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1806.08504
Nathan Harding
Nathan Harding, Ramil Nigmatullin, Mikhail Prokopenko
Thermodynamic efficiency of contagions: A statistical mechanical analysis of the SIS epidemic model
null
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present a novel approach to the study of epidemics on networks as thermodynamic phenomena, considering the thermodynamic efficiency of contagions, considered as distributed computational processes. Modelling SIS dynamics on a contact network statistical-mechanically, we follow the Maximum Entropy principle to obtain steady state distributions and derive, under certain assumptions, relevant thermodynamic quantities both analytically and numerically. In particular, we obtain closed form solutions for some cases, while interpreting key epidemic variables, such as the reproductive ratio $R_0$ of a SIS model, in a statistical mechanical setting. On the other hand, we consider configuration and free entropy, as well as the Fisher Information, in the epidemiological context. This allowed us to identify criticality and distinct phases of epidemic processes. For each of the considered thermodynamic quantities, we compare the analytical solutions informed by the Maximum Entropy principle with the numerical estimates for SIS epidemics simulated on Watts-Strogatz random graphs.
[ { "created": "Fri, 22 Jun 2018 05:55:22 GMT", "version": "v1" }, { "created": "Mon, 22 Oct 2018 22:21:11 GMT", "version": "v2" } ]
2018-10-24
[ [ "Harding", "Nathan", "" ], [ "Nigmatullin", "Ramil", "" ], [ "Prokopenko", "Mikhail", "" ] ]
We present a novel approach to the study of epidemics on networks as thermodynamic phenomena, considering the thermodynamic efficiency of contagions, considered as distributed computational processes. Modelling SIS dynamics on a contact network statistical-mechanically, we follow the Maximum Entropy principle to obtain steady state distributions and derive, under certain assumptions, relevant thermodynamic quantities both analytically and numerically. In particular, we obtain closed form solutions for some cases, while interpreting key epidemic variables, such as the reproductive ratio $R_0$ of a SIS model, in a statistical mechanical setting. On the other hand, we consider configuration and free entropy, as well as the Fisher Information, in the epidemiological context. This allowed us to identify criticality and distinct phases of epidemic processes. For each of the considered thermodynamic quantities, we compare the analytical solutions informed by the Maximum Entropy principle with the numerical estimates for SIS epidemics simulated on Watts-Strogatz random graphs.
0810.5222
Andrea De Martino
Andrea De Martino, Carlotta Martelli, Francesco A. Massucci
On the role of conserved moieties in shaping the robustness and production capabilities of reaction networks
6 pages
null
null
null
q-bio.MN cond-mat.dis-nn
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We study a simplified, solvable model of a fully-connected metabolic network with constrained quenched disorder to mimic the conservation laws imposed by stoichiometry on chemical reactions. Within a spin-glass type of approach, we show that in presence of a conserved metabolic pool the flux state corresponding to maximal growth is stationary independently of the pool size. In addition, and at odds with the case of unconstrained networks, the volume of optimal flux configurations remains finite, indicating that the frustration imposed by stoichiometric constraints, while reducing growth capabilities, confers robustness and flexibility to the system. These results have a clear biological interpretation and provide a basic, fully analytical explanation to features recently observed in real metabolic networks.
[ { "created": "Wed, 29 Oct 2008 09:31:40 GMT", "version": "v1" } ]
2008-10-30
[ [ "De Martino", "Andrea", "" ], [ "Martelli", "Carlotta", "" ], [ "Massucci", "Francesco A.", "" ] ]
We study a simplified, solvable model of a fully-connected metabolic network with constrained quenched disorder to mimic the conservation laws imposed by stoichiometry on chemical reactions. Within a spin-glass type of approach, we show that in presence of a conserved metabolic pool the flux state corresponding to maximal growth is stationary independently of the pool size. In addition, and at odds with the case of unconstrained networks, the volume of optimal flux configurations remains finite, indicating that the frustration imposed by stoichiometric constraints, while reducing growth capabilities, confers robustness and flexibility to the system. These results have a clear biological interpretation and provide a basic, fully analytical explanation to features recently observed in real metabolic networks.
q-bio/0608036
Tobias Ambjornsson
Tobias Ambjornsson, Suman K. Banik, Oleg Krichevsky, Ralf Metzler
Sequence sensitivity of breathing dynamics in heteropolymer DNA
4 pages, 5 figures, to appear in Physical Review Letters
null
10.1103/PhysRevLett.97.128105
null
q-bio.BM cond-mat.stat-mech
null
We study the fluctuation dynamics of localized denaturation bubbles in heteropolymer DNA with a master equation and complementary stochastic simulation based on novel DNA stability data. A significant dependence of opening probability and waiting time between bubble events on the local DNA sequence is revealed and quantified for a biological sequence of the T7 bacteriophage. Quantitative agreement with data from fluorescence correlation spectroscopy (FCS) is demonstrated.
[ { "created": "Thu, 24 Aug 2006 14:47:46 GMT", "version": "v1" } ]
2009-11-13
[ [ "Ambjornsson", "Tobias", "" ], [ "Banik", "Suman K.", "" ], [ "Krichevsky", "Oleg", "" ], [ "Metzler", "Ralf", "" ] ]
We study the fluctuation dynamics of localized denaturation bubbles in heteropolymer DNA with a master equation and complementary stochastic simulation based on novel DNA stability data. A significant dependence of opening probability and waiting time between bubble events on the local DNA sequence is revealed and quantified for a biological sequence of the T7 bacteriophage. Quantitative agreement with data from fluorescence correlation spectroscopy (FCS) is demonstrated.
1408.6079
Gerrit Ansmann
Gerrit Ansmann, Klaus Lehnertz
Surrogate-assisted analysis of weighted functional brain networks
null
Journal of Neuroscience Methods 208, 165-172 (2012)
10.1016/j.jneumeth.2012.05.008
null
q-bio.NC physics.med-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Graph-theoretical analyses of complex brain networks is a rapidly evolving field with a strong impact for neuroscientific and related clinical research. Due to a number of confounding variables, however, a reliable and meaningful characterization of particularly functional brain networks is a major challenge. Addressing this problem, we present an analysis approach for weighted networks that makes use of surrogate networks with preserved edge weights or vertex strengths. We first investigate whether characteristics of weighted networks are influenced by trivial properties of the edge weights or vertex strengths (e.g., their standard deviations). If so, these influences are then effectively segregated with an appropriate surrogate normalization of the respective network characteristic. We demonstrate this approach by re-examining, in a time-resolved manner, weighted functional brain networks of epilepsy patients and control subjects derived from simultaneous EEG/MEG recordings during different behavioral states. We show that this surrogate-assisted analysis approach reveals complementary information about these networks, can aid with their interpretation, and thus can prevent deriving inappropriate conclusions.
[ { "created": "Tue, 26 Aug 2014 11:32:27 GMT", "version": "v1" } ]
2014-08-27
[ [ "Ansmann", "Gerrit", "" ], [ "Lehnertz", "Klaus", "" ] ]
Graph-theoretical analyses of complex brain networks is a rapidly evolving field with a strong impact for neuroscientific and related clinical research. Due to a number of confounding variables, however, a reliable and meaningful characterization of particularly functional brain networks is a major challenge. Addressing this problem, we present an analysis approach for weighted networks that makes use of surrogate networks with preserved edge weights or vertex strengths. We first investigate whether characteristics of weighted networks are influenced by trivial properties of the edge weights or vertex strengths (e.g., their standard deviations). If so, these influences are then effectively segregated with an appropriate surrogate normalization of the respective network characteristic. We demonstrate this approach by re-examining, in a time-resolved manner, weighted functional brain networks of epilepsy patients and control subjects derived from simultaneous EEG/MEG recordings during different behavioral states. We show that this surrogate-assisted analysis approach reveals complementary information about these networks, can aid with their interpretation, and thus can prevent deriving inappropriate conclusions.
1101.3343
Gang Fang
Gang Fang, Wen Wang, Vanja Paunic, Benjamin Oately, Majda Haznadar, Michael Steinbach, Brian Van Ness, Chad L. Myers, Vipin Kumar
Construction and Functional Analysis of Human Genetic Interaction Networks with Genome-wide Association Data
null
null
null
null
q-bio.MN q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Genetic interaction measures how different genes collectively contribute to a phenotype, and can reveal functional compensation and buffering between pathways under genetic perturbations. Recently, genome-wide screening for genetic interactions has revealed genetic interaction networks that provide novel insights either when analyzed by themselves or when integrated with other functional genomic datasets. For higher eukaryotes such as human, the above reverse-genetics approaches are not straightforward since the phenotypes of interest for higher eukaryotes are difficult to study in a cell based assay. We propose a general framework for constructing and analyzing human genetic interaction networks from genome-wide single nucleotide polymorphism (SNP) data used for case-control studies on complex diseases. Specifically, the approach contains three major steps: (1) estimating SNP-SNP genetic interactions, (2) identifying linkage disequilibrium (LD) blocks and mapping SNP-SNP interactions to block-block interactions, and (3) functional mapping for LD blocks. We performed two sets of functional analyses for each of the six datasets used in the paper, and demonstrated that (i) the constructed genetic interaction networks are supported by functional evidence from independent biological databases, and (ii) the network can be used to discover pairs of compensatory gene modules (between-pathway models) in their joint association with a disease phenotype. The proposed framework should provide novel insights beyond existing approaches that either ignore interactions between SNPs or model different SNP-SNP pairs with genetic interactions separately. Furthermore, our study provides evidence that some of the core properties of genetic interaction networks based on reverse genetics in model organisms like yeast are also present in genetic interactions revealed by natural variation in human populations.
[ { "created": "Mon, 17 Jan 2011 22:10:09 GMT", "version": "v1" } ]
2015-03-17
[ [ "Fang", "Gang", "" ], [ "Wang", "Wen", "" ], [ "Paunic", "Vanja", "" ], [ "Oately", "Benjamin", "" ], [ "Haznadar", "Majda", "" ], [ "Steinbach", "Michael", "" ], [ "Van Ness", "Brian", "" ], [ "Mye...
Genetic interaction measures how different genes collectively contribute to a phenotype, and can reveal functional compensation and buffering between pathways under genetic perturbations. Recently, genome-wide screening for genetic interactions has revealed genetic interaction networks that provide novel insights either when analyzed by themselves or when integrated with other functional genomic datasets. For higher eukaryotes such as human, the above reverse-genetics approaches are not straightforward since the phenotypes of interest for higher eukaryotes are difficult to study in a cell based assay. We propose a general framework for constructing and analyzing human genetic interaction networks from genome-wide single nucleotide polymorphism (SNP) data used for case-control studies on complex diseases. Specifically, the approach contains three major steps: (1) estimating SNP-SNP genetic interactions, (2) identifying linkage disequilibrium (LD) blocks and mapping SNP-SNP interactions to block-block interactions, and (3) functional mapping for LD blocks. We performed two sets of functional analyses for each of the six datasets used in the paper, and demonstrated that (i) the constructed genetic interaction networks are supported by functional evidence from independent biological databases, and (ii) the network can be used to discover pairs of compensatory gene modules (between-pathway models) in their joint association with a disease phenotype. The proposed framework should provide novel insights beyond existing approaches that either ignore interactions between SNPs or model different SNP-SNP pairs with genetic interactions separately. Furthermore, our study provides evidence that some of the core properties of genetic interaction networks based on reverse genetics in model organisms like yeast are also present in genetic interactions revealed by natural variation in human populations.
1706.08041
Pavitra Krishnaswamy
Pavitra Krishnaswamy, Gabriel Obregon-Henao, Jyrki Ahveninen, Sheraz Khan, Behtash Babadi, Juan Eugenio Iglesias, Matti S. Hamalainen, Patrick L. Purdon
Sparsity Enables Estimation of both Subcortical and Cortical Activity from MEG and EEG
12 pages with 6 figures
null
10.1073/pnas.1705414114
null
q-bio.QM q-bio.NC stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Subcortical structures play a critical role in brain function. However, options for assessing electrophysiological activity in these structures are limited. Electromagnetic fields generated by neuronal activity in subcortical structures can be recorded non-invasively using magnetoencephalography (MEG) and electroencephalography (EEG). However, these subcortical signals are much weaker than those due to cortical activity. In addition, we show here that it is difficult to resolve subcortical sources, because distributed cortical activity can explain the MEG and EEG patterns due to deep sources. We then demonstrate that if the cortical activity can be assumed to be spatially sparse, both cortical and subcortical sources can be resolved with M/EEG. Building on this insight, we develop a novel hierarchical sparse inverse solution for M/EEG. We assess the performance of this algorithm on realistic simulations and auditory evoked response data and show that thalamic and brainstem sources can be correctly estimated in the presence of cortical activity. Our analysis and method suggest new opportunities and offer practical tools for characterizing electrophysiological activity in the subcortical structures of the human brain.
[ { "created": "Sun, 25 Jun 2017 06:52:23 GMT", "version": "v1" } ]
2022-06-01
[ [ "Krishnaswamy", "Pavitra", "" ], [ "Obregon-Henao", "Gabriel", "" ], [ "Ahveninen", "Jyrki", "" ], [ "Khan", "Sheraz", "" ], [ "Babadi", "Behtash", "" ], [ "Iglesias", "Juan Eugenio", "" ], [ "Hamalainen", "Mat...
Subcortical structures play a critical role in brain function. However, options for assessing electrophysiological activity in these structures are limited. Electromagnetic fields generated by neuronal activity in subcortical structures can be recorded non-invasively using magnetoencephalography (MEG) and electroencephalography (EEG). However, these subcortical signals are much weaker than those due to cortical activity. In addition, we show here that it is difficult to resolve subcortical sources, because distributed cortical activity can explain the MEG and EEG patterns due to deep sources. We then demonstrate that if the cortical activity can be assumed to be spatially sparse, both cortical and subcortical sources can be resolved with M/EEG. Building on this insight, we develop a novel hierarchical sparse inverse solution for M/EEG. We assess the performance of this algorithm on realistic simulations and auditory evoked response data and show that thalamic and brainstem sources can be correctly estimated in the presence of cortical activity. Our analysis and method suggest new opportunities and offer practical tools for characterizing electrophysiological activity in the subcortical structures of the human brain.
1806.08167
Thierry Mora
Christophe Gardella, Olivier Marre, Thierry Mora
Modeling the correlated activity of neural populations: A review
null
Neural Computation 31(2) 233-269 (2019)
10.1162/neco_a_01154
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The principles of neural encoding and computations are inherently collective and usually involve large populations of interacting neurons with highly correlated activities. While theories of neural function have long recognized the importance of collective effects in populations of neurons, only in the past two decades has it become possible to record from many cells simulatenously using advanced experimental techniques with single-spike resolution, and to relate these correlations to function and behaviour. This review focuses on the modeling and inference approaches that have been recently developed to describe the correlated spiking activity of populations of neurons. We cover a variety of models describing correlations between pairs of neurons as well as between larger groups, synchronous or delayed in time, with or without the explicit influence of the stimulus, and including or not latent variables. We discuss the advantages and drawbacks or each method, as well as the computational challenges related to their application to recordings of ever larger populations.
[ { "created": "Thu, 21 Jun 2018 11:00:13 GMT", "version": "v1" } ]
2019-05-14
[ [ "Gardella", "Christophe", "" ], [ "Marre", "Olivier", "" ], [ "Mora", "Thierry", "" ] ]
The principles of neural encoding and computations are inherently collective and usually involve large populations of interacting neurons with highly correlated activities. While theories of neural function have long recognized the importance of collective effects in populations of neurons, only in the past two decades has it become possible to record from many cells simulatenously using advanced experimental techniques with single-spike resolution, and to relate these correlations to function and behaviour. This review focuses on the modeling and inference approaches that have been recently developed to describe the correlated spiking activity of populations of neurons. We cover a variety of models describing correlations between pairs of neurons as well as between larger groups, synchronous or delayed in time, with or without the explicit influence of the stimulus, and including or not latent variables. We discuss the advantages and drawbacks or each method, as well as the computational challenges related to their application to recordings of ever larger populations.
1010.4735
David Wild
Nikolas S. Burkoff, Csilla Varnai, Stephen A. Wells and David L. Wild
Exploring the Energy Landscapes of Protein Folding Simulations with Bayesian Computation
28 pages, 16 figures. Under revision for Biophysical Journal
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Nested sampling is a Bayesian sampling technique developed to explore probability distributions lo- calised in an exponentially small area of the parameter space. The algorithm provides both posterior samples and an estimate of the evidence (marginal likelihood) of the model. The nested sampling algo- rithm also provides an efficient way to calculate free energies and the expectation value of thermodynamic observables at any temperature, through a simple post-processing of the output. Previous applications of the algorithm have yielded large efficiency gains over other sampling techniques, including parallel tempering (replica exchange). In this paper we describe a parallel implementation of the nested sampling algorithm and its application to the problem of protein folding in a Go-type force field of empirical potentials that were designed to stabilize secondary structure elements in room-temperature simulations. We demonstrate the method by conducting folding simulations on a number of small proteins which are commonly used for testing protein folding procedures: protein G, the SH3 domain of Src tyrosine kinase and chymotrypsin inhibitor 2. A topological analysis of the posterior samples is performed to produce energy landscape charts, which give a high level description of the potential energy surface for the protein folding simulations. These charts provide qualitative insights into both the folding process and the nature of the model and force field used.
[ { "created": "Fri, 22 Oct 2010 15:19:33 GMT", "version": "v1" }, { "created": "Thu, 13 Jan 2011 17:49:06 GMT", "version": "v2" }, { "created": "Wed, 27 Jul 2011 13:51:08 GMT", "version": "v3" }, { "created": "Thu, 22 Dec 2011 17:13:00 GMT", "version": "v4" } ]
2015-03-17
[ [ "Burkoff", "Nikolas S.", "" ], [ "Varnai", "Csilla", "" ], [ "Wells", "Stephen A.", "" ], [ "Wild", "David L.", "" ] ]
Nested sampling is a Bayesian sampling technique developed to explore probability distributions lo- calised in an exponentially small area of the parameter space. The algorithm provides both posterior samples and an estimate of the evidence (marginal likelihood) of the model. The nested sampling algo- rithm also provides an efficient way to calculate free energies and the expectation value of thermodynamic observables at any temperature, through a simple post-processing of the output. Previous applications of the algorithm have yielded large efficiency gains over other sampling techniques, including parallel tempering (replica exchange). In this paper we describe a parallel implementation of the nested sampling algorithm and its application to the problem of protein folding in a Go-type force field of empirical potentials that were designed to stabilize secondary structure elements in room-temperature simulations. We demonstrate the method by conducting folding simulations on a number of small proteins which are commonly used for testing protein folding procedures: protein G, the SH3 domain of Src tyrosine kinase and chymotrypsin inhibitor 2. A topological analysis of the posterior samples is performed to produce energy landscape charts, which give a high level description of the potential energy surface for the protein folding simulations. These charts provide qualitative insights into both the folding process and the nature of the model and force field used.
1009.5173
Laurent Jacob
Laurent Jacob, Pierre Neuvial, Sandrine Dudoit
Gains in Power from Structured Two-Sample Tests of Means on Graphs
null
Annals of Applied Statistics 2012, Vol. 6, No. 2, 561-600
10.1214/11-AOAS528
null
q-bio.QM stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We consider multivariate two-sample tests of means, where the location shift between the two populations is expected to be related to a known graph structure. An important application of such tests is the detection of differentially expressed genes between two patient populations, as shifts in expression levels are expected to be coherent with the structure of graphs reflecting gene properties such as biological process, molecular function, regulation, or metabolism. For a fixed graph of interest, we demonstrate that accounting for graph structure can yield more powerful tests under the assumption of smooth distribution shift on the graph. We also investigate the identification of non-homogeneous subgraphs of a given large graph, which poses both computational and multiple testing problems. The relevance and benefits of the proposed approach are illustrated on synthetic data and on breast cancer gene expression data analyzed in context of KEGG pathways.
[ { "created": "Mon, 27 Sep 2010 07:21:22 GMT", "version": "v1" } ]
2014-05-16
[ [ "Jacob", "Laurent", "" ], [ "Neuvial", "Pierre", "" ], [ "Dudoit", "Sandrine", "" ] ]
We consider multivariate two-sample tests of means, where the location shift between the two populations is expected to be related to a known graph structure. An important application of such tests is the detection of differentially expressed genes between two patient populations, as shifts in expression levels are expected to be coherent with the structure of graphs reflecting gene properties such as biological process, molecular function, regulation, or metabolism. For a fixed graph of interest, we demonstrate that accounting for graph structure can yield more powerful tests under the assumption of smooth distribution shift on the graph. We also investigate the identification of non-homogeneous subgraphs of a given large graph, which poses both computational and multiple testing problems. The relevance and benefits of the proposed approach are illustrated on synthetic data and on breast cancer gene expression data analyzed in context of KEGG pathways.
2212.06308
Luis Osorio-Olvera
Jorge Sober\'on and Luis Osorio-Olvera
A Dynamic Theory of the Area of Distribution
45 pages including appendixes, 12 figures, submitted to Journal of Biogeography
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
Aims To propose and analyze a general, dynamic, process-oriented theory of the area of distribution. Methods The area of distribution is modelled by combining (by multiplication) three matrices: one matrix represents movements, another niche tolerances, and a third, biotic interactions. Results are derived from general properties of this product and from simulation of a cellular automaton defined in terms of the matrix operations. Everything is implemented practically in an R package. Results Results are obtained by simulation and by mathematical analysis. We show that the mid-domain effect is a direct consequence of dispersal; that to include movements to Ecological Niche Modeling significantly affects results, but cannot be done without choosing an ancestral area of distribution. We discuss ways of estimating such ancestral areas. We show that, in our approach, movements and niche effects are mixed in ways almost impossible to disentangle, and show this is a consequence of the singularity of a matrix. We introduce a tool (the Connectivity-Suitability-Dispersal plot) to extend the results of simple niche modeling to understand the effects of dispersal. Main conclusions The conceptually straightforward scheme we present for the area of distribution integrates, in a mathematically sound and computationally feasible way, several key ideas in biogeography: the geographic and environmental matrix, the Grinnellian niche, dispersal capacity and the ancestral area of origin of groups of species. We show that although full simulations are indispensable to obtain the dynamics of an area of distribution, interesting results can be derived simply by analyzing the matrices representing the dynamics.
[ { "created": "Tue, 13 Dec 2022 01:28:22 GMT", "version": "v1" } ]
2022-12-14
[ [ "Soberón", "Jorge", "" ], [ "Osorio-Olvera", "Luis", "" ] ]
Aims To propose and analyze a general, dynamic, process-oriented theory of the area of distribution. Methods The area of distribution is modelled by combining (by multiplication) three matrices: one matrix represents movements, another niche tolerances, and a third, biotic interactions. Results are derived from general properties of this product and from simulation of a cellular automaton defined in terms of the matrix operations. Everything is implemented practically in an R package. Results Results are obtained by simulation and by mathematical analysis. We show that the mid-domain effect is a direct consequence of dispersal; that to include movements to Ecological Niche Modeling significantly affects results, but cannot be done without choosing an ancestral area of distribution. We discuss ways of estimating such ancestral areas. We show that, in our approach, movements and niche effects are mixed in ways almost impossible to disentangle, and show this is a consequence of the singularity of a matrix. We introduce a tool (the Connectivity-Suitability-Dispersal plot) to extend the results of simple niche modeling to understand the effects of dispersal. Main conclusions The conceptually straightforward scheme we present for the area of distribution integrates, in a mathematically sound and computationally feasible way, several key ideas in biogeography: the geographic and environmental matrix, the Grinnellian niche, dispersal capacity and the ancestral area of origin of groups of species. We show that although full simulations are indispensable to obtain the dynamics of an area of distribution, interesting results can be derived simply by analyzing the matrices representing the dynamics.
1501.06529
David Bardos
David C. Bardos, Gurutzeta Guillera-Arroita and Brendan A. Wintle
Valid auto-models for spatially autocorrelated occupancy and abundance data
Typos corrected in Table 1. Note that defaults in R package 'spdep' have changed in response to this paper; some results using defaults are therefore now version-dependent
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Auto-logistic and related auto-models, implemented approximately as autocovariate regression, provide simple and direct modelling of spatial dependence. The autologistic model has been widely applied in ecology since Augustin, Mugglestone and Buckland (J. Appl. Ecol., 1996, 33, 339) analysed red deer census data using a hybrid estimation approach, combining maximum pseudo-likelihood estimation with Gibbs sampling of missing data. However Dormann (Ecol. Model., 2007, 207, 234) questioned the validity of auto-logistic regression, giving examples of apparent underestimation of covariate parameters in analysis of simulated "snouter" data. Dormann et al. (Ecography, 2007, 30, 609) extended this analysis to auto-Poisson and auto-normal models, reporting similar anomalies. All the above studies employ neighbourhood weighting schemes inconsistent with conditions (Besag, J. R. Stat. Soc., Ser. B, 1974, 36, 192) required for auto-model validity; furthermore the auto-Poisson analysis fails to exclude cooperative interactions. We show that all "snouter" anomalies are resolved by correct auto-model implementation. Re-analysis of the red deer data shows that invalid neighbourhood weightings generate only small estimation errors for the full dataset, but larger errors occur on geographic subsamples. A substantial fraction of papers applying auto-logistic regression to ecological data use these invalid weightings, which are default options in the widely used "spdep" spatial dependence package for R. Auto-logistic analyses using invalid neighbourhood weightings will be erroneous to an extent that can vary widely. These analyses can easily be corrected by using valid neighbourhood weightings available in "spdep". The hybrid estimation approach for missing data is readily adapted for valid neighbourhood weighting schemes and is implemented here in R for application to sparse presence-absence data.
