Mar 2019 14:43:38 GMT", "version": "v1" } ]
2019-03-12
[ [ "Paradis", "Emmanuel", "", "ISEM" ] ]
The evolution of dispersal rate is studied with a model of several local populations linked by dispersal. Three dispersal strategies are considered where all, half, or none of the offspring disperse. The spatial scale (number of patches) and the temporal scale (probability of local extinction) of the environment are critical in determining the selective advantage of the different dispersal strategies. The results from the simulations suggest that an interaction between group selection and individual selection results in a different outcome in relation to the spatial and temporal scales of the environment. Such an interaction is able to maintain a polymorphism in dispersal strategies. The maintenance of this polymorphism is also scale-dependent. This study suggests a mechanism for the short-term evolution of dispersal, and provides a testable prediction of this hypothesis, namely that loss of dispersal abilities should be more frequent in spatially more continuous environments, or in temporally more stable environments.
1112.1391
Diogo Melo
Gabriel Marroig, Diogo Melo, Guilherme Garcia
Modularity, Noise and natural selection
null
Evolution, Vol. 66, Issue 5, pp 1506--1524 (Wiley, May 2012)
10.1111/j.1558-5646.2011.01555.x
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Most biological systems are formed by component parts that to some degree are inter-related. Groups of parts that are more associated among themselves and are relatively autonomous from others are called modules. One of the consequences of modularity is that biological systems usually present an unequal distribution of the genetic variation among variables. Estimating the covariance matrix that describes these systems is a difficult problem due to a number of factors such as poor sample sizes and measurement errors. We show that this problem will be exacerbated whenever matrix inversion is required, as in directional selection reconstruction analysis. We explore the consequences of varying degrees of modularity and signal-to-noise ratio on selection reconstruction. We then present and test the efficiency of available methods for controlling noise in matrix estimates. In our simulations, controlling matrices for noise vastly improves the reconstruction of selection gradients. We also perform an analysis of selection gradients reconstruction over a New World Monkeys skull database in order to illustrate the impact of noise on such analyses. Noise- controlled estimates render far more plausible interpretations that are in full agreement with previous results.
[ { "created": "Tue, 6 Dec 2011 20:18:04 GMT", "version": "v1" } ]
2013-08-12
[ [ "Marroig", "Gabriel", "" ], [ "Melo", "Diogo", "" ], [ "Garcia", "Guilherme", "" ] ]
Most biological systems are formed by component parts that to some degree are inter-related. Groups of parts that are more associated among themselves and are relatively autonomous from others are called modules. One of the consequences of modularity is that biological systems usually present an unequal distribution of the genetic variation among variables. Estimating the covariance matrix that describes these systems is a difficult problem due to a number of factors such as poor sample sizes and measurement errors. We show that this problem will be exacerbated whenever matrix inversion is required, as in directional selection reconstruction analysis. We explore the consequences of varying degrees of modularity and signal-to-noise ratio on selection reconstruction. We then present and test the efficiency of available methods for controlling noise in matrix estimates. In our simulations, controlling matrices for noise vastly improves the reconstruction of selection gradients. We also perform an analysis of selection gradients reconstruction over a New World Monkeys skull database in order to illustrate the impact of noise on such analyses. Noise- controlled estimates render far more plausible interpretations that are in full agreement with previous results.
1210.6295
Daniel Fisher
Daniel S. Fisher
Asexual Evolution Waves: Fluctuations and Universality
3 figures
null
10.1088/1742-5468/2013/01/P01011
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In large asexual populations, multiple beneficial mutations arise in the population, compete, interfere with each other, and accumulate on the same genome, before any of them fix. The resulting dynamics, although studied by many authors, is still not fully understood, fundamentally because the effects of fluctuations due to the small numbers of the fittest individuals are large even in enormous populations. In this paper, branching processes and various asymptotic methods for analyzing the stochastic dynamics are further developed and used to obtain information on fluctuations, time dependence, and the distributions of sizes of subpopulations, jumps in the mean fitness, and other properties. The focus is on the behavior of a broad class of models: those with a distribution of selective advantages of available beneficial mutations that falls off more rapidly than exponentially. For such distributions, many aspects of the dynamics are universal - quantitatively so for extremely large populations. On the most important time scale that controls coalescent properties and fluctuations of the speed, the dynamics is reduced to a simple stochastic model that couples the peak and the high-fitness "nose" of the fitness distribution. Extensions to other models and distributions of available mutations are discussed briefly.
[ { "created": "Tue, 23 Oct 2012 17:19:10 GMT", "version": "v1" } ]
2015-06-11
[ [ "Fisher", "Daniel S.", "" ] ]
In large asexual populations, multiple beneficial mutations arise in the population, compete, interfere with each other, and accumulate on the same genome, before any of them fix. The resulting dynamics, although studied by many authors, is still not fully understood, fundamentally because the effects of fluctuations due to the small numbers of the fittest individuals are large even in enormous populations. In this paper, branching processes and various asymptotic methods for analyzing the stochastic dynamics are further developed and used to obtain information on fluctuations, time dependence, and the distributions of sizes of subpopulations, jumps in the mean fitness, and other properties. The focus is on the behavior of a broad class of models: those with a distribution of selective advantages of available beneficial mutations that falls off more rapidly than exponentially. For such distributions, many aspects of the dynamics are universal - quantitatively so for extremely large populations. On the most important time scale that controls coalescent properties and fluctuations of the speed, the dynamics is reduced to a simple stochastic model that couples the peak and the high-fitness "nose" of the fitness distribution. Extensions to other models and distributions of available mutations are discussed briefly.
2403.00951
Eric Maris
Eric Maris
An internal sensory model allows for balance control based on non-actionable proprioceptive feedback
69 pages, 53 pages main text plus 3 figures
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by-nc-nd/4.0/
All motor tasks with a mechanical system (a human body, a rider on a bicycle) that is approximately linear in the part of the state space where it stays most of the time (e.g., upright balance control) have the following property: actionable sensory feedback allows for optimal control actions that are a simple linear combination of the sensory feedback. When only non-actionable sensory feedback is available, optimal control for these approximately linear mechanical systems is based on an internal dynamical system that estimates the states, and that can be implemented as a recurrent neural network (RNN). It uses a sensory model to update the state estimates with the non-actionable sensory feedback, and the weights of this RNN are fully specified by results from optimal feedback control. This is highly relevant for muscle spindle afferent firing rates which, under perfectly coordinated fusimotor and skeletomotor control, scale with the exafferent joint acceleration component. The resulting control mechanism balances a standing body and a rider-bicycle combination using realistic parameter values and with forcing torques that are feasible for humans.
[ { "created": "Fri, 1 Mar 2024 19:58:22 GMT", "version": "v1" }, { "created": "Tue, 5 Mar 2024 16:58:19 GMT", "version": "v2" }, { "created": "Fri, 29 Mar 2024 10:27:36 GMT", "version": "v3" } ]
2024-04-01
[ [ "Maris", "Eric", "" ] ]
All motor tasks with a mechanical system (a human body, a rider on a bicycle) that is approximately linear in the part of the state space where it stays most of the time (e.g., upright balance control) have the following property: actionable sensory feedback allows for optimal control actions that are a simple linear combination of the sensory feedback. When only non-actionable sensory feedback is available, optimal control for these approximately linear mechanical systems is based on an internal dynamical system that estimates the states, and that can be implemented as a recurrent neural network (RNN). It uses a sensory model to update the state estimates with the non-actionable sensory feedback, and the weights of this RNN are fully specified by results from optimal feedback control. This is highly relevant for muscle spindle afferent firing rates which, under perfectly coordinated fusimotor and skeletomotor control, scale with the exafferent joint acceleration component. The resulting control mechanism balances a standing body and a rider-bicycle combination using realistic parameter values and with forcing torques that are feasible for humans.
1406.7256
Seth Sullivant
Colby Long and Seth Sullivant
Identifiability of 3-Class Jukes-Cantor Mixtures
16 pages, 7 figures
null
null
null
q-bio.PE math.AG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We prove identifiability of the tree parameters of the 3-class Jukes-Cantor mixture model. The proof uses ideas from algebraic statistics, in particular: finding phylogenetic invariants that separate the varieties associated to different triples of trees; computing dimensions of the resulting phylogenetic varieties; and using the disentangling number to reduce to trees with a small number of leaves. Symbolic computation also plays a key role in handling the many different cases and finding relevant phylogenetic invariants.
[ { "created": "Fri, 27 Jun 2014 18:09:53 GMT", "version": "v1" }, { "created": "Sat, 9 Aug 2014 18:48:28 GMT", "version": "v2" } ]
2014-08-12
[ [ "Long", "Colby", "" ], [ "Sullivant", "Seth", "" ] ]
We prove identifiability of the tree parameters of the 3-class Jukes-Cantor mixture model. The proof uses ideas from algebraic statistics, in particular: finding phylogenetic invariants that separate the varieties associated to different triples of trees; computing dimensions of the resulting phylogenetic varieties; and using the disentangling number to reduce to trees with a small number of leaves. Symbolic computation also plays a key role in handling the many different cases and finding relevant phylogenetic invariants.
2301.06755
Claus Metzner
Claus Metzner, Achim Schilling, Maximilian Traxdorf, Holger Schulze, Konstantin Tziridis and Patrick Krauss
Extracting continuous sleep depth from EEG data without machine learning
null
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
The human sleep-cycle has been divided into discrete sleep stages that can be recognized in electroencephalographic (EEG) and other bio-signals by trained specialists or machine learning systems. It is however unclear whether these human-defined stages can be re-discovered with unsupervised methods of data analysis, using only a minimal amount of generic pre-processing. Based on EEG data, recorded overnight from sleeping human subjects, we investigate the degree of clustering of the sleep stages using the General Discrimination Value as a quantitative measure of class separability. Virtually no clustering is found in the raw data, even after transforming the EEG signals of each thirty-second epoch from the time domain into the more informative frequency domain. However, a Principal Component Analysis (PCA) of these epoch-wise frequency spectra reveals that the sleep stages separate significantly better in the low-dimensional sub-space of certain PCA components. In particular the component $C_1(t)$ can serve as a robust, continuous 'master variable' that encodes the depth of sleep and therefore correlates strongly with the 'hypnogram', a common plot of the discrete sleep stages over time. Moreover, $C_1(t)$ shows persistent trends during extended time periods where the sleep stage is constant, suggesting that sleep may be better understood as a continuum. These intriguing properties of $C_1(t)$ are not only relevant for understanding brain dynamics during sleep, but might also be exploited in low-cost single-channel sleep tracking devices for private and clinical use.
[ { "created": "Tue, 17 Jan 2023 08:39:34 GMT", "version": "v1" } ]
2023-01-18
[ [ "Metzner", "Claus", "" ], [ "Schilling", "Achim", "" ], [ "Traxdorf", "Maximilian", "" ], [ "Schulze", "Holger", "" ], [ "Tziridis", "Konstantin", "" ], [ "Krauss", "Patrick", "" ] ]
The human sleep-cycle has been divided into discrete sleep stages that can be recognized in electroencephalographic (EEG) and other bio-signals by trained specialists or machine learning systems. It is however unclear whether these human-defined stages can be re-discovered with unsupervised methods of data analysis, using only a minimal amount of generic pre-processing. Based on EEG data, recorded overnight from sleeping human subjects, we investigate the degree of clustering of the sleep stages using the General Discrimination Value as a quantitative measure of class separability. Virtually no clustering is found in the raw data, even after transforming the EEG signals of each thirty-second epoch from the time domain into the more informative frequency domain. However, a Principal Component Analysis (PCA) of these epoch-wise frequency spectra reveals that the sleep stages separate significantly better in the low-dimensional sub-space of certain PCA components. In particular the component $C_1(t)$ can serve as a robust, continuous 'master variable' that encodes the depth of sleep and therefore correlates strongly with the 'hypnogram', a common plot of the discrete sleep stages over time. Moreover, $C_1(t)$ shows persistent trends during extended time periods where the sleep stage is constant, suggesting that sleep may be better understood as a continuum. These intriguing properties of $C_1(t)$ are not only relevant for understanding brain dynamics during sleep, but might also be exploited in low-cost single-channel sleep tracking devices for private and clinical use.
1411.0159
Viktoras Veitas Mr.
David Weinbaum (Weaver) and Viktoras Veitas
Synthetic Cognitive Development: where intelligence comes from
Preprint. 28 pages LaTeX, 5 figures, 1 table; en-US proofreading; section 4.2 rewritten; bibliography corrected
null
null
null
q-bio.NC nlin.AO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The human cognitive system is a remarkable exemplar of a general intelligent system whose competence is not confined to a specific problem domain. Evidently, general cognitive competences are a product of a prolonged and complex process of cognitive development. Therefore, the process of cognitive development is a primary key to understanding the emergence of intelligent behavior. This paper develops the theoretical foundations for a model that generalizes the process of cognitive development. The model aims to provide a realistic scheme for the synthesis of scalable cognitive systems with an open-ended range of capabilities. Major concepts and theories of human cognitive development are introduced and briefly explored focusing on the enactive approach to cognition and the concept of sense-making. The initial scheme of human cognitive development is then generalized by introducing the philosophy of individuation and the abstract mechanism of transduction. The theory of individuation provides the ground for the necessary paradigmatic shift from cognitive systems as given products to cognitive development as a formative process of self-organization. Next, the conceptual model is specified as a scalable scheme of networks of agents. The mechanisms of individuation are formulated in context independent information theoretical terms. Finally, the paper discusses two concrete aspects of the generative model -- mechanisms of transduction and value modulating systems. These are topics of further research towards a computationally realizable model.
[ { "created": "Sat, 1 Nov 2014 19:28:51 GMT", "version": "v1" }, { "created": "Sat, 13 Dec 2014 18:57:14 GMT", "version": "v2" } ]
2014-12-16
[ [ "Weinbaum", "David", "", "Weaver" ], [ "Veitas", "Viktoras", "" ] ]
The human cognitive system is a remarkable exemplar of a general intelligent system whose competence is not confined to a specific problem domain. Evidently, general cognitive competences are a product of a prolonged and complex process of cognitive development. Therefore, the process of cognitive development is a primary key to understanding the emergence of intelligent behavior. This paper develops the theoretical foundations for a model that generalizes the process of cognitive development. The model aims to provide a realistic scheme for the synthesis of scalable cognitive systems with an open-ended range of capabilities. Major concepts and theories of human cognitive development are introduced and briefly explored focusing on the enactive approach to cognition and the concept of sense-making. The initial scheme of human cognitive development is then generalized by introducing the philosophy of individuation and the abstract mechanism of transduction. The theory of individuation provides the ground for the necessary paradigmatic shift from cognitive systems as given products to cognitive development as a formative process of self-organization. Next, the conceptual model is specified as a scalable scheme of networks of agents. The mechanisms of individuation are formulated in context independent information theoretical terms. Finally, the paper discusses two concrete aspects of the generative model -- mechanisms of transduction and value modulating systems. These are topics of further research towards a computationally realizable model.
2301.09569
Alessandro Sergi
Alessandro Sergi, Antonino Messina, Carmelo M. Vicario, Gabriella Martino
A Quantum-Classical Model of Brain Dynamics
Submitted to Entropy [MDPI], Special Issue "Quantum Processes in Living Systems"
null
10.3390/e25040592
null
q-bio.NC quant-ph
http://creativecommons.org/licenses/by/4.0/
The study of the human psyche has elucidated a bipartite structure of cognition reflecting the quantum-classical nature of any process that generates knowledge and learning governed by brain activity. Acknowledging the importance of such a finding for modelization, we posit an approach to study brain by means of the quantum-classical dynamics of a Mixed Weyl symbol. The Mixed Weyl symbol is used to describe brain processes at the microscopic level and provides a link to the results of measurements made at the mesoscopic scale. Within this approach, quantum variables (such as,for example, nuclear and electron spins, dipole momenta of particles or molecules, tunneling degrees of freedom, etc may be represented by spinors while the electromagnetic fields and phonon modes involved in the processes are treated either classically or semi-classically, by also considering quantum zero-point fluctuations. Zero-point quantum effects can be incorporated into numerical simulations by controlling the temperature of each field mode via coupling to a dedicated Nos\`e-Hoover chain thermostat. The temperature of each thermostat is chosen in order to reproduce quantum statistics in the canonical ensemble. In this first paper, we introduce a quantum-classical model of brain dynamics, clarifying its mathematical strucure and focusing the discussion on its predictive value. Analytical consequences of the model are not reported in this paper, since they are left for future work. Our treatment incorporates compatible features of three well-known quantum approaches to brain dynamics - namely the electromagnetic field theory approach, the orchestrated objective reduction theory, and the dissipative quantum model of the brain - and hints at convincing arguments that sustain the existence of quantum-classical processes in the brain activity. All three models are reviewed.
[ { "created": "Tue, 17 Jan 2023 15:16:21 GMT", "version": "v1" }, { "created": "Sat, 28 Jan 2023 02:06:55 GMT", "version": "v2" }, { "created": "Sun, 26 Feb 2023 23:06:09 GMT", "version": "v3" }, { "created": "Thu, 30 Mar 2023 10:31:39 GMT", "version": "v4" } ]
2023-04-19
[ [ "Sergi", "Alessandro", "" ], [ "Messina", "Antonino", "" ], [ "Vicario", "Carmelo M.", "" ], [ "Martino", "Gabriella", "" ] ]
The study of the human psyche has elucidated a bipartite structure of cognition reflecting the quantum-classical nature of any process that generates knowledge and learning governed by brain activity. Acknowledging the importance of such a finding for modelization, we posit an approach to study brain by means of the quantum-classical dynamics of a Mixed Weyl symbol. The Mixed Weyl symbol is used to describe brain processes at the microscopic level and provides a link to the results of measurements made at the mesoscopic scale. Within this approach, quantum variables (such as,for example, nuclear and electron spins, dipole momenta of particles or molecules, tunneling degrees of freedom, etc may be represented by spinors while the electromagnetic fields and phonon modes involved in the processes are treated either classically or semi-classically, by also considering quantum zero-point fluctuations. Zero-point quantum effects can be incorporated into numerical simulations by controlling the temperature of each field mode via coupling to a dedicated Nos\`e-Hoover chain thermostat. The temperature of each thermostat is chosen in order to reproduce quantum statistics in the canonical ensemble. In this first paper, we introduce a quantum-classical model of brain dynamics, clarifying its mathematical strucure and focusing the discussion on its predictive value. Analytical consequences of the model are not reported in this paper, since they are left for future work. Our treatment incorporates compatible features of three well-known quantum approaches to brain dynamics - namely the electromagnetic field theory approach, the orchestrated objective reduction theory, and the dissipative quantum model of the brain - and hints at convincing arguments that sustain the existence of quantum-classical processes in the brain activity. All three models are reviewed.
1311.1481
Chiara Poletto Miss
Chiara Poletto, Camille Pelat, Daniel Levy-Bruhl, Yazdan Yazdanpanah, Pierre-Yves Boelle, Vittoria Colizza
Assessment of the MERS-CoV epidemic situation in the Middle East region
in press on Eurosurveillance, 16 pages, 3 figures
Eurosurveillance Volume 19, Issue 23, 12/Jun/2014
10.2807/1560-7917.ES2014.19.23.20824
null
q-bio.PE q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The appearance of a novel coronavirus named Middle East (ME) Respiratory Syndrome Coronavirus (MERS-CoV) has raised global public health concerns regarding the current situation and its future evolution. Here we propose an integrative maximum likelihood analysis of both cluster data in the ME region and importations in Europe to assess transmission scenario and incidence of sporadic infections. Our approach is based on a spatial-transmission model integrating mobility data worldwide and allows for variations in the zoonotic/environmental transmission and underascertainment. Maximum likelihood estimates for the ME region indicate the occurrence of a subcritical epidemic (R=0.50, 95% confidence interval (CI) 0.30-0.77) associated with a 0.28 (95% CI 0.12-0.85) daily rate of sporadic introductions. Infections in the region appear to be mainly dominated by zoonotic/environmental transmissions, with possible underascertainment (95% CI of estimated to observed sporadic cases in the range 1.03-7.32). No time evolution of the situation emerges. Analyses of flight passenger data from the region indicate areas at high risk of importation. While dismissing an immediate threat for global health security, this analysis provides a baseline scenario for future reference and updates, suggests reinforced surveillance to limit underascertainment, and calls for increased alertness in high-risk areas worldwide.
[ { "created": "Wed, 6 Nov 2013 19:45:42 GMT", "version": "v1" }, { "created": "Mon, 5 May 2014 08:35:25 GMT", "version": "v2" } ]
2020-05-30
[ [ "Poletto", "Chiara", "" ], [ "Pelat", "Camille", "" ], [ "Levy-Bruhl", "Daniel", "" ], [ "Yazdanpanah", "Yazdan", "" ], [ "Boelle", "Pierre-Yves", "" ], [ "Colizza", "Vittoria", "" ] ]
The appearance of a novel coronavirus named Middle East (ME) Respiratory Syndrome Coronavirus (MERS-CoV) has raised global public health concerns regarding the current situation and its future evolution. Here we propose an integrative maximum likelihood analysis of both cluster data in the ME region and importations in Europe to assess transmission scenario and incidence of sporadic infections. Our approach is based on a spatial-transmission model integrating mobility data worldwide and allows for variations in the zoonotic/environmental transmission and underascertainment. Maximum likelihood estimates for the ME region indicate the occurrence of a subcritical epidemic (R=0.50, 95% confidence interval (CI) 0.30-0.77) associated with a 0.28 (95% CI 0.12-0.85) daily rate of sporadic introductions. Infections in the region appear to be mainly dominated by zoonotic/environmental transmissions, with possible underascertainment (95% CI of estimated to observed sporadic cases in the range 1.03-7.32). No time evolution of the situation emerges. Analyses of flight passenger data from the region indicate areas at high risk of importation. While dismissing an immediate threat for global health security, this analysis provides a baseline scenario for future reference and updates, suggests reinforced surveillance to limit underascertainment, and calls for increased alertness in high-risk areas worldwide.
0901.0990
Wojciech Waga
Jakub Kowalski, Wojciech Waga, Marta Zawierta, Stanislaw Cebrat
Phase transition in the genome evolution favours non-random distribution of genes on chromosomes
13 pages, 7 figures, publication
null
10.1142/S0129183109014370
null
q-bio.GN q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We have used the Monte Carlo based computer models to show that selection pressure could affect the distribution of recombination hotspots along the chromosome. Close to critical crossover rate, where genomes may switch between the Darwinian purifying selection or complementation of haplotypes, the distribution of recombination events and the force of selection exerted on genes affect the structure of chromosomes. The order of expression of gene s and their location on chromosome may decide about the extinction or survival of competing populations.