[ { "created": "Mon, 26 Jan 2015 19:14:57 GMT", "version": "v1" }, { "created": "Tue, 27 Jan 2015 16:51:07 GMT", "version": "v2" }, { "created": "Sun, 15 Feb 2015 14:30:45 GMT", "version": "v3" }, { "created": "Thu, 30 Apr 2015 17:17:06 GMT", "version": "v4" } ]
2015-05-01
[ [ "Bardos", "David C.", "" ], [ "Guillera-Arroita", "Gurutzeta", "" ], [ "Wintle", "Brendan A.", "" ] ]
Auto-logistic and related auto-models, implemented approximately as autocovariate regression, provide simple and direct modelling of spatial dependence. The autologistic model has been widely applied in ecology since Augustin, Mugglestone and Buckland (J. Appl. Ecol., 1996, 33, 339) analysed red deer census data using a hybrid estimation approach, combining maximum pseudo-likelihood estimation with Gibbs sampling of missing data. However Dormann (Ecol. Model., 2007, 207, 234) questioned the validity of auto-logistic regression, giving examples of apparent underestimation of covariate parameters in analysis of simulated "snouter" data. Dormann et al. (Ecography, 2007, 30, 609) extended this analysis to auto-Poisson and auto-normal models, reporting similar anomalies. All the above studies employ neighbourhood weighting schemes inconsistent with conditions (Besag, J. R. Stat. Soc., Ser. B, 1974, 36, 192) required for auto-model validity; furthermore the auto-Poisson analysis fails to exclude cooperative interactions. We show that all "snouter" anomalies are resolved by correct auto-model implementation. Re-analysis of the red deer data shows that invalid neighbourhood weightings generate only small estimation errors for the full dataset, but larger errors occur on geographic subsamples. A substantial fraction of papers applying auto-logistic regression to ecological data use these invalid weightings, which are default options in the widely used "spdep" spatial dependence package for R. Auto-logistic analyses using invalid neighbourhood weightings will be erroneous to an extent that can vary widely. These analyses can easily be corrected by using valid neighbourhood weightings available in "spdep". The hybrid estimation approach for missing data is readily adapted for valid neighbourhood weighting schemes and is implemented here in R for application to sparse presence-absence data.
1206.1029
Gopalakrishnan Tr Nair
Baby Jerald, T. R. Gopalakrishnan Nair
Influenza Virus Vaccine Efficacy Based On Conserved Sequence Alignment
International Conference on Biomedical Engineering (ICoBE), 2012 Date of Conference: 27-28 Feb. 2012 Page(s): 327 - 329, 2 figures, 3 pages
null
10.1109/ICoBE.2012.6179031
null
q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The rapid outbreak of bird flu challenges the outcome of effective vaccine for the upcoming years. The recent research established different norms to eliminate flu pandemics. This can be made possible with skilled experimental analyses and by tracking the recent virulent strain and can be broadly applicable with effective testing of vaccine efficacy. Every year World Health Organization (WHO) reveals the administration of drug and vaccine to counter arrest the spread of flu among the population. As there are recurrent failures in priming the population, the complete eradication of the flu pandemic is still appears to be an unresolved problem. To overcome the current scenario, high level efforts with theoretical and practical research is required and it can enhance the scope in this field. The recent advancements also allow the researchers to endeavor effective vaccine to meet the emerging flu types. Only the standardized vaccination among the population at the time of flu pandemics will revolutionalize the current propositions against influenza virus. This paper shows the deficiencies of vaccine fitness research as there are reported failures and less efficacy of vaccine even after priming the population from referred evidences and studies. It also shows simple experimental approach in detecting the effective vaccine among the vaccines announced by WHO.
[ { "created": "Sat, 2 Jun 2012 17:49:26 GMT", "version": "v1" } ]
2012-06-06
[ [ "Jerald", "Baby", "" ], [ "Nair", "T. R. Gopalakrishnan", "" ] ]
The rapid outbreak of bird flu challenges the outcome of effective vaccine for the upcoming years. The recent research established different norms to eliminate flu pandemics. This can be made possible with skilled experimental analyses and by tracking the recent virulent strain and can be broadly applicable with effective testing of vaccine efficacy. Every year World Health Organization (WHO) reveals the administration of drug and vaccine to counter arrest the spread of flu among the population. As there are recurrent failures in priming the population, the complete eradication of the flu pandemic is still appears to be an unresolved problem. To overcome the current scenario, high level efforts with theoretical and practical research is required and it can enhance the scope in this field. The recent advancements also allow the researchers to endeavor effective vaccine to meet the emerging flu types. Only the standardized vaccination among the population at the time of flu pandemics will revolutionalize the current propositions against influenza virus. This paper shows the deficiencies of vaccine fitness research as there are reported failures and less efficacy of vaccine even after priming the population from referred evidences and studies. It also shows simple experimental approach in detecting the effective vaccine among the vaccines announced by WHO.
1406.2497
Jennifer Conroy PhD
Jennifer Conroy, Navin K. Verma, Ronan J. Smith, Ehsan Rezvani, Georg S. Duesberg, Jonathan N. Coleman, Yuri Volkov
Biocompatibility of Pristine Graphene Monolayers, Nanosheets and Thin Films
null
null
null
null
q-bio.CB cond-mat.mes-hall physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
There is an increasing interest to develop nanoscale biocompatible graphene structures due to their desirable physicochemical properties, unlimited application opportunities and scalable production. Here we report the preparation, characterization and biocompatibility assessment of novel graphene flakes and their enabled thin films suitable for a wide range of biomedical and electronic applications. Graphene flakes were synthesized by a chemical vapour deposition method or a liquid-phase exfoliation procedure and then thin films were prepared by transferring graphene onto glass coverslips. Raman spectroscopy and transmission electron microscopy confirmed a predominantly monolayer and a high crystalline quality formation of graphene. The biocompatibility assessment of graphene thin films and graphene flakes was performed using cultured human lung epithelial cell line A549 employing a multimodal approach incorporating automated imaging, high content screening, real-time impedance sensing in combination with biochemical assays. No detectable changes in the cellular morphology or attachment of A549 cells growing on graphene thin films or cells exposed to graphene flakes (0.1 to 5 ug/mL) for 4 to 72 h was observed. Graphene treatments caused a very low level of increase in cellular production of reactive oxygen species in A549 cells, but no detectable damage to the nuclei such as changes in morphology, condensation or fragmentation was observed. In contrast, carbon black proved to be significantly more toxic than the graphene. These data open up a promising view of using graphene enabled composites for a diverse scope of safer applications.
[ { "created": "Tue, 10 Jun 2014 10:21:49 GMT", "version": "v1" } ]
2014-06-11
[ [ "Conroy", "Jennifer", "" ], [ "Verma", "Navin K.", "" ], [ "Smith", "Ronan J.", "" ], [ "Rezvani", "Ehsan", "" ], [ "Duesberg", "Georg S.", "" ], [ "Coleman", "Jonathan N.", "" ], [ "Volkov", "Yuri", "" ]...
There is an increasing interest to develop nanoscale biocompatible graphene structures due to their desirable physicochemical properties, unlimited application opportunities and scalable production. Here we report the preparation, characterization and biocompatibility assessment of novel graphene flakes and their enabled thin films suitable for a wide range of biomedical and electronic applications. Graphene flakes were synthesized by a chemical vapour deposition method or a liquid-phase exfoliation procedure and then thin films were prepared by transferring graphene onto glass coverslips. Raman spectroscopy and transmission electron microscopy confirmed a predominantly monolayer and a high crystalline quality formation of graphene. The biocompatibility assessment of graphene thin films and graphene flakes was performed using cultured human lung epithelial cell line A549 employing a multimodal approach incorporating automated imaging, high content screening, real-time impedance sensing in combination with biochemical assays. No detectable changes in the cellular morphology or attachment of A549 cells growing on graphene thin films or cells exposed to graphene flakes (0.1 to 5 ug/mL) for 4 to 72 h was observed. Graphene treatments caused a very low level of increase in cellular production of reactive oxygen species in A549 cells, but no detectable damage to the nuclei such as changes in morphology, condensation or fragmentation was observed. In contrast, carbon black proved to be significantly more toxic than the graphene. These data open up a promising view of using graphene enabled composites for a diverse scope of safer applications.
1305.3801
Ra\'ul Salgado-Garcia
R. Salgado-Garcia and E. Ugalde
Symbolic Complexity for Nucleotide Sequences: A Sign of the Genome Structure
4 pages, 3 figures
J. Phys. A: Math. Theor. 49 (2016) 445601 (21pp)
10.1088/1751-8113/49/44/445601
null
q-bio.PE math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We introduce a method to estimate the complexity function of symbolic dynamical systems from a finite sequence of symbols. We test such complexity estimator on several symbolic dynamical systems whose complexity functions are known exactly. We use this technique to estimate the complexity function for genomes of several organisms under the assumption that a genome is a sequence produced by a (unknown) dynamical system. We show that the genome of several organisms share the property that their complexity functions behaves exponentially for words of small length $\ell$ ($0\leq \ell \leq 10$) and linearly for word lengths in the range $11 \leq \ell \leq 50$. It is also found that the species which are phylogenetically close each other have similar complexity functions calculated from a sample of their corresponding coding regions.
[ { "created": "Thu, 16 May 2013 13:43:50 GMT", "version": "v1" } ]
2017-01-19
[ [ "Salgado-Garcia", "R.", "" ], [ "Ugalde", "E.", "" ] ]
We introduce a method to estimate the complexity function of symbolic dynamical systems from a finite sequence of symbols. We test such complexity estimator on several symbolic dynamical systems whose complexity functions are known exactly. We use this technique to estimate the complexity function for genomes of several organisms under the assumption that a genome is a sequence produced by a (unknown) dynamical system. We show that the genome of several organisms share the property that their complexity functions behaves exponentially for words of small length $\ell$ ($0\leq \ell \leq 10$) and linearly for word lengths in the range $11 \leq \ell \leq 50$. It is also found that the species which are phylogenetically close each other have similar complexity functions calculated from a sample of their corresponding coding regions.
1910.03263
Tobias B\"uscher
Tobias B\"uscher, Nirmalendu Ganai, Gerhard Gompper, Jens Elgeti
Tissue evolution: Mechanical interplay of adhesion, pressure, and heterogeneity
13 pages, 7 figures
New J. Phys. 22, 033048 (2020)
10.1088/1367-2630/ab74a5
null
q-bio.PE q-bio.TO
http://creativecommons.org/licenses/by/4.0/
The evolution of various competing cell types in tissues, and the resulting persistent tissue population, is studied numerically and analytically in a particle-based model of active tissues. Mutations change the properties of cells in various ways, including their mechanical properties. Each mutation results in an advantage or disadvantage to grow in the competition between different cell types. While changes in signaling processes and biochemistry play an important role, we focus on changes in the mechanical properties by studying the result of variation of growth force and adhesive cross-interactions between cell types. For independent mutations of growth force and adhesion strength, the tissue evolves towards cell types with high growth force and low internal adhesion strength, as both increase the homeostatic pressure. Motivated by biological evidence, we postulate a coupling between both parameters, such that an increased growth force comes at the cost of a higher internal adhesion strength or vice versa. This tradeoff controls the evolution of the tissue, ranging from unidirectional evolution to very heterogeneous and dynamic populations. The special case of two competing cell types reveals three distinct parameter regimes: Two in which one cell type outcompetes the other, and one in which both cell types coexist in a highly mixed state. Interestingly, a single mutated cell alone suffices to reach the mixed state, while a finite mutation rate affects the results only weakly. Finally, the coupling between changes in growth force and adhesion strength reveals a mechanical explanation for the evolution towards intra-tumor heterogeneity, in which multiple species coexist even under a constant evolutianary pressure.
[ { "created": "Tue, 8 Oct 2019 08:03:03 GMT", "version": "v1" } ]
2024-06-03
[ [ "Büscher", "Tobias", "" ], [ "Ganai", "Nirmalendu", "" ], [ "Gompper", "Gerhard", "" ], [ "Elgeti", "Jens", "" ] ]
The evolution of various competing cell types in tissues, and the resulting persistent tissue population, is studied numerically and analytically in a particle-based model of active tissues. Mutations change the properties of cells in various ways, including their mechanical properties. Each mutation results in an advantage or disadvantage to grow in the competition between different cell types. While changes in signaling processes and biochemistry play an important role, we focus on changes in the mechanical properties by studying the result of variation of growth force and adhesive cross-interactions between cell types. For independent mutations of growth force and adhesion strength, the tissue evolves towards cell types with high growth force and low internal adhesion strength, as both increase the homeostatic pressure. Motivated by biological evidence, we postulate a coupling between both parameters, such that an increased growth force comes at the cost of a higher internal adhesion strength or vice versa. This tradeoff controls the evolution of the tissue, ranging from unidirectional evolution to very heterogeneous and dynamic populations. The special case of two competing cell types reveals three distinct parameter regimes: Two in which one cell type outcompetes the other, and one in which both cell types coexist in a highly mixed state. Interestingly, a single mutated cell alone suffices to reach the mixed state, while a finite mutation rate affects the results only weakly. Finally, the coupling between changes in growth force and adhesion strength reveals a mechanical explanation for the evolution towards intra-tumor heterogeneity, in which multiple species coexist even under a constant evolutianary pressure.
1712.02866
Michael Green
Alisher M. Kariev and Michael E. Green
Quantum Calculations on the Kv1.2 Channel Voltage Sensing Domain Show H+ Transfer Provides the Gating Current
At the end of the paper, there is an extended supplement with the calculated coordinates for 14 out of 30 cases that were calculated (all those that turned out to make a significant contribution). The paper has 6 figures. Also, an earlier preprint, with a fraction of what is in the present submission, was posted on BioarXiv on 6/23/2017
null
10.1016/j.bpj.2017.11.2615
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Quantum calculations on the voltage sensing domain (VSD) of the Kv1.2 potassium channel (pdb: 3Lut)have been carried out on a 904 atoms subset of the VSD, plus 24 water molecules. Side chains pointing away from the center of the VSD were truncated; S1,S2,S3 end atoms were were fixed (all calculations); S4 end atoms could be fixed or free. Open conformations (membrane potentials >= 0) closely match the known X-ray structure of the open state with salt bridges in the in the VSD not ionized (H+ on the acid) whether S4 end atoms were fixed or free (slightly closer fixed than free).The S4 segment backbone, free or not, moves less than 2.5 A for positive to negative membrane potential switches, not entirely in the expected direction, leaving H+ motion as the principal component of the gating current. Groups of 3 - 5 side chains are important for proton transport, based on the calculations. A proton transfers from tyrosine (Y266), through arginine (R300), to glutamate (E183), accounting for approximately 20 - 25% of the gating charge. Clusters of amino acids that can transfer protons (acids, bases, tyrosine, histidine) are the main paths for proton transport. A group of five amino acids, bounded by the conserved aromatic F233, appears to exchange a proton. Dipole rotations may also contribute. A proton path (calculations still in progress) is proposed for the remainder of the VSD, suggesting a hypothesis for a complete gating mechanism.
[ { "created": "Thu, 7 Dec 2017 21:28:16 GMT", "version": "v1" } ]
2018-10-10
[ [ "Kariev", "Alisher M.", "" ], [ "Green", "Michael E.", "" ] ]
Quantum calculations on the voltage sensing domain (VSD) of the Kv1.2 potassium channel (pdb: 3Lut)have been carried out on a 904 atoms subset of the VSD, plus 24 water molecules. Side chains pointing away from the center of the VSD were truncated; S1,S2,S3 end atoms were were fixed (all calculations); S4 end atoms could be fixed or free. Open conformations (membrane potentials >= 0) closely match the known X-ray structure of the open state with salt bridges in the in the VSD not ionized (H+ on the acid) whether S4 end atoms were fixed or free (slightly closer fixed than free).The S4 segment backbone, free or not, moves less than 2.5 A for positive to negative membrane potential switches, not entirely in the expected direction, leaving H+ motion as the principal component of the gating current. Groups of 3 - 5 side chains are important for proton transport, based on the calculations. A proton transfers from tyrosine (Y266), through arginine (R300), to glutamate (E183), accounting for approximately 20 - 25% of the gating charge. Clusters of amino acids that can transfer protons (acids, bases, tyrosine, histidine) are the main paths for proton transport. A group of five amino acids, bounded by the conserved aromatic F233, appears to exchange a proton. Dipole rotations may also contribute. A proton path (calculations still in progress) is proposed for the remainder of the VSD, suggesting a hypothesis for a complete gating mechanism.
0712.3020
Leonid Mirny
Carlos Gomez-Uribe, George C. Verghese, and Leonid A. Mirny
Operating Regimes of Signaling Cycles: Statics, Dynamics, and Noise Filtering
to appear in PLoS Computational Biology
null
10.1371/journal.pcbi.0030246
null
q-bio.MN q-bio.BM q-bio.QM q-bio.SC
null
A ubiquitous building block of signaling pathways is a cycle of covalent modification (e.g., phosphorylation and dephosphorylation in MAPK cascades). Our paper explores the kind of information processing and filtering that can be accomplished by this simple biochemical circuit. Signaling cycles are particularly known for exhibiting a highly sigmoidal (ultrasensitive) input-output characteristic in a certain steady-state regime. Here we systematically study the cycle's steady-state behavior and its response to time-varying stimuli. We demonstrate that the cycle can actually operate in four different regimes, each with its specific input-output characteristics. These results are obtained using the total quasi-steady-state approximation, which is more generally valid than the typically used Michaelis-Menten approximation for enzymatic reactions. We invoke experimental data that suggests the possibility of signaling cycles operating in one of the new regimes. We then consider the cycle's dynamic behavior, which has so far been relatively neglected. We demonstrate that the intrinsic architecture of the cycles makes them act - in all four regimes - as tunable low-pass filters, filtering out high-frequency fluctuations or noise in signals and environmental cues. Moreover, the cutoff frequency can be adjusted by the cell. Numerical simulations show that our analytical results hold well even for noise of large amplitude. We suggest that noise filtering and tunability make signaling cycles versatile components of more elaborate cell signaling pathways.
[ { "created": "Tue, 18 Dec 2007 18:43:43 GMT", "version": "v1" } ]
2015-05-13
[ [ "Gomez-Uribe", "Carlos", "" ], [ "Verghese", "George C.", "" ], [ "Mirny", "Leonid A.", "" ] ]
A ubiquitous building block of signaling pathways is a cycle of covalent modification (e.g., phosphorylation and dephosphorylation in MAPK cascades). Our paper explores the kind of information processing and filtering that can be accomplished by this simple biochemical circuit. Signaling cycles are particularly known for exhibiting a highly sigmoidal (ultrasensitive) input-output characteristic in a certain steady-state regime. Here we systematically study the cycle's steady-state behavior and its response to time-varying stimuli. We demonstrate that the cycle can actually operate in four different regimes, each with its specific input-output characteristics. These results are obtained using the total quasi-steady-state approximation, which is more generally valid than the typically used Michaelis-Menten approximation for enzymatic reactions. We invoke experimental data that suggests the possibility of signaling cycles operating in one of the new regimes. We then consider the cycle's dynamic behavior, which has so far been relatively neglected. We demonstrate that the intrinsic architecture of the cycles makes them act - in all four regimes - as tunable low-pass filters, filtering out high-frequency fluctuations or noise in signals and environmental cues. Moreover, the cutoff frequency can be adjusted by the cell. Numerical simulations show that our analytical results hold well even for noise of large amplitude. We suggest that noise filtering and tunability make signaling cycles versatile components of more elaborate cell signaling pathways.
1810.03317
Nadav M. Shnerb
Yitzhak Yahalom and Nadav M. Shnerb
Phase diagram for a logistic system under bounded stochasticity
null
Phys. Rev. Lett. 122, 108102 (2019)
10.1103/PhysRevLett.122.108102
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Extinction is the ultimate absorbing state of any stochastic birth-death process, hence the time to extinction is an important characteristic of any natural population. Here we consider logistic and logistic-like systems under the combined effect of demographic and bounded environmental stochasticity. Three phases are identified: an inactive phase where the mean time to extinction $T$ increases logarithmically with the initial population size, an active phase where $T$ grows exponentially with the carrying capacity $N$, and temporal Griffiths phase, with power-law relationship between $T$ and $N$. The system supports an exponential phase only when the noise is bounded, in which case the continuum (diffusion) approximation breaks down within the Griffiths phase. This breakdown is associated with a crossover between qualitatively different survival statistics and decline modes. To study the power-law phase we present a new WKB scheme which is applicable both in the diffusive and in the non-diffusive regime.
[ { "created": "Mon, 8 Oct 2018 08:34:34 GMT", "version": "v1" }, { "created": "Sat, 16 Feb 2019 21:55:54 GMT", "version": "v2" } ]
2019-03-27
[ [ "Yahalom", "Yitzhak", "" ], [ "Shnerb", "Nadav M.", "" ] ]
Extinction is the ultimate absorbing state of any stochastic birth-death process, hence the time to extinction is an important characteristic of any natural population. Here we consider logistic and logistic-like systems under the combined effect of demographic and bounded environmental stochasticity. Three phases are identified: an inactive phase where the mean time to extinction $T$ increases logarithmically with the initial population size, an active phase where $T$ grows exponentially with the carrying capacity $N$, and temporal Griffiths phase, with power-law relationship between $T$ and $N$. The system supports an exponential phase only when the noise is bounded, in which case the continuum (diffusion) approximation breaks down within the Griffiths phase. This breakdown is associated with a crossover between qualitatively different survival statistics and decline modes. To study the power-law phase we present a new WKB scheme which is applicable both in the diffusive and in the non-diffusive regime.
1508.04561
Wlodzislaw Duch
W{\l}odzis{\l}aw Duch
Memetics and Neural Models of Conspiracy Theories
14 pages, 7 figures
null
null
null
q-bio.NC cs.AI cs.NE
http://creativecommons.org/licenses/by-nc-sa/4.0/
Conspiracy theories, or in general seriously distorted beliefs, are widespread. How and why are they formed in the brain is still more a matter of speculation rather than science. In this paper one plausible mechanisms is investigated: rapid freezing of high neuroplasticity (RFHN). Emotional arousal increases neuroplasticity and leads to creation of new pathways spreading neural activation. Using the language of neurodynamics a meme is defined as quasi-stable associative memory attractor state. Depending on the temporal characteristics of the incoming information and the plasticity of the network, memory may self-organize creating memes with large attractor basins, linking many unrelated input patterns. Memes with fake rich associations distort relations between memory states. Simulations of various neural network models trained with competitive Hebbian learning (CHL) on stationary and non-stationary data lead to the same conclusion: short learning with high plasticity followed by rapid decrease of plasticity leads to memes with large attraction basins, distorting input pattern representations in associative memory. Such system-level models may be used to understand creation of distorted beliefs and formation of conspiracy memes, understood as strong attractor states of the neurodynamics.
[ { "created": "Wed, 19 Aug 2015 08:20:17 GMT", "version": "v1" }, { "created": "Sun, 17 Jan 2021 17:38:40 GMT", "version": "v2" } ]
2021-01-19
[ [ "Duch", "Włodzisław", "" ] ]
Conspiracy theories, or in general seriously distorted beliefs, are widespread. How and why are they formed in the brain is still more a matter of speculation rather than science. In this paper one plausible mechanisms is investigated: rapid freezing of high neuroplasticity (RFHN). Emotional arousal increases neuroplasticity and leads to creation of new pathways spreading neural activation. Using the language of neurodynamics a meme is defined as quasi-stable associative memory attractor state. Depending on the temporal characteristics of the incoming information and the plasticity of the network, memory may self-organize creating memes with large attractor basins, linking many unrelated input patterns. Memes with fake rich associations distort relations between memory states. Simulations of various neural network models trained with competitive Hebbian learning (CHL) on stationary and non-stationary data lead to the same conclusion: short learning with high plasticity followed by rapid decrease of plasticity leads to memes with large attraction basins, distorting input pattern representations in associative memory. Such system-level models may be used to understand creation of distorted beliefs and formation of conspiracy memes, understood as strong attractor states of the neurodynamics.