[ { "created": "Thu, 8 Jan 2009 08:57:17 GMT", "version": "v1" } ]
2015-05-13
[ [ "Kowalski", "Jakub", "" ], [ "Waga", "Wojciech", "" ], [ "Zawierta", "Marta", "" ], [ "Cebrat", "Stanislaw", "" ] ]
We have used the Monte Carlo based computer models to show that selection pressure could affect the distribution of recombination hotspots along the chromosome. Close to critical crossover rate, where genomes may switch between the Darwinian purifying selection or complementation of haplotypes, the distribution of recombination events and the force of selection exerted on genes affect the structure of chromosomes. The order of expression of gene s and their location on chromosome may decide about the extinction or survival of competing populations.
2101.04411
Christoph M Augustin
Laura Marx, Justyna A. Niestrawska, Matthias A. F. Gsell, Federica Caforio, Gernot Plank, Christoph M. Augustin
Efficient identification of myocardial material parameters and the stress-free reference configuration for patient-specific human heart models
This research has received funding from the European Union's Horizon 2020 research and innovation programme under the ERA-NET co-fund action No. 680969 (ERA-CVD SICVALVES) funded by the Austrian Science Fund (FWF), Grant I 4652-B
null
null
null
q-bio.TO physics.bio-ph physics.med-ph
http://creativecommons.org/licenses/by-nc-nd/4.0/
Image-based computational models of the heart represent a powerful tool to shed new light on the mechanisms underlying physiological and pathological conditions in cardiac function and to improve diagnosis and therapy planning. However, in order to enable the clinical translation of such models, it is crucial to develop personalized models that are able to reproduce the physiological reality of a given patient. There have been numerous contributions in experimental and computational biomechanics to characterize the passive behavior of the myocardium. However, most of these studies suffer from severe limitations and are not applicable to high-resolution geometries. In this work, we present a novel methodology to perform an automated identification of in vivo properties of passive cardiac biomechanics. The highly-efficient algorithm fits material parameters against the shape of a patient-specific approximation of the end-diastolic pressure-volume relation (EDPVR). Simultaneously, a stress-free reference configuration is generated, where a novel fail-safe feature to improve convergence and robustness is implemented. Only clinical image data or previously generated meshes at one time point during diastole and one measured data point of the EDPVR are required as an input. The proposed method can be straightforwardly coupled to existing finite element (FE) software packages and is applicable to different constitutive laws and FE formulations. Sensitivity analysis demonstrates that the algorithm is robust with respect to initial input parameters.
[ { "created": "Tue, 12 Jan 2021 11:18:56 GMT", "version": "v1" }, { "created": "Thu, 14 Jan 2021 15:33:43 GMT", "version": "v2" } ]
2021-01-15
[ [ "Marx", "Laura", "" ], [ "Niestrawska", "Justyna A.", "" ], [ "Gsell", "Matthias A. F.", "" ], [ "Caforio", "Federica", "" ], [ "Plank", "Gernot", "" ], [ "Augustin", "Christoph M.", "" ] ]
Image-based computational models of the heart represent a powerful tool to shed new light on the mechanisms underlying physiological and pathological conditions in cardiac function and to improve diagnosis and therapy planning. However, in order to enable the clinical translation of such models, it is crucial to develop personalized models that are able to reproduce the physiological reality of a given patient. There have been numerous contributions in experimental and computational biomechanics to characterize the passive behavior of the myocardium. However, most of these studies suffer from severe limitations and are not applicable to high-resolution geometries. In this work, we present a novel methodology to perform an automated identification of in vivo properties of passive cardiac biomechanics. The highly-efficient algorithm fits material parameters against the shape of a patient-specific approximation of the end-diastolic pressure-volume relation (EDPVR). Simultaneously, a stress-free reference configuration is generated, where a novel fail-safe feature to improve convergence and robustness is implemented. Only clinical image data or previously generated meshes at one time point during diastole and one measured data point of the EDPVR are required as an input. The proposed method can be straightforwardly coupled to existing finite element (FE) software packages and is applicable to different constitutive laws and FE formulations. Sensitivity analysis demonstrates that the algorithm is robust with respect to initial input parameters.
1308.1446
Kimberly Schlesinger
Kimberly J. Schlesinger, Sean P. Stromberg, and Jean M. Carlson
Coevolutionary immune system dynamics driving pathogen speciation
main article: 16 pages, 5 figures; supporting information: 3 pages
PLoS ONE 9(7): e102821
10.1371/journal.pone.0102821
null
q-bio.PE physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We introduce and analyze a within-host dynamical model of the coevolution between rapidly mutating pathogens and the adaptive immune response. Pathogen mutation and a homeostatic constraint on lymphocytes both play a role in allowing the development of chronic infection, rather than quick pathogen clearance. The dynamics of these chronic infections display emergent structure, including branching patterns corresponding to asexual pathogen speciation, which is fundamentally driven by the coevolutionary interaction. Over time, continued branching creates an increasingly fragile immune system, and leads to the eventual catastrophic loss of immune control.
[ { "created": "Tue, 6 Aug 2013 23:35:00 GMT", "version": "v1" }, { "created": "Thu, 29 Aug 2013 20:42:32 GMT", "version": "v2" }, { "created": "Mon, 4 Aug 2014 23:40:20 GMT", "version": "v3" } ]
2014-08-06
[ [ "Schlesinger", "Kimberly J.", "" ], [ "Stromberg", "Sean P.", "" ], [ "Carlson", "Jean M.", "" ] ]
We introduce and analyze a within-host dynamical model of the coevolution between rapidly mutating pathogens and the adaptive immune response. Pathogen mutation and a homeostatic constraint on lymphocytes both play a role in allowing the development of chronic infection, rather than quick pathogen clearance. The dynamics of these chronic infections display emergent structure, including branching patterns corresponding to asexual pathogen speciation, which is fundamentally driven by the coevolutionary interaction. Over time, continued branching creates an increasingly fragile immune system, and leads to the eventual catastrophic loss of immune control.
1508.07244
J. C. Phillips
J. C. Phillips
Vaccine escape in 2013-4 and the hydropathic evolution of glycoproteins of A/H3N2 viruses
12 pages, 3 figures
null
10.1016/j.physa.2016.02.040
null
q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
More virulent strains of influenza virus subtypes H1N1 appeared widely in 2007 and H3N2 in 2011, and especially 2013-4, when the effectiveness of the H3N2 vaccine decreased nearly to zero. The amino acid differences of neuraminidase from prior less virulent strains appear to be small (<1%) when tabulated through sequence alignments and counting site identities and similarities. Here we show how analyzing fractal hydropathic forces responsible for neuraminidase globular compaction and modularity quantifies the mutational origins of increased virulence. It also predicts vaccine escape and specifies optimized targets for the 2015 H3N2 vaccine different from the WHO target. Unlike some earlier methods based on measuring hemagglutinin antigenic drift and ferret sera, which take several years, cover only a few candidate strains, and are ambiguous, the new methods are timely and can be completed, using NCBI and GISAID amino acid sequences only, in a few days.
[ { "created": "Thu, 27 Aug 2015 19:24:51 GMT", "version": "v1" } ]
2016-04-20
[ [ "Phillips", "J. C.", "" ] ]
More virulent strains of influenza virus subtypes H1N1 appeared widely in 2007 and H3N2 in 2011, and especially 2013-4, when the effectiveness of the H3N2 vaccine decreased nearly to zero. The amino acid differences of neuraminidase from prior less virulent strains appear to be small (<1%) when tabulated through sequence alignments and counting site identities and similarities. Here we show how analyzing fractal hydropathic forces responsible for neuraminidase globular compaction and modularity quantifies the mutational origins of increased virulence. It also predicts vaccine escape and specifies optimized targets for the 2015 H3N2 vaccine different from the WHO target. Unlike some earlier methods based on measuring hemagglutinin antigenic drift and ferret sera, which take several years, cover only a few candidate strains, and are ambiguous, the new methods are timely and can be completed, using NCBI and GISAID amino acid sequences only, in a few days.
1810.03602
Luis Aparicio
Luis Aparicio, Mykola Bordyuh, Andrew J. Blumberg, Raul Rabadan
Quasi-universality in single-cell sequencing data
Main text has 18 pages and 5 figures. Supplementary material (methods) has 21 pages and 16 figures
null
null
null
q-bio.QM cond-mat.stat-mech math.PR physics.app-ph physics.data-an
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The development of single-cell technologies provides the opportunity to identify new cellular states and reconstruct novel cell-to-cell relationships. Applications range from understanding the transcriptional and epigenetic processes involved in metazoan development to characterizing distinct cells types in heterogeneous populations like cancers or immune cells. However, analysis of the data is impeded by its unknown intrinsic biological and technical variability together with its sparseness; these factors complicate the identification of true biological signals amidst artifact and noise. Here we show that, across technologies, roughly 95% of the eigenvalues derived from each single-cell data set can be described by universal distributions predicted by Random Matrix Theory. Interestingly, 5% of the spectrum shows deviations from these distributions and present a phenomenon known as eigenvector localization, where information tightly concentrates in groups of cells. Some of the localized eigenvectors reflect underlying biological signal, and some are simply a consequence of the sparsity of single cell data; roughly 3% is artifactual. Based on the universal distributions and a technique for detecting sparsity induced localization, we present a strategy to identify the residual 2% of directions that encode biological information and thereby denoise single-cell data. We demonstrate the effectiveness of this approach by comparing with standard single-cell data analysis techniques in a variety of examples with marked cell populations.
[ { "created": "Fri, 5 Oct 2018 19:44:55 GMT", "version": "v1" } ]
2018-10-11
[ [ "Aparicio", "Luis", "" ], [ "Bordyuh", "Mykola", "" ], [ "Blumberg", "Andrew J.", "" ], [ "Rabadan", "Raul", "" ] ]
The development of single-cell technologies provides the opportunity to identify new cellular states and reconstruct novel cell-to-cell relationships. Applications range from understanding the transcriptional and epigenetic processes involved in metazoan development to characterizing distinct cells types in heterogeneous populations like cancers or immune cells. However, analysis of the data is impeded by its unknown intrinsic biological and technical variability together with its sparseness; these factors complicate the identification of true biological signals amidst artifact and noise. Here we show that, across technologies, roughly 95% of the eigenvalues derived from each single-cell data set can be described by universal distributions predicted by Random Matrix Theory. Interestingly, 5% of the spectrum shows deviations from these distributions and present a phenomenon known as eigenvector localization, where information tightly concentrates in groups of cells. Some of the localized eigenvectors reflect underlying biological signal, and some are simply a consequence of the sparsity of single cell data; roughly 3% is artifactual. Based on the universal distributions and a technique for detecting sparsity induced localization, we present a strategy to identify the residual 2% of directions that encode biological information and thereby denoise single-cell data. We demonstrate the effectiveness of this approach by comparing with standard single-cell data analysis techniques in a variety of examples with marked cell populations.
1202.4482
David Balduzzi
David Balduzzi, Pedro A Ortega, Michel Besserve
Metabolic cost as an organizing principle for cooperative learning
14 pages, 2 figures, to appear in Advances in Complex Systems
null
null
null
q-bio.NC cs.LG nlin.AO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This paper investigates how neurons can use metabolic cost to facilitate learning at a population level. Although decision-making by individual neurons has been extensively studied, questions regarding how neurons should behave to cooperate effectively remain largely unaddressed. Under assumptions that capture a few basic features of cortical neurons, we show that constraining reward maximization by metabolic cost aligns the information content of actions with their expected reward. Thus, metabolic cost provides a mechanism whereby neurons encode expected reward into their outputs. Further, aside from reducing energy expenditures, imposing a tight metabolic constraint also increases the accuracy of empirical estimates of rewards, increasing the robustness of distributed learning. Finally, we present two implementations of metabolically constrained learning that confirm our theoretical finding. These results suggest that metabolic cost may be an organizing principle underlying the neural code, and may also provide a useful guide to the design and analysis of other cooperating populations.
[ { "created": "Mon, 20 Feb 2012 22:02:16 GMT", "version": "v1" }, { "created": "Sat, 9 Feb 2013 21:34:51 GMT", "version": "v2" } ]
2013-02-12
[ [ "Balduzzi", "David", "" ], [ "Ortega", "Pedro A", "" ], [ "Besserve", "Michel", "" ] ]
This paper investigates how neurons can use metabolic cost to facilitate learning at a population level. Although decision-making by individual neurons has been extensively studied, questions regarding how neurons should behave to cooperate effectively remain largely unaddressed. Under assumptions that capture a few basic features of cortical neurons, we show that constraining reward maximization by metabolic cost aligns the information content of actions with their expected reward. Thus, metabolic cost provides a mechanism whereby neurons encode expected reward into their outputs. Further, aside from reducing energy expenditures, imposing a tight metabolic constraint also increases the accuracy of empirical estimates of rewards, increasing the robustness of distributed learning. Finally, we present two implementations of metabolically constrained learning that confirm our theoretical finding. These results suggest that metabolic cost may be an organizing principle underlying the neural code, and may also provide a useful guide to the design and analysis of other cooperating populations.
1512.02124
Nils Becker
Nils B. Becker, Andrew Mugler, Pieter Rein ten Wolde
Optimal Prediction by Cellular Signaling Networks
5 pages, 4 figures; 15 supplementary pages with 12 figures
null
10.1103/PhysRevLett.115.258103
null
q-bio.MN q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Living cells can enhance their fitness by anticipating environmental change. We study how accurately linear signaling networks in cells can predict future signals. We find that maximal predictive power results from a combination of input-noise suppression, linear extrapolation, and selective readout of correlated past signal values. Single-layer networks generate exponential response kernels, which suffice to predict Markovian signals optimally. Multilayer networks allow oscillatory kernels that can optimally predict non-Markovian signals. At low noise, these kernels exploit the signal derivative for extrapolation, while at high noise, they capitalize on signal values in the past that are strongly correlated with the future signal. We show how the common motifs of negative feedback and incoherent feed-forward can implement these optimal response functions. Simulations reveal that E. coli can reliably predict concentration changes for chemotaxis, and that the integration time of its response kernel arises from a trade-off between rapid response and noise suppression.
[ { "created": "Mon, 7 Dec 2015 17:10:49 GMT", "version": "v1" } ]
2016-01-20
[ [ "Becker", "Nils B.", "" ], [ "Mugler", "Andrew", "" ], [ "Wolde", "Pieter Rein ten", "" ] ]
Living cells can enhance their fitness by anticipating environmental change. We study how accurately linear signaling networks in cells can predict future signals. We find that maximal predictive power results from a combination of input-noise suppression, linear extrapolation, and selective readout of correlated past signal values. Single-layer networks generate exponential response kernels, which suffice to predict Markovian signals optimally. Multilayer networks allow oscillatory kernels that can optimally predict non-Markovian signals. At low noise, these kernels exploit the signal derivative for extrapolation, while at high noise, they capitalize on signal values in the past that are strongly correlated with the future signal. We show how the common motifs of negative feedback and incoherent feed-forward can implement these optimal response functions. Simulations reveal that E. coli can reliably predict concentration changes for chemotaxis, and that the integration time of its response kernel arises from a trade-off between rapid response and noise suppression.
2310.07275
Quentin Richard
Quentin Richard (IMAG), Marc Choisy (OUCRU), Rams\`es Djidjou-Demasse (MIVEGEC), Thierry Lef\`evre (MIVEGEC)
Epidemiological impacts of age structures on human malaria transmission
null
null
null
null
q-bio.PE math.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Malaria is one of the most common mosquito-borne diseases widespread in tropical and subtropical regions, causing thousands of deaths every year in the world. In a previous paper, we formulated an age-structured model containing three structural variables: (i) the chronological age of human and mosquito populations, (ii) the time since they are infected, and (iii) humans waning immunity (i.e. the progressive loss of protective antibodies after recovery). In the present paper, we expand the analysis of this age-structured model and focus on the derivation of entomological and epidemiological results commonly used in the literature, following the works of Smith and McKenzie. We generalize their results to the age-structured case. In order to quantify the impact of neglecting structuring variables such as chronological age, we assigned values from the literature to our model parameters. While some parameters values are readily accessible from the literature, at least those about the human population, the parameters concerning mosquitoes are less commonly documented and the values of a number of them (e.g. mosquito survival in the presence or in absence of infection) can be discussed extensively.
[ { "created": "Wed, 11 Oct 2023 07:57:05 GMT", "version": "v1" }, { "created": "Wed, 22 May 2024 09:05:35 GMT", "version": "v2" } ]
2024-05-24
[ [ "Richard", "Quentin", "", "IMAG" ], [ "Choisy", "Marc", "", "OUCRU" ], [ "Djidjou-Demasse", "Ramsès", "", "MIVEGEC" ], [ "Lefèvre", "Thierry", "", "MIVEGEC" ] ]
Malaria is one of the most common mosquito-borne diseases widespread in tropical and subtropical regions, causing thousands of deaths every year in the world. In a previous paper, we formulated an age-structured model containing three structural variables: (i) the chronological age of human and mosquito populations, (ii) the time since they are infected, and (iii) humans waning immunity (i.e. the progressive loss of protective antibodies after recovery). In the present paper, we expand the analysis of this age-structured model and focus on the derivation of entomological and epidemiological results commonly used in the literature, following the works of Smith and McKenzie. We generalize their results to the age-structured case. In order to quantify the impact of neglecting structuring variables such as chronological age, we assigned values from the literature to our model parameters. While some parameters values are readily accessible from the literature, at least those about the human population, the parameters concerning mosquitoes are less commonly documented and the values of a number of them (e.g. mosquito survival in the presence or in absence of infection) can be discussed extensively.
1309.4283
Thomas Pfeil
Thomas Pfeil, Anne-Christine Scherzer, Johannes Schemmel and Karlheinz Meier
Neuromorphic Learning towards Nano Second Precision
7 pages, 7 figures, presented at IJCNN 2013 in Dallas, TX, USA. IJCNN 2013. Corrected version with updated STDP curves IJCNN 2013
Neural Networks (IJCNN), The 2013 International Joint Conference on , pp. 1-5, 4-9 Aug. 2013
10.1109/IJCNN.2013.6706828
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Temporal coding is one approach to representing information in spiking neural networks. An example of its application is the location of sounds by barn owls that requires especially precise temporal coding. Dependent upon the azimuthal angle, the arrival times of sound signals are shifted between both ears. In order to deter- mine these interaural time differences, the phase difference of the signals is measured. We implemented this biologically inspired network on a neuromorphic hardware system and demonstrate spike-timing dependent plasticity on an analog, highly accelerated hardware substrate. Our neuromorphic implementation enables the resolution of time differences of less than 50 ns. On-chip Hebbian learning mechanisms select inputs from a pool of neurons which code for the same sound frequency. Hence, noise caused by different synaptic delays across these inputs is reduced. Furthermore, learning compensates for variations on neuronal and synaptic parameters caused by device mismatch intrinsic to the neuromorphic substrate.
[ { "created": "Tue, 17 Sep 2013 12:31:48 GMT", "version": "v1" }, { "created": "Wed, 18 Sep 2013 06:55:16 GMT", "version": "v2" } ]
2014-01-24
[ [ "Pfeil", "Thomas", "" ], [ "Scherzer", "Anne-Christine", "" ], [ "Schemmel", "Johannes", "" ], [ "Meier", "Karlheinz", "" ] ]
Temporal coding is one approach to representing information in spiking neural networks. An example of its application is the location of sounds by barn owls that requires especially precise temporal coding. Dependent upon the azimuthal angle, the arrival times of sound signals are shifted between both ears. In order to deter- mine these interaural time differences, the phase difference of the signals is measured. We implemented this biologically inspired network on a neuromorphic hardware system and demonstrate spike-timing dependent plasticity on an analog, highly accelerated hardware substrate. Our neuromorphic implementation enables the resolution of time differences of less than 50 ns. On-chip Hebbian learning mechanisms select inputs from a pool of neurons which code for the same sound frequency. Hence, noise caused by different synaptic delays across these inputs is reduced. Furthermore, learning compensates for variations on neuronal and synaptic parameters caused by device mismatch intrinsic to the neuromorphic substrate.
1801.05767
Denis Michel
Denis Michel and Philippe Ruelle
Polylogarithmic equilibrium treatment of molecular aggregation and critical concentrations
14 pages, 2 figures
Phys. Chem. Chem. Phys. 2017 Feb 15;19(7):5273-5284
10.1039/C6CP08369B
null
q-bio.QM cond-mat.soft
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A full equilibrium treatment of molecular aggregation is presented for prototypes of 1D and 3D aggregates, with and without nucleation. By skipping complex kinetic parameters like aggregate size-dependent diffusion, the equilibrium treatment allows to predict directly time-independent quantities such as critical concentrations. The relationships between the macroscopic equilibrium constants for the different paths are first established by statistical corrections and so as to comply with the detailed balance constraints imposed by nucleation, and the composition of the mixture resulting from homogeneous aggregation is then analyzed using the polylogarithm function. Several critical concentrations are distinguished: the residual monomer concentation in equilibrium (RMC) and the critical nucleation concentration (CNC), that is the threshold concentration of total subunits necessary for initiating aggregation. When increasing the concentration of total subunits, the RMC converges more strongly to its asymptotic value, the equilibrium constant of depolymerization, for 3D aggregates and in case of nucleation. The CNC moderately depends on the number of subunits in the nucleus, but sharply increases with the difference between the equilibrium constants of polymerization and nucleation. As the RMC and CNC can be numerically but not analytically determined, ansatz equations connecting them to thermodynamic parameters are proposed.
[ { "created": "Sun, 24 Dec 2017 08:21:13 GMT", "version": "v1" } ]
2018-01-24
[ [ "Michel", "Denis", "" ], [ "Ruelle", "Philippe", "" ] ]
A full equilibrium treatment of molecular aggregation is presented for prototypes of 1D and 3D aggregates, with and without nucleation. By skipping complex kinetic parameters like aggregate size-dependent diffusion, the equilibrium treatment allows to predict directly time-independent quantities such as critical concentrations. The relationships between the macroscopic equilibrium constants for the different paths are first established by statistical corrections and so as to comply with the detailed balance constraints imposed by nucleation, and the composition of the mixture resulting from homogeneous aggregation is then analyzed using the polylogarithm function. Several critical concentrations are distinguished: the residual monomer concentation in equilibrium (RMC) and the critical nucleation concentration (CNC), that is the threshold concentration of total subunits necessary for initiating aggregation. When increasing the concentration of total subunits, the RMC converges more strongly to its asymptotic value, the equilibrium constant of depolymerization, for 3D aggregates and in case of nucleation. The CNC moderately depends on the number of subunits in the nucleus, but sharply increases with the difference between the equilibrium constants of polymerization and nucleation. As the RMC and CNC can be numerically but not analytically determined, ansatz equations connecting them to thermodynamic parameters are proposed.