2005.13489
Ravi Kiran
Ravi Kiran, Swati Tyagi, Syed Abbas, Madhumita Roy, A. Taraphder
Immunomodulatory role of black tea in the mitigation of cancer induced by inorganic arsenic
23 pages, 15 figures
Eur. Phys. J. Plus (2020) 135: 735
10.1140/epjp/s13360-020-00766-1
null
q-bio.TO q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present a model analysis of the tumor and normal cell growth under the influence of a carcinogenic agent, an immunomdulator (IM) and variable influx of immune cells including relevant interactions. The tumor growth is facilitated by carcinogens such as inorganic arsenic while the IM considered here is black tea (Camellia sinesnsis). The model with variable influx of immune cells is observed to have considerable advantage over the constant influx model, and while the tumor cell population is greatly mitigated, normal cell population remains above healthy levels. The evolution of normal and tumor cells are computed from the proposed model and their local stabilities are investigated analytically. Numerical simulations are performed to study the long term dynamics and an estimation of the effects of various factors is made. This helps in developing a balanced strategy for tumor mitigation without the use of chemotherapeutic drugs that usually have strong side-effects.
[ { "created": "Wed, 27 May 2020 16:52:32 GMT", "version": "v1" }, { "created": "Tue, 29 Sep 2020 12:31:15 GMT", "version": "v2" } ]
2020-09-30
[ [ "Kiran", "Ravi", "" ], [ "Tyagi", "Swati", "" ], [ "Abbas", "Syed", "" ], [ "Roy", "Madhumita", "" ], [ "Taraphder", "A.", "" ] ]
We present a model analysis of the tumor and normal cell growth under the influence of a carcinogenic agent, an immunomdulator (IM) and variable influx of immune cells including relevant interactions. The tumor growth is facilitated by carcinogens such as inorganic arsenic while the IM considered here is black tea (Camellia sinesnsis). The model with variable influx of immune cells is observed to have considerable advantage over the constant influx model, and while the tumor cell population is greatly mitigated, normal cell population remains above healthy levels. The evolution of normal and tumor cells are computed from the proposed model and their local stabilities are investigated analytically. Numerical simulations are performed to study the long term dynamics and an estimation of the effects of various factors is made. This helps in developing a balanced strategy for tumor mitigation without the use of chemotherapeutic drugs that usually have strong side-effects.
1403.7064
Jack Dekker
J.L. Donnelly, D.C. Adams and J. Dekker
Weedy Adaptation in Setaria spp.: VI. S. faberi Seed hull shape as soil germination signal antenna
21 pages, 6 figures, 2 tables
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Ecological selection forces for weedy and domesticated traits have influenced the evolution of seed shape in Setaria resulting in similarity in seed shape that reflects similarity in ecological function rather than reflecting phylogenetic relatedness. Seeds from two diploid subspecies of Setaria viridis, consisting of one weedy subspecies and two races of the domesticated subspecies, and four other polyploidy weedy species of Setaria. We quantified seed shape from the silhouettes of the seeds in two separate views. Differences in shape were compared to ecological role (weed vs. crop) and the evolutionary trajectory of shape change by phylogenetic grouping from a single reference species was calculated. Idealized three-dimensional models were created to examine the differences in shape relative to surface area and volume. All populations were significantly different in shape, with crops easily distinguished from weeds, regardless of relatedness between the taxa. Trajectory of shape change varied by view, but separated crops from weeds and phylogenetic groupings. Three-dimensional models gave further evidence of differences in shape reflecting adaptation for environmental exploitation. The selective forces for weedy and domesticated traits have exceeded phylogenetic constraints, resulting in seed shape similarity due to ecological role rather than phylogenetic relatedness. Seed shape and surface-to-volume ratio likely reflect the importance of the water film that accumulates on the seed surface when in contact with soil particles. Seed shape may also be a mechanism of niche separation between taxa.
[ { "created": "Thu, 27 Mar 2014 15:01:14 GMT", "version": "v1" } ]
2014-03-28
[ [ "Donnelly", "J. L.", "" ], [ "Adams", "D. C.", "" ], [ "Dekker", "J.", "" ] ]
Ecological selection forces for weedy and domesticated traits have influenced the evolution of seed shape in Setaria resulting in similarity in seed shape that reflects similarity in ecological function rather than reflecting phylogenetic relatedness. Seeds from two diploid subspecies of Setaria viridis, consisting of one weedy subspecies and two races of the domesticated subspecies, and four other polyploidy weedy species of Setaria. We quantified seed shape from the silhouettes of the seeds in two separate views. Differences in shape were compared to ecological role (weed vs. crop) and the evolutionary trajectory of shape change by phylogenetic grouping from a single reference species was calculated. Idealized three-dimensional models were created to examine the differences in shape relative to surface area and volume. All populations were significantly different in shape, with crops easily distinguished from weeds, regardless of relatedness between the taxa. Trajectory of shape change varied by view, but separated crops from weeds and phylogenetic groupings. Three-dimensional models gave further evidence of differences in shape reflecting adaptation for environmental exploitation. The selective forces for weedy and domesticated traits have exceeded phylogenetic constraints, resulting in seed shape similarity due to ecological role rather than phylogenetic relatedness. Seed shape and surface-to-volume ratio likely reflect the importance of the water film that accumulates on the seed surface when in contact with soil particles. Seed shape may also be a mechanism of niche separation between taxa.
2210.08542
Malvina Marku
Malvina Marku, Vera Pancaldi
From time-series transcriptomics to gene regulatory networks: a review on inference methods
null
null
null
null
q-bio.MN
http://creativecommons.org/licenses/by-nc-sa/4.0/
Inference of gene regulatory networks has been an active area of research for around 20 years, leading to the development of sophisticated inference algorithms based on a variety of assumptions and approaches. With the always increasing demand for more accurate and powerful models, the inference problem remains of broad scientific interest. The abstract representation of biological systems through gene regulatory networks represents a powerful method to study such systems, encoding different amounts and types of information. In this review, we summarize the different types of inference algorithms specifically based on time-series transcriptomics, giving an overview of the main applications of gene regulatory networks in computational biology. This review is intended to give an updated overview of regulatory networks inference tools to biologists and researchers new to the topic and guide them in selecting the appropriate inference method that best fits their questions, aims and experimental data.
[ { "created": "Sun, 16 Oct 2022 13:59:39 GMT", "version": "v1" }, { "created": "Wed, 2 Nov 2022 15:19:16 GMT", "version": "v2" } ]
2022-11-03
[ [ "Marku", "Malvina", "" ], [ "Pancaldi", "Vera", "" ] ]
Inference of gene regulatory networks has been an active area of research for around 20 years, leading to the development of sophisticated inference algorithms based on a variety of assumptions and approaches. With the always increasing demand for more accurate and powerful models, the inference problem remains of broad scientific interest. The abstract representation of biological systems through gene regulatory networks represents a powerful method to study such systems, encoding different amounts and types of information. In this review, we summarize the different types of inference algorithms specifically based on time-series transcriptomics, giving an overview of the main applications of gene regulatory networks in computational biology. This review is intended to give an updated overview of regulatory networks inference tools to biologists and researchers new to the topic and guide them in selecting the appropriate inference method that best fits their questions, aims and experimental data.
1008.0237
Liaofu Luo
Liaofu Luo
Protein Folding as a Quantum Transition Between Conformational States: Basic Formulas and Applications
24 pages, 3 figures
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The protein folding is regarded as a quantum transition between torsion states on polypeptide chain. The deduction of the folding rate formula in our previous studies is reviewed. The rate formula is generalized to the case of frequency variation in folding. Then the following problems about the application of the rate theory are discussed: 1) The unified theory on the two-state and multi-state protein folding is given based on the concept of quantum transition. 2) The relationship of folding and unfolding rates vs denaturant concentration is studied. 3) The temperature dependence of folding rate is deduced and the non-Arrhenius behaviors of temperature dependence are interpreted in a natural way. 4) The inertial moment dependence of folding rate is calculated based on the model of dynamical contact order and consistent results are obtained by comparison with one-hundred-protein experimental dataset. 5) The exergonic and endergonic foldings are distinguished through the comparison between theoretical and experimental rates for each protein. The ultrafast folding problem is viewed from the point of quantum folding theory and a new folding speed limit is deduced from quantum uncertainty relation. And finally, 6) since only the torsion-accessible states are manageable in the present formulation of quantum transition how the set of torsion-accessible states can be expanded by using statistical energy landscape approach is discussed. All above discussions support the view that the protein folding is essentially a quantum transition between conformational states.
[ { "created": "Mon, 2 Aug 2010 07:00:42 GMT", "version": "v1" }, { "created": "Sun, 22 Aug 2010 07:56:01 GMT", "version": "v2" } ]
2010-08-24
[ [ "Luo", "Liaofu", "" ] ]
The protein folding is regarded as a quantum transition between torsion states on polypeptide chain. The deduction of the folding rate formula in our previous studies is reviewed. The rate formula is generalized to the case of frequency variation in folding. Then the following problems about the application of the rate theory are discussed: 1) The unified theory on the two-state and multi-state protein folding is given based on the concept of quantum transition. 2) The relationship of folding and unfolding rates vs denaturant concentration is studied. 3) The temperature dependence of folding rate is deduced and the non-Arrhenius behaviors of temperature dependence are interpreted in a natural way. 4) The inertial moment dependence of folding rate is calculated based on the model of dynamical contact order and consistent results are obtained by comparison with one-hundred-protein experimental dataset. 5) The exergonic and endergonic foldings are distinguished through the comparison between theoretical and experimental rates for each protein. The ultrafast folding problem is viewed from the point of quantum folding theory and a new folding speed limit is deduced from quantum uncertainty relation. And finally, 6) since only the torsion-accessible states are manageable in the present formulation of quantum transition how the set of torsion-accessible states can be expanded by using statistical energy landscape approach is discussed. All above discussions support the view that the protein folding is essentially a quantum transition between conformational states.
1710.10872
Caroline Gr\"onwall
Caroline Gronwall, Uta Hardt, Johanna T. Gustafsson, Kerstin Elvin, Kerstin Jensen-Urstad, Marika Kvarnstrom, Giorgia Grosso, Johan Ronnelid, Leonid Padyukov, Iva Gunnarsson, Gregg J. Silverman, Elisabet Svenungsson
Depressed serum IgM levels in SLE are restricted to defined subgroups
Clin Immunol. 2017 Sep 15
null
10.1016/j.clim.2017.09.013
null
q-bio.BM q-bio.CB
http://creativecommons.org/licenses/by-nc-sa/4.0/
Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Strikingly, an autoreactivity profile defined by IgG anti-Ro/La was associated with reduced levels of specific natural IgM anti-phosphorylcholine (PC) antigens and anti-malondialdehyde (MDA) modified-protein, as well total IgM, while no differences were detected in SLE patients with an autoreactivity profile defined by anti-cardiolipin/Beta2glycoprotein-I. We also observed an association of reduced IgM levels with the HLA-DRB1*03 allelic variant amongst SLE patients and controls. Associations of low IgM anti-PC with cardiovascular disease were primarily found in patients without antiphospholipid antibodies. These studies further highlight the clinical relevance of depressed IgM. Our results suggest that low IgM levels in SLE patients reflect immunological and genetic differences between SLE subgroups.
[ { "created": "Mon, 30 Oct 2017 11:16:40 GMT", "version": "v1" } ]
2017-10-31
[ [ "Gronwall", "Caroline", "" ], [ "Hardt", "Uta", "" ], [ "Gustafsson", "Johanna T.", "" ], [ "Elvin", "Kerstin", "" ], [ "Jensen-Urstad", "Kerstin", "" ], [ "Kvarnstrom", "Marika", "" ], [ "Grosso", "Giorgia", ...
Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Strikingly, an autoreactivity profile defined by IgG anti-Ro/La was associated with reduced levels of specific natural IgM anti-phosphorylcholine (PC) antigens and anti-malondialdehyde (MDA) modified-protein, as well total IgM, while no differences were detected in SLE patients with an autoreactivity profile defined by anti-cardiolipin/Beta2glycoprotein-I. We also observed an association of reduced IgM levels with the HLA-DRB1*03 allelic variant amongst SLE patients and controls. Associations of low IgM anti-PC with cardiovascular disease were primarily found in patients without antiphospholipid antibodies. These studies further highlight the clinical relevance of depressed IgM. Our results suggest that low IgM levels in SLE patients reflect immunological and genetic differences between SLE subgroups.
2010.14566
Alex McAvoy
Alex McAvoy, John Wakeley
Evaluating the structure-coefficient theorem of evolutionary game theory
52 pages; final version
null
10.1073/pnas.2119656119
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In order to accommodate the empirical fact that population structures are rarely simple, modern studies of evolutionary dynamics allow for complicated and highly-heterogeneous spatial structures. As a result, one of the most difficult obstacles lies in making analytical deductions, either qualitative or quantitative, about the long-term outcomes of evolution. The "structure-coefficient" theorem is a well-known approach to this problem for mutation-selection processes under weak selection, but a general method of evaluating the terms it comprises is lacking. Here, we provide such a method for populations of fixed (but arbitrary) size and structure, using easily interpretable demographic measures. This method encompasses a large family of evolutionary update mechanisms and extends the theorem to allow for asymmetric contests to provide a better understanding of the mutation-selection balance under more realistic circumstances. We apply the method to study social goods produced and distributed among individuals in spatially-heterogeneous populations, where asymmetric interactions emerge naturally and the outcome of selection varies dramatically depending on the nature of the social good, the spatial topology, and frequency with which mutations arise.
[ { "created": "Tue, 27 Oct 2020 19:15:49 GMT", "version": "v1" }, { "created": "Wed, 27 Oct 2021 16:23:13 GMT", "version": "v2" }, { "created": "Thu, 16 Jun 2022 20:42:16 GMT", "version": "v3" } ]
2022-07-07
[ [ "McAvoy", "Alex", "" ], [ "Wakeley", "John", "" ] ]
In order to accommodate the empirical fact that population structures are rarely simple, modern studies of evolutionary dynamics allow for complicated and highly-heterogeneous spatial structures. As a result, one of the most difficult obstacles lies in making analytical deductions, either qualitative or quantitative, about the long-term outcomes of evolution. The "structure-coefficient" theorem is a well-known approach to this problem for mutation-selection processes under weak selection, but a general method of evaluating the terms it comprises is lacking. Here, we provide such a method for populations of fixed (but arbitrary) size and structure, using easily interpretable demographic measures. This method encompasses a large family of evolutionary update mechanisms and extends the theorem to allow for asymmetric contests to provide a better understanding of the mutation-selection balance under more realistic circumstances. We apply the method to study social goods produced and distributed among individuals in spatially-heterogeneous populations, where asymmetric interactions emerge naturally and the outcome of selection varies dramatically depending on the nature of the social good, the spatial topology, and frequency with which mutations arise.
2004.00579
Julian Monge-Najera
Julian Monge-Najera
History of Onychophorology, 1826-2020
null
null
null
null
q-bio.OT
http://creativecommons.org/licenses/by-sa/4.0/
Velvet worms, or onychophorans, are animals of extraordinary importance in the study of evolution. This is the first history of their study. They were described by Lansdown Guilding (1797-1831). This paper identifies the landmarks of their study, in a worldwide level, for almost 200 years. The beginning, 1826-1879, was based on describing their anatomy with light miscroscopy, mostly by famous French naturalists such as Milne-Edwards and Blanchard. In 1880-1929 peiord, work concentrated in anatomy, physiology, behavior, biogeography and ecology, but the most important work was Bouvier`s mammoth monograph. The next period, 1930-1979, was important for the discovery of Cambrian species; Vachons explanation of how ancient distribution defined the existence of two families; Pioneer DNA and electron microscopy from Brazil; and primitive attempts at systematics using embryology or isolated anatomical characteristics. Finally, the 1980-2020 period, with research centered in Australia, Brazil, Costa Rica and Germany, is marked by an evolutionary approach to everything, from body and behavior to distribution; for the solution of the old problem of how they form their adhesive net and how the glue works; the reconstruction of Cambrian onychophoran communities, the first experimental taphonomy; the first countrywide map of conservation status (from Costa Rica); the first model of why they survive in cities; the discovery of new phenomena like food hiding, parental feeding investment and ontogenetic diet shift; and for the birth of a new research branh, Onychophoran Etnobiology, founded in 2015,
[ { "created": "Wed, 1 Apr 2020 17:10:00 GMT", "version": "v1" } ]
2020-04-02
[ [ "Monge-Najera", "Julian", "" ] ]
Velvet worms, or onychophorans, are animals of extraordinary importance in the study of evolution. This is the first history of their study. They were described by Lansdown Guilding (1797-1831). This paper identifies the landmarks of their study, in a worldwide level, for almost 200 years. The beginning, 1826-1879, was based on describing their anatomy with light miscroscopy, mostly by famous French naturalists such as Milne-Edwards and Blanchard. In 1880-1929 peiord, work concentrated in anatomy, physiology, behavior, biogeography and ecology, but the most important work was Bouvier`s mammoth monograph. The next period, 1930-1979, was important for the discovery of Cambrian species; Vachons explanation of how ancient distribution defined the existence of two families; Pioneer DNA and electron microscopy from Brazil; and primitive attempts at systematics using embryology or isolated anatomical characteristics. Finally, the 1980-2020 period, with research centered in Australia, Brazil, Costa Rica and Germany, is marked by an evolutionary approach to everything, from body and behavior to distribution; for the solution of the old problem of how they form their adhesive net and how the glue works; the reconstruction of Cambrian onychophoran communities, the first experimental taphonomy; the first countrywide map of conservation status (from Costa Rica); the first model of why they survive in cities; the discovery of new phenomena like food hiding, parental feeding investment and ontogenetic diet shift; and for the birth of a new research branh, Onychophoran Etnobiology, founded in 2015,
1108.5110
Linlin Su
Linlin Su, Colbert Sesanker, Roger Lui
Coexisting Stable Equilibria in a Multiple-allele Population Genetics Model
29 pages, 11 figures, 6 tables
null
null
null
q-bio.PE math.CA
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this paper we find and classify all patterns for a single locus three- and four-allele population genetics models in continuous time. A pattern for a $k$-allele model means all coexisting locally stable equilibria with respect to the flow defined by the equations $\dot{p}_i = p_i(r_i-r), i=1,...,k,$ where $p_i, r_i$ are the frequency and marginal fitness of allele $A_i$, respectively, and $r$ is the mean fitness of the population. It is well known that for the two-allele model there are only three patterns depending on the relative fitness between the homozygotes and the heterozygote. It turns out that for the three-allele model there are 14 patterns and for the four-allele model there are 117 patterns. With the help of computer simulations, we find 2351 patterns for the five-allele model. For the six-allele model, there are more than 60,000 patterns. In addition, for each pattern of the three-allele model, we also determine the asymptotic behavior of solutions of the above system of equations as $t \to \infty$. The problem of finding patterns has been studied in the past and it is an important problem because the results can be used to predict the long-term genetic makeup of a population.
[ { "created": "Thu, 25 Aug 2011 15:03:28 GMT", "version": "v1" } ]
2011-08-26
[ [ "Su", "Linlin", "" ], [ "Sesanker", "Colbert", "" ], [ "Lui", "Roger", "" ] ]
In this paper we find and classify all patterns for a single locus three- and four-allele population genetics models in continuous time. A pattern for a $k$-allele model means all coexisting locally stable equilibria with respect to the flow defined by the equations $\dot{p}_i = p_i(r_i-r), i=1,...,k,$ where $p_i, r_i$ are the frequency and marginal fitness of allele $A_i$, respectively, and $r$ is the mean fitness of the population. It is well known that for the two-allele model there are only three patterns depending on the relative fitness between the homozygotes and the heterozygote. It turns out that for the three-allele model there are 14 patterns and for the four-allele model there are 117 patterns. With the help of computer simulations, we find 2351 patterns for the five-allele model. For the six-allele model, there are more than 60,000 patterns. In addition, for each pattern of the three-allele model, we also determine the asymptotic behavior of solutions of the above system of equations as $t \to \infty$. The problem of finding patterns has been studied in the past and it is an important problem because the results can be used to predict the long-term genetic makeup of a population.
q-bio/0407008
Axel Brandenburg
Axel Brandenburg and Tuomas Multam\"aki
How Long can Left and Right Handed Life Forms Coexist?
submitted to Int. J. Astrobiol., 15 pages, 10 figs. submitted to Int. J. Astrobiol., 15 pages, 10 figs
Int.J.Astrobiol. 3 (2004) 209-219
10.1017/S1473550404001983
NORDITA-2004-58
q-bio.BM astro-ph cond-mat.dis-nn
null
Reaction-diffusion equations based on a polymerization model are solved to simulate the spreading of hypothetic left and right handed life forms on the Earth's surface. The equations exhibit front-like behavior as is familiar from the theory of the spreading of epidemics. It is shown that the relevant time scale for achieving global homochirality is not, however, the time scale of front propagation, but the much longer global diffusion time. The process can be sped up by turbulence and large scale flows. It is speculated that, if the deep layers of the early ocean were sufficiently quiescent, there may have been the possibility of competing early life forms with opposite handedness.
[ { "created": "Mon, 5 Jul 2004 21:27:06 GMT", "version": "v1" } ]
2007-05-23
[ [ "Brandenburg", "Axel", "" ], [ "Multamäki", "Tuomas", "" ] ]
Reaction-diffusion equations based on a polymerization model are solved to simulate the spreading of hypothetic left and right handed life forms on the Earth's surface. The equations exhibit front-like behavior as is familiar from the theory of the spreading of epidemics. It is shown that the relevant time scale for achieving global homochirality is not, however, the time scale of front propagation, but the much longer global diffusion time. The process can be sped up by turbulence and large scale flows. It is speculated that, if the deep layers of the early ocean were sufficiently quiescent, there may have been the possibility of competing early life forms with opposite handedness.
1704.06301
Veesler Stephane
Charline Gerard (CINaM), Gilles Ferry, Laurent Vuillard, Jean A Boutin, L\'eonard Chavas (SSOLEIL), Tiphaine Huet (SSOLEIL), Nathalie Ferte (CINaM), Romain Grossier (CINaM), Nadine Candoni (CINaM), St\'ephane Veesler (CINaM)
Crystallization via tubing microfluidics permits both in situ and ex situ X-ray diffraction
null
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We used a microfluidic platform to address the problems of obtaining diffraction quality crystals and crystal handling during transfer to the X-ray diffractometer. We optimize crystallization conditions of a pharmaceutical protein and collect X-ray data both in situ and ex situ.
[ { "created": "Wed, 22 Mar 2017 08:09:41 GMT", "version": "v1" } ]
2017-04-24
[ [ "Gerard", "Charline", "", "CINaM" ], [ "Ferry", "Gilles", "", "SSOLEIL" ], [ "Vuillard", "Laurent", "", "SSOLEIL" ], [ "Boutin", "Jean A", "", "SSOLEIL" ], [ "Chavas", "Léonard", "", "SSOLEIL" ], [ "Huet", ...
We used a microfluidic platform to address the problems of obtaining diffraction quality crystals and crystal handling during transfer to the X-ray diffractometer. We optimize crystallization conditions of a pharmaceutical protein and collect X-ray data both in situ and ex situ.
2201.12570
Asif Khan
Asif Khan, Alexander I. Cowen-Rivers, Antoine Grosnit, Derrick-Goh-Xin Deik, Philippe A. Robert, Victor Greiff, Eva Smorodina, Puneet Rawat, Kamil Dreczkowski, Rahmad Akbar, Rasul Tutunov, Dany Bou-Ammar, Jun Wang, Amos Storkey and Haitham Bou-Ammar
AntBO: Towards Real-World Automated Antibody Design with Combinatorial Bayesian Optimisation
null
null
null
null
q-bio.BM cs.AI cs.LG cs.NE stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Antibodies are canonically Y-shaped multimeric proteins capable of highly specific molecular recognition. The CDRH3 region located at the tip of variable chains of an antibody dominates antigen-binding specificity. Therefore, it is a priority to design optimal antigen-specific CDRH3 regions to develop therapeutic antibodies. However, the combinatorial nature of CDRH3 sequence space makes it impossible to search for an optimal binding sequence exhaustively and efficiently using computational approaches. Here, we present \texttt{AntBO}: a combinatorial Bayesian optimisation framework enabling efficient \textit{in silico} design of the CDRH3 region. Ideally, antibodies are expected to have high target specificity and developability. We introduce a CDRH3 trust region that restricts the search to sequences with favourable developability scores to achieve this goal. For benchmarking, \texttt{AntBO} uses the \texttt{Absolut!} software suite as a black-box oracle to score the target specificity and affinity of designed antibodies \textit{in silico} in an unconstrained fashion~\citep{robert2021one}. The experiments performed for $159$ discretised antigens used in \texttt{Absolut!} demonstrate the benefit of \texttt{AntBO} in designing CDRH3 regions with diverse biophysical properties. In under $200$ calls to black-box oracle, \texttt{AntBO} can suggest antibody sequences that outperform the best binding sequence drawn from 6.9 million experimentally obtained CDRH3s and a commonly used genetic algorithm baseline. Additionally, \texttt{AntBO} finds very-high affinity CDRH3 sequences in only 38 protein designs whilst requiring no domain knowledge. We conclude \texttt{AntBO} brings automated antibody design methods closer to what is practically viable for in vitro experimentation.