2408.07064
Hamza Coban
Hamza Coban
On Networks and their Applications: Stability of Gene Regulatory Networks and Gene Function Prediction using Autoencoders
null
null
null
null
q-bio.MN physics.bio-ph
http://creativecommons.org/licenses/by/4.0/
We prove that nested canalizing functions are the minimum-sensitivity Boolean functions for any activity ratio and we determine the functional form of this boundary which has a nontrivial fractal structure. We further observe that the majority of the gene regulatory functions found in known biological networks (submitted to the Cell Collective database) lie on the line of minimum sensitivity which paradoxically remains largely in the unstable regime. Our results provide a quantitative basis for the argument that an evolutionary preference for nested canalizing functions in gene regulation (e.g., for higher robustness) and for elasticity of gene activity are sufficient for concentration of such systems near the "edge of chaos." The original structure of gene regulatory networks is unknown due to the undiscovered functions of some genes. Most gene function discovery approaches make use of unsupervised clustering or classification methods that discover and exploit patterns in gene expression profiles. However, existing knowledge in the field derives from multiple and diverse sources. Incorporating this know-how for novel gene function prediction can, therefore, be expected to improve such predictions. We here propose a function-specific novel gene discovery tool that uses a semi-supervised autoencoder. Our method is thus able to address the needs of a modern researcher whose expertise is typically confined to a specific functional domain. Lastly, the dynamics of unorthodox learning approaches like biologically plausible learning algorithms are investigated and found to exhibit a general form of Einstein relation.
[ { "created": "Tue, 13 Aug 2024 17:57:11 GMT", "version": "v1" } ]
2024-08-14
[ [ "Coban", "Hamza", "" ] ]
We prove that nested canalizing functions are the minimum-sensitivity Boolean functions for any activity ratio and we determine the functional form of this boundary which has a nontrivial fractal structure. We further observe that the majority of the gene regulatory functions found in known biological networks (submitted to the Cell Collective database) lie on the line of minimum sensitivity which paradoxically remains largely in the unstable regime. Our results provide a quantitative basis for the argument that an evolutionary preference for nested canalizing functions in gene regulation (e.g., for higher robustness) and for elasticity of gene activity are sufficient for concentration of such systems near the "edge of chaos." The original structure of gene regulatory networks is unknown due to the undiscovered functions of some genes. Most gene function discovery approaches make use of unsupervised clustering or classification methods that discover and exploit patterns in gene expression profiles. However, existing knowledge in the field derives from multiple and diverse sources. Incorporating this know-how for novel gene function prediction can, therefore, be expected to improve such predictions. We here propose a function-specific novel gene discovery tool that uses a semi-supervised autoencoder. Our method is thus able to address the needs of a modern researcher whose expertise is typically confined to a specific functional domain. Lastly, the dynamics of unorthodox learning approaches like biologically plausible learning algorithms are investigated and found to exhibit a general form of Einstein relation.
1611.05150
Chi Keung Chan
Yu-Ting Huang, Yu-Lin Chang, Chun-Chung Chen, Pik-Yin Lai, C. K. Chan
Positive Feedback and Synchronized Bursts in Neuronal Cultures
12 pages, 8 figures
null
10.1371/journal.pone.0187276
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Synchronized bursts (SBs) with complex structures are common in neuronal cultures. Although the origin of SBs is still unclear, they have been studied for their information processing capabilities. Here, we investigate the properties of these SBs in a culture on multi-electrode array system. We find that structures of these SBs are related to the different developmental stages of the cultures. A model based on short term synaptic plasticity, recurrent connections and astrocytic recycling of neurotransmitters has been developed successfully to understand these structures. A phase diagram obtained from this model shows that networks exhibiting SBs are in an oscillatory state due to large enough positive feedback provided by synaptic facilitation and recurrent connections. In this model, the structures of the SBs are the results of intrinsic synaptic interactions; not information stored in the network.
[ { "created": "Wed, 16 Nov 2016 05:25:35 GMT", "version": "v1" } ]
2018-02-07
[ [ "Huang", "Yu-Ting", "" ], [ "Chang", "Yu-Lin", "" ], [ "Chen", "Chun-Chung", "" ], [ "Lai", "Pik-Yin", "" ], [ "Chan", "C. K.", "" ] ]
Synchronized bursts (SBs) with complex structures are common in neuronal cultures. Although the origin of SBs is still unclear, they have been studied for their information processing capabilities. Here, we investigate the properties of these SBs in a culture on multi-electrode array system. We find that structures of these SBs are related to the different developmental stages of the cultures. A model based on short term synaptic plasticity, recurrent connections and astrocytic recycling of neurotransmitters has been developed successfully to understand these structures. A phase diagram obtained from this model shows that networks exhibiting SBs are in an oscillatory state due to large enough positive feedback provided by synaptic facilitation and recurrent connections. In this model, the structures of the SBs are the results of intrinsic synaptic interactions; not information stored in the network.
1806.07218
Nele Vandersickel
Nele Vandersickel, Masaya Watanabe, Qian Tao, Jan Fostier, Katja Zeppenfeld, Alexander V Panfilov
Dynamical anchoring of distant Arrhythmia Sources by Fibrotic Regions via Restructuring of the Activation Pattern
16 pages, 7 figures
null
10.1371/journal.pcbi.1006637
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Rotors are functional reentry sources identified in clinically relevant cardiac arrhythmias, such as ventricular and atrial fibrillation. Ablation targeting rotor sites has resulted in arrhythmia termination. Recent clinical, experimental and modelling studies demonstrate that rotors are often anchored around fibrotic scars or regions with increased fibrosis. However the mechanisms leading to abundance of rotors at these locations are not clear. The current study explores the hypothesis whether fibrotic scars just serve as anchoring sites for the rotors or whether there are other active processes which drive the rotors to these fibrotic regions. Rotors were induced at different distances from fibrotic scars of various sizes and degree of fibrosis. Simulations were performed in a 2D model of human ventricular tissue and in a patient-specific model of the left ventricle of a patient with remote myocardial infarction. In both the 2D and the patient-specific model we found that without fibrotic scars, the rotors were stable at the site of their initiation. However, in the presence of a scar, rotors were eventually dynamically anchored from large distances by the fibrotic scar via a process of dynamical reorganization of the excitation pattern. This process coalesces with a change from polymorphic to monomorphic ventricular tachycardia.
[ { "created": "Tue, 19 Jun 2018 13:38:18 GMT", "version": "v1" } ]
2019-03-06
[ [ "Vandersickel", "Nele", "" ], [ "Watanabe", "Masaya", "" ], [ "Tao", "Qian", "" ], [ "Fostier", "Jan", "" ], [ "Zeppenfeld", "Katja", "" ], [ "Panfilov", "Alexander V", "" ] ]
Rotors are functional reentry sources identified in clinically relevant cardiac arrhythmias, such as ventricular and atrial fibrillation. Ablation targeting rotor sites has resulted in arrhythmia termination. Recent clinical, experimental and modelling studies demonstrate that rotors are often anchored around fibrotic scars or regions with increased fibrosis. However the mechanisms leading to abundance of rotors at these locations are not clear. The current study explores the hypothesis whether fibrotic scars just serve as anchoring sites for the rotors or whether there are other active processes which drive the rotors to these fibrotic regions. Rotors were induced at different distances from fibrotic scars of various sizes and degree of fibrosis. Simulations were performed in a 2D model of human ventricular tissue and in a patient-specific model of the left ventricle of a patient with remote myocardial infarction. In both the 2D and the patient-specific model we found that without fibrotic scars, the rotors were stable at the site of their initiation. However, in the presence of a scar, rotors were eventually dynamically anchored from large distances by the fibrotic scar via a process of dynamical reorganization of the excitation pattern. This process coalesces with a change from polymorphic to monomorphic ventricular tachycardia.
2301.06638
Yixiang Wu
Shanshan Chen, Jie Liu, Yixiang Wu
Evolution of dispersal in advective patchy environments with varying drift rates
null
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
In this paper, we study a two stream species Lotka-Volterra competition patch model with the patches aligned along a line. The two species are supposed to be identical except for the diffusion rates. For each species, the diffusion rates between patches are the same, while the drift rates vary. Our results show that the convexity of the drift rates has a significant impact on the competition outcomes: if the drift rates are convex, then the species with larger diffusion rate wins the competition; if the drift rates are concave, then the species with smaller diffusion rate wins the competition.
[ { "created": "Mon, 16 Jan 2023 23:44:50 GMT", "version": "v1" } ]
2023-01-18
[ [ "Chen", "Shanshan", "" ], [ "Liu", "Jie", "" ], [ "Wu", "Yixiang", "" ] ]
In this paper, we study a two stream species Lotka-Volterra competition patch model with the patches aligned along a line. The two species are supposed to be identical except for the diffusion rates. For each species, the diffusion rates between patches are the same, while the drift rates vary. Our results show that the convexity of the drift rates has a significant impact on the competition outcomes: if the drift rates are convex, then the species with larger diffusion rate wins the competition; if the drift rates are concave, then the species with smaller diffusion rate wins the competition.
1505.05328
Sriganesh Srihari Dr
Sriganesh Srihari, Chern Han Yong, Ashwini Patil and Limsoon Wong
Methods for protein complex prediction and their contributions towards understanding the organization, function and dynamics of complexes
1 Table
null
10.1016/j.febslet.2015.04.026
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Complexes of physically interacting proteins constitute fundamental functional units responsible for driving biological processes within cells. A faithful reconstruction of the entire set of complexes is therefore essential to understand the functional organization of cells. In this review, we discuss the key contributions of computational methods developed till date (approximately between 2003 and 2015) for identifying complexes from the network of interacting proteins (PPI network). We evaluate in depth the performance of these methods on PPI datasets from yeast, and highlight challenges faced by these methods, in particular detection of sparse and small or sub- complexes and discerning of overlapping complexes. We describe methods for integrating diverse information including expression profiles and 3D structures of proteins with PPI networks to understand the dynamics of complex formation, for instance, of time-based assembly of complex subunits and formation of fuzzy complexes from intrinsically disordered proteins. Finally, we discuss methods for identifying dysfunctional complexes in human diseases, an application that is proving invaluable to understand disease mechanisms and to discover novel therapeutic targets. We hope this review aptly commemorates a decade of research on computational prediction of complexes and constitutes a valuable reference for further advancements in this exciting area.
[ { "created": "Wed, 20 May 2015 11:45:19 GMT", "version": "v1" } ]
2015-05-21
[ [ "Srihari", "Sriganesh", "" ], [ "Yong", "Chern Han", "" ], [ "Patil", "Ashwini", "" ], [ "Wong", "Limsoon", "" ] ]
Complexes of physically interacting proteins constitute fundamental functional units responsible for driving biological processes within cells. A faithful reconstruction of the entire set of complexes is therefore essential to understand the functional organization of cells. In this review, we discuss the key contributions of computational methods developed till date (approximately between 2003 and 2015) for identifying complexes from the network of interacting proteins (PPI network). We evaluate in depth the performance of these methods on PPI datasets from yeast, and highlight challenges faced by these methods, in particular detection of sparse and small or sub- complexes and discerning of overlapping complexes. We describe methods for integrating diverse information including expression profiles and 3D structures of proteins with PPI networks to understand the dynamics of complex formation, for instance, of time-based assembly of complex subunits and formation of fuzzy complexes from intrinsically disordered proteins. Finally, we discuss methods for identifying dysfunctional complexes in human diseases, an application that is proving invaluable to understand disease mechanisms and to discover novel therapeutic targets. We hope this review aptly commemorates a decade of research on computational prediction of complexes and constitutes a valuable reference for further advancements in this exciting area.
2105.09010
Mar\'ia Vallet-Regi
Carlotta Pontremoli, Isabel Izquierdo-Barba, Giorgia Montalbano, Maria Vallet-Regi, Chiara Vitale-Brovarone, Sonia Fiorilli
Strontium-releasing mesoporous bioactive glasses with anti-adhesive zwitterionic surface as advanced biomaterials for bone tissue regeneration
26 pages, 8 figures
Journal of Colloid and Interface Science 563, 92-103 (2020)
10.1016/j.jcis.2019.12.047
null
q-bio.TO physics.bio-ph
http://creativecommons.org/licenses/by-nc-nd/4.0/
Hypothesis The treatment of bone fractures still represents a challenging clinical issue when complications due to impaired bone remodelling (i.e. osteoporosis) or infections occur. These clinical needs still require a radical improvement of the existing therapeutic approach through the design of advanced biomaterials combining the ability to promote bone regeneration with anti-fouling/anti-adhesive properties able to minimise unspecific biomolecules adsorption and bacterial adhesion. Strontium-containing mesoporous bioactive glasses (Sr-MBG), able to exert a pro-osteogenic effect by releasing Sr2+ ions, have been successfully functionalised to provide mixed-charge surface groups with low-fouling abilities. Experiments Sr-MBG have been post-synthesis modified by co-grafting hydrolysable short chain silanes containing amino (aminopropylsilanetriol) and carboxylate (carboxyethylsilanetriol) moieties to achieve a zwitterionic zero-charge surface and then characterised in terms of textural-structural properties, bioactivity, cytotoxicity, pro-osteogenic and low-fouling capabilities. Findings After zwitterionization the in vitro bioactivity is maintained, as well as the ability to release Sr2+ ions capable to induce a mineralization process. Irrespective of their size, Sr-MBG particles did not exhibit any cytotoxicity in pre-osteoblastic MC3T3-E1 up to the concentration of 75 ug/mL. Finally, the zwitterionic Sr-MBGs show a significant reduction of serum protein adhesion with respect to pristine ones. These results open promising future expectations in the design of nanosystems combining pro-osteogenic and anti-adhesive properties.
[ { "created": "Wed, 19 May 2021 09:24:29 GMT", "version": "v1" } ]
2021-05-20
[ [ "Pontremoli", "Carlotta", "" ], [ "Izquierdo-Barba", "Isabel", "" ], [ "Montalbano", "Giorgia", "" ], [ "Vallet-Regi", "Maria", "" ], [ "Vitale-Brovarone", "Chiara", "" ], [ "Fiorilli", "Sonia", "" ] ]
Hypothesis The treatment of bone fractures still represents a challenging clinical issue when complications due to impaired bone remodelling (i.e. osteoporosis) or infections occur. These clinical needs still require a radical improvement of the existing therapeutic approach through the design of advanced biomaterials combining the ability to promote bone regeneration with anti-fouling/anti-adhesive properties able to minimise unspecific biomolecules adsorption and bacterial adhesion. Strontium-containing mesoporous bioactive glasses (Sr-MBG), able to exert a pro-osteogenic effect by releasing Sr2+ ions, have been successfully functionalised to provide mixed-charge surface groups with low-fouling abilities. Experiments Sr-MBG have been post-synthesis modified by co-grafting hydrolysable short chain silanes containing amino (aminopropylsilanetriol) and carboxylate (carboxyethylsilanetriol) moieties to achieve a zwitterionic zero-charge surface and then characterised in terms of textural-structural properties, bioactivity, cytotoxicity, pro-osteogenic and low-fouling capabilities. Findings After zwitterionization the in vitro bioactivity is maintained, as well as the ability to release Sr2+ ions capable to induce a mineralization process. Irrespective of their size, Sr-MBG particles did not exhibit any cytotoxicity in pre-osteoblastic MC3T3-E1 up to the concentration of 75 ug/mL. Finally, the zwitterionic Sr-MBGs show a significant reduction of serum protein adhesion with respect to pristine ones. These results open promising future expectations in the design of nanosystems combining pro-osteogenic and anti-adhesive properties.
1203.5863
Jonas Cremer
Jonas Cremer and Anna Melbinger and Erwin Frey
Growth dynamics and the evolution of cooperation in microbial populations
26 pages, 6 figures
Scientific Reports 2,281 (2012)
10.1038/srep00281
null
q-bio.PE cond-mat.stat-mech physics.bio-ph
http://creativecommons.org/licenses/by-nc-sa/3.0/
Microbes providing public goods are widespread in nature despite running the risk of being exploited by free-riders. However, the precise ecological factors supporting cooperation are still puzzling. Following recent experiments, we consider the role of population growth and the repetitive fragmentation of populations into new colonies mimicking simple microbial life-cycles. Individual-based modeling reveals that demographic fluctuations, which lead to a large variance in the composition of colonies, promote cooperation. Biased by population dynamics these fluctuations result in two qualitatively distinct regimes of robust cooperation under repetitive fragmentation into groups. First, if the level of cooperation exceeds a threshold, cooperators will take over the whole population. Second, cooperators can also emerge from a single mutant leading to a robust coexistence between cooperators and free-riders. We find frequency and size of population bottlenecks, and growth dynamics to be the major ecological factors determining the regimes and thereby the evolutionary pathway towards cooperation.
[ { "created": "Tue, 27 Mar 2012 04:00:36 GMT", "version": "v1" } ]
2012-03-28
[ [ "Cremer", "Jonas", "" ], [ "Melbinger", "Anna", "" ], [ "Frey", "Erwin", "" ] ]
Microbes providing public goods are widespread in nature despite running the risk of being exploited by free-riders. However, the precise ecological factors supporting cooperation are still puzzling. Following recent experiments, we consider the role of population growth and the repetitive fragmentation of populations into new colonies mimicking simple microbial life-cycles. Individual-based modeling reveals that demographic fluctuations, which lead to a large variance in the composition of colonies, promote cooperation. Biased by population dynamics these fluctuations result in two qualitatively distinct regimes of robust cooperation under repetitive fragmentation into groups. First, if the level of cooperation exceeds a threshold, cooperators will take over the whole population. Second, cooperators can also emerge from a single mutant leading to a robust coexistence between cooperators and free-riders. We find frequency and size of population bottlenecks, and growth dynamics to be the major ecological factors determining the regimes and thereby the evolutionary pathway towards cooperation.
1705.09392
Tomislav Plesa Mr
Tomislav Plesa, Konstantinos C. Zygalakis, David F. Anderson, Radek Erban
Noise Control for DNA Computing
null
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Synthetic biology is a growing interdisciplinary field, with far-reaching applications, which aims to design biochemical systems that behave in a desired manner. With the advancement of strand-displacement DNA computing, a large class of abstract biochemical networks may be physically realized using DNA molecules. Methods for systematic design of the abstract systems with prescribed behaviors have been predominantly developed at the (less-detailed) deterministic level. However, stochastic effects, neglected at the deterministic level, are increasingly found to play an important role in biochemistry. In such circumstances, methods for controlling the intrinsic noise in the system are necessary for a successful network design at the (more-detailed) stochastic level. To bridge the gap, the noise-control algorithm for designing biochemical networks is developed in this paper. The algorithm structurally modifies any given reaction network under mass-action kinetics, in such a way that (i) controllable state-dependent noise is introduced into the stochastic dynamics, while (ii) the deterministic dynamics are preserved. The capabilities of the algorithm are demonstrated on a production-decay reaction system, and on an exotic system displaying bistability. For the production-decay system, it is shown that the algorithm may be used to redesign the network to achieve noise-induced multistability. For the exotic system, the algorithm is used to redesign the network to control the stochastic switching, and achieve noise-induced oscillations.
[ { "created": "Thu, 25 May 2017 23:01:46 GMT", "version": "v1" }, { "created": "Mon, 29 May 2017 12:29:30 GMT", "version": "v2" }, { "created": "Sat, 3 Jun 2017 00:15:15 GMT", "version": "v3" }, { "created": "Sat, 17 Jun 2017 19:28:44 GMT", "version": "v4" }, { "created": "Tue, 20 Jun 2017 16:40:08 GMT", "version": "v5" } ]
2017-06-21
[ [ "Plesa", "Tomislav", "" ], [ "Zygalakis", "Konstantinos C.", "" ], [ "Anderson", "David F.", "" ], [ "Erban", "Radek", "" ] ]
Synthetic biology is a growing interdisciplinary field, with far-reaching applications, which aims to design biochemical systems that behave in a desired manner. With the advancement of strand-displacement DNA computing, a large class of abstract biochemical networks may be physically realized using DNA molecules. Methods for systematic design of the abstract systems with prescribed behaviors have been predominantly developed at the (less-detailed) deterministic level. However, stochastic effects, neglected at the deterministic level, are increasingly found to play an important role in biochemistry. In such circumstances, methods for controlling the intrinsic noise in the system are necessary for a successful network design at the (more-detailed) stochastic level. To bridge the gap, the noise-control algorithm for designing biochemical networks is developed in this paper. The algorithm structurally modifies any given reaction network under mass-action kinetics, in such a way that (i) controllable state-dependent noise is introduced into the stochastic dynamics, while (ii) the deterministic dynamics are preserved. The capabilities of the algorithm are demonstrated on a production-decay reaction system, and on an exotic system displaying bistability. For the production-decay system, it is shown that the algorithm may be used to redesign the network to achieve noise-induced multistability. For the exotic system, the algorithm is used to redesign the network to control the stochastic switching, and achieve noise-induced oscillations.
1208.1652
Gibran Manasseh
Gibran Manasseh, Chloe de Balthasar, Bruno Sanguinetti, Enrico Pomarico, Nicolas Gisin, Rolando Grave de Peralta, Sara L. Gonzalez
Retinal and post-retinal contributions to the quantum efficiency of the human eye
null
null
null
null
q-bio.NC quant-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The retina is one of the best known quantum detectors with rods able to respond to a single photon. However, estimates on the number of photons eliciting conscious perception, based on signal detection theory, are systematically above these values. One possibility is that post-retinal processing significantly contributes to the decrease in the quantum efficiency determined by signal detection. We carried out experiments in humans using controlled sources of light while recording EEG and reaction times. Half of the participants behaved as noisy detectors reporting perception in trials where no light was sent. DN subjects were significantly faster to take decisions. Reaction times significantly increased with the decrease in the number of photons. This trend was reflected in the latency and onset of the EEG responses over frontal and parietal contacts where the first significant differences in latency comparable to differences in reaction time appeared. Delays in latency of neural responses across intensities were observed later over visual areas suggesting that they are due to the time required to reach the decision threshold in decision areas rather than to longer integration times at sensory areas. Our results suggest that post-retinal processing significantly contribute to increase detection noise and thresholds, decreasing the efficiency of the retina brain detector system.
[ { "created": "Wed, 8 Aug 2012 12:40:19 GMT", "version": "v1" } ]
2012-08-09
[ [ "Manasseh", "Gibran", "" ], [ "de Balthasar", "Chloe", "" ], [ "Sanguinetti", "Bruno", "" ], [ "Pomarico", "Enrico", "" ], [ "Gisin", "Nicolas", "" ], [ "de Peralta", "Rolando Grave", "" ], [ "Gonzalez", "Sara L.", "" ] ]
The retina is one of the best known quantum detectors with rods able to respond to a single photon. However, estimates on the number of photons eliciting conscious perception, based on signal detection theory, are systematically above these values. One possibility is that post-retinal processing significantly contributes to the decrease in the quantum efficiency determined by signal detection. We carried out experiments in humans using controlled sources of light while recording EEG and reaction times. Half of the participants behaved as noisy detectors reporting perception in trials where no light was sent. DN subjects were significantly faster to take decisions. Reaction times significantly increased with the decrease in the number of photons. This trend was reflected in the latency and onset of the EEG responses over frontal and parietal contacts where the first significant differences in latency comparable to differences in reaction time appeared. Delays in latency of neural responses across intensities were observed later over visual areas suggesting that they are due to the time required to reach the decision threshold in decision areas rather than to longer integration times at sensory areas. Our results suggest that post-retinal processing significantly contribute to increase detection noise and thresholds, decreasing the efficiency of the retina brain detector system.
2404.16040
Megan Witherow
Megan A. Witherow, Norou Diawara, Janice Keener, John W. Harrington, and Khan M. Iftekharuddin
Pilot Study to Discover Candidate Biomarkers for Autism based on Perception and Production of Facial Expressions
18 pages, 3 figures, 5 tables
null
null
null
q-bio.NC cs.HC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Purpose: Facial expression production and perception in autism spectrum disorder (ASD) suggest potential presence of behavioral biomarkers that may stratify individuals on the spectrum into prognostic or treatment subgroups. Construct validity and group discriminability have been recommended as criteria for identification of candidate stratification biomarkers. Methods: In an online pilot study of 11 children and young adults diagnosed with ASD and 11 age- and gender-matched neurotypical (NT) individuals, participants recognize and mimic static and dynamic facial expressions of 3D avatars. Webcam-based eye-tracking (ET) and facial video tracking (VT), including activation and asymmetry of action units (AUs) from the Facial Action Coding System (FACS) are collected. We assess validity of constructs for each dependent variable (DV) based on the expected response in the NT group. Then, the Boruta statistical method identifies DVs that are significant to group discriminability (ASD or NT). Results: We identify one candidate ET biomarker (percentage gaze duration to the face while mimicking static 'disgust' expression) and 14 additional DVs of interest for future study, including 4 ET DVs, 5 DVs related to VT AU activation, and 4 DVs related to AU asymmetry in VT. Based on a power analysis, we provide sample size recommendations for future studies. Conclusion: This pilot study provides a framework for ASD stratification biomarker discovery based on perception and production of facial expressions.
[ { "created": "Wed, 27 Mar 2024 01:43:50 GMT", "version": "v1" } ]
2024-04-26
[ [ "Witherow", "Megan A.", "" ], [ "Diawara", "Norou", "" ], [ "Keener", "Janice", "" ], [ "Harrington", "John W.", "" ], [ "Iftekharuddin", "Khan M.", "" ] ]
Purpose: Facial expression production and perception in autism spectrum disorder (ASD) suggest potential presence of behavioral biomarkers that may stratify individuals on the spectrum into prognostic or treatment subgroups. Construct validity and group discriminability have been recommended as criteria for identification of candidate stratification biomarkers. Methods: In an online pilot study of 11 children and young adults diagnosed with ASD and 11 age- and gender-matched neurotypical (NT) individuals, participants recognize and mimic static and dynamic facial expressions of 3D avatars. Webcam-based eye-tracking (ET) and facial video tracking (VT), including activation and asymmetry of action units (AUs) from the Facial Action Coding System (FACS) are collected. We assess validity of constructs for each dependent variable (DV) based on the expected response in the NT group. Then, the Boruta statistical method identifies DVs that are significant to group discriminability (ASD or NT). Results: We identify one candidate ET biomarker (percentage gaze duration to the face while mimicking static 'disgust' expression) and 14 additional DVs of interest for future study, including 4 ET DVs, 5 DVs related to VT AU activation, and 4 DVs related to AU asymmetry in VT. Based on a power analysis, we provide sample size recommendations for future studies. Conclusion: This pilot study provides a framework for ASD stratification biomarker discovery based on perception and production of facial expressions.
1805.04619
Stevan Harnad
Fernanda P\'erez-Gay, Tomy Sicotte, Christian Th\'eriault, Stevan Harnad
Category learning can alter perception and its neural correlates
40 pages, 15 figures, 8 tables
PLOS ONE 14(12): e0226000 (2019)
10.1371/journal.pone.0226000
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Learned Categorical Perception (CP) occurs when the members of different categories come to look more dissimilar (between-category separation) and/or members of the same category come to look more similar (within-category compression) after a new category has been learned. To measure learned CP and its physiological correlates we compared dissimilarity judgments and Event Related Potentials (ERPs) before and after learning to sort multi-featured visual textures into two categories by trial and error with corrective feedback. With the same number of trials and feedback, about half the participants succeeded in learning the categories (learners: criterion 80% accuracy) and the rest did not (non-learners). At both lower and higher levels of difficulty, successful learners showed significant between-category separation in pairwise dissimilarity judgments after learning compared to before; their late parietal ERP positivity (LPC, usually interpreted as decisional) also increased and their occipital negativity (N1) (usually interpreted as perceptual) decreased. LPC increased with response accuracy and N1 amplitude decreased with between-category separation for the Learners. Non-learners showed no significant changes in dissimilarity judgments, LPC or N1, within or between categories. This is behavioral and physiological evidence that category learning can alter perception. We sketch a neural net model for this effect.
[ { "created": "Fri, 11 May 2018 23:44:01 GMT", "version": "v1" }, { "created": "Mon, 14 Jan 2019 22:20:51 GMT", "version": "v2" }, { "created": "Tue, 10 Dec 2019 22:54:05 GMT", "version": "v3" } ]
2019-12-12
[ [ "Pérez-Gay", "Fernanda", "" ], [ "Sicotte", "Tomy", "" ], [ "Thériault", "Christian", "" ], [ "Harnad", "Stevan", "" ] ]
Learned Categorical Perception (CP) occurs when the members of different categories come to look more dissimilar (between-category separation) and/or members of the same category come to look more similar (within-category compression) after a new category has been learned. To measure learned CP and its physiological correlates we compared dissimilarity judgments and Event Related Potentials (ERPs) before and after learning to sort multi-featured visual textures into two categories by trial and error with corrective feedback. With the same number of trials and feedback, about half the participants succeeded in learning the categories (learners: criterion 80% accuracy) and the rest did not (non-learners). At both lower and higher levels of difficulty, successful learners showed significant between-category separation in pairwise dissimilarity judgments after learning compared to before; their late parietal ERP positivity (LPC, usually interpreted as decisional) also increased and their occipital negativity (N1) (usually interpreted as perceptual) decreased. LPC increased with response accuracy and N1 amplitude decreased with between-category separation for the Learners. Non-learners showed no significant changes in dissimilarity judgments, LPC or N1, within or between categories. This is behavioral and physiological evidence that category learning can alter perception. We sketch a neural net model for this effect.
1309.4952
Akira Kinjo
Ken Nishikawa and Akira R. Kinjo
Cooperation between genetic mutations and phenotypic plasticity can bypass the Weismann barrier: The cooperative model of evolution
23 pages, 1 figure
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The Weismann barrier, or the impossibility of inheritance of acquired traits, comprises a foundation of modern biology, and it has been a major obstacle in establishing the connection between evolution and ontogenesis. We propose the cooperative model based on the assumption that evolution is achieved by a cooperation between genetic mutations and acquired changes (phenotypic plasticity). It is also assumed in this model that natural selection operates on phenotypes, rather than genotypes, of individuals, and that the relationship between phenotypes and genotypes is one-to-many. In the simulations based on these assumptions, individuals exhibited phenotypic changes in response to an environmental change, corresponding multiple genetic mutations were increasingly accumulated in individuals in the population, and phenotypic plasticity was gradually replaced with genetic mutations. This result suggests that Lamarck's law of use and disuse can effectively hold without conflicting the Weismann barrier, and thus evolution can be logically connected with ontogenesis.
[ { "created": "Thu, 19 Sep 2013 12:24:56 GMT", "version": "v1" } ]
2013-09-20
[ [ "Nishikawa", "Ken", "" ], [ "Kinjo", "Akira R.", "" ] ]
The Weismann barrier, or the impossibility of inheritance of acquired traits, comprises a foundation of modern biology, and it has been a major obstacle in establishing the connection between evolution and ontogenesis. We propose the cooperative model based on the assumption that evolution is achieved by a cooperation between genetic mutations and acquired changes (phenotypic plasticity). It is also assumed in this model that natural selection operates on phenotypes, rather than genotypes, of individuals, and that the relationship between phenotypes and genotypes is one-to-many. In the simulations based on these assumptions, individuals exhibited phenotypic changes in response to an environmental change, corresponding multiple genetic mutations were increasingly accumulated in individuals in the population, and phenotypic plasticity was gradually replaced with genetic mutations. This result suggests that Lamarck's law of use and disuse can effectively hold without conflicting the Weismann barrier, and thus evolution can be logically connected with ontogenesis.
1411.5179
Constantino Antonio Garc\'ia
Constantino A. Garc\'ia, Abraham Otero, Xos\'e Vila, David G. M\'arquez
A new algorithm for wavelet-based heart rate variability analysis
null
Biomedical Signal Processing and Control, Volume 8, Issue 6, November 2013, Pages 542-550
10.1016/j.bspc.2013.05.006
null
q-bio.QM physics.med-ph stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
One of the most promising non-invasive markers of the activity of the autonomic nervous system is Heart Rate Variability (HRV). HRV analysis toolkits often provide spectral analysis techniques using the Fourier transform, which assumes that the heart rate series is stationary. To overcome this issue, the Short Time Fourier Transform is often used (STFT). However, the wavelet transform is thought to be a more suitable tool for analyzing non-stationary signals than the STFT. Given the lack of support for wavelet-based analysis in HRV toolkits, such analysis must be implemented by the researcher. This has made this technique underutilized. This paper presents a new algorithm to perform HRV power spectrum analysis based on the Maximal Overlap Discrete Wavelet Packet Transform (MODWPT). The algorithm calculates the power in any spectral band with a given tolerance for the band's boundaries. The MODWPT decomposition tree is pruned to avoid calculating unnecessary wavelet coefficients, thereby optimizing execution time. The center of energy shift correction is applied to achieve optimum alignment of the wavelet coefficients. This algorithm has been implemented in RHRV, an open-source package for HRV analysis. To the best of our knowledge, RHRV is the first HRV toolkit with support for wavelet-based spectral analysis.
[ { "created": "Wed, 19 Nov 2014 11:11:45 GMT", "version": "v1" } ]
2014-11-20
[ [ "García", "Constantino A.", "" ], [ "Otero", "Abraham", "" ], [ "Vila", "Xosé", "" ], [ "Márquez", "David G.", "" ] ]
One of the most promising non-invasive markers of the activity of the autonomic nervous system is Heart Rate Variability (HRV). HRV analysis toolkits often provide spectral analysis techniques using the Fourier transform, which assumes that the heart rate series is stationary. To overcome this issue, the Short Time Fourier Transform is often used (STFT). However, the wavelet transform is thought to be a more suitable tool for analyzing non-stationary signals than the STFT. Given the lack of support for wavelet-based analysis in HRV toolkits, such analysis must be implemented by the researcher. This has made this technique underutilized. This paper presents a new algorithm to perform HRV power spectrum analysis based on the Maximal Overlap Discrete Wavelet Packet Transform (MODWPT). The algorithm calculates the power in any spectral band with a given tolerance for the band's boundaries. The MODWPT decomposition tree is pruned to avoid calculating unnecessary wavelet coefficients, thereby optimizing execution time. The center of energy shift correction is applied to achieve optimum alignment of the wavelet coefficients. This algorithm has been implemented in RHRV, an open-source package for HRV analysis. To the best of our knowledge, RHRV is the first HRV toolkit with support for wavelet-based spectral analysis.
2303.12058
Jane Ivy Coons
Jane Ivy Coons and Benjamin Hollering
Identifiability of the Rooted Tree Parameter under the Cavender-Farris-Neyman Model with a Molecular Clock
6 pages, 1 figure
null
null
null
q-bio.PE math.CO math.ST stat.TH
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Identifiability of the discrete tree parameter is a key property for phylogenetic models since it is necessary for statistically consistent estimation of the tree from sequence data. Algebraic methods have proven to be very effective at showing that tree and network parameters of phylogenetic models are identifiable, especially when the underlying models are group-based. However, since group-based models are time-reversible, only the unrooted tree topology is identifiable and the location of the root is not. In this note we show that the rooted tree parameter of the Cavender-Farris-Neyman Model with a Molecular Clock is generically identifiable by using the invariants of the model which were characterized by Coons and Sullivant.
[ { "created": "Tue, 21 Mar 2023 17:50:37 GMT", "version": "v1" } ]
2023-03-22
[ [ "Coons", "Jane Ivy", "" ], [ "Hollering", "Benjamin", "" ] ]
Identifiability of the discrete tree parameter is a key property for phylogenetic models since it is necessary for statistically consistent estimation of the tree from sequence data. Algebraic methods have proven to be very effective at showing that tree and network parameters of phylogenetic models are identifiable, especially when the underlying models are group-based. However, since group-based models are time-reversible, only the unrooted tree topology is identifiable and the location of the root is not. In this note we show that the rooted tree parameter of the Cavender-Farris-Neyman Model with a Molecular Clock is generically identifiable by using the invariants of the model which were characterized by Coons and Sullivant.
q-bio/0404017
Natasa Przulj
Natasa Przulj, Derek G. Corneil, Igor Jurisica
Modeling Interactome: Scale-Free or Geometric?
53 pages, 18 figures, 5 tables
null
null
null
q-bio.MN
null
Networks have been used to model many real-world phenomena to better understand the phenomena and to guide experiments in order to predict their behavior. Since incorrect models lead to incorrect predictions, it is vital to have a correct model. As a result, new techniques and models for analyzing and modeling real-world networks have recently been introduced. One example of large and complex networks involves protein-protein interaction (PPI) networks. We demonstrate that the currently popular scale-free model of PPI networks fails to fit the data in several respects. We show that a random geometric model provides a much more accurate model of the PPI data.
[ { "created": "Sat, 17 Apr 2004 02:36:10 GMT", "version": "v1" } ]
2007-05-23
[ [ "Przulj", "Natasa", "" ], [ "Corneil", "Derek G.", "" ], [ "Jurisica", "Igor", "" ] ]
Networks have been used to model many real-world phenomena to better understand the phenomena and to guide experiments in order to predict their behavior. Since incorrect models lead to incorrect predictions, it is vital to have a correct model. As a result, new techniques and models for analyzing and modeling real-world networks have recently been introduced. One example of large and complex networks involves protein-protein interaction (PPI) networks. We demonstrate that the currently popular scale-free model of PPI networks fails to fit the data in several respects. We show that a random geometric model provides a much more accurate model of the PPI data.
2010.02346
Alexander Kaiser
Alexander D. Kaiser, Rohan Shad, William Hiesinger, Alison L. Marsden
A Design-Based Model of the Aortic Valve for Fluid-Structure Interaction
null
null
10.1007/s10237-021-01516-7
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This paper presents a new method for modeling the mechanics of the aortic valve, and simulates its interaction with blood. As much as possible, the model construction is based on first principles, but such that the model is consistent with experimental observations. We require that tension in the leaflets must support a pressure, then derive a system of partial differential equations governing its mechanical equilibrium. The solution to these differential equations is referred to as the predicted loaded configuration; it includes the loaded leaflet geometry, fiber orientations and tensions needed to support the prescribed load. From this configuration, we derive a reference configuration and constitutive law. In fluid-structure interaction simulations with the immersed boundary method, the model seals reliably under physiological pressures, and opens freely over multiple cardiac cycles. Further, model closure is robust to extreme hypo- and hypertensive pressures. Then, exploiting the unique features of this model construction, we conduct experiments on reference configurations, constitutive laws, and gross morphology. These experiments suggest the following conclusions, which are directly applicable to the design of prosthetic aortic valves. (i) The loaded geometry, tensions and tangent moduli primarily determine model function. (ii) Alterations to the reference configuration have little effect if the predicted loaded configuration is identical. (iii) The leaflets must have sufficiently nonlinear material response to function over a variety of pressures. (iv) Valve performance is highly sensitive to free edge length and leaflet height. For future use, our aortic valve modeling framework offers flexibility in patient-specific models of cardiac flow.
[ { "created": "Mon, 5 Oct 2020 21:43:59 GMT", "version": "v1" }, { "created": "Sat, 4 Sep 2021 18:34:01 GMT", "version": "v2" } ]
2021-10-15
[ [ "Kaiser", "Alexander D.", "" ], [ "Shad", "Rohan", "" ], [ "Hiesinger", "William", "" ], [ "Marsden", "Alison L.", "" ] ]
This paper presents a new method for modeling the mechanics of the aortic valve, and simulates its interaction with blood. As much as possible, the model construction is based on first principles, but such that the model is consistent with experimental observations. We require that tension in the leaflets must support a pressure, then derive a system of partial differential equations governing its mechanical equilibrium. The solution to these differential equations is referred to as the predicted loaded configuration; it includes the loaded leaflet geometry, fiber orientations and tensions needed to support the prescribed load. From this configuration, we derive a reference configuration and constitutive law. In fluid-structure interaction simulations with the immersed boundary method, the model seals reliably under physiological pressures, and opens freely over multiple cardiac cycles. Further, model closure is robust to extreme hypo- and hypertensive pressures. Then, exploiting the unique features of this model construction, we conduct experiments on reference configurations, constitutive laws, and gross morphology. These experiments suggest the following conclusions, which are directly applicable to the design of prosthetic aortic valves. (i) The loaded geometry, tensions and tangent moduli primarily determine model function. (ii) Alterations to the reference configuration have little effect if the predicted loaded configuration is identical. (iii) The leaflets must have sufficiently nonlinear material response to function over a variety of pressures. (iv) Valve performance is highly sensitive to free edge length and leaflet height. For future use, our aortic valve modeling framework offers flexibility in patient-specific models of cardiac flow.
2103.06145
Abhishek Singh
Abhishek Narain Singh
GraphBreak: Tool for Network Community based Regulatory Medicine, Gene co-expression, Linkage Disequilibrium analysis, functional annotation and more
null
null
null
null
q-bio.GN cs.AI cs.DC
http://creativecommons.org/licenses/by/4.0/
Graph network science is becoming increasingly popular, notably in big-data perspective where understanding individual entities for individual functional roles is complex and time consuming. It is likely when a set of genes are regulated by a set of genetic variants, the genes set is recruited for a common or related functional purpose. Grouping and extracting communities from network of associations becomes critical to understand system complexity, thus prioritizing genes for dis-ease and functional associations. Workload is reduced when studying entities one at a time. For this, we present GraphBreak, a suite of tools for community detection application, such as for gene co-expression, protein interaction, regulation network, etc.Although developed for use case of eQTLs regulatory genomic net-work community study -- results shown with our analysis with sample eQTL data. Graphbreak can be deployed for other studies if input data has been fed in requisite format, including but not limited to gene co-expression networks, protein-protein interaction network, signaling pathway and metabolic network. Graph-Break showed critical use case value in its downstream analysis for disease association of communities detected. If all independent steps of community detection and analysis are a step-by-step sub-part of the algorithm, GraphBreak can be considered a new algorithm for community based functional characterization. Combination of various algorithmic implementation modules into a single script for this purpose illustrates GraphBreak novelty. Compared to other similar tools, with GraphBreak we can better detect communities with over-representation of its member genes for statistical association with diseases, therefore target genes which can be prioritized for drug-positioning or drug-re-positioning as the case be.
[ { "created": "Wed, 24 Feb 2021 15:16:38 GMT", "version": "v1" } ]
2021-03-11
[ [ "Singh", "Abhishek Narain", "" ] ]
Graph network science is becoming increasingly popular, notably in big-data perspective where understanding individual entities for individual functional roles is complex and time consuming. It is likely when a set of genes are regulated by a set of genetic variants, the genes set is recruited for a common or related functional purpose. Grouping and extracting communities from network of associations becomes critical to understand system complexity, thus prioritizing genes for dis-ease and functional associations. Workload is reduced when studying entities one at a time. For this, we present GraphBreak, a suite of tools for community detection application, such as for gene co-expression, protein interaction, regulation network, etc.Although developed for use case of eQTLs regulatory genomic net-work community study -- results shown with our analysis with sample eQTL data. Graphbreak can be deployed for other studies if input data has been fed in requisite format, including but not limited to gene co-expression networks, protein-protein interaction network, signaling pathway and metabolic network. Graph-Break showed critical use case value in its downstream analysis for disease association of communities detected. If all independent steps of community detection and analysis are a step-by-step sub-part of the algorithm, GraphBreak can be considered a new algorithm for community based functional characterization. Combination of various algorithmic implementation modules into a single script for this purpose illustrates GraphBreak novelty. Compared to other similar tools, with GraphBreak we can better detect communities with over-representation of its member genes for statistical association with diseases, therefore target genes which can be prioritized for drug-positioning or drug-re-positioning as the case be.
1910.14098
Sahar Hojjatinia
Sahar Hojjatinia, Constantino M. Lagoa
Comparison of Different Spike Sorting Subtechniques Based on Rat Brain Basolateral Amygdala Neuronal Activity
8 pages, 12 figures
null
null
null
q-bio.NC cs.LG stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Developing electrophysiological recordings of brain neuronal activity and their analysis provide a basis for exploring the structure of brain function and nervous system investigation. The recorded signals are typically a combination of spikes and noise. High amounts of background noise and possibility of electric signaling recording from several neurons adjacent to the recording site have led scientists to develop neuronal signal processing tools such as spike sorting to facilitate brain data analysis. Spike sorting plays a pivotal role in understanding the electrophysiological activity of neuronal networks. This process prepares recorded data for interpretations of neurons interactions and understanding the overall structure of brain functions. Spike sorting consists of three steps: spike detection, feature extraction, and spike clustering. There are several methods to implement each of spike sorting steps. This paper provides a systematic comparison of various spike sorting sub-techniques applied to real extracellularly recorded data from a rat brain basolateral amygdala. An efficient sorted data resulted from careful choice of spike sorting sub-methods leads to better interpretation of the brain structures connectivity under different conditions, which is a very sensitive concept in diagnosis and treatment of neurological disorders. Here, spike detection is performed by appropriate choice of threshold level via three different approaches. Feature extraction is done through PCA and Kernel PCA methods, which Kernel PCA outperforms. We have applied four different algorithms for spike clustering including K-means, Fuzzy C-means, Bayesian and Fuzzy maximum likelihood estimation. As one requirement of most clustering algorithms, optimal number of clusters is achieved through validity indices for each method. Finally, the sorting results are evaluated using inter-spike interval histograms.