[ { "created": "Sat, 29 Jan 2022 12:03:04 GMT", "version": "v1" }, { "created": "Wed, 16 Feb 2022 13:08:36 GMT", "version": "v2" }, { "created": "Fri, 11 Mar 2022 09:40:17 GMT", "version": "v3" }, { "created": "Fri, 14 Oct 2022 18:31:22 GMT", "version": "v4" } ]
2022-10-18
[ [ "Khan", "Asif", "" ], [ "Cowen-Rivers", "Alexander I.", "" ], [ "Grosnit", "Antoine", "" ], [ "Deik", "Derrick-Goh-Xin", "" ], [ "Robert", "Philippe A.", "" ], [ "Greiff", "Victor", "" ], [ "Smorodina", "Eva", ...
Antibodies are canonically Y-shaped multimeric proteins capable of highly specific molecular recognition. The CDRH3 region located at the tip of variable chains of an antibody dominates antigen-binding specificity. Therefore, it is a priority to design optimal antigen-specific CDRH3 regions to develop therapeutic antibodies. However, the combinatorial nature of CDRH3 sequence space makes it impossible to search for an optimal binding sequence exhaustively and efficiently using computational approaches. Here, we present \texttt{AntBO}: a combinatorial Bayesian optimisation framework enabling efficient \textit{in silico} design of the CDRH3 region. Ideally, antibodies are expected to have high target specificity and developability. We introduce a CDRH3 trust region that restricts the search to sequences with favourable developability scores to achieve this goal. For benchmarking, \texttt{AntBO} uses the \texttt{Absolut!} software suite as a black-box oracle to score the target specificity and affinity of designed antibodies \textit{in silico} in an unconstrained fashion~\citep{robert2021one}. The experiments performed for $159$ discretised antigens used in \texttt{Absolut!} demonstrate the benefit of \texttt{AntBO} in designing CDRH3 regions with diverse biophysical properties. In under $200$ calls to black-box oracle, \texttt{AntBO} can suggest antibody sequences that outperform the best binding sequence drawn from 6.9 million experimentally obtained CDRH3s and a commonly used genetic algorithm baseline. Additionally, \texttt{AntBO} finds very-high affinity CDRH3 sequences in only 38 protein designs whilst requiring no domain knowledge. We conclude \texttt{AntBO} brings automated antibody design methods closer to what is practically viable for in vitro experimentation.
1501.01469
Vincent Niviere
Julien Valton (LCBM - UMR 5249), Laurent Filisetti, Marc Fontecave (LCBM - UMR 5249), Vincent Nivi\`ere (LCBM - UMR 5249)
A two-component flavin-dependent monooxygenase involved in actinorhodin biosynthesis in Streptomyces coelicolor
null
The journal of biological chemistry, American Society for Biochemistry and Molecular Biology, 2004, 279, pp.44362-9
10.1074/jbc.M407722200
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The two-component flavin-dependent monooxygenases belong to an emerging class of enzymes involved in oxidation reactions in a number of metabolic and biosynthetic pathways in microorganisms. One component is a NAD(P)H:flavin oxidoreductase, which provides a reduced flavin to the second component, the proper monooxygenase. There, the reduced flavin activates molecular oxygen for substrate oxidation. Here, we study the flavin reductase ActVB and ActVA-ORF5 gene product, both reported to be involved in the last step of biosynthesis of the natural antibiotic actinorhodin in Streptomyces coelicolor. For the first time we show that ActVA-ORF5 is a FMN-dependent monooxygenase that together with the help of the flavin reductase ActVB catalyzes the oxidation reaction. The mechanism of the transfer of reduced FMN between ActVB and ActVA-ORF5 has been investigated. Dissociation constant values for oxidized and reduced flavin (FMNox and FMNred) with regard to ActVB and ActVA-ORF5 have been determined. The data clearly demonstrate a thermodynamic transfer of FMNred from ActVB to ActVA-ORF5 without involving a particular interaction between the two protein components. In full agreement with these data, we propose a reaction mechanism in which FMNox binds to ActVB, where it is reduced, and the resulting FMNred moves to ActVA-ORF5, where it reacts with O2 to generate a flavinperoxide intermediate. A direct spectroscopic evidence for the formation of such species within ActVA-ORF5 is reported.
[ { "created": "Wed, 7 Jan 2015 12:42:09 GMT", "version": "v1" } ]
2015-01-08
[ [ "Valton", "Julien", "", "LCBM - UMR 5249" ], [ "Filisetti", "Laurent", "", "LCBM - UMR 5249" ], [ "Fontecave", "Marc", "", "LCBM - UMR 5249" ], [ "Nivière", "Vincent", "", "LCBM - UMR 5249" ] ]
The two-component flavin-dependent monooxygenases belong to an emerging class of enzymes involved in oxidation reactions in a number of metabolic and biosynthetic pathways in microorganisms. One component is a NAD(P)H:flavin oxidoreductase, which provides a reduced flavin to the second component, the proper monooxygenase. There, the reduced flavin activates molecular oxygen for substrate oxidation. Here, we study the flavin reductase ActVB and ActVA-ORF5 gene product, both reported to be involved in the last step of biosynthesis of the natural antibiotic actinorhodin in Streptomyces coelicolor. For the first time we show that ActVA-ORF5 is a FMN-dependent monooxygenase that together with the help of the flavin reductase ActVB catalyzes the oxidation reaction. The mechanism of the transfer of reduced FMN between ActVB and ActVA-ORF5 has been investigated. Dissociation constant values for oxidized and reduced flavin (FMNox and FMNred) with regard to ActVB and ActVA-ORF5 have been determined. The data clearly demonstrate a thermodynamic transfer of FMNred from ActVB to ActVA-ORF5 without involving a particular interaction between the two protein components. In full agreement with these data, we propose a reaction mechanism in which FMNox binds to ActVB, where it is reduced, and the resulting FMNred moves to ActVA-ORF5, where it reacts with O2 to generate a flavinperoxide intermediate. A direct spectroscopic evidence for the formation of such species within ActVA-ORF5 is reported.
1911.05895
Duncan Kirby
Duncan Kirby, Jeremy Rothschild, Matthew Smart and Anton Zilman
Pleiotropy enables specific and accurate signaling in the presence of ligand cross talk
null
Phys. Rev. E 103, 042401 (2021)
10.1103/PhysRevE.103.042401
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Living cells sense their environment through the binding of extra-cellular molecular ligands to cell surface receptors. Puzzlingly, vast numbers of signaling pathways exhibit a high degree of cross talk between different signals whereby different ligands act through the same receptor or shared components downstream. It remains unclear how a cell can accurately process information from the environment in such cross-wired pathways. We show that a feature which commonly accompanies cross talk - signaling pleiotropy (the ability of a receptor to produce multiple outputs) - offers a solution to the cross talk problem. In a minimal model we show that a single pleiotropic receptor can simultaneously identify and accurately sense the concentrations of arbitrary unknown ligands present individually or in a mixture. We calculate the fundamental limits of the signaling specificity and accuracy of such signaling schemes. The model serves as an elementary "building block" towards understanding more complex cross-wired receptor-ligand signaling networks.
[ { "created": "Thu, 14 Nov 2019 02:09:27 GMT", "version": "v1" }, { "created": "Wed, 3 Mar 2021 17:00:26 GMT", "version": "v2" }, { "created": "Thu, 11 Mar 2021 21:26:18 GMT", "version": "v3" }, { "created": "Fri, 2 Apr 2021 00:59:20 GMT", "version": "v4" } ]
2021-04-07
[ [ "Kirby", "Duncan", "" ], [ "Rothschild", "Jeremy", "" ], [ "Smart", "Matthew", "" ], [ "Zilman", "Anton", "" ] ]
Living cells sense their environment through the binding of extra-cellular molecular ligands to cell surface receptors. Puzzlingly, vast numbers of signaling pathways exhibit a high degree of cross talk between different signals whereby different ligands act through the same receptor or shared components downstream. It remains unclear how a cell can accurately process information from the environment in such cross-wired pathways. We show that a feature which commonly accompanies cross talk - signaling pleiotropy (the ability of a receptor to produce multiple outputs) - offers a solution to the cross talk problem. In a minimal model we show that a single pleiotropic receptor can simultaneously identify and accurately sense the concentrations of arbitrary unknown ligands present individually or in a mixture. We calculate the fundamental limits of the signaling specificity and accuracy of such signaling schemes. The model serves as an elementary "building block" towards understanding more complex cross-wired receptor-ligand signaling networks.
2407.17938
Ninad Aithal
Debanjali Bhattacharya, Ninad Aithal, Manish Jayswal and Neelam Sinha
Analyzing Brain Tumor Connectomics using Graphs and Persistent Homology
15 Pages, 7 Figures, 2 Tables, TGI3-MICCAI Workshop
null
null
null
q-bio.NC cs.CV math.AT
http://creativecommons.org/licenses/by-nc-nd/4.0/
Recent advances in molecular and genetic research have identified a diverse range of brain tumor sub-types, shedding light on differences in their molecular mechanisms, heterogeneity, and origins. The present study performs whole-brain connectome analysis using diffusionweighted images. To achieve this, both graph theory and persistent homology - a prominent approach in topological data analysis are employed in order to quantify changes in the structural connectivity of the wholebrain connectome in subjects with brain tumors. Probabilistic tractography is used to map the number of streamlines connecting 84 distinct brain regions, as delineated by the Desikan-Killiany atlas from FreeSurfer. These streamline mappings form the connectome matrix, on which persistent homology based analysis and graph theoretical analysis are executed to evaluate the discriminatory power between tumor sub-types that include meningioma and glioma. A detailed statistical analysis is conducted on persistent homology-derived topological features and graphical features to identify the brain regions where differences between study groups are statistically significant (p < 0.05). For classification purpose, graph-based local features are utilized, achieving a highest accuracy of 88%. In classifying tumor sub-types, an accuracy of 80% is attained. The findings obtained from this study underscore the potential of persistent homology and graph theoretical analysis of the whole-brain connectome in detecting alterations in structural connectivity patterns specific to different types of brain tumors.
[ { "created": "Thu, 25 Jul 2024 10:55:19 GMT", "version": "v1" } ]
2024-07-26
[ [ "Bhattacharya", "Debanjali", "" ], [ "Aithal", "Ninad", "" ], [ "Jayswal", "Manish", "" ], [ "Sinha", "Neelam", "" ] ]
Recent advances in molecular and genetic research have identified a diverse range of brain tumor sub-types, shedding light on differences in their molecular mechanisms, heterogeneity, and origins. The present study performs whole-brain connectome analysis using diffusionweighted images. To achieve this, both graph theory and persistent homology - a prominent approach in topological data analysis are employed in order to quantify changes in the structural connectivity of the wholebrain connectome in subjects with brain tumors. Probabilistic tractography is used to map the number of streamlines connecting 84 distinct brain regions, as delineated by the Desikan-Killiany atlas from FreeSurfer. These streamline mappings form the connectome matrix, on which persistent homology based analysis and graph theoretical analysis are executed to evaluate the discriminatory power between tumor sub-types that include meningioma and glioma. A detailed statistical analysis is conducted on persistent homology-derived topological features and graphical features to identify the brain regions where differences between study groups are statistically significant (p < 0.05). For classification purpose, graph-based local features are utilized, achieving a highest accuracy of 88%. In classifying tumor sub-types, an accuracy of 80% is attained. The findings obtained from this study underscore the potential of persistent homology and graph theoretical analysis of the whole-brain connectome in detecting alterations in structural connectivity patterns specific to different types of brain tumors.
1605.01661
Ramon Ferrer-i-Cancho
R. Ferrer-i-Cancho, D. Lusseau and B. McCowan
Parallels of human language in the behavior of bottlenose dolphins
In press in Linguistic Frontiers
Linguistic Frontiers (2022) 5(1), 1-7
10.2478/lf-2022-0002
null
q-bio.NC cs.CL
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A short review of similarities between dolphins and humans with the help of quantitative linguistics and information theory.
[ { "created": "Thu, 5 May 2016 17:38:42 GMT", "version": "v1" }, { "created": "Fri, 25 Mar 2022 09:06:07 GMT", "version": "v2" } ]
2022-09-22
[ [ "Ferrer-i-Cancho", "R.", "" ], [ "Lusseau", "D.", "" ], [ "McCowan", "B.", "" ] ]
A short review of similarities between dolphins and humans with the help of quantitative linguistics and information theory.
2108.09747
Vikram Singh
Neha Choudhary and Vikram Singh
Neuromodulators in food ingredients: insights from network pharmacological evaluation of Ayurvedic herbs
22 pages, 6 figures
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by-nc-nd/4.0/
The global burden of neurological diseases, the second leading cause of death after heart dis-eases constitutes one of the major challenges of modern medicine. Ayurveda, the traditional Indian medicinal systemenrooted in the Vedic literature and considered as a schema for the holistic management of health, characterizes various neurological diseases disorders (NDDs) and prescribes several herbs, formulations, and bio-cleansing regimes for their care and cure. In this work, we examined neuro-phytoregulatory potential of 34,472 phytochemicals among 3,038 herbs (including their varieties) mentioned in Ayurveda using network pharmacology approach and found that 45% of these Ayurvedic phytochemicals (APCs) have regulatory associations with 1,643 approved protein targets. Metabolite interconversion enzymes and protein modifying enzymes were found to be the major target classes of APCs against NDDs. The study further suggests that the actions of Ayurvedic herbs in managing NDDs were majorly via regulating signalling processes, like, G-protein signaling, acetylcholine signaling, chemokine signaling pathway and GnRH signaling. A high confidence network specific to 219 pharmaceutically relevant neuro-phytoregulators (NPRs) from 1,197 Ayurvedic herbs against 102 approved protein-targets involved in NDDs was developed and analyzed for gaining mechanistic insights. The key protein targets of NPRs to elicit their neuro-regulatory effect were highlighted as CYP and TRPA, while estradiol and melatonin were identified as the NPRs with high multi-targeting ability. 32 herbs enriched in NPRs were identified that include some of the well-known Ayurvedic neurological recommendations, like, Papaver somniferum, Glycyrrhiza glabra, Citrus aurantium, Cannabis sativa etc. Herbs enriched in NPRs may be used as a chemical source library for drug-discovery against NDDs from systems medicine perspectives.
[ { "created": "Sun, 22 Aug 2021 15:05:16 GMT", "version": "v1" } ]
2021-08-24
[ [ "Choudhary", "Neha", "" ], [ "Singh", "Vikram", "" ] ]
The global burden of neurological diseases, the second leading cause of death after heart dis-eases constitutes one of the major challenges of modern medicine. Ayurveda, the traditional Indian medicinal systemenrooted in the Vedic literature and considered as a schema for the holistic management of health, characterizes various neurological diseases disorders (NDDs) and prescribes several herbs, formulations, and bio-cleansing regimes for their care and cure. In this work, we examined neuro-phytoregulatory potential of 34,472 phytochemicals among 3,038 herbs (including their varieties) mentioned in Ayurveda using network pharmacology approach and found that 45% of these Ayurvedic phytochemicals (APCs) have regulatory associations with 1,643 approved protein targets. Metabolite interconversion enzymes and protein modifying enzymes were found to be the major target classes of APCs against NDDs. The study further suggests that the actions of Ayurvedic herbs in managing NDDs were majorly via regulating signalling processes, like, G-protein signaling, acetylcholine signaling, chemokine signaling pathway and GnRH signaling. A high confidence network specific to 219 pharmaceutically relevant neuro-phytoregulators (NPRs) from 1,197 Ayurvedic herbs against 102 approved protein-targets involved in NDDs was developed and analyzed for gaining mechanistic insights. The key protein targets of NPRs to elicit their neuro-regulatory effect were highlighted as CYP and TRPA, while estradiol and melatonin were identified as the NPRs with high multi-targeting ability. 32 herbs enriched in NPRs were identified that include some of the well-known Ayurvedic neurological recommendations, like, Papaver somniferum, Glycyrrhiza glabra, Citrus aurantium, Cannabis sativa etc. Herbs enriched in NPRs may be used as a chemical source library for drug-discovery against NDDs from systems medicine perspectives.
2205.05143
Nicholas Fuhr
Nicholas E. Fuhr, Mohamed Azize, David J. Bishop
Coronavirus RNA Sensor Using Single-Stranded DNA Bonded to Sub-Percolated Gold Films on Monolayer Graphene Field-Effect Transistors
15 pages, 6 figures Keywords: transcriptome, virus, monolayer graphene, percolated gold, 2DEG, field-effect transistor
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by/4.0/
Electrical detection of messenger ribonucleic acid (mRNA) is a promising approach to enhancing transcriptomics and disease diagnostics because of its sensitivity, rapidity, and modularity. Reported here is a fast SARS-CoV-2 mRNA biosensor (<1 minute) with a limit of detection of 1 aM, and dynamic range of 4 orders of magnitude and a linear sensitivity of 22 mV per molar decade. These figures of merit were obtained on photoresistlessly patterned monolayer graphene field-effect transistors (FETs) derived from commercial four-inch graphene on 90 nm of silicon dioxide on p-type silicon. Then, to facilitate mRNA hybridization, graphene sensing mesa were coated with an ultrathin sub-percolation threshold gold film for bonding 3'-thiolated single-stranded deoxyribonucleic acid (ssDNA) probes complementary to SARS-CoV-2 nucleocapsid phosphoprotein (N) gene. Sub-percolated gold was used to minimize the distance between the graphene material and surface hybridization events. The liquid-transfer characteristics of the graphene FETs repeatedly shows correlation between the Dirac voltage and the copy number of polynucleotide. Ultrathin percolated gold films on graphene FETs facilitate two-dimensional electron gas (2DEG) mRNA biosensors for transcriptomic profiling.
[ { "created": "Tue, 10 May 2022 19:51:02 GMT", "version": "v1" } ]
2022-05-12
[ [ "Fuhr", "Nicholas E.", "" ], [ "Azize", "Mohamed", "" ], [ "Bishop", "David J.", "" ] ]
Electrical detection of messenger ribonucleic acid (mRNA) is a promising approach to enhancing transcriptomics and disease diagnostics because of its sensitivity, rapidity, and modularity. Reported here is a fast SARS-CoV-2 mRNA biosensor (<1 minute) with a limit of detection of 1 aM, and dynamic range of 4 orders of magnitude and a linear sensitivity of 22 mV per molar decade. These figures of merit were obtained on photoresistlessly patterned monolayer graphene field-effect transistors (FETs) derived from commercial four-inch graphene on 90 nm of silicon dioxide on p-type silicon. Then, to facilitate mRNA hybridization, graphene sensing mesa were coated with an ultrathin sub-percolation threshold gold film for bonding 3'-thiolated single-stranded deoxyribonucleic acid (ssDNA) probes complementary to SARS-CoV-2 nucleocapsid phosphoprotein (N) gene. Sub-percolated gold was used to minimize the distance between the graphene material and surface hybridization events. The liquid-transfer characteristics of the graphene FETs repeatedly shows correlation between the Dirac voltage and the copy number of polynucleotide. Ultrathin percolated gold films on graphene FETs facilitate two-dimensional electron gas (2DEG) mRNA biosensors for transcriptomic profiling.
q-bio/0606042
Frank M. Hilker
Frank M. Hilker, Frank H. Westerhoff
Preventing extinction and outbreaks in chaotic populations
10 pages, 6 figures
American Naturalist 170, 232-241 (2007)
10.1086/518949
null
q-bio.PE nlin.CD
null
Interactions in ecological communities are inherently nonlinear and can lead to complex population dynamics including irregular fluctuations induced by chaos. Chaotic population dynamics can exhibit violent oscillations with extremely small or large population abundances that might cause extinction and recurrent outbreaks, respectively. We present a simple method that can guide management efforts to prevent crashes, peaks, or any other undesirable state. At the same time, the irregularity of the dynamics can be preserved when chaos is desirable for the population. The control scheme is easy to implement because it relies on time series information only. The method is illustrated by two examples: control of crashes in the Ricker map and control of outbreaks in a stage-structured model of the flour beetle Tribolium. It turns out to be effective even with few available data and in the presence of noise, as is typical for ecological settings.
[ { "created": "Fri, 30 Jun 2006 18:11:27 GMT", "version": "v1" }, { "created": "Thu, 20 Jul 2006 10:19:48 GMT", "version": "v2" }, { "created": "Thu, 21 Sep 2006 01:38:39 GMT", "version": "v3" }, { "created": "Wed, 29 Aug 2007 17:56:24 GMT", "version": "v4" } ]
2007-08-29
[ [ "Hilker", "Frank M.", "" ], [ "Westerhoff", "Frank H.", "" ] ]
Interactions in ecological communities are inherently nonlinear and can lead to complex population dynamics including irregular fluctuations induced by chaos. Chaotic population dynamics can exhibit violent oscillations with extremely small or large population abundances that might cause extinction and recurrent outbreaks, respectively. We present a simple method that can guide management efforts to prevent crashes, peaks, or any other undesirable state. At the same time, the irregularity of the dynamics can be preserved when chaos is desirable for the population. The control scheme is easy to implement because it relies on time series information only. The method is illustrated by two examples: control of crashes in the Ricker map and control of outbreaks in a stage-structured model of the flour beetle Tribolium. It turns out to be effective even with few available data and in the presence of noise, as is typical for ecological settings.
1002.1428
Krishnakumar Garikipati
H Narayanan, S N Verner, K.L. Mills, R. Kemkemer and K. Garikipati
In silico estimates of the free energy rates in growing tumor spheroids
27 pages with 5 figures and 2 tables. Figures and tables appear at the end of the paper
Journal of Physics: Condensed Matter, Special Issue on Cell-Substrate Interactions. 22 (2010), 194122.
10.1088/0953-8984/22/19/194122
null
q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The physics of solid tumor growth can be considered at three distinct size scales: the tumor scale, the cell-extracellular matrix (ECM) scale and the sub-cellular scale. In this paper we consider the tumor scale in the interest of eventually developing a system-level understanding of the progression of cancer. At this scale, cell populations and chemical species are best treated as concentration fields that vary with time and space. The cells have chemo-mechanical interactions with each other and with the ECM, consume glucose and oxygen that are transported through the tumor, and create chemical byproducts. We present a continuum mathematical model for the biochemical dynamics and mechanics that govern tumor growth. The biochemical dynamics and mechanics also engender free energy changes that serve as universal measures for comparison of these processes. Within our mathematical framework we therefore consider the free energy inequality, which arises from the first and second laws of thermodynamics. With the model we compute preliminary estimates of the free energy rates of a growing tumor in its pre-vascular stage by using currently available data from single cells and multicellular tumor spheroids.
[ { "created": "Sun, 7 Feb 2010 04:06:14 GMT", "version": "v1" }, { "created": "Mon, 26 Apr 2010 16:18:23 GMT", "version": "v2" } ]
2010-04-27
[ [ "Narayanan", "H", "" ], [ "Verner", "S N", "" ], [ "Mills", "K. L.", "" ], [ "Kemkemer", "R.", "" ], [ "Garikipati", "K.", "" ] ]
The physics of solid tumor growth can be considered at three distinct size scales: the tumor scale, the cell-extracellular matrix (ECM) scale and the sub-cellular scale. In this paper we consider the tumor scale in the interest of eventually developing a system-level understanding of the progression of cancer. At this scale, cell populations and chemical species are best treated as concentration fields that vary with time and space. The cells have chemo-mechanical interactions with each other and with the ECM, consume glucose and oxygen that are transported through the tumor, and create chemical byproducts. We present a continuum mathematical model for the biochemical dynamics and mechanics that govern tumor growth. The biochemical dynamics and mechanics also engender free energy changes that serve as universal measures for comparison of these processes. Within our mathematical framework we therefore consider the free energy inequality, which arises from the first and second laws of thermodynamics. With the model we compute preliminary estimates of the free energy rates of a growing tumor in its pre-vascular stage by using currently available data from single cells and multicellular tumor spheroids.
1312.0570
Mikhail Tikhonov
Mikhail Tikhonov, Robert W. Leach and Ned S. Wingreen
Interpreting 16S metagenomic data without clustering to achieve sub-OTU resolution
Updated to match the published version. 12 pages, 5 figures + supplement. Significantly revised for clarity, references added, results not changed
The ISME Journal (2015) 9, 68-80
10.1038/ismej.2014.117
null
q-bio.QM q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The standard approach to analyzing 16S tag sequence data, which relies on clustering reads by sequence similarity into Operational Taxonomic Units (OTUs), underexploits the accuracy of modern sequencing technology. We present a clustering-free approach to multi-sample Illumina datasets that can identify independent bacterial subpopulations regardless of the similarity of their 16S tag sequences. Using published data from a longitudinal time-series study of human tongue microbiota, we are able to resolve within standard 97% similarity OTUs up to 20 distinct subpopulations, all ecologically distinct but with 16S tags differing by as little as 1 nucleotide (99.2% similarity). A comparative analysis of oral communities of two cohabiting individuals reveals that most such subpopulations are shared between the two communities at 100% sequence identity, and that dynamical similarity between subpopulations in one host is strongly predictive of dynamical similarity between the same subpopulations in the other host. Our method can also be applied to samples collected in cross-sectional studies and can be used with the 454 sequencing platform. We discuss how the sub-OTU resolution of our approach can provide new insight into factors shaping community assembly.