[ { "created": "Sun, 27 Oct 2019 00:44:24 GMT", "version": "v1" } ]
2019-11-01
[ [ "Hojjatinia", "Sahar", "" ], [ "Lagoa", "Constantino M.", "" ] ]
Developing electrophysiological recordings of brain neuronal activity and their analysis provide a basis for exploring the structure of brain function and nervous system investigation. The recorded signals are typically a combination of spikes and noise. High amounts of background noise and possibility of electric signaling recording from several neurons adjacent to the recording site have led scientists to develop neuronal signal processing tools such as spike sorting to facilitate brain data analysis. Spike sorting plays a pivotal role in understanding the electrophysiological activity of neuronal networks. This process prepares recorded data for interpretations of neurons interactions and understanding the overall structure of brain functions. Spike sorting consists of three steps: spike detection, feature extraction, and spike clustering. There are several methods to implement each of spike sorting steps. This paper provides a systematic comparison of various spike sorting sub-techniques applied to real extracellularly recorded data from a rat brain basolateral amygdala. An efficient sorted data resulted from careful choice of spike sorting sub-methods leads to better interpretation of the brain structures connectivity under different conditions, which is a very sensitive concept in diagnosis and treatment of neurological disorders. Here, spike detection is performed by appropriate choice of threshold level via three different approaches. Feature extraction is done through PCA and Kernel PCA methods, which Kernel PCA outperforms. We have applied four different algorithms for spike clustering including K-means, Fuzzy C-means, Bayesian and Fuzzy maximum likelihood estimation. As one requirement of most clustering algorithms, optimal number of clusters is achieved through validity indices for each method. Finally, the sorting results are evaluated using inter-spike interval histograms.
2305.13254
Rafael Mena-Yedra
Rafael Mena-Yedra, Juana L. Redondo, Horacio P\'erez-S\'anchez, Pilar M. Ortigosa
ALMERIA: Boosting pairwise molecular contrasts with scalable methods
null
null
null
null
q-bio.BM cs.CE cs.LG
http://creativecommons.org/licenses/by-nc-nd/4.0/
Searching for potential active compounds in large databases is a necessary step to reduce time and costs in modern drug discovery pipelines. Such virtual screening methods seek to provide predictions that allow the search space to be narrowed down. Although cheminformatics has made great progress in exploiting the potential of available big data, caution is needed to avoid introducing bias and provide useful predictions with new compounds. In this work, we propose the decision-support tool ALMERIA (Advanced Ligand Multiconformational Exploration with Robust Interpretable Artificial Intelligence) for estimating compound similarities and activity prediction based on pairwise molecular contrasts while considering their conformation variability. The methodology covers the entire pipeline from data preparation to model selection and hyperparameter optimization. It has been implemented using scalable software and methods to exploit large volumes of data -- in the order of several terabytes -- , offering a very quick response even for a large batch of queries. The implementation and experiments have been performed in a distributed computer cluster using a benchmark, the public access DUD-E database. In addition to cross-validation, detailed data split criteria have been used to evaluate the models on different data partitions to assess their true generalization ability with new compounds. Experiments show state-of-the-art performance for molecular activity prediction (ROC AUC: $0.99$, $0.96$, $0.87$), proving that the chosen data representation and modeling have good properties to generalize. Molecular conformations -- prediction performance and sensitivity analysis -- have also been evaluated. Finally, an interpretability analysis has been performed using the SHAP method.
[ { "created": "Fri, 28 Apr 2023 16:27:06 GMT", "version": "v1" } ]
2023-05-23
[ [ "Mena-Yedra", "Rafael", "" ], [ "Redondo", "Juana L.", "" ], [ "Pérez-Sánchez", "Horacio", "" ], [ "Ortigosa", "Pilar M.", "" ] ]
Searching for potential active compounds in large databases is a necessary step to reduce time and costs in modern drug discovery pipelines. Such virtual screening methods seek to provide predictions that allow the search space to be narrowed down. Although cheminformatics has made great progress in exploiting the potential of available big data, caution is needed to avoid introducing bias and provide useful predictions with new compounds. In this work, we propose the decision-support tool ALMERIA (Advanced Ligand Multiconformational Exploration with Robust Interpretable Artificial Intelligence) for estimating compound similarities and activity prediction based on pairwise molecular contrasts while considering their conformation variability. The methodology covers the entire pipeline from data preparation to model selection and hyperparameter optimization. It has been implemented using scalable software and methods to exploit large volumes of data -- in the order of several terabytes -- , offering a very quick response even for a large batch of queries. The implementation and experiments have been performed in a distributed computer cluster using a benchmark, the public access DUD-E database. In addition to cross-validation, detailed data split criteria have been used to evaluate the models on different data partitions to assess their true generalization ability with new compounds. Experiments show state-of-the-art performance for molecular activity prediction (ROC AUC: $0.99$, $0.96$, $0.87$), proving that the chosen data representation and modeling have good properties to generalize. Molecular conformations -- prediction performance and sensitivity analysis -- have also been evaluated. Finally, an interpretability analysis has been performed using the SHAP method.
1606.04875
Jesse Greener
Francois Paquet-Mercier, Mazeyar Parvinzadeh Gashti, Julien Bellavance, Seyed Mohammad Taghavi, Jesse Greener
Effect of NaCl on Pseudomonas biofilm viscosity by continuous, non-intrusive microfluidic-based approach
Manuscript: 6 pages, 6 figures. Supporting information: 5 pages, 4 figures
null
null
null
q-bio.QM physics.flu-dyn
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A method combining video imaging in parallel microchannels with a semi-empirical mathematical model provides non-intrusive, high-throughput measurements of time-varying biofilm viscosity. The approach is demonstrated for early growth Pseudomonas sp. biofilms exposed to constant flow streams of nutrient solutions with different ionic strengths. The ability to measure viscosities at early growth stages, without inducing a shear-thickening response, enabled measurements that are among the lowest reported to date. In addition, good time resolution enabled the detection of a rapid thickening phase, which occurred at different times after the exponential growth phase finished, depending on the ionic strength. The technique opens the way for a combinatorial approach to beter understand the complex dynamical response of biofilm mechanical properties under well-controlled physical, chemical and biological growth conditions and time-limited perturbations.
[ { "created": "Wed, 15 Jun 2016 17:36:41 GMT", "version": "v1" } ]
2016-06-16
[ [ "Paquet-Mercier", "Francois", "" ], [ "Gashti", "Mazeyar Parvinzadeh", "" ], [ "Bellavance", "Julien", "" ], [ "Taghavi", "Seyed Mohammad", "" ], [ "Greener", "Jesse", "" ] ]
A method combining video imaging in parallel microchannels with a semi-empirical mathematical model provides non-intrusive, high-throughput measurements of time-varying biofilm viscosity. The approach is demonstrated for early growth Pseudomonas sp. biofilms exposed to constant flow streams of nutrient solutions with different ionic strengths. The ability to measure viscosities at early growth stages, without inducing a shear-thickening response, enabled measurements that are among the lowest reported to date. In addition, good time resolution enabled the detection of a rapid thickening phase, which occurred at different times after the exponential growth phase finished, depending on the ionic strength. The technique opens the way for a combinatorial approach to beter understand the complex dynamical response of biofilm mechanical properties under well-controlled physical, chemical and biological growth conditions and time-limited perturbations.
1101.5814
Jacopo Grilli
Jacopo Grilli, Bruno Bassetti, Sergei Maslov and Marco Cosentino Lagomarsino
Joint scaling laws in functional and evolutionary categories in prokaryotic genomes
39 pages, 21 figures
Nucleic Acids Research (2012) 40 (2): 530-540
10.1093/nar/gkr711
null
q-bio.GN q-bio.MN q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We propose and study a class-expansion/innovation/loss model of genome evolution taking into account biological roles of genes and their constituent domains. In our model numbers of genes in different functional categories are coupled to each other. For example, an increase in the number of metabolic enzymes in a genome is usually accompanied by addition of new transcription factors regulating these enzymes. Such coupling can be thought of as a proportional "recipe" for genome composition of the type "a spoonful of sugar for each egg yolk". The model jointly reproduces two known empirical laws: the distribution of family sizes and the nonlinear scaling of the number of genes in certain functional categories (e.g. transcription factors) with genome size. In addition, it allows us to derive a novel relation between the exponents characterising these two scaling laws, establishing a direct quantitative connection between evolutionary and functional categories. It predicts that functional categories that grow faster-than-linearly with genome size to be characterised by flatter-than-average family size distributions. This relation is confirmed by our bioinformatics analysis of prokaryotic genomes. This proves that the joint quantitative trends of functional and evolutionary classes can be understood in terms of evolutionary growth with proportional recipes.
[ { "created": "Sun, 30 Jan 2011 20:23:10 GMT", "version": "v1" }, { "created": "Tue, 8 Mar 2011 10:35:36 GMT", "version": "v2" }, { "created": "Tue, 9 Aug 2011 19:11:58 GMT", "version": "v3" } ]
2015-03-18
[ [ "Grilli", "Jacopo", "" ], [ "Bassetti", "Bruno", "" ], [ "Maslov", "Sergei", "" ], [ "Lagomarsino", "Marco Cosentino", "" ] ]
We propose and study a class-expansion/innovation/loss model of genome evolution taking into account biological roles of genes and their constituent domains. In our model numbers of genes in different functional categories are coupled to each other. For example, an increase in the number of metabolic enzymes in a genome is usually accompanied by addition of new transcription factors regulating these enzymes. Such coupling can be thought of as a proportional "recipe" for genome composition of the type "a spoonful of sugar for each egg yolk". The model jointly reproduces two known empirical laws: the distribution of family sizes and the nonlinear scaling of the number of genes in certain functional categories (e.g. transcription factors) with genome size. In addition, it allows us to derive a novel relation between the exponents characterising these two scaling laws, establishing a direct quantitative connection between evolutionary and functional categories. It predicts that functional categories that grow faster-than-linearly with genome size to be characterised by flatter-than-average family size distributions. This relation is confirmed by our bioinformatics analysis of prokaryotic genomes. This proves that the joint quantitative trends of functional and evolutionary classes can be understood in terms of evolutionary growth with proportional recipes.
1902.10700
Imon Banerjee
Imon Banerjee, Luis de Sisternes, Joelle Hallak, Theodore Leng, Aaron Osborne, Mary Durbin, Daniel Rubin
A Deep-learning Approach for Prognosis of Age-Related Macular Degeneration Disease using SD-OCT Imaging Biomarkers
null
null
null
null
q-bio.QM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We propose a hybrid sequential deep learning model to predict the risk of AMD progression in non-exudative AMD eyes at multiple timepoints, starting from short-term progression (3-months) up to long-term progression (21-months). Proposed model combines radiomics and deep learning to handle challenges related to imperfect ratio of OCT scan dimension and training cohort size. We considered a retrospective clinical trial dataset that includes 671 fellow eyes with 13,954 dry AMD observations for training and validating the machine learning models on a 10-fold cross validation setting. The proposed RNN model achieved high accuracy (0.96 AUCROC) for the prediction of both short term and long-term AMD progression, and outperformed the traditional random forest model trained. High accuracy achieved by the RNN establishes the ability to identify AMD patients at risk of progressing to advanced AMD at an early stage which could have a high clinical impact as it allows for optimal clinical follow-up, with more frequent screening and potential earlier treatment for those patients at high risk.
[ { "created": "Wed, 27 Feb 2019 06:16:12 GMT", "version": "v1" } ]
2019-03-01
[ [ "Banerjee", "Imon", "" ], [ "de Sisternes", "Luis", "" ], [ "Hallak", "Joelle", "" ], [ "Leng", "Theodore", "" ], [ "Osborne", "Aaron", "" ], [ "Durbin", "Mary", "" ], [ "Rubin", "Daniel", "" ] ]
We propose a hybrid sequential deep learning model to predict the risk of AMD progression in non-exudative AMD eyes at multiple timepoints, starting from short-term progression (3-months) up to long-term progression (21-months). Proposed model combines radiomics and deep learning to handle challenges related to imperfect ratio of OCT scan dimension and training cohort size. We considered a retrospective clinical trial dataset that includes 671 fellow eyes with 13,954 dry AMD observations for training and validating the machine learning models on a 10-fold cross validation setting. The proposed RNN model achieved high accuracy (0.96 AUCROC) for the prediction of both short term and long-term AMD progression, and outperformed the traditional random forest model trained. High accuracy achieved by the RNN establishes the ability to identify AMD patients at risk of progressing to advanced AMD at an early stage which could have a high clinical impact as it allows for optimal clinical follow-up, with more frequent screening and potential earlier treatment for those patients at high risk.
2107.04036
Abicumaran Uthamacumaran
Abicumaran Uthamacumaran
Pattern Detection on Glioblastoma's Waddington landscape via Generative Adversarial Networks
15 pages, 3 figures
Cybernetics and Systems (2021)
10.1080/01969722.2021.1982160
https://doi.org/10.1080/01969722.2021.1982160
q-bio.OT nlin.CD physics.bio-ph
http://creativecommons.org/licenses/by-nc-sa/4.0/
Glioblastoma (GBM) is a highly morbid and lethal disease with poor prognosis. Their emergent properties such as cellular heterogeneity, therapy resistance, and self-renewal are largely attributed to the interactions between a subset of their population known as glioblastoma-derived stem cells (GSCs) and their microenvironment. Identifying causal patterns in the developmental trajectories between GSCs and the mature, well-differentiated GBM phenotypes remains a challenging problem in oncology. The paper presents a blueprint of complex systems approaches to infer attractor dynamics from the single-cell gene expression datasets of pediatric GBM and adult GSCs. These algorithms include Waddington landscape reconstruction, Generative Adversarial Networks, and fractal dimension analysis. Here I show, a Rossler-like strange attractor with a fractal dimension of roughly 1.7 emerged in the GAN-reconstructed patterns of all twelve patients. The findings suggest a strange attractor may be driving the complex dynamics and adaptive behaviors of GBM in signaling state-space.
[ { "created": "Thu, 8 Jul 2021 17:49:52 GMT", "version": "v1" }, { "created": "Mon, 12 Jul 2021 18:56:20 GMT", "version": "v2" }, { "created": "Thu, 23 Sep 2021 23:23:47 GMT", "version": "v3" } ]
2021-10-11
[ [ "Uthamacumaran", "Abicumaran", "" ] ]
Glioblastoma (GBM) is a highly morbid and lethal disease with poor prognosis. Their emergent properties such as cellular heterogeneity, therapy resistance, and self-renewal are largely attributed to the interactions between a subset of their population known as glioblastoma-derived stem cells (GSCs) and their microenvironment. Identifying causal patterns in the developmental trajectories between GSCs and the mature, well-differentiated GBM phenotypes remains a challenging problem in oncology. The paper presents a blueprint of complex systems approaches to infer attractor dynamics from the single-cell gene expression datasets of pediatric GBM and adult GSCs. These algorithms include Waddington landscape reconstruction, Generative Adversarial Networks, and fractal dimension analysis. Here I show, a Rossler-like strange attractor with a fractal dimension of roughly 1.7 emerged in the GAN-reconstructed patterns of all twelve patients. The findings suggest a strange attractor may be driving the complex dynamics and adaptive behaviors of GBM in signaling state-space.
1901.06139
Sean Murray
Sean M. Murray and Martin Howard
Centre-finding in E. coli and the role of mathematical modelling: past, present and future
15 pages, 3 figures
Journal of Molecular Biology 2019
null
null
q-bio.SC physics.bio-ph
http://creativecommons.org/licenses/by-nc-sa/4.0/
We review the key role played by mathematical modelling in elucidating two centre-finding patterning systems in E. coli: midcell division positioning by the MinCDE system and DNA partitioning by the ParABS system. We focus particularly on how, despite much experimental effort, these systems were simply too complex to unravel by experiments alone, and instead required key injections of quantitative, mathematical thinking. We conclude the review by analysing the frequency of modelling approaches in microbiology over time. We find that while such methods are increasing in popularity, they are still probably heavily under-utilised for optimal progress on complex biological questions.
[ { "created": "Fri, 18 Jan 2019 09:06:58 GMT", "version": "v1" } ]
2019-01-21
[ [ "Murray", "Sean M.", "" ], [ "Howard", "Martin", "" ] ]
We review the key role played by mathematical modelling in elucidating two centre-finding patterning systems in E. coli: midcell division positioning by the MinCDE system and DNA partitioning by the ParABS system. We focus particularly on how, despite much experimental effort, these systems were simply too complex to unravel by experiments alone, and instead required key injections of quantitative, mathematical thinking. We conclude the review by analysing the frequency of modelling approaches in microbiology over time. We find that while such methods are increasing in popularity, they are still probably heavily under-utilised for optimal progress on complex biological questions.
1811.00973
Marek Cieplak
Karol Wolek and Marek Cieplak
Self-assembly of model proteins into virus capsids
13 figures
J. Phys.:Cond. Matter 47, 474003 (2017)
10.1088/1361-648X/aa9351
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We consider self-assembly of proteins into a virus capsid by the methods of molecular dynamics. The capsid corresponds either to SPMV or CCMV and is studied with and without the RNA molecule inside. The proteins are flexible and described by the structure-based coarse-grained model augmented by electrostatic interactions. Previous studies of the capsid self-assembly involved solid objects of a supramolecular scale, e.g. corresponding to capsomeres, with engineered couplings and stochastic movements. In our approach, a single capsid is dissociated by an application of a high temperature for a variable period and then the system is cooled down to allow for self-assembly. The restoration of the capsid proceeds to various extent, depending on the nature of the dissociated state, but is rarely complete because some proteins depart too far unless the process takes place in a confined space.
[ { "created": "Fri, 2 Nov 2018 16:37:59 GMT", "version": "v1" } ]
2018-11-05
[ [ "Wolek", "Karol", "" ], [ "Cieplak", "Marek", "" ] ]
We consider self-assembly of proteins into a virus capsid by the methods of molecular dynamics. The capsid corresponds either to SPMV or CCMV and is studied with and without the RNA molecule inside. The proteins are flexible and described by the structure-based coarse-grained model augmented by electrostatic interactions. Previous studies of the capsid self-assembly involved solid objects of a supramolecular scale, e.g. corresponding to capsomeres, with engineered couplings and stochastic movements. In our approach, a single capsid is dissociated by an application of a high temperature for a variable period and then the system is cooled down to allow for self-assembly. The restoration of the capsid proceeds to various extent, depending on the nature of the dissociated state, but is rarely complete because some proteins depart too far unless the process takes place in a confined space.
2107.10966
David Hughes Dr
David J. Hughes, Joseph R Crosswell, Martina A. Doblin, Kevin Oxborough, Peter J. Ralph, Deepa Varkey and David J. Suggett
Dynamic variability of the phytoplankton electron requirement for carbon fixation in eastern Australian waters
57 pages, 14 figures, accepted version
J. Mar. Syst. 2020:103252
10.1016/j.jmarsys.2019.103252
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Fast Repetition Rate fluorometry (FRRf) generates high-resolution measures of phytoplankton primary productivity as electron transport rates (ETRs). How ETRs scale to corresponding inorganic carbon (C) uptake rates (the so-called electron requirement for carbon fixation, e,C), inherently describes the extent and effectiveness with which absorbed light energy drives C-fixation. However, it remains unclear whether and how e,C follows predictable patterns for oceanographic datasets spanning physically dynamic, and complex, environmental gradients. We utilise a unique high-throughput approach, coupling ETRs and 14C-incubations to produce a semi-continuous dataset of e,C (n = 80), predominantly from surface waters, along the Australian coast (Brisbane to the Tasman Sea), including the East Australian Current (EAC). Environmental conditions along this transect could be generally grouped into cooler, more nutrient-rich waters dominated by larger size-fractionated Chl-a (>10 um) versus warmer nutrient-poorer waters dominated by smaller size-fractionated Chl-a (< 2 um). Whilst e,C was higher for warmer water samples, environmental conditions alone explained less than 20% variance of e,C, and changes in predominant size-fraction(s) distributions of Chl-a (biomass) failed to explain variance of e,C. Instead, NPQNSV was a better predictor of e,C, explaining 55% of observed variability. NPQNSV is a physiological descriptor that accounts for changes in both long-term driven acclimation in non-radiative decay, and quasi-instantaneous PSII downregulation, and thus may prove a useful predictor of e,C across physically-dynamic regimes, provided the slope describing their relationship is predictable.
[ { "created": "Fri, 23 Jul 2021 00:12:41 GMT", "version": "v1" } ]
2021-07-26
[ [ "Hughes", "David J.", "" ], [ "Crosswell", "Joseph R", "" ], [ "Doblin", "Martina A.", "" ], [ "Oxborough", "Kevin", "" ], [ "Ralph", "Peter J.", "" ], [ "Varkey", "Deepa", "" ], [ "Suggett", "David J.", "" ] ]
Fast Repetition Rate fluorometry (FRRf) generates high-resolution measures of phytoplankton primary productivity as electron transport rates (ETRs). How ETRs scale to corresponding inorganic carbon (C) uptake rates (the so-called electron requirement for carbon fixation, e,C), inherently describes the extent and effectiveness with which absorbed light energy drives C-fixation. However, it remains unclear whether and how e,C follows predictable patterns for oceanographic datasets spanning physically dynamic, and complex, environmental gradients. We utilise a unique high-throughput approach, coupling ETRs and 14C-incubations to produce a semi-continuous dataset of e,C (n = 80), predominantly from surface waters, along the Australian coast (Brisbane to the Tasman Sea), including the East Australian Current (EAC). Environmental conditions along this transect could be generally grouped into cooler, more nutrient-rich waters dominated by larger size-fractionated Chl-a (>10 um) versus warmer nutrient-poorer waters dominated by smaller size-fractionated Chl-a (< 2 um). Whilst e,C was higher for warmer water samples, environmental conditions alone explained less than 20% variance of e,C, and changes in predominant size-fraction(s) distributions of Chl-a (biomass) failed to explain variance of e,C. Instead, NPQNSV was a better predictor of e,C, explaining 55% of observed variability. NPQNSV is a physiological descriptor that accounts for changes in both long-term driven acclimation in non-radiative decay, and quasi-instantaneous PSII downregulation, and thus may prove a useful predictor of e,C across physically-dynamic regimes, provided the slope describing their relationship is predictable.
1611.04077
Christoph Adami
Christoph Adami, Jory Schossau, and Arend Hintze
The Reasonable Effectiveness of Agent-Based Simulations in Evolutionary Game Theory
5 pages. To appear in Physics of Life Reviews
Physics of Life Reviews 19 (2016) 38-42
10.1016/j.plrev.2016.11.005
null
q-bio.PE cs.GT nlin.AO q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This is a Reply to comments published in Physics of Life Reviews, on our article "Evolutionary game theory using agent-based methods" (Physics of Life Reviews, 2016, arXiv:1404.0994).
[ { "created": "Sun, 13 Nov 2016 03:54:34 GMT", "version": "v1" } ]
2016-12-07
[ [ "Adami", "Christoph", "" ], [ "Schossau", "Jory", "" ], [ "Hintze", "Arend", "" ] ]
This is a Reply to comments published in Physics of Life Reviews, on our article "Evolutionary game theory using agent-based methods" (Physics of Life Reviews, 2016, arXiv:1404.0994).
0802.4361
Luca Sbano
L. Sbano and M. Kirkilionis
Multiscale Analysis of Reaction Networks
null
null
null
12/2007
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In most natural sciences there is currently the insight that it is necessary to bridge gaps between different processes which can be observed on different scales. This is especially true in the field of chemical reactions where the abilities to form bonds between different types of atoms and molecules create much of the properties we experience in our everyday life, especially in all biological activity. There are essentially two types of processes related to biochemical reaction networks, the interactions among molecules and interactions involving their conformational changes, so in a sense, their internal state. The first type of processes can be conveniently approximated by the so-called mass-action kinetics, but this is not necessarily so for the second kind where molecular states do not define any kind of density or concentration. In this paper we demonstrate the necessity to study reaction networks in a stochastic formulation for which we can construct a coherent approximation in terms of specific space-time scales and the number of particles. The continuum limit procedure naturally creates equations of Fokker-Planck type where the evolution of the concentration occurs on a slower time scale when compared to the evolution of the conformational changes, for example triggered by binding or unbinding events with other (typically smaller) molecules. We apply the asymptotic theory to derive the effective, i.e. macroscopic dynamics of the biochemical reaction system. The theory can also be applied to other processes where entities can be described by finitely many internal states, with changes of states occuring by arrival of other entities described by a birth-death process.
[ { "created": "Fri, 29 Feb 2008 11:19:35 GMT", "version": "v1" } ]
2008-03-03
[ [ "Sbano", "L.", "" ], [ "Kirkilionis", "M.", "" ] ]
In most natural sciences there is currently the insight that it is necessary to bridge gaps between different processes which can be observed on different scales. This is especially true in the field of chemical reactions where the abilities to form bonds between different types of atoms and molecules create much of the properties we experience in our everyday life, especially in all biological activity. There are essentially two types of processes related to biochemical reaction networks, the interactions among molecules and interactions involving their conformational changes, so in a sense, their internal state. The first type of processes can be conveniently approximated by the so-called mass-action kinetics, but this is not necessarily so for the second kind where molecular states do not define any kind of density or concentration. In this paper we demonstrate the necessity to study reaction networks in a stochastic formulation for which we can construct a coherent approximation in terms of specific space-time scales and the number of particles. The continuum limit procedure naturally creates equations of Fokker-Planck type where the evolution of the concentration occurs on a slower time scale when compared to the evolution of the conformational changes, for example triggered by binding or unbinding events with other (typically smaller) molecules. We apply the asymptotic theory to derive the effective, i.e. macroscopic dynamics of the biochemical reaction system. The theory can also be applied to other processes where entities can be described by finitely many internal states, with changes of states occuring by arrival of other entities described by a birth-death process.
2203.15888
Brenda Delamonica
Brenda Delamonica, Gabor Balazsi, Michael Shub
Cusp Bifurcation in Metastatic Breast Cancer Cells
57 pages, 22 figures, code included
null
null
null
q-bio.CB math.DS
http://creativecommons.org/licenses/by/4.0/
Ordinary differential equations (ODEs) can model the transition of cell states over time. Bifurcation theory is a branch of dynamical systems which studies changes in the behavior of an ODE system while one or more parameters are varied. We have found that concepts in bifurcation theory may be applied to model metastatic cell behavior. Our results show how a specific phenomenon called a cusp bifurcation describes metastatic cell state transitions, separating two qualitatively different transition modalities. Moreover, we show how the cusp bifurcation models other genetic networks, and we relate the dynamics after the bifurcation to observed phenomena in commitment to enter the cell cycle.
[ { "created": "Tue, 29 Mar 2022 20:21:57 GMT", "version": "v1" }, { "created": "Thu, 31 Mar 2022 12:39:03 GMT", "version": "v2" }, { "created": "Wed, 5 Jul 2023 14:28:54 GMT", "version": "v3" } ]
2023-07-06
[ [ "Delamonica", "Brenda", "" ], [ "Balazsi", "Gabor", "" ], [ "Shub", "Michael", "" ] ]
Ordinary differential equations (ODEs) can model the transition of cell states over time. Bifurcation theory is a branch of dynamical systems which studies changes in the behavior of an ODE system while one or more parameters are varied. We have found that concepts in bifurcation theory may be applied to model metastatic cell behavior. Our results show how a specific phenomenon called a cusp bifurcation describes metastatic cell state transitions, separating two qualitatively different transition modalities. Moreover, we show how the cusp bifurcation models other genetic networks, and we relate the dynamics after the bifurcation to observed phenomena in commitment to enter the cell cycle.
1103.0675
Diana Clausznitzer
Diana Clausznitzer, Robert G Endres
Noise characteristics of the Escherichia coli rotary motor
22 pages, 7 figures, 3 tutorials, supplementary information; submitted manuscript
null
null
null
q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The chemotaxis pathway in the bacterium Escherichia coli allows cells to detect changes in external ligand concentration (e.g. nutrients). The pathway regulates the flagellated rotary motors and hence the cells' swimming behaviour, steering them towards more favourable environments. While the molecular components are well characterised, the motor behaviour measured by tethered cell experiments has been difficult to interpret. Here, we study the effects of sensing and signalling noise on the motor behaviour. Specifically, we consider fluctuations stemming from ligand concentration, receptor switching between their signalling states, adaptation, modification of proteins by phosphorylation, and motor switching between its two rotational states. We develop a model which includes all signalling steps in the pathway, and discuss a simplified version, which captures the essential features of the full model. We find that the noise characteristics of the motor contain signatures from all these processes, albeit with varying magnitudes. This allows us to address how cell-to-cell variation affects motor behaviour and the question of optimal pathway design. A similar comprehensive analysis can be applied to other two-component signalling pathways.
[ { "created": "Thu, 3 Mar 2011 12:54:55 GMT", "version": "v1" } ]
2011-03-04
[ [ "Clausznitzer", "Diana", "" ], [ "Endres", "Robert G", "" ] ]
The chemotaxis pathway in the bacterium Escherichia coli allows cells to detect changes in external ligand concentration (e.g. nutrients). The pathway regulates the flagellated rotary motors and hence the cells' swimming behaviour, steering them towards more favourable environments. While the molecular components are well characterised, the motor behaviour measured by tethered cell experiments has been difficult to interpret. Here, we study the effects of sensing and signalling noise on the motor behaviour. Specifically, we consider fluctuations stemming from ligand concentration, receptor switching between their signalling states, adaptation, modification of proteins by phosphorylation, and motor switching between its two rotational states. We develop a model which includes all signalling steps in the pathway, and discuss a simplified version, which captures the essential features of the full model. We find that the noise characteristics of the motor contain signatures from all these processes, albeit with varying magnitudes. This allows us to address how cell-to-cell variation affects motor behaviour and the question of optimal pathway design. A similar comprehensive analysis can be applied to other two-component signalling pathways.
1002.0559
Randen Patterson
Gaurav Bhardwaj, Zhenhai Zhang, Yoojin Hong, Kyung Dae Ko, Gue Su Chang, Evan J. Smith, Lindsay A. Kline, D. Nicholas Hartranft, Edward C. Holmes, Randen L. Patterson, and Damian B. van Rossum
Theories on PHYlogenetic ReconstructioN (PHYRN)
13 pages, 6 figures
null
null
null
q-bio.PE q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The inability to resolve deep node relationships of highly divergent/rapidly evolving protein families is a major factor that stymies evolutionary studies. In this manuscript, we propose a Multiple Sequence Alignment (MSA) independent method to infer evolutionary relationships. We previously demonstrated that phylogenetic profiles built using position specific scoring matrices (PSSMs) are capable of constructing informative evolutionary histories(1;2). In this manuscript, we theorize that PSSMs derived specifically from the query sequences used to construct the phylogenetic tree will improve this method for the study of rapidly evolving proteins. To test this theory, we performed phylogenetic analyses of a benchmark protein superfamily (reverse transcriptases (RT)) as well as simulated datasets. When we compare the results obtained from our method, PHYlogenetic ReconstructioN (PHYRN), with other MSA dependent methods, we observe that PHYRN provides a 4- to 100-fold increase in accurate measurements at deep nodes. As phylogenetic profiles are used as the information source, rather than MSA, we propose PHYRN as a paradigm shift in studying evolution when MSA approaches fail. Perhaps most importantly, due to the improvements in our computational approach and the availability of vast amount of sequencing data, PHYRN is scalable to thousands of sequences. Taken together with PHYRNs adaptability to any protein family, this method can serve as a tool for resolving ambiguities in evolutionary studies of rapidly evolving/highly divergent protein families.
[ { "created": "Tue, 2 Feb 2010 18:13:11 GMT", "version": "v1" }, { "created": "Fri, 26 Feb 2010 16:12:58 GMT", "version": "v2" } ]
2010-02-26
[ [ "Bhardwaj", "Gaurav", "" ], [ "Zhang", "Zhenhai", "" ], [ "Hong", "Yoojin", "" ], [ "Ko", "Kyung Dae", "" ], [ "Chang", "Gue Su", "" ], [ "Smith", "Evan J.", "" ], [ "Kline", "Lindsay A.", "" ], [ "Hartranft", "D. Nicholas", "" ], [ "Holmes", "Edward C.", "" ], [ "Patterson", "Randen L.", "" ], [ "van Rossum", "Damian B.", "" ] ]
The inability to resolve deep node relationships of highly divergent/rapidly evolving protein families is a major factor that stymies evolutionary studies. In this manuscript, we propose a Multiple Sequence Alignment (MSA) independent method to infer evolutionary relationships. We previously demonstrated that phylogenetic profiles built using position specific scoring matrices (PSSMs) are capable of constructing informative evolutionary histories(1;2). In this manuscript, we theorize that PSSMs derived specifically from the query sequences used to construct the phylogenetic tree will improve this method for the study of rapidly evolving proteins. To test this theory, we performed phylogenetic analyses of a benchmark protein superfamily (reverse transcriptases (RT)) as well as simulated datasets. When we compare the results obtained from our method, PHYlogenetic ReconstructioN (PHYRN), with other MSA dependent methods, we observe that PHYRN provides a 4- to 100-fold increase in accurate measurements at deep nodes. As phylogenetic profiles are used as the information source, rather than MSA, we propose PHYRN as a paradigm shift in studying evolution when MSA approaches fail. Perhaps most importantly, due to the improvements in our computational approach and the availability of vast amount of sequencing data, PHYRN is scalable to thousands of sequences. Taken together with PHYRNs adaptability to any protein family, this method can serve as a tool for resolving ambiguities in evolutionary studies of rapidly evolving/highly divergent protein families.
2311.17969
Sonish Sivarajkumar
Sonish Sivarajkumar, Pratyush Tandale, Ankit Bhardwaj, Kipp W. Johnson, Anoop Titus, Benjamin S. Glicksberg, Shameer Khader, Kamlesh K. Yadav, Lakshminarayanan Subramanian
Generation of a Compendium of Transcription Factor Cascades and Identification of Potential Therapeutic Targets using Graph Machine Learning
null
null
null
null
q-bio.MN cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Transcription factors (TFs) play a vital role in the regulation of gene expression thereby making them critical to many cellular processes. In this study, we used graph machine learning methods to create a compendium of TF cascades using data extracted from the STRING database. A TF cascade is a sequence of TFs that regulate each other, forming a directed path in the TF network. We constructed a knowledge graph of 81,488 unique TF cascades, with the longest cascade consisting of 62 TFs. Our results highlight the complex and intricate nature of TF interactions, where multiple TFs work together to regulate gene expression. We also identified 10 TFs with the highest regulatory influence based on centrality measurements, providing valuable information for researchers interested in studying specific TFs. Furthermore, our pathway enrichment analysis revealed significant enrichment of various pathways and functional categories, including those involved in cancer and other diseases, as well as those involved in development, differentiation, and cell signaling. The enriched pathways identified in this study may have potential as targets for therapeutic intervention in diseases associated with dysregulation of transcription factors. We have released the dataset, knowledge graph, and graphML methods for the TF cascades, and created a website to display the results, which can be accessed by researchers interested in using this dataset. Our study provides a valuable resource for understanding the complex network of interactions between TFs and their regulatory roles in cellular processes.
[ { "created": "Wed, 29 Nov 2023 15:31:58 GMT", "version": "v1" } ]
2023-12-01
[ [ "Sivarajkumar", "Sonish", "" ], [ "Tandale", "Pratyush", "" ], [ "Bhardwaj", "Ankit", "" ], [ "Johnson", "Kipp W.", "" ], [ "Titus", "Anoop", "" ], [ "Glicksberg", "Benjamin S.", "" ], [ "Khader", "Shameer", "" ], [ "Yadav", "Kamlesh K.", "" ], [ "Subramanian", "Lakshminarayanan", "" ] ]
Transcription factors (TFs) play a vital role in the regulation of gene expression thereby making them critical to many cellular processes. In this study, we used graph machine learning methods to create a compendium of TF cascades using data extracted from the STRING database. A TF cascade is a sequence of TFs that regulate each other, forming a directed path in the TF network. We constructed a knowledge graph of 81,488 unique TF cascades, with the longest cascade consisting of 62 TFs. Our results highlight the complex and intricate nature of TF interactions, where multiple TFs work together to regulate gene expression. We also identified 10 TFs with the highest regulatory influence based on centrality measurements, providing valuable information for researchers interested in studying specific TFs. Furthermore, our pathway enrichment analysis revealed significant enrichment of various pathways and functional categories, including those involved in cancer and other diseases, as well as those involved in development, differentiation, and cell signaling. The enriched pathways identified in this study may have potential as targets for therapeutic intervention in diseases associated with dysregulation of transcription factors. We have released the dataset, knowledge graph, and graphML methods for the TF cascades, and created a website to display the results, which can be accessed by researchers interested in using this dataset. Our study provides a valuable resource for understanding the complex network of interactions between TFs and their regulatory roles in cellular processes.
1108.4575
Piero Olla
Piero Olla
Demographic fluctuations in a population of anomalously diffusing individuals
10 pages, 6 figures
Phys. Rev. E; 85, 021125 (2012)
10.1103/PhysRevE.85.021125
null
q-bio.PE cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The phenomenon of spatial clustering induced by death and reproduction in a population of anomalously diffusing individuals is studied analytically. The possibility of social behaviors affecting the migration strategies has been taken into exam, in the case anomalous diffusion is produced by means of a continuous time random walk (CTRW). In the case of independently diffusing individuals, the dynamics appears to coincide with that of (dying and reproducing) Brownian walkers. In the strongly social case, the dynamics coincides with that of non-migrating individuals. In both limits, the growth rate of the fluctuations becomes independent of the Hurst exponent of the CTRW. The social behaviors that arise when transport in a population is induced by a spatial distribution of random traps, have been analyzed.
[ { "created": "Tue, 23 Aug 2011 13:03:17 GMT", "version": "v1" }, { "created": "Thu, 15 Mar 2012 14:08:34 GMT", "version": "v2" } ]
2015-05-30
[ [ "Olla", "Piero", "" ] ]
The phenomenon of spatial clustering induced by death and reproduction in a population of anomalously diffusing individuals is studied analytically. The possibility of social behaviors affecting the migration strategies has been taken into exam, in the case anomalous diffusion is produced by means of a continuous time random walk (CTRW). In the case of independently diffusing individuals, the dynamics appears to coincide with that of (dying and reproducing) Brownian walkers. In the strongly social case, the dynamics coincides with that of non-migrating individuals. In both limits, the growth rate of the fluctuations becomes independent of the Hurst exponent of the CTRW. The social behaviors that arise when transport in a population is induced by a spatial distribution of random traps, have been analyzed.
1709.05059
David Warne
David J. Warne (1), Ruth E. Baker (2), Matthew J. Simpson (1) ((1) Queensland University of Technology, (2) University of Oxford)
Optimal quantification of contact inhibition in cell populations
null
null
10.1016/j.bpj.2017.09.016
null
q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Contact inhibition refers to a reduction in the rate of cell migration and/or cell proliferation in regions of high cell density. Under normal conditions contact inhibition is associated with the proper functioning tissues, whereas abnormal regulation of contact inhibition is associated with pathological conditions, such as tumor spreading. Unfortunately, standard mathematical modeling practices mask the importance of parameters that control contact inhibition through scaling arguments. Furthermore, standard experimental protocols are insufficient to quantify the effects of contact inhibition because they focus on data describing early time, low-density dynamics only. Here we use the logistic growth equation as a caricature model of contact inhibition to make recommendations as to how to best mitigate these issues. Taking a Bayesian approach we quantify the trade-off between different features of experimental design and estimates of parameter uncertainty so that we can re-formulate a standard cell proliferation assay to provide estimates of both the low-density intrinsic growth rate, $\lambda$, and the carrying capacity density, $K$, which is a measure of contact inhibition.
[ { "created": "Fri, 15 Sep 2017 04:52:56 GMT", "version": "v1" } ]
2018-03-01
[ [ "Warne", "David J.", "" ], [ "Baker", "Ruth E.", "" ], [ "Simpson", "Matthew J.", "" ] ]
Contact inhibition refers to a reduction in the rate of cell migration and/or cell proliferation in regions of high cell density. Under normal conditions contact inhibition is associated with the proper functioning tissues, whereas abnormal regulation of contact inhibition is associated with pathological conditions, such as tumor spreading. Unfortunately, standard mathematical modeling practices mask the importance of parameters that control contact inhibition through scaling arguments. Furthermore, standard experimental protocols are insufficient to quantify the effects of contact inhibition because they focus on data describing early time, low-density dynamics only. Here we use the logistic growth equation as a caricature model of contact inhibition to make recommendations as to how to best mitigate these issues. Taking a Bayesian approach we quantify the trade-off between different features of experimental design and estimates of parameter uncertainty so that we can re-formulate a standard cell proliferation assay to provide estimates of both the low-density intrinsic growth rate, $\lambda$, and the carrying capacity density, $K$, which is a measure of contact inhibition.
2108.02545
Claus Metzner
Claus Metzner and Patrick Krauss
Dynamical Phases and Resonance Phenomena in Information-Processing Recurrent Neural Networks
null
null
null
null
q-bio.NC nlin.CD physics.bio-ph
http://creativecommons.org/licenses/by/4.0/
Recurrent neural networks (RNNs) are complex dynamical systems, capable of ongoing activity without any driving input. The long-term behavior of free-running RNNs, described by periodic, chaotic and fixed point attractors, is controlled by the statistics of the neural connection weights, such as the density $d$ of non-zero connections, or the balance $b$ between excitatory and inhibitory connections. However, for information processing purposes, RNNs need to receive external input signals, and it is not clear which of the dynamical regimes is optimal for this information import. We use both the average correlations $C$ and the mutual information $I$ between the momentary input vector and the next system state vector as quantitative measures of information import and analyze their dependence on the balance and density of the network. Remarkably, both resulting phase diagrams $C(b,d)$ and $I(b,d)$ are highly consistent, pointing to a link between the dynamical systems and the information-processing approach to complex systems. Information import is maximal not at the 'edge of chaos', which is optimally suited for computation, but surprisingly in the low-density chaotic regime and at the border between the chaotic and fixed point regime. Moreover, we find a completely new type of resonance phenomenon, called 'Import Resonance' (IR), where the information import shows a maximum, i.e. a peak-like dependence on the coupling strength between the RNN and its input. IR complements Recurrence Resonance (RR), where correlation and mutual information of successive system states peak for a certain amplitude of noise added to the system. Both IR and RR can be exploited to optimize information processing in artificial neural networks and might also play a crucial role in biological neural systems.
[ { "created": "Thu, 5 Aug 2021 11:59:56 GMT", "version": "v1" } ]
2021-08-06
[ [ "Metzner", "Claus", "" ], [ "Krauss", "Patrick", "" ] ]
Recurrent neural networks (RNNs) are complex dynamical systems, capable of ongoing activity without any driving input. The long-term behavior of free-running RNNs, described by periodic, chaotic and fixed point attractors, is controlled by the statistics of the neural connection weights, such as the density $d$ of non-zero connections, or the balance $b$ between excitatory and inhibitory connections. However, for information processing purposes, RNNs need to receive external input signals, and it is not clear which of the dynamical regimes is optimal for this information import. We use both the average correlations $C$ and the mutual information $I$ between the momentary input vector and the next system state vector as quantitative measures of information import and analyze their dependence on the balance and density of the network. Remarkably, both resulting phase diagrams $C(b,d)$ and $I(b,d)$ are highly consistent, pointing to a link between the dynamical systems and the information-processing approach to complex systems. Information import is maximal not at the 'edge of chaos', which is optimally suited for computation, but surprisingly in the low-density chaotic regime and at the border between the chaotic and fixed point regime. Moreover, we find a completely new type of resonance phenomenon, called 'Import Resonance' (IR), where the information import shows a maximum, i.e. a peak-like dependence on the coupling strength between the RNN and its input. IR complements Recurrence Resonance (RR), where correlation and mutual information of successive system states peak for a certain amplitude of noise added to the system. Both IR and RR can be exploited to optimize information processing in artificial neural networks and might also play a crucial role in biological neural systems.
1908.07520
Akram Yazdani PhD
Akram Yazdani, Raul Mendez-Giraldez, Michael R Kosorok, Panos Roussos
Transcriptomic Causal Networks identified patterns of differential gene regulation in human brain from Schizophrenia cases versus controls
null
null
null
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Common and complex traits are the consequence of the interaction and regulation of multiple genes simultaneously, which work in a coordinated way. However, the vast majority of studies focus on the differential expression of one individual gene at a time. Here, we aim to provide insight into the underlying relationships of the genes expressed in the human brain in cases with schizophrenia (SCZ) and controls. We introduced a novel approach to identify differential gene regulatory patterns and identify a set of essential genes in the brain tissue. Our method integrates genetic, transcriptomic, and Hi-C data and generates a transcriptomic-causal network. Employing this approach for analysis of RNA-seq data from CommonMind Consortium, we identified differential regulatory patterns for SCZ cases and control groups to unveil the mechanisms that control the transcription of the genes in the human brain. Our analysis identified modules with a high number of SCZ-associated genes as well as assessing the relationship of the hubs with their down-stream genes in both, cases and controls. In addition, the results identified essential genes for brain function and suggested new genes putatively related to SCZ.