[ { "created": "Mon, 2 Dec 2013 19:58:41 GMT", "version": "v1" }, { "created": "Thu, 29 Jan 2015 00:13:16 GMT", "version": "v2" } ]
2015-01-30
[ [ "Tikhonov", "Mikhail", "" ], [ "Leach", "Robert W.", "" ], [ "Wingreen", "Ned S.", "" ] ]
The standard approach to analyzing 16S tag sequence data, which relies on clustering reads by sequence similarity into Operational Taxonomic Units (OTUs), underexploits the accuracy of modern sequencing technology. We present a clustering-free approach to multi-sample Illumina datasets that can identify independent bacterial subpopulations regardless of the similarity of their 16S tag sequences. Using published data from a longitudinal time-series study of human tongue microbiota, we are able to resolve within standard 97% similarity OTUs up to 20 distinct subpopulations, all ecologically distinct but with 16S tags differing by as little as 1 nucleotide (99.2% similarity). A comparative analysis of oral communities of two cohabiting individuals reveals that most such subpopulations are shared between the two communities at 100% sequence identity, and that dynamical similarity between subpopulations in one host is strongly predictive of dynamical similarity between the same subpopulations in the other host. Our method can also be applied to samples collected in cross-sectional studies and can be used with the 454 sequencing platform. We discuss how the sub-OTU resolution of our approach can provide new insight into factors shaping community assembly.
0908.1960
Moritz Helias
M. Helias, M. Deger, S. Rotter, M. Diesmann
A Fokker-Planck formalism for diffusion with finite increments and absorbing boundaries
Consists of two parts: main article (3 figures) plus supplementary text (3 extra figures)
null
10.1371/journal.pcbi.1000929
null
q-bio.QM q-bio.OT q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Gaussian white noise is frequently used to model fluctuations in physical systems. In Fokker-Planck theory, this leads to a vanishing probability density near the absorbing boundary of threshold models. Here we derive the boundary condition for the stationary density of a first-order stochastic differential equation for additive finite-grained Poisson noise and show that the response properties of threshold units are qualitatively altered. Applied to the integrate-and-fire neuron model, the response turns out to be instantaneous rather than exhibiting low-pass characteristics, highly non-linear, and asymmetric for excitation and inhibition. The novel mechanism is exhibited on the network level and is a generic property of pulse-coupled systems of threshold units.
[ { "created": "Thu, 13 Aug 2009 19:18:49 GMT", "version": "v1" }, { "created": "Thu, 13 Aug 2009 21:24:01 GMT", "version": "v2" }, { "created": "Fri, 13 Nov 2009 05:58:02 GMT", "version": "v3" } ]
2010-09-17
[ [ "Helias", "M.", "" ], [ "Deger", "M.", "" ], [ "Rotter", "S.", "" ], [ "Diesmann", "M.", "" ] ]
Gaussian white noise is frequently used to model fluctuations in physical systems. In Fokker-Planck theory, this leads to a vanishing probability density near the absorbing boundary of threshold models. Here we derive the boundary condition for the stationary density of a first-order stochastic differential equation for additive finite-grained Poisson noise and show that the response properties of threshold units are qualitatively altered. Applied to the integrate-and-fire neuron model, the response turns out to be instantaneous rather than exhibiting low-pass characteristics, highly non-linear, and asymmetric for excitation and inhibition. The novel mechanism is exhibited on the network level and is a generic property of pulse-coupled systems of threshold units.
2011.06837
Rapha\"el Candelier
Benjamin Gallois and Rapha\"el Candelier
FastTrack: an open-source software for tracking varying numbers of deformable objects
null
null
10.1371/journal.pcbi.1008697
null
q-bio.QM cs.CV
http://creativecommons.org/licenses/by/4.0/
Analyzing the dynamical properties of mobile objects requires to extract trajectories from recordings, which is often done by tracking movies. We compiled a database of two-dimensional movies for very different biological and physical systems spanning a wide range of length scales and developed a general-purpose, optimized, open-source, cross-platform, easy to install and use, self-updating software called FastTrack. It can handle a changing number of deformable objects in a region of interest, and is particularly suitable for animal and cell tracking in two-dimensions. Furthermore, we introduce the probability of incursions as a new measure of a movie's trackability that doesn't require the knowledge of ground truth trajectories, since it is resilient to small amounts of errors and can be computed on the basis of an ad hoc tracking. We also leveraged the versatility and speed of FastTrack to implement an iterative algorithm determining a set of nearly-optimized tracking parameters -- yet further reducing the amount of human intervention -- and demonstrate that FastTrack can be used to explore the space of tracking parameters to optimize the number of swaps for a batch of similar movies. A benchmark shows that FastTrack is orders of magnitude faster than state-of-the-art tracking algorithms, with a comparable tracking accuracy. The source code is available under the GNU GPLv3 at https://github.com/FastTrackOrg/FastTrack and pre-compiled binaries for Windows, Mac and Linux are available at http://www.fasttrack.sh.
[ { "created": "Fri, 13 Nov 2020 09:52:58 GMT", "version": "v1" } ]
2021-06-09
[ [ "Gallois", "Benjamin", "" ], [ "Candelier", "Raphaël", "" ] ]
Analyzing the dynamical properties of mobile objects requires to extract trajectories from recordings, which is often done by tracking movies. We compiled a database of two-dimensional movies for very different biological and physical systems spanning a wide range of length scales and developed a general-purpose, optimized, open-source, cross-platform, easy to install and use, self-updating software called FastTrack. It can handle a changing number of deformable objects in a region of interest, and is particularly suitable for animal and cell tracking in two-dimensions. Furthermore, we introduce the probability of incursions as a new measure of a movie's trackability that doesn't require the knowledge of ground truth trajectories, since it is resilient to small amounts of errors and can be computed on the basis of an ad hoc tracking. We also leveraged the versatility and speed of FastTrack to implement an iterative algorithm determining a set of nearly-optimized tracking parameters -- yet further reducing the amount of human intervention -- and demonstrate that FastTrack can be used to explore the space of tracking parameters to optimize the number of swaps for a batch of similar movies. A benchmark shows that FastTrack is orders of magnitude faster than state-of-the-art tracking algorithms, with a comparable tracking accuracy. The source code is available under the GNU GPLv3 at https://github.com/FastTrackOrg/FastTrack and pre-compiled binaries for Windows, Mac and Linux are available at http://www.fasttrack.sh.
q-bio/0605023
Tihamer Geyer
Tihamer Geyer
Form follows function -- how PufX increases the efficiency of the light-harvesting complexes of Rhodobacter sphaeroides
Mostly rewritten and shortened text, now also deals with thermal disorder, more focussed on the biological relevance of the results. 16 pages LaTeX article, 7 figures. Submitted to Biophys. J
null
null
null
q-bio.QM
null
Some species of purple bacteria as, e.g., Rhodobacter sphaeroides contain the protein PufX. Concurrently, the light harvesting complexes 1 (LH1) form dimers of open rings. In mutants without PufX, the LH1s are closed rings and photosynthesis breaks down, because the ubiquinone exchange at the reaction center is blocked. Thus, PufX is regarded essential for quinone exchange. In contrast to this view, which implicitly treats the LH1s as obstacles to photosynthesis, we propose that the primary purpose of PufX is to improve the efficiency of light harvesting by inducing the LH1 dimerization. Calculations with a dipole model, which compare the photosynthetic efficiency of various configurations of monomeric and dimeric core complexes, show that the dimer can absorb photons directly into the RC about 30% more efficient, when related to the number of bacteriochlorophylls, but that the performance of the more sophisticated dimeric LH1 antenna degrades faster with structural perturbations. The calculations predict an optimal orientation of the reaction centers relative to the LH1 dimer, which agrees well with the experimentally found configuration. For the increased required rigidity of the dimer additional modifications of the LH1 subunits are necessary, which would lead to the observed ubiquinone blockage, when PufX is missing.
[ { "created": "Tue, 16 May 2006 12:17:06 GMT", "version": "v1" }, { "created": "Fri, 16 Mar 2007 14:42:40 GMT", "version": "v2" } ]
2007-05-23
[ [ "Geyer", "Tihamer", "" ] ]
Some species of purple bacteria as, e.g., Rhodobacter sphaeroides contain the protein PufX. Concurrently, the light harvesting complexes 1 (LH1) form dimers of open rings. In mutants without PufX, the LH1s are closed rings and photosynthesis breaks down, because the ubiquinone exchange at the reaction center is blocked. Thus, PufX is regarded essential for quinone exchange. In contrast to this view, which implicitly treats the LH1s as obstacles to photosynthesis, we propose that the primary purpose of PufX is to improve the efficiency of light harvesting by inducing the LH1 dimerization. Calculations with a dipole model, which compare the photosynthetic efficiency of various configurations of monomeric and dimeric core complexes, show that the dimer can absorb photons directly into the RC about 30% more efficient, when related to the number of bacteriochlorophylls, but that the performance of the more sophisticated dimeric LH1 antenna degrades faster with structural perturbations. The calculations predict an optimal orientation of the reaction centers relative to the LH1 dimer, which agrees well with the experimentally found configuration. For the increased required rigidity of the dimer additional modifications of the LH1 subunits are necessary, which would lead to the observed ubiquinone blockage, when PufX is missing.
2201.03164
Yue Wang
Yue Wang, Siqi He
Inference on autoregulation in gene expression
null
null
null
null
q-bio.MN
http://creativecommons.org/licenses/by/4.0/
Some genes can promote or repress their own expressions, which is called autoregulation. Although gene regulation is a central topic in biology, autoregulation is much less studied. In general, it is extremely difficult to determine the existence of autoregulation with direct biochemical approaches. Nevertheless, some papers have observed that certain types of autoregulations are linked to noise levels in gene expression. We generalize these results by two propositions on discrete-state continuous-time Markov chains. These two propositions form a simple but robust method to infer the existence of autoregulation from gene expression data. This method only needs to compare the mean and variance of the gene expression level. Compared to other methods for inferring autoregulation, our method only requires non-interventional one-time data, and does not need to estimate parameters. Besides, our method has few restrictions on the model. We apply this method to four groups of experimental data and find some genes that might have autoregulation. Some inferred autoregulations have been verified by experiments or other theoretical works.
[ { "created": "Mon, 10 Jan 2022 05:18:37 GMT", "version": "v1" }, { "created": "Tue, 18 Jan 2022 20:51:09 GMT", "version": "v2" }, { "created": "Wed, 23 Mar 2022 04:30:43 GMT", "version": "v3" }, { "created": "Sat, 2 Jul 2022 00:48:53 GMT", "version": "v4" }, { "cr...
2022-08-30
[ [ "Wang", "Yue", "" ], [ "He", "Siqi", "" ] ]
Some genes can promote or repress their own expressions, which is called autoregulation. Although gene regulation is a central topic in biology, autoregulation is much less studied. In general, it is extremely difficult to determine the existence of autoregulation with direct biochemical approaches. Nevertheless, some papers have observed that certain types of autoregulations are linked to noise levels in gene expression. We generalize these results by two propositions on discrete-state continuous-time Markov chains. These two propositions form a simple but robust method to infer the existence of autoregulation from gene expression data. This method only needs to compare the mean and variance of the gene expression level. Compared to other methods for inferring autoregulation, our method only requires non-interventional one-time data, and does not need to estimate parameters. Besides, our method has few restrictions on the model. We apply this method to four groups of experimental data and find some genes that might have autoregulation. Some inferred autoregulations have been verified by experiments or other theoretical works.
1101.3983
Lipi Acharya
Lipi Acharya, Thair Judeh, Zhansheng Duan, Michael Rabbat and Dongxiao Zhu
GSGS: A Computational Framework to Reconstruct Signaling Pathways from Gene Sets
null
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We propose a novel two-stage Gene Set Gibbs Sampling (GSGS) framework, to reverse engineer signaling pathways from gene sets inferred from molecular profiling data. We hypothesize that signaling pathways are structurally an ensemble of overlapping linear signal transduction events which we encode as Information Flow Gene Sets (IFGS's). We infer pathways from gene sets corresponding to these events subjected to a random permutation of genes within each set. In Stage I, we use a source separation algorithm to derive unordered and overlapping IFGS's from molecular profiling data, allowing cross talk among IFGS's. In Stage II, we develop a Gibbs sampling like algorithm, Gene Set Gibbs Sampler, to reconstruct signaling pathways from the latent IFGS's derived in Stage I. The novelty of this framework lies in the seamless integration of the two stages and the hypothesis of IFGS's as the basic building blocks for signal pathways. In the proof-of-concept studies, our approach is shown to outperform the existing Bayesian network approaches using both continuous and discrete data generated from benchmark networks in the DREAM initiative. We perform a comprehensive sensitivity analysis to assess the robustness of the approach. Finally, we implement the GSGS framework to reconstruct signaling pathways in breast cancer cells.
[ { "created": "Thu, 20 Jan 2011 18:08:48 GMT", "version": "v1" }, { "created": "Sun, 23 Jan 2011 07:22:58 GMT", "version": "v2" }, { "created": "Thu, 13 Oct 2011 21:53:19 GMT", "version": "v3" } ]
2011-10-17
[ [ "Acharya", "Lipi", "" ], [ "Judeh", "Thair", "" ], [ "Duan", "Zhansheng", "" ], [ "Rabbat", "Michael", "" ], [ "Zhu", "Dongxiao", "" ] ]
We propose a novel two-stage Gene Set Gibbs Sampling (GSGS) framework, to reverse engineer signaling pathways from gene sets inferred from molecular profiling data. We hypothesize that signaling pathways are structurally an ensemble of overlapping linear signal transduction events which we encode as Information Flow Gene Sets (IFGS's). We infer pathways from gene sets corresponding to these events subjected to a random permutation of genes within each set. In Stage I, we use a source separation algorithm to derive unordered and overlapping IFGS's from molecular profiling data, allowing cross talk among IFGS's. In Stage II, we develop a Gibbs sampling like algorithm, Gene Set Gibbs Sampler, to reconstruct signaling pathways from the latent IFGS's derived in Stage I. The novelty of this framework lies in the seamless integration of the two stages and the hypothesis of IFGS's as the basic building blocks for signal pathways. In the proof-of-concept studies, our approach is shown to outperform the existing Bayesian network approaches using both continuous and discrete data generated from benchmark networks in the DREAM initiative. We perform a comprehensive sensitivity analysis to assess the robustness of the approach. Finally, we implement the GSGS framework to reconstruct signaling pathways in breast cancer cells.
1509.01638
Susan Martonosi
Harry J. Dudley, Abhishek Goenka, Cesar J. Orellana, Susan E. Martonosi
Multi-year optimization of malaria intervention: a mathematical model
27 pages, 9 figures, 6 tables. Under review
null
10.1186/s12936-016-1182-0
null
q-bio.PE math.OC physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Malaria is a mosquito-borne, lethal disease that affects millions and kills hundreds of thousands of people each year. In this paper, we develop a model for allocating malaria interventions across geographic regions and time, subject to budget constraints, with the aim of minimizing the number of person-days of malaria infection. The model considers a range of several conditions: climatic characteristics, treatment efficacy, distribution costs, and treatment coverage. We couple an expanded susceptible-infected-recovered (SIR) compartment model for the disease dynamics with an integer linear programming (ILP) model for selecting the disease interventions. Our model produces an intervention plan for all regions, identifying which combination of interventions, with which level of coverage, to use in each region and year in a five-year planning horizon. Simulations using the model yield high-level, qualitative insights on optimal intervention policies: The optimal policy is different when considering a five-year time horizon than when considering only a single year, due to the effects that interventions have on the disease transmission dynamics. The vaccine intervention is rarely selected, except if its assumed cost is significantly lower than that predicted in the literature. Increasing the available budget causes the number of person-days of malaria infection to decrease linearly up to a point, after which the benefit of increased budget starts to taper. The optimal policy is highly dependent on assumptions about mosquito density, selecting different interventions for wet climates with high density than for dry climates with low density, and the interventions are found to be less effective at controlling malaria in the wet climates when attainable intervention coverage is 60% or lower. However, when intervention coverage of 80% is attainable, then malaria prevalence drops quickly.
[ { "created": "Fri, 4 Sep 2015 23:33:32 GMT", "version": "v1" }, { "created": "Thu, 4 Feb 2016 19:25:15 GMT", "version": "v2" } ]
2023-09-28
[ [ "Dudley", "Harry J.", "" ], [ "Goenka", "Abhishek", "" ], [ "Orellana", "Cesar J.", "" ], [ "Martonosi", "Susan E.", "" ] ]
Malaria is a mosquito-borne, lethal disease that affects millions and kills hundreds of thousands of people each year. In this paper, we develop a model for allocating malaria interventions across geographic regions and time, subject to budget constraints, with the aim of minimizing the number of person-days of malaria infection. The model considers a range of several conditions: climatic characteristics, treatment efficacy, distribution costs, and treatment coverage. We couple an expanded susceptible-infected-recovered (SIR) compartment model for the disease dynamics with an integer linear programming (ILP) model for selecting the disease interventions. Our model produces an intervention plan for all regions, identifying which combination of interventions, with which level of coverage, to use in each region and year in a five-year planning horizon. Simulations using the model yield high-level, qualitative insights on optimal intervention policies: The optimal policy is different when considering a five-year time horizon than when considering only a single year, due to the effects that interventions have on the disease transmission dynamics. The vaccine intervention is rarely selected, except if its assumed cost is significantly lower than that predicted in the literature. Increasing the available budget causes the number of person-days of malaria infection to decrease linearly up to a point, after which the benefit of increased budget starts to taper. The optimal policy is highly dependent on assumptions about mosquito density, selecting different interventions for wet climates with high density than for dry climates with low density, and the interventions are found to be less effective at controlling malaria in the wet climates when attainable intervention coverage is 60% or lower. However, when intervention coverage of 80% is attainable, then malaria prevalence drops quickly.
q-bio/0411003
Kai Wang
Kai Wang, Nilanjana Banerjee, Adam Margolin, Ilya Nemenman, Katia Basso, Riccardo Favera, Andrea Califano
Conditional Network Analysis Identifies Candidate Regulator Genes in Human B Cells
Submitted to RECOMB 2005 (11 pages, 4 figures, 2 tables)
null
null
null
q-bio.MN q-bio.GN q-bio.QM
null
Cellular phenotypes are determined by the dynamical activity of networks of co-regulated genes. Elucidating such networks is crucial for the understanding of normal cell physiology as well as for the dissection of complex pathologic phenotypes. Existing methods for such "reverse engineering" of genetic networks from microarray expression data have been successful only in prokaryotes (E. coli) and lower eukaryotes (S. cerevisiae) with relatively simple genomes. Additionally, they have mostly attempted to reconstruct average properties about the network connectivity without capturing the highly conditional nature of the interactions. In this paper we extend the ARACNE algorithm, which we recently introduced and successfully applied to the reconstruction of whole-genome transcriptional networks from mammalian cells, precisely to link the existence of specific network structures to the expression or lack thereof of specific regulator genes. This is accomplished by analyzing thousands of alternative network topologies generated by constraining the data set on the presence or absence of putative regulator genes. By considering interactions that are consistently supported across several such constraints, we identify many transcriptional interactions that would not have been detectable by the original method. By selecting genes that produce statistically significant changes in network topology, we identify novel candidate regulator genes. Further analysis shows that transcription factors, kinases, phosphatases, and other gene families known to effect biochemical interactions, are significantly overrepresented among the set of candidate regulator genes identified in silico, indirectly supporting the validity of the approach.
[ { "created": "Sat, 30 Oct 2004 22:40:45 GMT", "version": "v1" } ]
2007-05-23
[ [ "Wang", "Kai", "" ], [ "Banerjee", "Nilanjana", "" ], [ "Margolin", "Adam", "" ], [ "Nemenman", "Ilya", "" ], [ "Basso", "Katia", "" ], [ "Favera", "Riccardo", "" ], [ "Califano", "Andrea", "" ] ]
Cellular phenotypes are determined by the dynamical activity of networks of co-regulated genes. Elucidating such networks is crucial for the understanding of normal cell physiology as well as for the dissection of complex pathologic phenotypes. Existing methods for such "reverse engineering" of genetic networks from microarray expression data have been successful only in prokaryotes (E. coli) and lower eukaryotes (S. cerevisiae) with relatively simple genomes. Additionally, they have mostly attempted to reconstruct average properties about the network connectivity without capturing the highly conditional nature of the interactions. In this paper we extend the ARACNE algorithm, which we recently introduced and successfully applied to the reconstruction of whole-genome transcriptional networks from mammalian cells, precisely to link the existence of specific network structures to the expression or lack thereof of specific regulator genes. This is accomplished by analyzing thousands of alternative network topologies generated by constraining the data set on the presence or absence of putative regulator genes. By considering interactions that are consistently supported across several such constraints, we identify many transcriptional interactions that would not have been detectable by the original method. By selecting genes that produce statistically significant changes in network topology, we identify novel candidate regulator genes. Further analysis shows that transcription factors, kinases, phosphatases, and other gene families known to effect biochemical interactions, are significantly overrepresented among the set of candidate regulator genes identified in silico, indirectly supporting the validity of the approach.
2301.11812
Johannes Kleiner
Johannes Kleiner and Tim Ludwig
What is a Mathematical Structure of Conscious Experience?
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In consciousness science, several promising approaches have been developed for how to represent conscious experience in terms of mathematical spaces and structures. What is missing, however, is an explicit definition of what a 'mathematical structure of conscious experience' is. Here, we propose such a definition. This definition provides a link between the abstract formal entities of mathematics and the concreta of conscious experience; it complements recent approaches that study quality spaces, qualia spaces or phenomenal spaces; it provides a general method to identify and investigate structures of conscious experience; and it may serve as a framework to unify the various approaches from different fields. We hope that ultimately this work provides a basis for developing a common formal language to study consciousness.
[ { "created": "Thu, 26 Jan 2023 15:25:19 GMT", "version": "v1" } ]
2023-01-30
[ [ "Kleiner", "Johannes", "" ], [ "Ludwig", "Tim", "" ] ]
In consciousness science, several promising approaches have been developed for how to represent conscious experience in terms of mathematical spaces and structures. What is missing, however, is an explicit definition of what a 'mathematical structure of conscious experience' is. Here, we propose such a definition. This definition provides a link between the abstract formal entities of mathematics and the concreta of conscious experience; it complements recent approaches that study quality spaces, qualia spaces or phenomenal spaces; it provides a general method to identify and investigate structures of conscious experience; and it may serve as a framework to unify the various approaches from different fields. We hope that ultimately this work provides a basis for developing a common formal language to study consciousness.
2105.05382
Arna Ghosh
Luke Y. Prince, Roy Henha Eyono, Ellen Boven, Arna Ghosh, Joe Pemberton, Franz Scherr, Claudia Clopath, Rui Ponte Costa, Wolfgang Maass, Blake A. Richards, Cristina Savin, Katharina Anna Wilmes
Current State and Future Directions for Learning in Biological Recurrent Neural Networks: A Perspective Piece
null
null
null
null
q-bio.NC cs.AI
http://creativecommons.org/licenses/by/4.0/
We provide a brief review of the common assumptions about biological learning with findings from experimental neuroscience and contrast them with the efficiency of gradient-based learning in recurrent neural networks. The key issues discussed in this review include: synaptic plasticity, neural circuits, theory-experiment divide, and objective functions. We conclude with recommendations for both theoretical and experimental neuroscientists when designing new studies that could help bring clarity to these issues.
[ { "created": "Wed, 12 May 2021 00:59:40 GMT", "version": "v1" }, { "created": "Wed, 5 Jan 2022 16:47:02 GMT", "version": "v2" } ]
2022-01-06
[ [ "Prince", "Luke Y.", "" ], [ "Eyono", "Roy Henha", "" ], [ "Boven", "Ellen", "" ], [ "Ghosh", "Arna", "" ], [ "Pemberton", "Joe", "" ], [ "Scherr", "Franz", "" ], [ "Clopath", "Claudia", "" ], [ "Co...
We provide a brief review of the common assumptions about biological learning with findings from experimental neuroscience and contrast them with the efficiency of gradient-based learning in recurrent neural networks. The key issues discussed in this review include: synaptic plasticity, neural circuits, theory-experiment divide, and objective functions. We conclude with recommendations for both theoretical and experimental neuroscientists when designing new studies that could help bring clarity to these issues.
2106.09000
Xin Yang
Xin Yang, Ning Zhang, Donglin Wang
Deriving Autism Spectrum Disorder Functional Networks from RS-FMRI Data using Group ICA and Dictionary Learning
Conference
null
10.5121/csit.2021.110714
null
q-bio.NC cs.LG eess.IV
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The objective of this study is to derive functional networks for the autism spectrum disorder (ASD) population using the group ICA and dictionary learning model together and to classify ASD and typically developing (TD) participants using the functional connectivity calculated from the derived functional networks. In our experiments, the ASD functional networks were derived from resting-state functional magnetic resonance imaging (rs-fMRI) data. We downloaded a total of 120 training samples, including 58 ASD and 62 TD participants, which were obtained from the public repository: Autism Brain Imaging Data Exchange I (ABIDE I). Our methodology and results have five main parts. First, we utilize a group ICA model to extract functional networks from the ASD group and rank the top 20 regions of interest (ROIs). Second, we utilize a dictionary learning model to extract functional networks from the ASD group and rank the top 20 ROIs. Third, we merged the 40 selected ROIs from the two models together as the ASD functional networks. Fourth, we generate three corresponding masks based on the 20 selected ROIs from group ICA, the 20 ROIs selected from dictionary learning, and the 40 combined ROIs selected from both. Finally, we extract ROIs for all training samples using the above three masks, and the calculated functional connectivity was used as features for ASD and TD classification. The classification results showed that the functional networks derived from ICA and dictionary learning together outperform those derived from a single ICA model or a single dictionary learning model.