[ { "created": "Tue, 20 Aug 2019 16:24:28 GMT", "version": "v1" } ]
2019-08-22
[ [ "Yazdani", "Akram", "" ], [ "Mendez-Giraldez", "Raul", "" ], [ "Kosorok", "Michael R", "" ], [ "Roussos", "Panos", "" ] ]
Common and complex traits are the consequence of the interaction and regulation of multiple genes simultaneously, which work in a coordinated way. However, the vast majority of studies focus on the differential expression of one individual gene at a time. Here, we aim to provide insight into the underlying relationships of the genes expressed in the human brain in cases with schizophrenia (SCZ) and controls. We introduced a novel approach to identify differential gene regulatory patterns and identify a set of essential genes in the brain tissue. Our method integrates genetic, transcriptomic, and Hi-C data and generates a transcriptomic-causal network. Employing this approach for analysis of RNA-seq data from CommonMind Consortium, we identified differential regulatory patterns for SCZ cases and control groups to unveil the mechanisms that control the transcription of the genes in the human brain. Our analysis identified modules with a high number of SCZ-associated genes as well as assessing the relationship of the hubs with their down-stream genes in both, cases and controls. In addition, the results identified essential genes for brain function and suggested new genes putatively related to SCZ.
2309.16261
Pierre Haas
Yu Meng, Szabolcs Horv\'at, Carl D. Modes, Pierre A. Haas
Impossible ecologies: Interaction networks and stability of coexistence in ecological communities
14 pages, 6 figures, 3 supplementary figures
null
null
null
q-bio.PE physics.bio-ph
http://creativecommons.org/licenses/by/4.0/
Does an ecological community allow stable coexistence? Identifying the general principles that determine the answer to this question is a central problem of theoretical ecology. Random matrix theory approaches have uncovered the general trends of the effect of competitive, mutualistic, and predator-prey interactions between species on stability of coexistence. However, an ecological community is determined not only by the counts of these different interaction types, but also by their network arrangement. This cannot be accounted for in a direct statistical description that would enable random matrix theory approaches. Here, we therefore develop a different approach, of exhaustive analysis of small ecological communities, to show that this arrangement of interactions can influence stability of coexistence more than these general trends. We analyse all interaction networks of $N\leqslant 5$ species with Lotka-Volterra dynamics by combining exact results for $N\leqslant 3$ species and numerical exploration. Surprisingly, we find that a very small subset of these networks are "impossible ecologies", in which stable coexistence is non-trivially impossible. We prove that the possibility of stable coexistence in general ecologies is determined by similarly rare "irreducible ecologies". By random sampling of interaction strengths, we then show that the probability of stable coexistence varies over many orders of magnitude even in ecologies that differ only in the network arrangement of identical ecological interactions. Finally, we demonstrate that our approach can reveal the effect of evolutionary or environmental perturbations of the interaction network. Overall, this work reveals the importance of the full structure of the network of interactions for stability of coexistence in ecological communities.
[ { "created": "Thu, 28 Sep 2023 08:54:28 GMT", "version": "v1" } ]
2023-09-29
[ [ "Meng", "Yu", "" ], [ "Horvát", "Szabolcs", "" ], [ "Modes", "Carl D.", "" ], [ "Haas", "Pierre A.", "" ] ]
Does an ecological community allow stable coexistence? Identifying the general principles that determine the answer to this question is a central problem of theoretical ecology. Random matrix theory approaches have uncovered the general trends of the effect of competitive, mutualistic, and predator-prey interactions between species on stability of coexistence. However, an ecological community is determined not only by the counts of these different interaction types, but also by their network arrangement. This cannot be accounted for in a direct statistical description that would enable random matrix theory approaches. Here, we therefore develop a different approach, of exhaustive analysis of small ecological communities, to show that this arrangement of interactions can influence stability of coexistence more than these general trends. We analyse all interaction networks of $N\leqslant 5$ species with Lotka-Volterra dynamics by combining exact results for $N\leqslant 3$ species and numerical exploration. Surprisingly, we find that a very small subset of these networks are "impossible ecologies", in which stable coexistence is non-trivially impossible. We prove that the possibility of stable coexistence in general ecologies is determined by similarly rare "irreducible ecologies". By random sampling of interaction strengths, we then show that the probability of stable coexistence varies over many orders of magnitude even in ecologies that differ only in the network arrangement of identical ecological interactions. Finally, we demonstrate that our approach can reveal the effect of evolutionary or environmental perturbations of the interaction network. Overall, this work reveals the importance of the full structure of the network of interactions for stability of coexistence in ecological communities.
1401.4938
A. Dietrich
Axel Dietrich and Willem Been
Consciousness and Learning based on DNA Recombination and Memristor Quality of Microtubules
11 pages, 3 figures
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This paper is a completion of an earlier model proposed by us. In the model different memories are attached at cell surface determinants which are the result of DNA recombination. Our earlier experiments strongly suggest that DNA recombination actually takes place during a short period of early development in the brain in a limited number of neurons. In the present paper a model is presented in which switchboard neurons play a key role in the storage and retrieving of memory. And as a consequence, they play a major role in the process of learning and form the basic material for consciousness. In the original model there was insufficient explanation for the realization of the internal connection of one cell surface determinant to the other. We realized that tubulin should play a role in these intracellular connections. The tubulin molecules can form a connective wire because of a change of shape of the individual tubulin dimers. This way the fast switch is realized by the switch of the tubulin dimer configuration. Because the cell should remember which switch was activated and which one was not or less activated, we postulate the memristor quality of microtubules.
[ { "created": "Fri, 17 Jan 2014 10:07:47 GMT", "version": "v1" } ]
2014-01-21
[ [ "Dietrich", "Axel", "" ], [ "Been", "Willem", "" ] ]
This paper is a completion of an earlier model proposed by us. In the model different memories are attached at cell surface determinants which are the result of DNA recombination. Our earlier experiments strongly suggest that DNA recombination actually takes place during a short period of early development in the brain in a limited number of neurons. In the present paper a model is presented in which switchboard neurons play a key role in the storage and retrieving of memory. And as a consequence, they play a major role in the process of learning and form the basic material for consciousness. In the original model there was insufficient explanation for the realization of the internal connection of one cell surface determinant to the other. We realized that tubulin should play a role in these intracellular connections. The tubulin molecules can form a connective wire because of a change of shape of the individual tubulin dimers. This way the fast switch is realized by the switch of the tubulin dimer configuration. Because the cell should remember which switch was activated and which one was not or less activated, we postulate the memristor quality of microtubules.
1501.05880
Peter Solymos
Peter Solymos, Subhash R. Lele
Revisiting resource selection probability functions and single-visit methods: Clarification and extensions
Forum article and rebuttal to Knape, J., & Korner-Nievergelt, F., 2015. Estimates from non-replicated population surveys rely on critical assumptions. Methods in Ecology and Evolution, 6, 298--306
Methods in Ecology and Evolution 7(2), 196--205, 2016
10.1111/2041-210X.12432
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Models accounting for imperfect detection are important. Single-visit methods have been proposed as an alternative to multiple-visits methods to relax the assumption of closed population. Knape and Korner-Nievergelt (2015) showed that under certain models of probability of detection single-visit methods are statistically non-identifiable leading to biased population estimates. There is a close relationship between estimation of the resource selection probability function (RSPF) using weighted distributions and single-visit methods for occupancy and abundance estimation. We explain the precise mathematical conditions needed for RSPF estimation as stated in Lele and Keim (2006). The identical conditions, that remained unstated in our papers on single-visit methodology, are needed for single-visit methodology to work. We show that the class of admissible models is quite broad and does not excessively restrict the application of the RSPF or the single-visit methodology. To complement the work by Knape and Korner-Nievergelt, we study the performance of multiple-visit methods under the scaled logistic detection function and a much wider set of situations. In general, under the scaled logistic detection function multiple-visits methods also lead to biased estimates. As a solution to this problem, we extend the single-visit methodology to a class of models that allows use of scaled probability function. We propose a Multinomial extension of single visit methodology that can be used to check whether the detection function satisfies the RSPF condition or not. Furthermore, we show that if the scaling factor depends on covariates, then it can also be estimated.
[ { "created": "Fri, 23 Jan 2015 17:12:07 GMT", "version": "v1" }, { "created": "Thu, 19 Mar 2015 18:28:03 GMT", "version": "v2" }, { "created": "Tue, 9 Jun 2015 22:16:04 GMT", "version": "v3" }, { "created": "Fri, 12 Jun 2015 17:00:18 GMT", "version": "v4" } ]
2016-02-24
[ [ "Solymos", "Peter", "" ], [ "Lele", "Subhash R.", "" ] ]
Models accounting for imperfect detection are important. Single-visit methods have been proposed as an alternative to multiple-visits methods to relax the assumption of closed population. Knape and Korner-Nievergelt (2015) showed that under certain models of probability of detection single-visit methods are statistically non-identifiable leading to biased population estimates. There is a close relationship between estimation of the resource selection probability function (RSPF) using weighted distributions and single-visit methods for occupancy and abundance estimation. We explain the precise mathematical conditions needed for RSPF estimation as stated in Lele and Keim (2006). The identical conditions, that remained unstated in our papers on single-visit methodology, are needed for single-visit methodology to work. We show that the class of admissible models is quite broad and does not excessively restrict the application of the RSPF or the single-visit methodology. To complement the work by Knape and Korner-Nievergelt, we study the performance of multiple-visit methods under the scaled logistic detection function and a much wider set of situations. In general, under the scaled logistic detection function multiple-visits methods also lead to biased estimates. As a solution to this problem, we extend the single-visit methodology to a class of models that allows use of scaled probability function. We propose a Multinomial extension of single visit methodology that can be used to check whether the detection function satisfies the RSPF condition or not. Furthermore, we show that if the scaling factor depends on covariates, then it can also be estimated.
1610.00161
Blake Richards
Jordan Guergiuev, Timothy P. Lillicrap and Blake A. Richards
Towards deep learning with segregated dendrites
41 pages, 11 figures
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Deep learning has led to significant advances in artificial intelligence, in part, by adopting strategies motivated by neurophysiology. However, it is unclear whether deep learning could occur in the real brain. Here, we show that a deep learning algorithm that utilizes multi-compartment neurons might help us to understand how the brain optimizes cost functions. Like neocortical pyramidal neurons, neurons in our model receive sensory information and higher-order feedback in electrotonically segregated compartments. Thanks to this segregation, the neurons in different layers of the network can coordinate synaptic weight updates. As a result, the network can learn to categorize images better than a single layer network. Furthermore, we show that our algorithm takes advantage of multilayer architectures to identify useful representations---the hallmark of deep learning. This work demonstrates that deep learning can be achieved using segregated dendritic compartments, which may help to explain the dendritic morphology of neocortical pyramidal neurons.
[ { "created": "Sat, 1 Oct 2016 17:37:34 GMT", "version": "v1" }, { "created": "Wed, 2 Nov 2016 18:07:26 GMT", "version": "v2" }, { "created": "Fri, 7 Apr 2017 18:45:30 GMT", "version": "v3" } ]
2017-04-11
[ [ "Guergiuev", "Jordan", "" ], [ "Lillicrap", "Timothy P.", "" ], [ "Richards", "Blake A.", "" ] ]
Deep learning has led to significant advances in artificial intelligence, in part, by adopting strategies motivated by neurophysiology. However, it is unclear whether deep learning could occur in the real brain. Here, we show that a deep learning algorithm that utilizes multi-compartment neurons might help us to understand how the brain optimizes cost functions. Like neocortical pyramidal neurons, neurons in our model receive sensory information and higher-order feedback in electrotonically segregated compartments. Thanks to this segregation, the neurons in different layers of the network can coordinate synaptic weight updates. As a result, the network can learn to categorize images better than a single layer network. Furthermore, we show that our algorithm takes advantage of multilayer architectures to identify useful representations---the hallmark of deep learning. This work demonstrates that deep learning can be achieved using segregated dendritic compartments, which may help to explain the dendritic morphology of neocortical pyramidal neurons.
q-bio/0511026
Luca Giuggioli
L. Giuggioli, G. Abramson, V.M. Kenkre, R.R. Parmenter, T.L. Yates
Theory of Home Range Estimation from Mark-Recapture Measurements of Animal Populations
21 pages, 7 figures, in press Journal of Theoretical Biology
null
null
null
q-bio.PE q-bio.OT
null
A theory is provided for the estimation of home ranges of animals from the standard mark-recapture technique in which data are collected by capturing, tagging and recapturing the animals. The theoretical tool used is the Fokker-Planck equation, its characteristic quantities being the diffusion constant which describes the motion of the animals, and the attractive potential which addresses their tendency to live near their burrows. The measurement technique is shown to correspond to the calculation of a certain kind of mean square displacement of the animals relevant to the specific probing window in space corresponding to the trapping region. The output of the theory is a sigmoid curve of the observable mean square displacement as a function of the ratio of distances characteristic of the home range and the trapping region, along with an explicit prescription to extract the home range form observations. Applications of the theory to rodent movement in Panama and New Mexico are pointed out. An analysis is given of the sensitivity of our theory to the choice of the confining potential via the use of various representative cases. A comparison is provided between home range size inferred from our method and from other procedures employed in the literature. Consequences of home range overlap are also discussed.
[ { "created": "Tue, 15 Nov 2005 22:44:44 GMT", "version": "v1" } ]
2007-05-23
[ [ "Giuggioli", "L.", "" ], [ "Abramson", "G.", "" ], [ "Kenkre", "V. M.", "" ], [ "Parmenter", "R. R.", "" ], [ "Yates", "T. L.", "" ] ]
A theory is provided for the estimation of home ranges of animals from the standard mark-recapture technique in which data are collected by capturing, tagging and recapturing the animals. The theoretical tool used is the Fokker-Planck equation, its characteristic quantities being the diffusion constant which describes the motion of the animals, and the attractive potential which addresses their tendency to live near their burrows. The measurement technique is shown to correspond to the calculation of a certain kind of mean square displacement of the animals relevant to the specific probing window in space corresponding to the trapping region. The output of the theory is a sigmoid curve of the observable mean square displacement as a function of the ratio of distances characteristic of the home range and the trapping region, along with an explicit prescription to extract the home range form observations. Applications of the theory to rodent movement in Panama and New Mexico are pointed out. An analysis is given of the sensitivity of our theory to the choice of the confining potential via the use of various representative cases. A comparison is provided between home range size inferred from our method and from other procedures employed in the literature. Consequences of home range overlap are also discussed.
1004.2821
David Zwicker
David Zwicker, David K. Lubensky, Pieter Rein ten Wolde
Robust circadian clocks from coupled protein modification and transcription-translation cycles
main text: 7 pages including 5 figures, supplementary information: 13 pages including 9 figures
P Natl Acad Sci Usa (2010) vol. 107 (52) pp. 22540-5
10.1073/pnas.1007613107
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The cyanobacterium Synechococcus elongatus uses both a protein phosphorylation cycle and a transcription-translation cycle to generate circadian rhythms that are highly robust against biochemical noise. We use stochastic simulations to analyze how these cycles interact to generate stable rhythms in growing, dividing cells. We find that a protein phosphorylation cycle by itself is robust when protein turnover is low. For high decay or dilution rates (and co mpensating synthesis rate), however, the phosphorylation-based oscillator loses its integrity. Circadian rhythms thus cannot be generated with a phosphorylation cycle alone when the growth rate, and consequently the rate of protein dilution, is high enough; in practice, a purely post-translational clock ceases to function well when the cell doubling time drops below the 24 hour clock period. At higher growth rates, a transcription-translation cycle becomes essential for generating robust circadian rhythms. Interestingly, while a transcription-translation cycle is necessary to sustain a phosphorylation cycle at high growth rates, a phosphorylation cycle can dramatically enhance the robustness of a transcription-translation cycle at lower protein decay or dilution rates. Our analysis thus predicts that both cycles are required to generate robust circadian rhythms over the full range of growth conditions.
[ { "created": "Fri, 16 Apr 2010 11:39:56 GMT", "version": "v1" } ]
2012-02-16
[ [ "Zwicker", "David", "" ], [ "Lubensky", "David K.", "" ], [ "Wolde", "Pieter Rein ten", "" ] ]
The cyanobacterium Synechococcus elongatus uses both a protein phosphorylation cycle and a transcription-translation cycle to generate circadian rhythms that are highly robust against biochemical noise. We use stochastic simulations to analyze how these cycles interact to generate stable rhythms in growing, dividing cells. We find that a protein phosphorylation cycle by itself is robust when protein turnover is low. For high decay or dilution rates (and co mpensating synthesis rate), however, the phosphorylation-based oscillator loses its integrity. Circadian rhythms thus cannot be generated with a phosphorylation cycle alone when the growth rate, and consequently the rate of protein dilution, is high enough; in practice, a purely post-translational clock ceases to function well when the cell doubling time drops below the 24 hour clock period. At higher growth rates, a transcription-translation cycle becomes essential for generating robust circadian rhythms. Interestingly, while a transcription-translation cycle is necessary to sustain a phosphorylation cycle at high growth rates, a phosphorylation cycle can dramatically enhance the robustness of a transcription-translation cycle at lower protein decay or dilution rates. Our analysis thus predicts that both cycles are required to generate robust circadian rhythms over the full range of growth conditions.
1801.01876
Yi Sun
Yi Sun
Root Mean Square Minimum Distance as a Quality Metric for Localization Nanoscopy Images
11 pages, 5 figures
Y. Sun, "Root mean square minimum distance as a quality metric for stochastic optical localization nanoscopy images," Scientific Reports, 8(1), Nov. 21, 2018
10.1038/s41598-018-35053-8
null
q-bio.QM eess.IV
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A localization algorithm in stochastic optical localization nanoscopy plays an important role in obtaining a high-quality image. A universal and objective metric is crucial and necessary to evaluate qualities of nanoscopy images and performances of localization algorithms. In this paper, we propose root mean square minimum distance (RMSMD) as a quality metric for localization nanoscopy images. RMSMD measures an average, local, and mutual fitness between two sets of points. Its properties common to a distance metric as well as unique to itself are presented. The ambiguity, discontinuity, and inappropriateness of the metrics of accuracy, precision, recall, and Jaccard index, which are currently used in the literature, are analyzed. A numerical example demonstrates the advantages of RMSMD over the four existing metrics that fail to distinguish qualities of different nanoscopy images in certain conditions. The unbiased Gaussian estimator that achieves the Fisher information and Cramer-Rao lower bound (CRLB) of a single data frame is proposed to benchmark the quality of localization nanoscopy images and the performance of localization algorithms. The information-achieving estimator is simulated in an example and the result demonstrates the superior sensitivity of RMSMD over the other four metrics. As a universal and objective metric, RMSMD can be broadly employed in various applications to measure the mutual fitness of two sets of points.
[ { "created": "Sat, 6 Jan 2018 13:34:51 GMT", "version": "v1" }, { "created": "Mon, 15 Oct 2018 18:04:04 GMT", "version": "v2" }, { "created": "Thu, 22 Nov 2018 17:58:02 GMT", "version": "v3" } ]
2018-11-26
[ [ "Sun", "Yi", "" ] ]
A localization algorithm in stochastic optical localization nanoscopy plays an important role in obtaining a high-quality image. A universal and objective metric is crucial and necessary to evaluate qualities of nanoscopy images and performances of localization algorithms. In this paper, we propose root mean square minimum distance (RMSMD) as a quality metric for localization nanoscopy images. RMSMD measures an average, local, and mutual fitness between two sets of points. Its properties common to a distance metric as well as unique to itself are presented. The ambiguity, discontinuity, and inappropriateness of the metrics of accuracy, precision, recall, and Jaccard index, which are currently used in the literature, are analyzed. A numerical example demonstrates the advantages of RMSMD over the four existing metrics that fail to distinguish qualities of different nanoscopy images in certain conditions. The unbiased Gaussian estimator that achieves the Fisher information and Cramer-Rao lower bound (CRLB) of a single data frame is proposed to benchmark the quality of localization nanoscopy images and the performance of localization algorithms. The information-achieving estimator is simulated in an example and the result demonstrates the superior sensitivity of RMSMD over the other four metrics. As a universal and objective metric, RMSMD can be broadly employed in various applications to measure the mutual fitness of two sets of points.
1411.7338
Katherine St. John
Daniel Irving Bernstein, Lam Si Tung Ho, Colby Long, Mike Steel, Katherine St. John, Seth Sullivant
Bounds on the Expected Size of the Maximum Agreement Subtree
Revised version
null
null
null
q-bio.PE cs.DS
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We prove polynomial upper and lower bounds on the expected size of the maximum agreement subtree of two random binary phylogenetic trees under both the uniform distribution and Yule-Harding distribution. This positively answers a question posed in earlier work. Determining tight upper and lower bounds remains an open problem.
[ { "created": "Wed, 26 Nov 2014 19:20:08 GMT", "version": "v1" }, { "created": "Mon, 31 Aug 2015 11:44:57 GMT", "version": "v2" } ]
2015-09-01
[ [ "Bernstein", "Daniel Irving", "" ], [ "Ho", "Lam Si Tung", "" ], [ "Long", "Colby", "" ], [ "Steel", "Mike", "" ], [ "John", "Katherine St.", "" ], [ "Sullivant", "Seth", "" ] ]
We prove polynomial upper and lower bounds on the expected size of the maximum agreement subtree of two random binary phylogenetic trees under both the uniform distribution and Yule-Harding distribution. This positively answers a question posed in earlier work. Determining tight upper and lower bounds remains an open problem.
2208.07983
Grzegorz A Rempala
Istvan Z. Kiss, Eben Kenah, Grzegorz A. Rempala
Necessary and sufficient conditions for exact closures of epidemic equations on configuration model networks
null
null
null
null
q-bio.PE math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We prove that the exact closure of SIR pairwise epidemic equations on a configuration model network is possible if and only if the degree distribution is Poisson, Binomial, or Negative Binomial. The proof relies on establishing, for these specific degree distributions, the equivalence of the closed pairwise model and the so-called dynamical survival analysis (DSA) edge-based model which was previously shown to be exact. Indeed, as we show here, the DSA model is equivalent to the well-known edge-based Volz model. We use this result to provide reductions of the closed pairwise and Volz models to the same single equation involving only susceptibles, which has a useful statistical interpretation in terms of the times to infection. We illustrate our findings with some numerical examples.