[ { "created": "Mon, 7 Jun 2021 07:58:52 GMT", "version": "v1" } ]
2021-06-17
[ [ "Yang", "Xin", "" ], [ "Zhang", "Ning", "" ], [ "Wang", "Donglin", "" ] ]
The objective of this study is to derive functional networks for the autism spectrum disorder (ASD) population using the group ICA and dictionary learning model together and to classify ASD and typically developing (TD) participants using the functional connectivity calculated from the derived functional networks. In our experiments, the ASD functional networks were derived from resting-state functional magnetic resonance imaging (rs-fMRI) data. We downloaded a total of 120 training samples, including 58 ASD and 62 TD participants, which were obtained from the public repository: Autism Brain Imaging Data Exchange I (ABIDE I). Our methodology and results have five main parts. First, we utilize a group ICA model to extract functional networks from the ASD group and rank the top 20 regions of interest (ROIs). Second, we utilize a dictionary learning model to extract functional networks from the ASD group and rank the top 20 ROIs. Third, we merged the 40 selected ROIs from the two models together as the ASD functional networks. Fourth, we generate three corresponding masks based on the 20 selected ROIs from group ICA, the 20 ROIs selected from dictionary learning, and the 40 combined ROIs selected from both. Finally, we extract ROIs for all training samples using the above three masks, and the calculated functional connectivity was used as features for ASD and TD classification. The classification results showed that the functional networks derived from ICA and dictionary learning together outperform those derived from a single ICA model or a single dictionary learning model.
2206.11129
Olga Shishkov
O. Shishkov and O. Peleg
Social Insects and Beyond: The Physics of Soft, Dense Invertebrate Aggregations
23 pages, 6 figures
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by-nc-nd/4.0/
Aggregation is a common behavior by which groups of organisms arrange into cohesive groups. Whether suspended in the air (like honey bee clusters), built on the ground (such as army ant bridges), or immersed in water (such as sludge worm blobs), these collectives serve a multitude of biological functions, from protection against predation to the ability to maintain a relatively desirable local environment despite a variable ambient environment. In this review, we survey dense aggregations of a variety of insects, other arthropods, and worms from a soft matter standpoint. An aggregation can be orders of magnitude larger than its individual organisms, consisting of tens to hundreds of thousands of individuals, and yet functions as a coherent entity. Understanding how aggregating organisms coordinate with one another to form a superorganism requires an interdisciplinary approach. We discuss how the physics of the aggregation can yield additional insights to those gained from ecological and physiological considerations, given that the aggregating individuals exchange information, energy, and matter continually with the environment and one another. While the connection between animal aggregations and the physics of non-living materials has been proposed since the early 1900s, the recent advent of physics of behavior studies provides new insights into social interactions governed by physical principles. Current efforts focus on eusocial insects; however, we show that these may just be the tip of an iceberg of superorganisms that take advantage of physical interactions and simple behavioral rules to adapt to changing environments. By bringing attention to a wide range of invertebrate aggregations, we wish to inspire a new generation of scientists to explore collective dynamics and bring a deeper understanding of the physics of dense living aggregations.
[ { "created": "Wed, 22 Jun 2022 14:21:53 GMT", "version": "v1" } ]
2022-06-23
[ [ "Shishkov", "O.", "" ], [ "Peleg", "O.", "" ] ]
Aggregation is a common behavior by which groups of organisms arrange into cohesive groups. Whether suspended in the air (like honey bee clusters), built on the ground (such as army ant bridges), or immersed in water (such as sludge worm blobs), these collectives serve a multitude of biological functions, from protection against predation to the ability to maintain a relatively desirable local environment despite a variable ambient environment. In this review, we survey dense aggregations of a variety of insects, other arthropods, and worms from a soft matter standpoint. An aggregation can be orders of magnitude larger than its individual organisms, consisting of tens to hundreds of thousands of individuals, and yet functions as a coherent entity. Understanding how aggregating organisms coordinate with one another to form a superorganism requires an interdisciplinary approach. We discuss how the physics of the aggregation can yield additional insights to those gained from ecological and physiological considerations, given that the aggregating individuals exchange information, energy, and matter continually with the environment and one another. While the connection between animal aggregations and the physics of non-living materials has been proposed since the early 1900s, the recent advent of physics of behavior studies provides new insights into social interactions governed by physical principles. Current efforts focus on eusocial insects; however, we show that these may just be the tip of an iceberg of superorganisms that take advantage of physical interactions and simple behavioral rules to adapt to changing environments. By bringing attention to a wide range of invertebrate aggregations, we wish to inspire a new generation of scientists to explore collective dynamics and bring a deeper understanding of the physics of dense living aggregations.
2103.03292
Francesco Zamponi
Jeanne Trinquier, Guido Uguzzoni, Andrea Pagnani, Francesco Zamponi, Martin Weigt
Efficient generative modeling of protein sequences using simple autoregressive models
12 pages, 4 Figures + Supplementary Material
Nature Communications 12, 5800 (2021)
10.1038/s41467-021-25756-4
null
q-bio.BM cond-mat.dis-nn cond-mat.stat-mech q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Generative models emerge as promising candidates for novel sequence-data driven approaches to protein design, and for the extraction of structural and functional information about proteins deeply hidden in rapidly growing sequence databases. Here we propose simple autoregressive models as highly accurate but computationally efficient generative sequence models. We show that they perform similarly to existing approaches based on Boltzmann machines or deep generative models, but at a substantially lower computational cost (by a factor between $10^2$ and $10^3$). Furthermore, the simple structure of our models has distinctive mathematical advantages, which translate into an improved applicability in sequence generation and evaluation. Within these models, we can easily estimate both the probability of a given sequence, and, using the model's entropy, the size of the functional sequence space related to a specific protein family. In the example of response regulators, we find a huge number of ca. $10^{68}$ possible sequences, which nevertheless constitute only the astronomically small fraction $10^{-80}$ of all amino-acid sequences of the same length. These findings illustrate the potential and the difficulty in exploring sequence space via generative sequence models.
[ { "created": "Thu, 4 Mar 2021 20:05:58 GMT", "version": "v1" }, { "created": "Mon, 13 Sep 2021 14:16:33 GMT", "version": "v2" }, { "created": "Tue, 9 Nov 2021 08:00:41 GMT", "version": "v3" } ]
2021-11-10
[ [ "Trinquier", "Jeanne", "" ], [ "Uguzzoni", "Guido", "" ], [ "Pagnani", "Andrea", "" ], [ "Zamponi", "Francesco", "" ], [ "Weigt", "Martin", "" ] ]
Generative models emerge as promising candidates for novel sequence-data driven approaches to protein design, and for the extraction of structural and functional information about proteins deeply hidden in rapidly growing sequence databases. Here we propose simple autoregressive models as highly accurate but computationally efficient generative sequence models. We show that they perform similarly to existing approaches based on Boltzmann machines or deep generative models, but at a substantially lower computational cost (by a factor between $10^2$ and $10^3$). Furthermore, the simple structure of our models has distinctive mathematical advantages, which translate into an improved applicability in sequence generation and evaluation. Within these models, we can easily estimate both the probability of a given sequence, and, using the model's entropy, the size of the functional sequence space related to a specific protein family. In the example of response regulators, we find a huge number of ca. $10^{68}$ possible sequences, which nevertheless constitute only the astronomically small fraction $10^{-80}$ of all amino-acid sequences of the same length. These findings illustrate the potential and the difficulty in exploring sequence space via generative sequence models.
1611.08310
Jiaying Zhang Jiaying Zhang
Xuehai Wu, Jiaying Zhang, Zaixu Cui, Weijun Tang, Chunhong Shao, Jin Hu, Jianhong Zhu, Liangfu Zhou, Yao Zhao, Lu Lu, Gang Chen, Georg Northoff, Gaolang Gong, Ying Mao, Yong He
White matter deficits underlie the loss of consciousness level and predict recovery outcome in disorders of consciousness
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This study aimed to identify white matter (WM) deficits underlying the loss of consciousness in disorder of consciousness (DOC) patients using Diffusion Tensor Imaging (DTI) and to demonstrate the potential value of DTI parameters in predicting recovery outcomes of DOC patients. With 30 DOC patients (8 comatose, 8 unresponsive wakefulness syndrome/vegetative state, and 14 minimal conscious state) and 25 patient controls, we performed group comparison of DTI parameters across 48 core WM regions of interest (ROIs) using Analysis of Covariance. Compared with controls, DOC patients had decreased Fractional anisotropy (FA) and increased diffusivities in widespread WM area.The corresponding DTI parameters of those WM deficits in DOC patients significantly correlated with the consciousness level evaluated by Coma Recovery Scale Revised (CRS-R) and Glasgow Coma Scale (GCS). As for predicting the recovery outcomes (i.e., regaining consciousness or not, grouped by their Glasgow Outcome Scale more than 2 or not) at 3 months post scan, radial diffusivity of left superior cerebellar peduncle and FA of right sagittal stratum reached an accuracy of 87.5% and 75% respectively. Our findings showed multiple WM deficits underlying the loss of consciousness level, and demonstrated the potential value of these WM areas in predicting the recovery outcomes of DOC patients who have lost awareness of the environment and themselves.
[ { "created": "Thu, 24 Nov 2016 21:09:55 GMT", "version": "v1" } ]
2016-11-28
[ [ "Wu", "Xuehai", "" ], [ "Zhang", "Jiaying", "" ], [ "Cui", "Zaixu", "" ], [ "Tang", "Weijun", "" ], [ "Shao", "Chunhong", "" ], [ "Hu", "Jin", "" ], [ "Zhu", "Jianhong", "" ], [ "Zhou", "Liangfu...
This study aimed to identify white matter (WM) deficits underlying the loss of consciousness in disorder of consciousness (DOC) patients using Diffusion Tensor Imaging (DTI) and to demonstrate the potential value of DTI parameters in predicting recovery outcomes of DOC patients. With 30 DOC patients (8 comatose, 8 unresponsive wakefulness syndrome/vegetative state, and 14 minimal conscious state) and 25 patient controls, we performed group comparison of DTI parameters across 48 core WM regions of interest (ROIs) using Analysis of Covariance. Compared with controls, DOC patients had decreased Fractional anisotropy (FA) and increased diffusivities in widespread WM area.The corresponding DTI parameters of those WM deficits in DOC patients significantly correlated with the consciousness level evaluated by Coma Recovery Scale Revised (CRS-R) and Glasgow Coma Scale (GCS). As for predicting the recovery outcomes (i.e., regaining consciousness or not, grouped by their Glasgow Outcome Scale more than 2 or not) at 3 months post scan, radial diffusivity of left superior cerebellar peduncle and FA of right sagittal stratum reached an accuracy of 87.5% and 75% respectively. Our findings showed multiple WM deficits underlying the loss of consciousness level, and demonstrated the potential value of these WM areas in predicting the recovery outcomes of DOC patients who have lost awareness of the environment and themselves.
0705.0912
Erzs\'ebet Ravasz Regan
Erzsebet Ravasz, S. Gnanakaran and Zoltan Toroczkai
Network Structure of Protein Folding Pathways
15 pages, 4 figures
null
null
null
q-bio.BM q-bio.MN
null
The classical approach to protein folding inspired by statistical mechanics avoids the high dimensional structure of the conformation space by using effective coordinates. Here we introduce a network approach to capture the statistical properties of the structure of conformation spaces. Conformations are represented as nodes of the network, while links are transitions via elementary rotations around a chemical bond. Self-avoidance of a polypeptide chain introduces degree correlations in the conformation network, which in turn lead to energy landscape correlations. Folding can be interpreted as a biased random walk on the conformation network. We show that the folding pathways along energy gradients organize themselves into scale free networks, thus explaining previous observations made via molecular dynamics simulations. We also show that these energy landscape correlations are essential for recovering the observed connectivity exponent, which belongs to a different universality class than that of random energy models. In addition, we predict that the exponent and therefore the structure of the folding network fundamentally changes at high temperatures, as verified by our simulations on the AK peptide.
[ { "created": "Mon, 7 May 2007 14:12:07 GMT", "version": "v1" } ]
2007-05-23
[ [ "Ravasz", "Erzsebet", "" ], [ "Gnanakaran", "S.", "" ], [ "Toroczkai", "Zoltan", "" ] ]
The classical approach to protein folding inspired by statistical mechanics avoids the high dimensional structure of the conformation space by using effective coordinates. Here we introduce a network approach to capture the statistical properties of the structure of conformation spaces. Conformations are represented as nodes of the network, while links are transitions via elementary rotations around a chemical bond. Self-avoidance of a polypeptide chain introduces degree correlations in the conformation network, which in turn lead to energy landscape correlations. Folding can be interpreted as a biased random walk on the conformation network. We show that the folding pathways along energy gradients organize themselves into scale free networks, thus explaining previous observations made via molecular dynamics simulations. We also show that these energy landscape correlations are essential for recovering the observed connectivity exponent, which belongs to a different universality class than that of random energy models. In addition, we predict that the exponent and therefore the structure of the folding network fundamentally changes at high temperatures, as verified by our simulations on the AK peptide.
2208.04774
Peter Boldog
Peter Boldog
Exact lattice-based stochastic cell culture simulation algorithms incorporating spontaneous and contact-dependent reactions
22 pages, 6 figures
null
null
null
q-bio.PE cond-mat.soft cond-mat.stat-mech q-bio.CB q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this paper, we address the modeling issues of cell movement and division with a special focus on the phenomenon of volume exclusion in a lattice-based, exact stochastic simulation framework. We propose a new exact method, called Reduced Rate Method -- RRM, that is substantially quicker than the previously used exclusion method, for large number of cells. In addition, we introduce three novel reaction types: the contact-inhibited, the contact-promoted, and the spontaneous reactions. To the best of our knowledge, these reaction types have not been taken into account in lattice-based stochastic simulations of cell cultures. These new types of events may be easily applied to complicated systems, enabling the generation of biologically feasible stochastic cell culture simulations. Furthermore, we show that the exclusion algorithm and our RRM algorithm are mathematically equivalent in the sense that the next reaction to be realized and the corresponding sojourn time both belong to the same reaction and time distributions in the two approaches -- even with the newly introduced reaction types. Exact, agent-based, stochastic methods of cell culture simulations seem to be undervalued and are mostly used as benchmarking tools to validate deterministic approximations of the corresponding stochastic models. Our proposed methods are exact, they are easy to implement, have a high predictive value, and can be conveniently extended with new features. Therefore, these approaches promise a great potential.
[ { "created": "Tue, 9 Aug 2022 13:36:18 GMT", "version": "v1" } ]
2022-08-10
[ [ "Boldog", "Peter", "" ] ]
In this paper, we address the modeling issues of cell movement and division with a special focus on the phenomenon of volume exclusion in a lattice-based, exact stochastic simulation framework. We propose a new exact method, called Reduced Rate Method -- RRM, that is substantially quicker than the previously used exclusion method, for large number of cells. In addition, we introduce three novel reaction types: the contact-inhibited, the contact-promoted, and the spontaneous reactions. To the best of our knowledge, these reaction types have not been taken into account in lattice-based stochastic simulations of cell cultures. These new types of events may be easily applied to complicated systems, enabling the generation of biologically feasible stochastic cell culture simulations. Furthermore, we show that the exclusion algorithm and our RRM algorithm are mathematically equivalent in the sense that the next reaction to be realized and the corresponding sojourn time both belong to the same reaction and time distributions in the two approaches -- even with the newly introduced reaction types. Exact, agent-based, stochastic methods of cell culture simulations seem to be undervalued and are mostly used as benchmarking tools to validate deterministic approximations of the corresponding stochastic models. Our proposed methods are exact, they are easy to implement, have a high predictive value, and can be conveniently extended with new features. Therefore, these approaches promise a great potential.
1907.04820
Stefan Schuster
Stefan Schuster, Jan Ewald, Thomas Dandekar, Sybille D\"uhring
Optimizing defence, counter-defence and counter-counter defence in parasitic and trophic interactions -- A modelling study
20 pages, 6 figures
null
null
null
q-bio.SC
http://creativecommons.org/publicdomain/zero/1.0/
In host-pathogen interactions, often the host (attacked organism) defends itself by some toxic compound and the parasite, in turn, responds by producing an enzyme that inactivates that compound. In some cases, the host can respond by producing an inhibitor of that enzyme, which can be considered as a counter-counter defence. An example is provided by cephalosporins, beta-lactamases and clavulanic acid (an inhibitor of beta-lactamases). Here, we tackle the question under which conditions it pays, during evolution, to establish a counter-counter defence rather than to intensify or widen the defence mechanisms. We establish a mathematical model describing this phenomenon, based on enzyme kinetics for competitive inhibition. We use an objective function based on Haber's rule, which says that the toxic effect is proportional to the time integral of toxin concentration. The optimal allocation of defence and counter-counter defence can be calculated in an analytical way despite the nonlinearity in the underlying differential equation. The calculation provides a threshold value for the dissociation constant of the inhibitor. Only if the inhibition constant is below that threshold, that is, in the case of strong binding of the inhibitor, it pays to have a counter-counter defence. This theoretical prediction accounts for the observation that not for all defence mechanisms, a counter-counter defence exists. Our results should be of interest for computing optimal mixtures of beta-lactam antibiotics and beta-lactamase inhibitors such as sulbactam, as well as for plant-herbivore and other molecular-ecological interactions and to fight antibiotic resistance in general.
[ { "created": "Wed, 10 Jul 2019 16:35:00 GMT", "version": "v1" } ]
2019-07-11
[ [ "Schuster", "Stefan", "" ], [ "Ewald", "Jan", "" ], [ "Dandekar", "Thomas", "" ], [ "Dühring", "Sybille", "" ] ]
In host-pathogen interactions, often the host (attacked organism) defends itself by some toxic compound and the parasite, in turn, responds by producing an enzyme that inactivates that compound. In some cases, the host can respond by producing an inhibitor of that enzyme, which can be considered as a counter-counter defence. An example is provided by cephalosporins, beta-lactamases and clavulanic acid (an inhibitor of beta-lactamases). Here, we tackle the question under which conditions it pays, during evolution, to establish a counter-counter defence rather than to intensify or widen the defence mechanisms. We establish a mathematical model describing this phenomenon, based on enzyme kinetics for competitive inhibition. We use an objective function based on Haber's rule, which says that the toxic effect is proportional to the time integral of toxin concentration. The optimal allocation of defence and counter-counter defence can be calculated in an analytical way despite the nonlinearity in the underlying differential equation. The calculation provides a threshold value for the dissociation constant of the inhibitor. Only if the inhibition constant is below that threshold, that is, in the case of strong binding of the inhibitor, it pays to have a counter-counter defence. This theoretical prediction accounts for the observation that not for all defence mechanisms, a counter-counter defence exists. Our results should be of interest for computing optimal mixtures of beta-lactam antibiotics and beta-lactamase inhibitors such as sulbactam, as well as for plant-herbivore and other molecular-ecological interactions and to fight antibiotic resistance in general.
0901.0663
Joachim Krug
Andrea Wolff and Joachim Krug
Robustness and epistasis in mutation-selection models
20 pages, 14 figures
Physical Biology 6 (2009) 036007 (with some revisions)
10.1088/1478-3975/6/3/036007
null
q-bio.PE cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We investigate the fitness advantage associated with the robustness of a phenotype against deleterious mutations using deterministic mutation-selection models of quasispecies type equipped with a mesa shaped fitness landscape. We obtain analytic results for the robustness effect which become exact in the limit of infinite sequence length. Thereby, we are able to clarify a seeming contradiction between recent rigorous work and an earlier heuristic treatment based on a mapping to a Schr\"odinger equation. We exploit the quantum mechanical analogy to calculate a correction term for finite sequence lengths and verify our analytic results by numerical studies. In addition, we investigate the occurrence of an error threshold for a general class of epistatic landscape and show that diminishing epistasis is a necessary but not sufficient condition for error threshold behavior.
[ { "created": "Tue, 6 Jan 2009 16:16:39 GMT", "version": "v1" } ]
2015-05-13
[ [ "Wolff", "Andrea", "" ], [ "Krug", "Joachim", "" ] ]
We investigate the fitness advantage associated with the robustness of a phenotype against deleterious mutations using deterministic mutation-selection models of quasispecies type equipped with a mesa shaped fitness landscape. We obtain analytic results for the robustness effect which become exact in the limit of infinite sequence length. Thereby, we are able to clarify a seeming contradiction between recent rigorous work and an earlier heuristic treatment based on a mapping to a Schr\"odinger equation. We exploit the quantum mechanical analogy to calculate a correction term for finite sequence lengths and verify our analytic results by numerical studies. In addition, we investigate the occurrence of an error threshold for a general class of epistatic landscape and show that diminishing epistasis is a necessary but not sufficient condition for error threshold behavior.
1208.6350
Mengyao Zhao
Mengyao Zhao, Wan-Ping Lee, Erik Garrison and Gabor T. Marth
SSW Library: An SIMD Smith-Waterman C/C++ Library for Use in Genomic Applications
3 pages, 2 figures
null
10.1371/journal.pone.0082138
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Summary: The Smith Waterman (SW) algorithm, which produces the optimal pairwise alignment between two sequences, is frequently used as a key component of fast heuristic read mapping and variation detection tools, but current implementations are either designed as monolithic protein database searching tools or are embedded into other tools. To facilitate easy integration of the fast Single Instruction Multiple Data (SIMD) SW algorithm into third party software, we wrote a C/C++ library, which extends Farrars Striped SW (SSW) to return alignment information in addition to the optimal SW score. Availability: SSW is available both as a C/C++ software library, as well as a stand alone alignment tool wrapping the librarys functionality at https://github.com/mengyao/Complete- Striped-Smith-Waterman-Library Contact: marth@bc.edu
[ { "created": "Fri, 31 Aug 2012 02:03:43 GMT", "version": "v1" }, { "created": "Fri, 26 Apr 2013 22:02:44 GMT", "version": "v2" } ]
2014-03-05
[ [ "Zhao", "Mengyao", "" ], [ "Lee", "Wan-Ping", "" ], [ "Garrison", "Erik", "" ], [ "Marth", "Gabor T.", "" ] ]
Summary: The Smith Waterman (SW) algorithm, which produces the optimal pairwise alignment between two sequences, is frequently used as a key component of fast heuristic read mapping and variation detection tools, but current implementations are either designed as monolithic protein database searching tools or are embedded into other tools. To facilitate easy integration of the fast Single Instruction Multiple Data (SIMD) SW algorithm into third party software, we wrote a C/C++ library, which extends Farrars Striped SW (SSW) to return alignment information in addition to the optimal SW score. Availability: SSW is available both as a C/C++ software library, as well as a stand alone alignment tool wrapping the librarys functionality at https://github.com/mengyao/Complete- Striped-Smith-Waterman-Library Contact: marth@bc.edu
q-bio/0703035
Brigitte Gaillard
S. Bourgeon (DEPE-Iphc), T. Raclot (DEPE-Iphc), Y. Le Maho (DEPE-Iphc), D. Ricquier (CREMD), F. Criscuolo (CREMD)
Innate immunity, assessed by plasma NO measurements, is not suppressed during the incubation fast in eiders
null
Dev. Comp. Immunol. (19/12/2006) 29 pages
10.1016/j.dci.2006.11.009
null
q-bio.PE
null
Immunity is hypothesized to share limited resources with other physiological functions and may mediate life history trade-offs, for example between reproduction and survival. However, vertebrate immune defense is a complex system that consists of three components. To date, no study has assessed all of these components for the same animal model and within a given situation. Previous studies have determined that the acquired immunity of common eiders (Somateria mollissima) is suppressed during incubation. The present paper aims to assess the innate immune response in fasting eiders in relation to their initial body condition. Innate immunity was assessed by measuring plasma nitric oxide (NO) levels, prior to and after injection of lipopolysaccharides (LPS), a method which is easily applicable to many wild animals. Body condition index and corticosterone levels were subsequently determined as indicators of body condition and stress level prior to LPS injection. The innate immune response in eiders did not vary significantly throughout the incubation period. The innate immune response of eiders did not vary significantly in relation to their initial body condition but decreased significantly when corticosterone levels increased. However, NO levels after LPS injection were significantly and positively related to initial body condition, while there was a significant negative relationship with plasma corticosterone levels. Our study suggests that female eiders preserve an effective innate immune response during incubation and this response might be partially determined by the initial body condition.