[ { "created": "Tue, 16 Aug 2022 22:46:05 GMT", "version": "v1" } ]
2022-08-18
[ [ "Kiss", "Istvan Z.", "" ], [ "Kenah", "Eben", "" ], [ "Rempala", "Grzegorz A.", "" ] ]
We prove that the exact closure of SIR pairwise epidemic equations on a configuration model network is possible if and only if the degree distribution is Poisson, Binomial, or Negative Binomial. The proof relies on establishing, for these specific degree distributions, the equivalence of the closed pairwise model and the so-called dynamical survival analysis (DSA) edge-based model which was previously shown to be exact. Indeed, as we show here, the DSA model is equivalent to the well-known edge-based Volz model. We use this result to provide reductions of the closed pairwise and Volz models to the same single equation involving only susceptibles, which has a useful statistical interpretation in terms of the times to infection. We illustrate our findings with some numerical examples.
1904.12341
Gota Morota
Gota Morota, Diego Jarquin, Malachy T. Campbell, and Hiroyoshi Iwata
Statistical methods for the quantitative genetic analysis of high-throughput phenotyping data
null
null
null
null
q-bio.GN
http://creativecommons.org/licenses/by/4.0/
The advent of plant phenomics, coupled with the wealth of genotypic data generated by next-generation sequencing technologies, provides exciting new resources for investigations into and improvement of complex traits. However, these new technologies also bring new challenges in quantitative genetics, namely, a need for the development of robust frameworks that can accommodate these high-dimensional data. In this chapter, we describe methods for the statistical analysis of high-throughput phenotyping (HTP) data with the goal of enhancing the prediction accuracy of genomic selection (GS). Following the Introduction in Section 1, Section 2 discusses field-based HTP, including the use of unmanned aerial vehicles and light detection and ranging, as well as how we can achieve increased genetic gain by utilizing image data derived from HTP. Section 3 considers extending commonly used GS models to integrate HTP data as covariates associated with the principal trait response, such as yield. Particular focus is placed on single-trait, multi-trait, and genotype by environment interaction models. One unique aspect of HTP data is that phenomics platforms often produce large-scale data with high spatial and temporal resolution for capturing dynamic growth, development, and stress responses. Section 4 discusses the utility of a random regression model for performing longitudinal GS. The chapter concludes with a discussion of some standing issues.
[ { "created": "Sun, 28 Apr 2019 16:32:06 GMT", "version": "v1" } ]
2019-04-30
[ [ "Morota", "Gota", "" ], [ "Jarquin", "Diego", "" ], [ "Campbell", "Malachy T.", "" ], [ "Iwata", "Hiroyoshi", "" ] ]
The advent of plant phenomics, coupled with the wealth of genotypic data generated by next-generation sequencing technologies, provides exciting new resources for investigations into and improvement of complex traits. However, these new technologies also bring new challenges in quantitative genetics, namely, a need for the development of robust frameworks that can accommodate these high-dimensional data. In this chapter, we describe methods for the statistical analysis of high-throughput phenotyping (HTP) data with the goal of enhancing the prediction accuracy of genomic selection (GS). Following the Introduction in Section 1, Section 2 discusses field-based HTP, including the use of unmanned aerial vehicles and light detection and ranging, as well as how we can achieve increased genetic gain by utilizing image data derived from HTP. Section 3 considers extending commonly used GS models to integrate HTP data as covariates associated with the principal trait response, such as yield. Particular focus is placed on single-trait, multi-trait, and genotype by environment interaction models. One unique aspect of HTP data is that phenomics platforms often produce large-scale data with high spatial and temporal resolution for capturing dynamic growth, development, and stress responses. Section 4 discusses the utility of a random regression model for performing longitudinal GS. The chapter concludes with a discussion of some standing issues.
2306.11756
Markus D. Solbach
Markus D. Solbach, John K. Tsotsos
The Psychophysics of Human Three-Dimensional Active Visuospatial Problem-Solving
Submitted at PNAS Nexus
null
null
null
q-bio.NC cs.CV
http://creativecommons.org/licenses/by/4.0/
Our understanding of how visual systems detect, analyze and interpret visual stimuli has advanced greatly. However, the visual systems of all animals do much more; they enable visual behaviours. How well the visual system performs while interacting with the visual environment and how vision is used in the real world have not been well studied, especially in humans. It has been suggested that comparison is the most primitive of psychophysical tasks. Thus, as a probe into these active visual behaviours, we use a same-different task: are two physical 3D objects visually the same? This task seems to be a fundamental cognitive ability. We pose this question to human subjects who are free to move about and examine two real objects in an actual 3D space. Past work has dealt solely with a 2D static version of this problem. We have collected detailed, first-of-its-kind data of humans performing a visuospatial task in hundreds of trials. Strikingly, humans are remarkably good at this task without any training, with a mean accuracy of 93.82%. No learning effect was observed on accuracy after many trials, but some effect was seen for response time, number of fixations and extent of head movement. Subjects demonstrated a variety of complex strategies involving a range of movement and eye fixation changes, suggesting that solutions were developed dynamically and tailored to the specific task.
[ { "created": "Mon, 19 Jun 2023 19:36:42 GMT", "version": "v1" } ]
2023-06-22
[ [ "Solbach", "Markus D.", "" ], [ "Tsotsos", "John K.", "" ] ]
Our understanding of how visual systems detect, analyze and interpret visual stimuli has advanced greatly. However, the visual systems of all animals do much more; they enable visual behaviours. How well the visual system performs while interacting with the visual environment and how vision is used in the real world have not been well studied, especially in humans. It has been suggested that comparison is the most primitive of psychophysical tasks. Thus, as a probe into these active visual behaviours, we use a same-different task: are two physical 3D objects visually the same? This task seems to be a fundamental cognitive ability. We pose this question to human subjects who are free to move about and examine two real objects in an actual 3D space. Past work has dealt solely with a 2D static version of this problem. We have collected detailed, first-of-its-kind data of humans performing a visuospatial task in hundreds of trials. Strikingly, humans are remarkably good at this task without any training, with a mean accuracy of 93.82%. No learning effect was observed on accuracy after many trials, but some effect was seen for response time, number of fixations and extent of head movement. Subjects demonstrated a variety of complex strategies involving a range of movement and eye fixation changes, suggesting that solutions were developed dynamically and tailored to the specific task.
1504.06110
Bassam AlKindy Mr.
Bassam AlKindy, Huda Al-Nayyef, Christophe Guyeux, Jean-Fran\c{c}ois Couchot, Michel Salomon, Jacques M. Bahi
Improved Core Genes Prediction for Constructing well-supported Phylogenetic Trees in large sets of Plant Species
12 pages, 7 figures, IWBBIO 2015 (3rd International Work-Conference on Bioinformatics and Biomedical Engineering)
Springer LNBI 9043, 2015, 379--390
10.1007/978-3-319-16483-0_38
null
q-bio.GN cs.CE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The way to infer well-supported phylogenetic trees that precisely reflect the evolutionary process is a challenging task that completely depends on the way the related core genes have been found. In previous computational biology studies, many similarity based algorithms, mainly dependent on calculating sequence alignment matrices, have been proposed to find them. In these kinds of approaches, a significantly high similarity score between two coding sequences extracted from a given annotation tool means that one has the same genes. In a previous work article, we presented a quality test approach (QTA) that improves the core genes quality by combining two annotation tools (namely NCBI, a partially human-curated database, and DOGMA, an efficient annotation algorithm for chloroplasts). This method takes the advantages from both sequence similarity and gene features to guarantee that the core genome contains correct and well-clustered coding sequences (\emph{i.e.}, genes). We then show in this article how useful are such well-defined core genes for biomolecular phylogenetic reconstructions, by investigating various subsets of core genes at various family or genus levels, leading to subtrees with strong bootstraps that are finally merged in a well-supported supertree.
[ { "created": "Thu, 23 Apr 2015 09:45:07 GMT", "version": "v1" } ]
2015-04-24
[ [ "AlKindy", "Bassam", "" ], [ "Al-Nayyef", "Huda", "" ], [ "Guyeux", "Christophe", "" ], [ "Couchot", "Jean-François", "" ], [ "Salomon", "Michel", "" ], [ "Bahi", "Jacques M.", "" ] ]
The way to infer well-supported phylogenetic trees that precisely reflect the evolutionary process is a challenging task that completely depends on the way the related core genes have been found. In previous computational biology studies, many similarity based algorithms, mainly dependent on calculating sequence alignment matrices, have been proposed to find them. In these kinds of approaches, a significantly high similarity score between two coding sequences extracted from a given annotation tool means that one has the same genes. In a previous work article, we presented a quality test approach (QTA) that improves the core genes quality by combining two annotation tools (namely NCBI, a partially human-curated database, and DOGMA, an efficient annotation algorithm for chloroplasts). This method takes the advantages from both sequence similarity and gene features to guarantee that the core genome contains correct and well-clustered coding sequences (\emph{i.e.}, genes). We then show in this article how useful are such well-defined core genes for biomolecular phylogenetic reconstructions, by investigating various subsets of core genes at various family or genus levels, leading to subtrees with strong bootstraps that are finally merged in a well-supported supertree.
1406.7441
Alkan Kabak\c{c}io\u{g}lu
Nese Aral and Alkan Kabakcioglu
Coherent regulation in yeast cell cycle network
17 pages, 6 figures, 4 tables. Extensively revised and submitted for publication
Physical Biology 12.3 (2015), 036002
10.1088/1478-3975/12/3/036002
null
q-bio.QM q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We define a measure of coherent activity for gene regulatory networks, a property that reflects the unity of purpose between the regulatory agents with a common target. We propose that such harmonious regulatory action is desirable under a demand for energy efficiency and may be selected for under evolutionary pressures. We consider two recent models of the cell-cycle regulatory network of the budding yeast, Saccharomyces cerevisiae, as a case study and calculate their degree of coherence. A comparison with random networks of similar size and composition reveals that the yeast's cell-cycle regulation is wired to yield and exceptionally high level of coherent regulatory activity. We also investigate the mean degree of coherence as a function of the network size, connectivity and the fraction of repressory/activatory interactions.
[ { "created": "Sat, 28 Jun 2014 21:21:17 GMT", "version": "v1" }, { "created": "Sun, 14 Dec 2014 09:32:08 GMT", "version": "v2" } ]
2015-07-30
[ [ "Aral", "Nese", "" ], [ "Kabakcioglu", "Alkan", "" ] ]
We define a measure of coherent activity for gene regulatory networks, a property that reflects the unity of purpose between the regulatory agents with a common target. We propose that such harmonious regulatory action is desirable under a demand for energy efficiency and may be selected for under evolutionary pressures. We consider two recent models of the cell-cycle regulatory network of the budding yeast, Saccharomyces cerevisiae, as a case study and calculate their degree of coherence. A comparison with random networks of similar size and composition reveals that the yeast's cell-cycle regulation is wired to yield and exceptionally high level of coherent regulatory activity. We also investigate the mean degree of coherence as a function of the network size, connectivity and the fraction of repressory/activatory interactions.
2006.16006
John Vandermeer
John Vandermeer, Zachary Hajian-Forooshani, Nicholas Medina, Ivette Perfecto
New forms of structure in ecosystems revealed with the Kuramoto model
18 pages, 5 figures
null
null
null
q-bio.PE nlin.AO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Ecological systems, as is often noted, are complex. Equally notable is the generalization that complex systems tend to be oscillatory, whether Huygens simple patterns of pendulum entrainment or the twisted chaotic orbits of Lorenz convection rolls. The analytics of oscillators may thus provide insight into the structure of ecological systems. One of the most popular analytical tools for such study is the Kuramoto model of coupled oscillators. Using a well-studied system of pests and their enemies in an agroecosystem, we apply this model as a stylized vision of the dynamics of that real system, to ask whether its actual natural history is reflected in the dynamics of the qualitatively instantiated Kuramoto model. Emerging from the model is a series of synchrony groups generally corresponding to subnetworks of the natural system, with an overlying chimeric structure, depending on the strength of the inter-oscillator coupling. We conclude that the Kuramoto model presents a novel window through which interesting questions about the structure of ecological systems may emerge.
[ { "created": "Mon, 29 Jun 2020 12:46:25 GMT", "version": "v1" } ]
2020-06-30
[ [ "Vandermeer", "John", "" ], [ "Hajian-Forooshani", "Zachary", "" ], [ "Medina", "Nicholas", "" ], [ "Perfecto", "Ivette", "" ] ]
Ecological systems, as is often noted, are complex. Equally notable is the generalization that complex systems tend to be oscillatory, whether Huygens simple patterns of pendulum entrainment or the twisted chaotic orbits of Lorenz convection rolls. The analytics of oscillators may thus provide insight into the structure of ecological systems. One of the most popular analytical tools for such study is the Kuramoto model of coupled oscillators. Using a well-studied system of pests and their enemies in an agroecosystem, we apply this model as a stylized vision of the dynamics of that real system, to ask whether its actual natural history is reflected in the dynamics of the qualitatively instantiated Kuramoto model. Emerging from the model is a series of synchrony groups generally corresponding to subnetworks of the natural system, with an overlying chimeric structure, depending on the strength of the inter-oscillator coupling. We conclude that the Kuramoto model presents a novel window through which interesting questions about the structure of ecological systems may emerge.
1509.01577
J. C. Phillips
J. C. Phillips
Autoantibody recognition mechanisms of p53 epitopes
20 pages, 12 figures
null
10.1016/j.physa.2016.01.021
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
There is an urgent need for economical blood based, noninvasive molecular biomarkers to assist in the detection and diagnosis of cancers in a cost effective manner at an early stage, when curative interventions are still possible. Serum autoantibodies are attractive biomarkers for early cancer detection, but their development has been hindered by the punctuated genetic nature of the ten million known cancer mutations. A recent study of 50,000 patients (Pedersen et al., 2013) showed p53 15mer epitopes are much more sensitive colon cancer biomarkers than p53, which in turn is a more sensitive cancer biomarker than any other protein. The function of p53 as a nearly universal tumor suppressor is well established, because of its strong immunogenicity in terms of not only antibody recruitment, but also stimulation of autoantibodies. Here we examine bioinformatic fractal scaling analysis for identifying sensitive epitopes from the p53 amino acid sequence, and show how it could be used for early cancer detection (ECD). We trim 15mers to 7mers, and identify specific 7mers from other species that could be more sensitive to aggressive human cancers, such as liver cancer.
[ { "created": "Fri, 4 Sep 2015 19:54:44 GMT", "version": "v1" } ]
2016-03-23
[ [ "Phillips", "J. C.", "" ] ]
There is an urgent need for economical blood based, noninvasive molecular biomarkers to assist in the detection and diagnosis of cancers in a cost effective manner at an early stage, when curative interventions are still possible. Serum autoantibodies are attractive biomarkers for early cancer detection, but their development has been hindered by the punctuated genetic nature of the ten million known cancer mutations. A recent study of 50,000 patients (Pedersen et al., 2013) showed p53 15mer epitopes are much more sensitive colon cancer biomarkers than p53, which in turn is a more sensitive cancer biomarker than any other protein. The function of p53 as a nearly universal tumor suppressor is well established, because of its strong immunogenicity in terms of not only antibody recruitment, but also stimulation of autoantibodies. Here we examine bioinformatic fractal scaling analysis for identifying sensitive epitopes from the p53 amino acid sequence, and show how it could be used for early cancer detection (ECD). We trim 15mers to 7mers, and identify specific 7mers from other species that could be more sensitive to aggressive human cancers, such as liver cancer.
1807.07669
\'Eric Merle
\'Eric Merle
Modelling of consciousness and interpretation of quantum mechanics
117 pages, 13 figures
null
null
null
q-bio.NC quant-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
I start from the fundamental principles of non-relativistic quantum mechanics, without probability, and interpret them using the notion of coexistence: a quantum state can be read, not uniquely, as a coexistence of other quantum states, which are pairwise orthogonal. In this formalism, I prove that a conscious observer is necessarily a physical object that can memorize local events by setting one of its parts in an exactly specified constant quantum state (hypotheses H1, H2 and H3). Then I define the probability of a future event as the proportion of initial observers, all identical, who will actually experience that event. It then becomes possible to establish the usual results of quantum mechanics. Furthermore, I detail the link between probabilities and relative frequencies. Additionally, I study the biological feasibility of this modelling of observer's mind. The second part of this paper completes the neuronal description of the mind functions, based on current neuroscientific knowledge. It provides a model that is compatible with the assumptions of the first part and consistent with our daily conscious experience. In particular, it develops a model of self-consciousness based on an explicit use of the random component of neuron behaviour; according to the first part, that random is in fact the coexistence of a multiplicity of possibilities. So, when the mind measures the random part of certain neurons in the brain, he goes himself within each of these possibilities. The mind has a decision-making component that is active in this situation, appearing then as the cause of the choice of this possibility among all the others. This models the self-consciousness which then ensures the unity of our conscious experience by equating this experience with ``what the ego is conscious about''. The conclusion details the points that remain to be developed.
[ { "created": "Fri, 20 Jul 2018 00:09:41 GMT", "version": "v1" } ]
2018-07-23
[ [ "Merle", "Éric", "" ] ]
I start from the fundamental principles of non-relativistic quantum mechanics, without probability, and interpret them using the notion of coexistence: a quantum state can be read, not uniquely, as a coexistence of other quantum states, which are pairwise orthogonal. In this formalism, I prove that a conscious observer is necessarily a physical object that can memorize local events by setting one of its parts in an exactly specified constant quantum state (hypotheses H1, H2 and H3). Then I define the probability of a future event as the proportion of initial observers, all identical, who will actually experience that event. It then becomes possible to establish the usual results of quantum mechanics. Furthermore, I detail the link between probabilities and relative frequencies. Additionally, I study the biological feasibility of this modelling of observer's mind. The second part of this paper completes the neuronal description of the mind functions, based on current neuroscientific knowledge. It provides a model that is compatible with the assumptions of the first part and consistent with our daily conscious experience. In particular, it develops a model of self-consciousness based on an explicit use of the random component of neuron behaviour; according to the first part, that random is in fact the coexistence of a multiplicity of possibilities. So, when the mind measures the random part of certain neurons in the brain, he goes himself within each of these possibilities. The mind has a decision-making component that is active in this situation, appearing then as the cause of the choice of this possibility among all the others. This models the self-consciousness which then ensures the unity of our conscious experience by equating this experience with ``what the ego is conscious about''. The conclusion details the points that remain to be developed.
2106.04377
Aditya Sarkar
Aditya Sarkar, Arnav Bhavsar
Virtual Screening of Pharmaceutical Compounds with hERG Inhibitory Activity (Cardiotoxicity) using Ensemble Learning
23 pages, 2 figures, 5 tables
Proceedings of the 14th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2021) - Volume 2: BIOIMAGING,
10.5220/0010267701520159
null
q-bio.QM cs.AI cs.LG
http://creativecommons.org/licenses/by/4.0/
In silico prediction of cardiotoxicity with high sensitivity and specificity for potential drug molecules can be of immense value. Hence, building machine learning classification models, based on some features extracted from the molecular structure of drugs, which are capable of efficiently predicting cardiotoxicity is critical. In this paper, we consider the application of various machine learning approaches, and then propose an ensemble classifier for the prediction of molecular activity on a Drug Discovery Hackathon (DDH) (1st reference) dataset. We have used only 2-D descriptors of SMILE notations for our prediction. Our ensemble classification uses 5 classifiers (2 Random Forest Classifiers, 2 Support Vector Machines and a Dense Neural Network) and uses Max-Voting technique and Weighted-Average technique for final decision.
[ { "created": "Sat, 5 Jun 2021 16:57:35 GMT", "version": "v1" } ]
2021-06-09
[ [ "Sarkar", "Aditya", "" ], [ "Bhavsar", "Arnav", "" ] ]
In silico prediction of cardiotoxicity with high sensitivity and specificity for potential drug molecules can be of immense value. Hence, building machine learning classification models, based on some features extracted from the molecular structure of drugs, which are capable of efficiently predicting cardiotoxicity is critical. In this paper, we consider the application of various machine learning approaches, and then propose an ensemble classifier for the prediction of molecular activity on a Drug Discovery Hackathon (DDH) (1st reference) dataset. We have used only 2-D descriptors of SMILE notations for our prediction. Our ensemble classification uses 5 classifiers (2 Random Forest Classifiers, 2 Support Vector Machines and a Dense Neural Network) and uses Max-Voting technique and Weighted-Average technique for final decision.
1810.13373
David Barrett
David G.T. Barrett, Ari S. Morcos and Jakob H. Macke
Analyzing biological and artificial neural networks: challenges with opportunities for synergy?
null
null
null
null
q-bio.NC cs.AI cs.CV cs.LG stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Deep neural networks (DNNs) transform stimuli across multiple processing stages to produce representations that can be used to solve complex tasks, such as object recognition in images. However, a full understanding of how they achieve this remains elusive. The complexity of biological neural networks substantially exceeds the complexity of DNNs, making it even more challenging to understand the representations that they learn. Thus, both machine learning and computational neuroscience are faced with a shared challenge: how can we analyze their representations in order to understand how they solve complex tasks? We review how data-analysis concepts and techniques developed by computational neuroscientists can be useful for analyzing representations in DNNs, and in turn, how recently developed techniques for analysis of DNNs can be useful for understanding representations in biological neural networks. We explore opportunities for synergy between the two fields, such as the use of DNNs as in-silico model systems for neuroscience, and how this synergy can lead to new hypotheses about the operating principles of biological neural networks.
[ { "created": "Wed, 31 Oct 2018 16:09:44 GMT", "version": "v1" } ]
2018-11-01
[ [ "Barrett", "David G. T.", "" ], [ "Morcos", "Ari S.", "" ], [ "Macke", "Jakob H.", "" ] ]
Deep neural networks (DNNs) transform stimuli across multiple processing stages to produce representations that can be used to solve complex tasks, such as object recognition in images. However, a full understanding of how they achieve this remains elusive. The complexity of biological neural networks substantially exceeds the complexity of DNNs, making it even more challenging to understand the representations that they learn. Thus, both machine learning and computational neuroscience are faced with a shared challenge: how can we analyze their representations in order to understand how they solve complex tasks? We review how data-analysis concepts and techniques developed by computational neuroscientists can be useful for analyzing representations in DNNs, and in turn, how recently developed techniques for analysis of DNNs can be useful for understanding representations in biological neural networks. We explore opportunities for synergy between the two fields, such as the use of DNNs as in-silico model systems for neuroscience, and how this synergy can lead to new hypotheses about the operating principles of biological neural networks.