[ { "created": "Thu, 15 Mar 2007 12:44:23 GMT", "version": "v1" } ]
2007-05-23
[ [ "Bourgeon", "S.", "", "DEPE-Iphc" ], [ "Raclot", "T.", "", "DEPE-Iphc" ], [ "Maho", "Y. Le", "", "DEPE-Iphc" ], [ "Ricquier", "D.", "", "CREMD" ], [ "Criscuolo", "F.", "", "CREMD" ] ]
Immunity is hypothesized to share limited resources with other physiological functions and may mediate life history trade-offs, for example between reproduction and survival. However, vertebrate immune defense is a complex system that consists of three components. To date, no study has assessed all of these components for the same animal model and within a given situation. Previous studies have determined that the acquired immunity of common eiders (Somateria mollissima) is suppressed during incubation. The present paper aims to assess the innate immune response in fasting eiders in relation to their initial body condition. Innate immunity was assessed by measuring plasma nitric oxide (NO) levels, prior to and after injection of lipopolysaccharides (LPS), a method which is easily applicable to many wild animals. Body condition index and corticosterone levels were subsequently determined as indicators of body condition and stress level prior to LPS injection. The innate immune response in eiders did not vary significantly throughout the incubation period. The innate immune response of eiders did not vary significantly in relation to their initial body condition but decreased significantly when corticosterone levels increased. However, NO levels after LPS injection were significantly and positively related to initial body condition, while there was a significant negative relationship with plasma corticosterone levels. Our study suggests that female eiders preserve an effective innate immune response during incubation and this response might be partially determined by the initial body condition.
1003.2366
Henrik Jeldtoft Jensen
Tomas Alarcon and Henrik Jeldtoft Jensen
From gene regulatory networks to population dynamics: robustness, diversity and their role in progression to cancer
16 pages, 6 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The aim of this paper is to discuss the role of robustness and diversity in population dynamics in particular to some properties of the multi-step from healthy tissue to fully malignant tumours. Recent evidence shows that diversity within the cell population of a neoplasm, a pre-tumoural lession that can develop into a fully malignant tumour, is the best predictor for its evolving into a tumour. By studying the dynamics of a population described by a multi-type, population-size limited branching process in terms of the evolutionary formalism, we show some general principles regarding the probability of a resident population to being invaded by a mutant population in terms of the number of types present in the population and their resilience. We show that, although diversity in the mutant population poses a barrier for the emergence of the initial (benign) lession, under appropiate conditions, namely, the phenotypes in the mutant population being more resilient than those of the resident population, a more variable noeplastic population is more likely to be invaded by a more malignant one. Analysis of a model of gene regulatory networks suggest possible mechanisms giving rise to mutants with increased phenotypic diversity and robustness. We then go on to show how these results may help us to interpret some recent data regarding the evolution of Barrett's oesophagus into throat cancer.
[ { "created": "Thu, 11 Mar 2010 17:26:44 GMT", "version": "v1" } ]
2010-03-12
[ [ "Alarcon", "Tomas", "" ], [ "Jensen", "Henrik Jeldtoft", "" ] ]
The aim of this paper is to discuss the role of robustness and diversity in population dynamics in particular to some properties of the multi-step from healthy tissue to fully malignant tumours. Recent evidence shows that diversity within the cell population of a neoplasm, a pre-tumoural lession that can develop into a fully malignant tumour, is the best predictor for its evolving into a tumour. By studying the dynamics of a population described by a multi-type, population-size limited branching process in terms of the evolutionary formalism, we show some general principles regarding the probability of a resident population to being invaded by a mutant population in terms of the number of types present in the population and their resilience. We show that, although diversity in the mutant population poses a barrier for the emergence of the initial (benign) lession, under appropiate conditions, namely, the phenotypes in the mutant population being more resilient than those of the resident population, a more variable noeplastic population is more likely to be invaded by a more malignant one. Analysis of a model of gene regulatory networks suggest possible mechanisms giving rise to mutants with increased phenotypic diversity and robustness. We then go on to show how these results may help us to interpret some recent data regarding the evolution of Barrett's oesophagus into throat cancer.
1304.2917
Flavia Maria Darcie Marquitti
Flavia Maria Darcie Marquitti, Paulo Roberto Guimaraes Jr., Mathias Mistretta Pires, Luiz Fernando Bittencourt
MODULAR: Software for the Autonomous Computation of Modularity in Large Network Sets
null
null
null
null
q-bio.QM cs.SI physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Ecological systems can be seen as networks of interactions between individual, species, or habitat patches. A key feature of many ecological networks is their organization into modules, which are subsets of elements that are more connected to each other than to the other elements in the network. We introduce MODULAR to perform rapid and autonomous calculation of modularity in sets of networks. MODULAR reads a set of files with matrices or edge lists that represent unipartite or bipartite networks, and identify modules using two different modularity metrics that have been previously used in studies of ecological networks. To find the network partition that maximizes modularity, the software offers five optimization methods to the user. We also included two of the most common null models that are used in studies of ecological networks to verify how the modularity found by the maximization of each metric differs from a theoretical benchmark.
[ { "created": "Tue, 9 Apr 2013 14:37:44 GMT", "version": "v1" } ]
2013-04-11
[ [ "Marquitti", "Flavia Maria Darcie", "" ], [ "Guimaraes", "Paulo Roberto", "Jr." ], [ "Pires", "Mathias Mistretta", "" ], [ "Bittencourt", "Luiz Fernando", "" ] ]
Ecological systems can be seen as networks of interactions between individual, species, or habitat patches. A key feature of many ecological networks is their organization into modules, which are subsets of elements that are more connected to each other than to the other elements in the network. We introduce MODULAR to perform rapid and autonomous calculation of modularity in sets of networks. MODULAR reads a set of files with matrices or edge lists that represent unipartite or bipartite networks, and identify modules using two different modularity metrics that have been previously used in studies of ecological networks. To find the network partition that maximizes modularity, the software offers five optimization methods to the user. We also included two of the most common null models that are used in studies of ecological networks to verify how the modularity found by the maximization of each metric differs from a theoretical benchmark.
2109.11358
Jari Pronold
Jari Pronold, Jakob Jordan, Brian J. N. Wylie, Itaru Kitayama, Markus Diesmann, Susanne Kunkel
Routing brain traffic through the von Neumann bottleneck: Parallel sorting and refactoring
null
null
10.3389/fninf.2021.785068
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Generic simulation code for spiking neuronal networks spends the major part of time in the phase where spikes have arrived at a compute node and need to be delivered to their target neurons. These spikes were emitted over the last interval between communication steps by source neurons distributed across many compute nodes and are inherently irregular with respect to their targets. For finding the targets, the spikes need to be dispatched to a three-dimensional data structure with decisions on target thread and synapse type to be made on the way. With growing network size a compute node receives spikes from an increasing number of different source neurons until in the limit each synapse on the compute node has a unique source. Here we show analytically how this sparsity emerges over the practically relevant range of network sizes from a hundred thousand to a billion neurons. By profiling a production code we investigate opportunities for algorithmic changes to avoid indirections and branching. Every thread hosts an equal share of the neurons on a compute node. In the original algorithm all threads search through all spikes to pick out the relevant ones. With increasing network size the fraction of hits remains invariant but the absolute number of rejections grows. An alternative algorithm equally divides the spikes among the threads and sorts them in parallel according to target thread and synapse type. After this every thread completes delivery solely of the section of spikes for its own neurons. The new algorithm halves the number of instructions in spike delivery which leads to a reduction of simulation time of up to 40 %. Thus, spike delivery is a fully parallelizable process with a single synchronization point and thereby well suited for many-core systems. Our analysis indicates that further progress requires a reduction of the latency instructions experience in accessing memory.
[ { "created": "Thu, 23 Sep 2021 13:15:34 GMT", "version": "v1" }, { "created": "Fri, 24 Sep 2021 07:11:12 GMT", "version": "v2" }, { "created": "Thu, 10 Mar 2022 11:35:47 GMT", "version": "v3" } ]
2022-03-14
[ [ "Pronold", "Jari", "" ], [ "Jordan", "Jakob", "" ], [ "Wylie", "Brian J. N.", "" ], [ "Kitayama", "Itaru", "" ], [ "Diesmann", "Markus", "" ], [ "Kunkel", "Susanne", "" ] ]
Generic simulation code for spiking neuronal networks spends the major part of time in the phase where spikes have arrived at a compute node and need to be delivered to their target neurons. These spikes were emitted over the last interval between communication steps by source neurons distributed across many compute nodes and are inherently irregular with respect to their targets. For finding the targets, the spikes need to be dispatched to a three-dimensional data structure with decisions on target thread and synapse type to be made on the way. With growing network size a compute node receives spikes from an increasing number of different source neurons until in the limit each synapse on the compute node has a unique source. Here we show analytically how this sparsity emerges over the practically relevant range of network sizes from a hundred thousand to a billion neurons. By profiling a production code we investigate opportunities for algorithmic changes to avoid indirections and branching. Every thread hosts an equal share of the neurons on a compute node. In the original algorithm all threads search through all spikes to pick out the relevant ones. With increasing network size the fraction of hits remains invariant but the absolute number of rejections grows. An alternative algorithm equally divides the spikes among the threads and sorts them in parallel according to target thread and synapse type. After this every thread completes delivery solely of the section of spikes for its own neurons. The new algorithm halves the number of instructions in spike delivery which leads to a reduction of simulation time of up to 40 %. Thus, spike delivery is a fully parallelizable process with a single synchronization point and thereby well suited for many-core systems. Our analysis indicates that further progress requires a reduction of the latency instructions experience in accessing memory.
2401.00024
Yixun Xing
Yixun Xing, Casey Moore, Debabrata Saha, Dan Nguyen, MaryLena Bleile, Xun Jia, Robert Timmerman, Hao Peng, Steve Jiang
Mathematical Modeling of the Synergetic Effect between Radiotherapy and Immunotherapy
null
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by-sa/4.0/
Achieving effective synergy between radiotherapy and immunotherapy is critical for optimizing tumor control and treatment outcomes. To explore the underlying mechanisms of this synergy, we have investigated a novel treatment approach known as personalized ultra-fractionated stereotactic adaptive radiation therapy (PULSAR), which emphasizes the impact of radiation timing on treatment efficacy. However, the precise mechanism remains unclear. Building on insights from small animal PULSAR studies, we developed a mathematical framework consisting of multiple ordinary differential equations to elucidate the temporal dynamics of tumor control resulting from radiation and the adaptive immune response. The model accounts for the migration and infiltration of T-cells within the tumor microenvironment. This proposed model establishes a causal and quantitative link between radiation therapy and immunotherapy, providing a valuable in-silico analysis tool for designing future PULSAR trials.
[ { "created": "Thu, 28 Dec 2023 23:29:11 GMT", "version": "v1" } ]
2024-01-02
[ [ "Xing", "Yixun", "" ], [ "Moore", "Casey", "" ], [ "Saha", "Debabrata", "" ], [ "Nguyen", "Dan", "" ], [ "Bleile", "MaryLena", "" ], [ "Jia", "Xun", "" ], [ "Timmerman", "Robert", "" ], [ "Peng", ...
Achieving effective synergy between radiotherapy and immunotherapy is critical for optimizing tumor control and treatment outcomes. To explore the underlying mechanisms of this synergy, we have investigated a novel treatment approach known as personalized ultra-fractionated stereotactic adaptive radiation therapy (PULSAR), which emphasizes the impact of radiation timing on treatment efficacy. However, the precise mechanism remains unclear. Building on insights from small animal PULSAR studies, we developed a mathematical framework consisting of multiple ordinary differential equations to elucidate the temporal dynamics of tumor control resulting from radiation and the adaptive immune response. The model accounts for the migration and infiltration of T-cells within the tumor microenvironment. This proposed model establishes a causal and quantitative link between radiation therapy and immunotherapy, providing a valuable in-silico analysis tool for designing future PULSAR trials.
2005.14700
Omar El Housni
Omar El Housni, Mika Sumida, Paat Rusmevichientong, Huseyin Topaloglu, Serhan Ziya
Can Testing Ease Social Distancing Measures? Future Evolution of COVID-19 in NYC
null
null
null
null
q-bio.PE physics.soc-ph stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The "New York State on Pause" executive order came into effect on March 22 with the goal of ensuring adequate social distancing to alleviate the spread of COVID-19. Pause will remain effective in New York City in some form until early June. We use a compartmentalized model to study the effects of testing capacity and social distancing measures on the evolution of the pandemic in the "post-Pause" period in the City. We find that testing capacity must increase dramatically if it is to counterbalance even relatively small relaxations in social distancing measures in the immediate post-Pause period. In particular, if the City performs 20,000 tests per day and relaxes the social distancing measures to the pre-Pause norms, then the total number of deaths by the end of September can reach 250,000. By keeping the social distancing measures to somewhere halfway between the pre- and in-Pause norms and performing 100,000 tests per day, the total number of deaths by the end of September can be kept at around 27,000. Going back to the pre-Pause social distancing norms quickly must be accompanied by an exorbitant testing capacity, if one is to suppress excessive deaths. If the City is to go back to the "pre-Pause" social distancing norms in the immediate post-Pause period and keep the total number of deaths by the end of September at around 35,000, then it should be performing 500,000 tests per day. Our findings have important implications on the magnitude of the testing capacity the City needs as it relaxes the social distancing measures to reopen its economy.
[ { "created": "Wed, 27 May 2020 22:08:34 GMT", "version": "v1" } ]
2020-06-01
[ [ "Housni", "Omar El", "" ], [ "Sumida", "Mika", "" ], [ "Rusmevichientong", "Paat", "" ], [ "Topaloglu", "Huseyin", "" ], [ "Ziya", "Serhan", "" ] ]
The "New York State on Pause" executive order came into effect on March 22 with the goal of ensuring adequate social distancing to alleviate the spread of COVID-19. Pause will remain effective in New York City in some form until early June. We use a compartmentalized model to study the effects of testing capacity and social distancing measures on the evolution of the pandemic in the "post-Pause" period in the City. We find that testing capacity must increase dramatically if it is to counterbalance even relatively small relaxations in social distancing measures in the immediate post-Pause period. In particular, if the City performs 20,000 tests per day and relaxes the social distancing measures to the pre-Pause norms, then the total number of deaths by the end of September can reach 250,000. By keeping the social distancing measures to somewhere halfway between the pre- and in-Pause norms and performing 100,000 tests per day, the total number of deaths by the end of September can be kept at around 27,000. Going back to the pre-Pause social distancing norms quickly must be accompanied by an exorbitant testing capacity, if one is to suppress excessive deaths. If the City is to go back to the "pre-Pause" social distancing norms in the immediate post-Pause period and keep the total number of deaths by the end of September at around 35,000, then it should be performing 500,000 tests per day. Our findings have important implications on the magnitude of the testing capacity the City needs as it relaxes the social distancing measures to reopen its economy.
1309.1086
David Hsu
David Hsu, Murielle Hsu, Heidi L. Grabenstatter, Gregory A. Worrell, and Thomas P. Sutula
Characterization of high frequency oscillations and EEG frequency spectra using the damped-oscillator oscillator detector (DOOD)
25 pages, 10 figures
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Objective: The surgical resection of brain areas with high rates of visually identified high frequency oscillations (HFOs) on EEG has been correlated with improved seizure control. However, it can be difficult to distinguish normal from pathological HFOs, and the visual detection of HFOs is very time-intensive. An automated algorithm for detecting HFOs and for wide-band spectral analysis is desirable. Methods: The damped-oscillator oscillator detector (DOOD) is adapted for HFO detection, and tested on recordings from one rat and one human. The rat data consist of recordings from the hippocampus just prior to induction of status epilepticus, and again 6 weeks after induction, after the rat is epileptic. The human data are temporal lobe depth electrode recordings from a patient who underwent pre-surgical evaluation. Results: Sensitivities and positive predictive values are presented which depend on specifying a threshold value for HFO detection. Wide-band time-frequency and HFO-associated frequency spectra are also presented. In the rat data, four high frequency bands are identified at 80-250 Hz, 250-500 Hz, 600-900 Hz and 1000-3000 Hz. The human data was low-passed filtered at 1000 Hz and showed HFO-associated bands at 15 Hz, 85 Hz, 400 Hz and 700 Hz. Conclusion: The DOOD algorithm is capable of high resolution time-frequency spectra, and it can be adapted to detect HFOs with high positive predictive value. HFO-associated wide-band data show intricate low-frequency structure. Significance: DOOD may ease the labor intensity of HFO detection. DOOD wide-band analysis may in future help distinguish normal from pathological HFOs.
[ { "created": "Wed, 4 Sep 2013 16:10:02 GMT", "version": "v1" } ]
2013-09-05
[ [ "Hsu", "David", "" ], [ "Hsu", "Murielle", "" ], [ "Grabenstatter", "Heidi L.", "" ], [ "Worrell", "Gregory A.", "" ], [ "Sutula", "Thomas P.", "" ] ]
Objective: The surgical resection of brain areas with high rates of visually identified high frequency oscillations (HFOs) on EEG has been correlated with improved seizure control. However, it can be difficult to distinguish normal from pathological HFOs, and the visual detection of HFOs is very time-intensive. An automated algorithm for detecting HFOs and for wide-band spectral analysis is desirable. Methods: The damped-oscillator oscillator detector (DOOD) is adapted for HFO detection, and tested on recordings from one rat and one human. The rat data consist of recordings from the hippocampus just prior to induction of status epilepticus, and again 6 weeks after induction, after the rat is epileptic. The human data are temporal lobe depth electrode recordings from a patient who underwent pre-surgical evaluation. Results: Sensitivities and positive predictive values are presented which depend on specifying a threshold value for HFO detection. Wide-band time-frequency and HFO-associated frequency spectra are also presented. In the rat data, four high frequency bands are identified at 80-250 Hz, 250-500 Hz, 600-900 Hz and 1000-3000 Hz. The human data was low-passed filtered at 1000 Hz and showed HFO-associated bands at 15 Hz, 85 Hz, 400 Hz and 700 Hz. Conclusion: The DOOD algorithm is capable of high resolution time-frequency spectra, and it can be adapted to detect HFOs with high positive predictive value. HFO-associated wide-band data show intricate low-frequency structure. Significance: DOOD may ease the labor intensity of HFO detection. DOOD wide-band analysis may in future help distinguish normal from pathological HFOs.
2007.05800
Dimitrios Adamos Dr
Nikolaos Laskaris, Dimitrios A. Adamos, Anastasios Bezerianos
A Tutorial on Graph Theory for Brain Signal Analysis
To appear in Springer Handbook of Neuroengineering
null
null
null
q-bio.NC cs.LG eess.SP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This tutorial paper refers to the use of graph-theoretic concepts for analyzing brain signals. For didactic purposes it splits into two parts: theory and application. In the first part, we commence by introducing some basic elements from graph theory and stemming algorithmic tools, which can be employed for data-analytic purposes. Next, we describe how these concepts are adapted for handling evolving connectivity and gaining insights into network reorganization. Finally, the notion of signals residing on a given graph is introduced and elements from the emerging field of graph signal processing (GSP) are provided. The second part serves as a pragmatic demonstration of the tools and techniques described earlier. It is based on analyzing a multi-trial dataset containing single-trial responses from a visual ERP paradigm. The paper ends with a brief outline of the most recent trends in graph theory that are about to shape brain signal processing in the near future and a more general discussion on the relevance of graph-theoretic methodologies for analyzing continuous-mode neural recordings.
[ { "created": "Sat, 11 Jul 2020 15:36:52 GMT", "version": "v1" } ]
2020-07-14
[ [ "Laskaris", "Nikolaos", "" ], [ "Adamos", "Dimitrios A.", "" ], [ "Bezerianos", "Anastasios", "" ] ]
This tutorial paper refers to the use of graph-theoretic concepts for analyzing brain signals. For didactic purposes it splits into two parts: theory and application. In the first part, we commence by introducing some basic elements from graph theory and stemming algorithmic tools, which can be employed for data-analytic purposes. Next, we describe how these concepts are adapted for handling evolving connectivity and gaining insights into network reorganization. Finally, the notion of signals residing on a given graph is introduced and elements from the emerging field of graph signal processing (GSP) are provided. The second part serves as a pragmatic demonstration of the tools and techniques described earlier. It is based on analyzing a multi-trial dataset containing single-trial responses from a visual ERP paradigm. The paper ends with a brief outline of the most recent trends in graph theory that are about to shape brain signal processing in the near future and a more general discussion on the relevance of graph-theoretic methodologies for analyzing continuous-mode neural recordings.
1906.10729
Farzad Khalvati
Yucheng Zhang, Edrise M. Lobo-Mueller, Paul Karanicolas, Steven Gallinger, Masoom A. Haider, Farzad Khalvati
CNN-based Survival Model for Pancreatic Ductal Adenocarcinoma in Medical Imaging
null
null
null
null
q-bio.QM cs.CV cs.LG eess.IV
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Cox proportional hazard model (CPH) is commonly used in clinical research for survival analysis. In quantitative medical imaging (radiomics) studies, CPH plays an important role in feature reduction and modeling. However, the underlying linear assumption of CPH model limits the prognostic performance. In addition, the multicollinearity of radiomic features and multiple testing problem further impedes the CPH models performance. In this work, using transfer learning, a convolutional neural network (CNN) based survival model was built and tested on preoperative CT images of resectable Pancreatic Ductal Adenocarcinoma (PDAC) patients. The proposed CNN-based survival model outperformed the traditional CPH-based radiomics approach in terms of concordance index by 22%, providing a better fit for patients' survival patterns. The proposed CNN-based survival model outperforms CPH-based radiomics pipeline in PDAC prognosis. This approach offers a better fit for survival patterns based on CT images and overcomes the limitations of conventional survival models.
[ { "created": "Tue, 25 Jun 2019 19:12:39 GMT", "version": "v1" } ]
2019-06-27
[ [ "Zhang", "Yucheng", "" ], [ "Lobo-Mueller", "Edrise M.", "" ], [ "Karanicolas", "Paul", "" ], [ "Gallinger", "Steven", "" ], [ "Haider", "Masoom A.", "" ], [ "Khalvati", "Farzad", "" ] ]
Cox proportional hazard model (CPH) is commonly used in clinical research for survival analysis. In quantitative medical imaging (radiomics) studies, CPH plays an important role in feature reduction and modeling. However, the underlying linear assumption of CPH model limits the prognostic performance. In addition, the multicollinearity of radiomic features and multiple testing problem further impedes the CPH models performance. In this work, using transfer learning, a convolutional neural network (CNN) based survival model was built and tested on preoperative CT images of resectable Pancreatic Ductal Adenocarcinoma (PDAC) patients. The proposed CNN-based survival model outperformed the traditional CPH-based radiomics approach in terms of concordance index by 22%, providing a better fit for patients' survival patterns. The proposed CNN-based survival model outperforms CPH-based radiomics pipeline in PDAC prognosis. This approach offers a better fit for survival patterns based on CT images and overcomes the limitations of conventional survival models.
2003.11864
Meltem Civas
Ozgur B. Akan, Hamideh Ramezani, Meltem Civas, Oktay Cetinkaya, Bilgesu A. Bilgin, Naveed A. Abbasi
Information and Communication Theoretical Understanding and Treatment of Spinal Cord Injuries: State-of-the-art and Research Challenges
IEEE Reviews in Biomedical Engineering
null
10.1109/RBME.2021.3056455
null
q-bio.NC cs.ET
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Among the various key networks in the human body, the nervous system occupies central importance. The debilitating effects of spinal cord injuries (SCI) impact a significant number of people throughout the world, and to date, there is no satisfactory method to treat them. In this paper, we review the major treatment techniques for SCI that include promising solutions based on information and communication technology (ICT) and identify the key characteristics of such systems. We then introduce two novel ICT-based treatment approaches for SCI. The first proposal is based on neural interface systems (NIS) with enhanced feedback, where the external machines are interfaced with the brain and the spinal cord such that the brain signals are directly routed to the limbs for movement. The second proposal relates to the design of self-organizing artificial neurons (ANs) that can be used to replace the injured or dead biological neurons. Apart from SCI treatment, the proposed methods may also be utilized as enabling technologies for neural interface applications by acting as bio-cyber interfaces between the nervous system and machines. Furthermore, under the framework of Internet of Bio- Nano Things (IoBNT), experience gained from SCI treatment techniques can be transferred to nano communication research.
[ { "created": "Thu, 26 Mar 2020 12:32:46 GMT", "version": "v1" }, { "created": "Thu, 11 Mar 2021 16:50:07 GMT", "version": "v2" } ]
2021-03-12
[ [ "Akan", "Ozgur B.", "" ], [ "Ramezani", "Hamideh", "" ], [ "Civas", "Meltem", "" ], [ "Cetinkaya", "Oktay", "" ], [ "Bilgin", "Bilgesu A.", "" ], [ "Abbasi", "Naveed A.", "" ] ]
Among the various key networks in the human body, the nervous system occupies central importance. The debilitating effects of spinal cord injuries (SCI) impact a significant number of people throughout the world, and to date, there is no satisfactory method to treat them. In this paper, we review the major treatment techniques for SCI that include promising solutions based on information and communication technology (ICT) and identify the key characteristics of such systems. We then introduce two novel ICT-based treatment approaches for SCI. The first proposal is based on neural interface systems (NIS) with enhanced feedback, where the external machines are interfaced with the brain and the spinal cord such that the brain signals are directly routed to the limbs for movement. The second proposal relates to the design of self-organizing artificial neurons (ANs) that can be used to replace the injured or dead biological neurons. Apart from SCI treatment, the proposed methods may also be utilized as enabling technologies for neural interface applications by acting as bio-cyber interfaces between the nervous system and machines. Furthermore, under the framework of Internet of Bio- Nano Things (IoBNT), experience gained from SCI treatment techniques can be transferred to nano communication research.
1807.00509
David Hofmann
Chenfei Zhang, David Hofmann, Andreas Neef and Fred Wolf
Ultrafast population coding and axo-somatic compartmentalization
15 pages, 6 figures
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
Cortical neurons in the fluctuation driven regime can realize ultrafast population encoding. The underlying biophysical mechanisms, however, are not well understood. Reducing the sharpness of the action potential onset can impair ultrafast population encoding, but it is not clear whether a sharp action potential onset is sufficient for ultrafast population encoding. One hypothesis proposes that the sharp action potential onset is caused by the electrotonic separation of the site of action potential initiation from the soma, and that this spatial separation also results in ultrafast population encoding. Here we examined this hypothesis by studying the linear response properties of model neurons with a defined initiation site. We find that placing the initiation site at different axonal positions has only a weak impact on the linear response function of the model. It fails to generate the ultrafast response and high bandwidth that is observed in cortical neurons. Furthermore, the high frequency regime of the linear response function of this model is insensitive to correlation times of the input current contradicting empirical evidence. When we increase the voltage sensitivity of sodium channels at the initiation site, the two empirically observed phenomena can be recovered. We provide an explanation for the dissociation of sharp action potential onset and ultrafast response. By investigating varying soma sizes, we furthermore highlight the effect of neuron morphology on the linear response. Our results show that a sharp onset of action potentials is not sufficient for the ultrafast response. In the light of recent reports of activity-dependent repositioning of the axon initial segment, our study predicts that a more distal initiation site can lead to an increased sharpness of the somatic waveform but it does not affect the linear response of a population of neurons.
[ { "created": "Mon, 2 Jul 2018 08:04:57 GMT", "version": "v1" }, { "created": "Tue, 3 Jul 2018 09:24:14 GMT", "version": "v2" } ]
2018-07-04
[ [ "Zhang", "Chenfei", "" ], [ "Hofmann", "David", "" ], [ "Neef", "Andreas", "" ], [ "Wolf", "Fred", "" ] ]
Cortical neurons in the fluctuation driven regime can realize ultrafast population encoding. The underlying biophysical mechanisms, however, are not well understood. Reducing the sharpness of the action potential onset can impair ultrafast population encoding, but it is not clear whether a sharp action potential onset is sufficient for ultrafast population encoding. One hypothesis proposes that the sharp action potential onset is caused by the electrotonic separation of the site of action potential initiation from the soma, and that this spatial separation also results in ultrafast population encoding. Here we examined this hypothesis by studying the linear response properties of model neurons with a defined initiation site. We find that placing the initiation site at different axonal positions has only a weak impact on the linear response function of the model. It fails to generate the ultrafast response and high bandwidth that is observed in cortical neurons. Furthermore, the high frequency regime of the linear response function of this model is insensitive to correlation times of the input current contradicting empirical evidence. When we increase the voltage sensitivity of sodium channels at the initiation site, the two empirically observed phenomena can be recovered. We provide an explanation for the dissociation of sharp action potential onset and ultrafast response. By investigating varying soma sizes, we furthermore highlight the effect of neuron morphology on the linear response. Our results show that a sharp onset of action potentials is not sufficient for the ultrafast response. In the light of recent reports of activity-dependent repositioning of the axon initial segment, our study predicts that a more distal initiation site can lead to an increased sharpness of the somatic waveform but it does not affect the linear response of a population of neurons.
1411.1176
Masaki Watabe
Masaki Watabe, Satya N. V. Arjunan, Seiya Fukushima, Kazunari Iwamoto, Jun Kozuka, Satomi Matsuoka, Yuki Shindo, Masahiro Ueda and Koichi Takahashi
A computational framework for bioimaging simulation
57 pages
null
10.1371/journal.pone.0130089
null
q-bio.QM physics.bio-ph physics.optics
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Using bioimaging technology, biologists have attempted to identify and document analytical interpretations that underlie biological phenomena in biological cells. Theoretical biology aims at distilling those interpretations into knowledge in the mathematical form of biochemical reaction networks and understanding how higher level functions emerge from the combined action of biomolecules. However, there still remain formidable challenges in bridging the gap between bioimaging and mathematical modeling. Generally, measurements using fluorescence microscopy systems are influenced by systematic effects that arise from stochastic nature of biological cells, the imaging apparatus, and optical physics. Such systematic effects are always present in all bioimaging systems and hinder quantitative comparison between the cell model and bioimages. Computational tools for such a comparison are still unavailable. Thus, in this work, we present a computational framework for handling the parameters of the cell models and the optical physics governing bioimaging systems. Simulation using this framework can generate digital images of cell simulation results after accounting for the systematic effects. We then demonstrate that such a framework enables comparison at the level of photon-counting units.
[ { "created": "Wed, 5 Nov 2014 07:54:02 GMT", "version": "v1" }, { "created": "Thu, 13 Nov 2014 10:01:16 GMT", "version": "v2" }, { "created": "Mon, 8 Dec 2014 06:09:01 GMT", "version": "v3" }, { "created": "Thu, 19 Mar 2015 09:57:18 GMT", "version": "v4" }, { "cre...
2015-07-08
[ [ "Watabe", "Masaki", "" ], [ "Arjunan", "Satya N. V.", "" ], [ "Fukushima", "Seiya", "" ], [ "Iwamoto", "Kazunari", "" ], [ "Kozuka", "Jun", "" ], [ "Matsuoka", "Satomi", "" ], [ "Shindo", "Yuki", "" ], ...
Using bioimaging technology, biologists have attempted to identify and document analytical interpretations that underlie biological phenomena in biological cells. Theoretical biology aims at distilling those interpretations into knowledge in the mathematical form of biochemical reaction networks and understanding how higher level functions emerge from the combined action of biomolecules. However, there still remain formidable challenges in bridging the gap between bioimaging and mathematical modeling. Generally, measurements using fluorescence microscopy systems are influenced by systematic effects that arise from stochastic nature of biological cells, the imaging apparatus, and optical physics. Such systematic effects are always present in all bioimaging systems and hinder quantitative comparison between the cell model and bioimages. Computational tools for such a comparison are still unavailable. Thus, in this work, we present a computational framework for handling the parameters of the cell models and the optical physics governing bioimaging systems. Simulation using this framework can generate digital images of cell simulation results after accounting for the systematic effects. We then demonstrate that such a framework enables comparison at the level of photon-counting units.
1304.4216
Natalia Denesyuk
Natalia A. Denesyuk and D. Thirumalai
A Coarse-Grained Model for Predicting RNA Folding Thermodynamics
null
null
10.1021/jp401087x
null
q-bio.BM cond-mat.soft physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present a thermodynamically robust coarse-grained model to simulate folding of RNA in monovalent salt solutions. The model includes stacking, hydrogen bond and electrostatic interactions as fundamental components in describing the stability of RNA structures. The stacking interactions are parametrized using a set of nucleotide-specific parameters, which were calibrated against the thermodynamic measurements for single-base stacks and base-pair stacks. All hydrogen bonds are assumed to have the same strength, regardless of their context in the RNA structure. The ionic buffer is modeled implicitly, using the concept of counterion condensation and the Debye-H\"uckel theory. The three adjustable parameters in the model were determined by fitting the experimental data for two RNA hairpins and a pseudoknot. A single set of parameters provides good agreement with thermodynamic data for the three RNA molecules over a wide range of temperatures and salt concentrations. In the process of calibrating the model, we establish the extent of counterion condensation onto the single-stranded RNA backbone. The reduced backbone charge is independent of the ionic strength and is 60% of the RNA bare charge at 37 degrees Celsius. Our model can be used to predict the folding thermodynamics for any RNA molecule in the presence of monovalent ions.
[ { "created": "Mon, 15 Apr 2013 19:44:13 GMT", "version": "v1" } ]
2013-04-16
[ [ "Denesyuk", "Natalia A.", "" ], [ "Thirumalai", "D.", "" ] ]
We present a thermodynamically robust coarse-grained model to simulate folding of RNA in monovalent salt solutions. The model includes stacking, hydrogen bond and electrostatic interactions as fundamental components in describing the stability of RNA structures. The stacking interactions are parametrized using a set of nucleotide-specific parameters, which were calibrated against the thermodynamic measurements for single-base stacks and base-pair stacks. All hydrogen bonds are assumed to have the same strength, regardless of their context in the RNA structure. The ionic buffer is modeled implicitly, using the concept of counterion condensation and the Debye-H\"uckel theory. The three adjustable parameters in the model were determined by fitting the experimental data for two RNA hairpins and a pseudoknot. A single set of parameters provides good agreement with thermodynamic data for the three RNA molecules over a wide range of temperatures and salt concentrations. In the process of calibrating the model, we establish the extent of counterion condensation onto the single-stranded RNA backbone. The reduced backbone charge is independent of the ionic strength and is 60% of the RNA bare charge at 37 degrees Celsius. Our model can be used to predict the folding thermodynamics for any RNA molecule in the presence of monovalent ions.
1609.00658
Alexandre Castro
Alexandre de Castro
On the quantum principles of cognitive learning
null
Behav Brain Sci. 2013 Jun;36(3):281-2
10.1017/S0140525X12002919
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Pothos & Busemeyer's (P&B's) query about whether quantum probability can provide a foundation for the cognitive modeling embodies so many underlying implications that the subject is far from exhausted. In this brief commentary, however, I suggest that the conceptual thresholds of the meaningful learning give rise to a typical Boltzmann's weighting measure, which indicates a statistical verisimilitude of quantum behavior in the human cognitive ensemble.
[ { "created": "Sun, 14 Aug 2016 06:03:55 GMT", "version": "v1" } ]
2016-09-05
[ [ "de Castro", "Alexandre", "" ] ]
Pothos & Busemeyer's (P&B's) query about whether quantum probability can provide a foundation for the cognitive modeling embodies so many underlying implications that the subject is far from exhausted. In this brief commentary, however, I suggest that the conceptual thresholds of the meaningful learning give rise to a typical Boltzmann's weighting measure, which indicates a statistical verisimilitude of quantum behavior in the human cognitive ensemble.
1911.03839
Dongrui Wu
Bo Zhang and Yuqi Cui and Meng Wang and Jingjing Li and Lei Jin and Dongrui Wu
In Vitro Fertilization (IVF) Cumulative Pregnancy Rate Prediction from Basic Patient Characteristics
null
null
null
null
q-bio.QM cs.CY cs.LG stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Tens of millions of women suffer from infertility worldwide each year. In vitro fertilization (IVF) is the best choice for many such patients. However, IVF is expensive, time-consuming, and both physically and emotionally demanding. The first question that a patient usually asks before the IVF is how likely she will conceive, given her basic medical examination information. This paper proposes three approaches to predict the cumulative pregnancy rate after multiple oocyte pickup cycles. Experiments on 11,190 patients showed that first clustering the patients into different groups and then building a support vector machine model for each group can achieve the best overall performance. Our model could be a quick and economic approach for reliably estimating the cumulative pregnancy rate for a patient, given only her basic medical examination information, well before starting the actual IVF procedure. The predictions can help the patient make optimal decisions on whether to use her own oocyte or donor oocyte, how many oocyte pickup cycles she may need, whether to use embryo frozen, etc. They will also reduce the patient's cost and time to pregnancy, and improve her quality of life.
[ { "created": "Sun, 10 Nov 2019 03:00:07 GMT", "version": "v1" } ]
2019-11-12
[ [ "Zhang", "Bo", "" ], [ "Cui", "Yuqi", "" ], [ "Wang", "Meng", "" ], [ "Li", "Jingjing", "" ], [ "Jin", "Lei", "" ], [ "Wu", "Dongrui", "" ] ]
Tens of millions of women suffer from infertility worldwide each year. In vitro fertilization (IVF) is the best choice for many such patients. However, IVF is expensive, time-consuming, and both physically and emotionally demanding. The first question that a patient usually asks before the IVF is how likely she will conceive, given her basic medical examination information. This paper proposes three approaches to predict the cumulative pregnancy rate after multiple oocyte pickup cycles. Experiments on 11,190 patients showed that first clustering the patients into different groups and then building a support vector machine model for each group can achieve the best overall performance. Our model could be a quick and economic approach for reliably estimating the cumulative pregnancy rate for a patient, given only her basic medical examination information, well before starting the actual IVF procedure. The predictions can help the patient make optimal decisions on whether to use her own oocyte or donor oocyte, how many oocyte pickup cycles she may need, whether to use embryo frozen, etc. They will also reduce the patient's cost and time to pregnancy, and improve her quality of life.
1407.5586
Conrad Cabral
Conrad Cabral, Chintamani Pai, Kashmira Prasade, Smruti Deoghare, Urooz Kazi, Sonalia Fernandes
Variation in Microbial Growth under Hypergravity
6 pages, 4 figures
null
null
null
q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We report bacterial growth under hypergravitational stress. Cultures of E. coli and B. subtilis were subjected to the gravitational stress (38g) and their growth curves were measured using UV-VIS spectrophotometer. Experiments were also carried out to investigate nutrient consumption under hypergravitational conditions. Our results show considerable difference between samples subjected to hypergravity and normal conditions. This study has importance to understand bacterial response to external stress factors like gravity and changes in bacterial system in order to adapt with stress conditions for its survival.
[ { "created": "Mon, 21 Jul 2014 18:16:55 GMT", "version": "v1" } ]
2014-07-22
[ [ "Cabral", "Conrad", "" ], [ "Pai", "Chintamani", "" ], [ "Prasade", "Kashmira", "" ], [ "Deoghare", "Smruti", "" ], [ "Kazi", "Urooz", "" ], [ "Fernandes", "Sonalia", "" ] ]
We report bacterial growth under hypergravitational stress. Cultures of E. coli and B. subtilis were subjected to the gravitational stress (38g) and their growth curves were measured using UV-VIS spectrophotometer. Experiments were also carried out to investigate nutrient consumption under hypergravitational conditions. Our results show considerable difference between samples subjected to hypergravity and normal conditions. This study has importance to understand bacterial response to external stress factors like gravity and changes in bacterial system in order to adapt with stress conditions for its survival.
2208.07369
Norichika Ogata
Norichika Ogata and Aoi Hosaka
Cellular liberality is measurable as Lempel-Ziv complexity of fastq files
6 pages, single table, 4 figures
null
null
null
q-bio.QM cs.IT math.IT
http://creativecommons.org/licenses/by-nc-nd/4.0/
Many studies used the Shannon entropy of transcriptome data to determine cell dedifferentiation and differentiation. The collection of evidence has strengthened the certainty that the transcriptome's Shannon entropy may be used to quantify cellular dedifferentiation and differentiation. Quantifying this cellular status is being justified, we propose the term liberality for the quantitative value of cellular dedifferentiation and differentiation. In previous studies, we must convert the raw transcriptome data into quantitative transcriptome data through mapping, tag counting, assembling, and more bioinformatic processing to calculate the liberality. If we could remove this conversion step from estimating liberality, we could save computing resources and time and remove technical difficulties in using the computer. In this study, we propose a method of calculating cellular liberality without those transcriptome data conversion processes. We could calculate liberality by measuring the compression rate of raw transcriptome data. This technique, independent of reference genome data, increased the generality of cellular liberality.
[ { "created": "Sun, 14 Aug 2022 09:10:16 GMT", "version": "v1" }, { "created": "Fri, 2 Sep 2022 13:11:50 GMT", "version": "v2" }, { "created": "Mon, 3 Oct 2022 08:17:28 GMT", "version": "v3" }, { "created": "Wed, 19 Oct 2022 15:51:49 GMT", "version": "v4" } ]
2022-10-20
[ [ "Ogata", "Norichika", "" ], [ "Hosaka", "Aoi", "" ] ]
Many studies used the Shannon entropy of transcriptome data to determine cell dedifferentiation and differentiation. The collection of evidence has strengthened the certainty that the transcriptome's Shannon entropy may be used to quantify cellular dedifferentiation and differentiation. Quantifying this cellular status is being justified, we propose the term liberality for the quantitative value of cellular dedifferentiation and differentiation. In previous studies, we must convert the raw transcriptome data into quantitative transcriptome data through mapping, tag counting, assembling, and more bioinformatic processing to calculate the liberality. If we could remove this conversion step from estimating liberality, we could save computing resources and time and remove technical difficulties in using the computer. In this study, we propose a method of calculating cellular liberality without those transcriptome data conversion processes. We could calculate liberality by measuring the compression rate of raw transcriptome data. This technique, independent of reference genome data, increased the generality of cellular liberality.
1511.04345
Lilianne Mujica-Parodi
D.J. DeDora, S. Nedic, P. Katti, S. Arnab, L.L. Wald, A. Takahashi, K.R.A. Van Dijk, H.H. Strey, L.R. Mujica-Parodi
Signal Fluctuation Sensitivity: an improved metric for optimizing detection of resting-state fMRI networks
27 pages, 4 figures, 2 tables. Contact Information: Lilianne R. Mujica-Parodi, Laboratory for Computational Neurodiagnostics, Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, Lilianne.Strey@stonybrook.edu (www.lcneuro.org)
https://www.frontiersin.org/article/10.3389/fnins.2016.00180
10.3389/fnins.2016.00180
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Task-free connectivity analyses have emerged as a powerful tool in functional neuroimaging. Because the cross-correlations that underlie connectivity measures are sensitive to distortion of time-series, here we used a novel dynamic phantom to provide a ground truth for dynamic fidelity between blood oxygen level dependent (BOLD)-like inputs and fMRI outputs. We found that the de facto quality-metric for task-free fMRI, temporal signal to noise ratio (tSNR), correlated inversely with dynamic fidelity; thus, studies optimized for tSNR actually produced time-series that showed the greatest distortion of signal dynamics. Instead, the phantom showed that dynamic fidelity is reasonably approximated by a measure that, unlike tSNR, dissociates signal dynamics from scanner artifact. We then tested this measure, signal fluctuation sensitivity (SFS), against human resting-state data. As predicted by the phantom, SFS--and not tSNR--is associated with enhanced sensitivity to both local and long-range connectivity within the brain's default mode network.
[ { "created": "Fri, 13 Nov 2015 16:34:14 GMT", "version": "v1" } ]
2020-02-05
[ [ "DeDora", "D. J.", "" ], [ "Nedic", "S.", "" ], [ "Katti", "P.", "" ], [ "Arnab", "S.", "" ], [ "Wald", "L. L.", "" ], [ "Takahashi", "A.", "" ], [ "Van Dijk", "K. R. A.", "" ], [ "Strey", "H. H...
Task-free connectivity analyses have emerged as a powerful tool in functional neuroimaging. Because the cross-correlations that underlie connectivity measures are sensitive to distortion of time-series, here we used a novel dynamic phantom to provide a ground truth for dynamic fidelity between blood oxygen level dependent (BOLD)-like inputs and fMRI outputs. We found that the de facto quality-metric for task-free fMRI, temporal signal to noise ratio (tSNR), correlated inversely with dynamic fidelity; thus, studies optimized for tSNR actually produced time-series that showed the greatest distortion of signal dynamics. Instead, the phantom showed that dynamic fidelity is reasonably approximated by a measure that, unlike tSNR, dissociates signal dynamics from scanner artifact. We then tested this measure, signal fluctuation sensitivity (SFS), against human resting-state data. As predicted by the phantom, SFS--and not tSNR--is associated with enhanced sensitivity to both local and long-range connectivity within the brain's default mode network.
1001.4584
Yohsuke Murase
Yohsuke Murase, Takashi Shimada, Nobuyasu Ito, Per Arne Rikvold
Effects of demographic stochasticity on biological community assembly on evolutionary time scales
null
Phys. Rev. E 81, 041908 (2010)
10.1103/PhysRevE.81.041908
null
q-bio.PE cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We study the effects of demographic stochasticity on the long-term dynamics of biological coevolution models of community assembly. The noise is induced in order to check the validity of deterministic population dynamics. While mutualistic communities show little dependence on the stochastic population fluctuations, predator-prey models show strong dependence on the stochasticity, indicating the relevance of the finiteness of the populations. For a predator-prey model, the noise causes drastic decreases in diversity and total population size. The communities that emerge under influence of the noise consist of species strongly coupled with each other and have stronger linear stability around the fixed-point populations than the corresponding noiseless model. The dynamics on evolutionary time scales for the predator-prey model are also altered by the noise. Approximate $1/f$ fluctuations are observed with noise, while $1/f^{2}$ fluctuations are found for the model without demographic noise.
[ { "created": "Tue, 26 Jan 2010 02:42:18 GMT", "version": "v1" }, { "created": "Sun, 4 Apr 2010 02:59:09 GMT", "version": "v2" } ]
2010-04-16
[ [ "Murase", "Yohsuke", "" ], [ "Shimada", "Takashi", "" ], [ "Ito", "Nobuyasu", "" ], [ "Rikvold", "Per Arne", "" ] ]
We study the effects of demographic stochasticity on the long-term dynamics of biological coevolution models of community assembly. The noise is induced in order to check the validity of deterministic population dynamics. While mutualistic communities show little dependence on the stochastic population fluctuations, predator-prey models show strong dependence on the stochasticity, indicating the relevance of the finiteness of the populations. For a predator-prey model, the noise causes drastic decreases in diversity and total population size. The communities that emerge under influence of the noise consist of species strongly coupled with each other and have stronger linear stability around the fixed-point populations than the corresponding noiseless model. The dynamics on evolutionary time scales for the predator-prey model are also altered by the noise. Approximate $1/f$ fluctuations are observed with noise, while $1/f^{2}$ fluctuations are found for the model without demographic noise.
1210.6089
Gabriele Scheler
Gabriele Scheler
Self-organization of signal transduction
updated version, 13 pages, 4 figures, 3 Tables, supplemental table
F1000Research 2013, 2:116
10.12688/f1000research.2-116.v1
null
q-bio.MN q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We propose a model of parameter learning for signal transduction, where the objective function is defined by signal transmission efficiency. We apply this to learn kinetic rates as a form of evolutionary learning, and look for parameters which satisfy the objective. This is a novel approach compared to the usual technique of adjusting parameters only on the basis of experimental data. The resulting model is self-organizing, i.e. perturbations in protein concentrations or changes in extracellular signaling will automatically lead to adaptation. We systematically perturb protein concentrations and observe the response of the system. We find compensatory or co-regulation of protein expression levels. In a novel experiment, we alter the distribution of extracellular signaling, and observe adaptation based on optimizing signal transmission. We also discuss the relationship between signaling with and without transients. Signaling by transients may involve maximization of signal transmission efficiency for the peak response, but a minimization in steady-state responses. With an appropriate objective function, this can also be achieved by concentration adjustment. Self-organizing systems may be predictive of unwanted drug interference effects, since they aim to mimic complex cellular adaptation in a unified way.
[ { "created": "Tue, 23 Oct 2012 00:07:56 GMT", "version": "v1" }, { "created": "Tue, 8 Jan 2013 06:07:29 GMT", "version": "v2" } ]
2014-08-12
[ [ "Scheler", "Gabriele", "" ] ]
We propose a model of parameter learning for signal transduction, where the objective function is defined by signal transmission efficiency. We apply this to learn kinetic rates as a form of evolutionary learning, and look for parameters which satisfy the objective. This is a novel approach compared to the usual technique of adjusting parameters only on the basis of experimental data. The resulting model is self-organizing, i.e. perturbations in protein concentrations or changes in extracellular signaling will automatically lead to adaptation. We systematically perturb protein concentrations and observe the response of the system. We find compensatory or co-regulation of protein expression levels. In a novel experiment, we alter the distribution of extracellular signaling, and observe adaptation based on optimizing signal transmission. We also discuss the relationship between signaling with and without transients. Signaling by transients may involve maximization of signal transmission efficiency for the peak response, but a minimization in steady-state responses. With an appropriate objective function, this can also be achieved by concentration adjustment. Self-organizing systems may be predictive of unwanted drug interference effects, since they aim to mimic complex cellular adaptation in a unified way.
1906.03958
Collins Assisi
Rishika Mohanta and Collins Assisi
Parallel scalable simulations of biological neural networks using TensorFlow: A beginner's guide
Download the associated tutorials from https://github.com/neurorishika/PSST or http://doi.org/10.17605/OSF.IO/YBZKQ. You can also find them online as a JupyterBook here: https://neurorishika.github.io/PSST. Revision Notes: The manuscript and the online tutorials have been edited for clarity and enhanced readability based on NBDT reviewers' recommendations
null
null
null
q-bio.NC q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Biological neural networks are often modeled as systems of coupled, nonlinear, ordinary or partial differential equations. The number of differential equations used to model a network increases with the size of the network and the level of detail used to model individual neurons and synapses. As one scales up the size of the simulation, it becomes essential to utilize powerful computing platforms. While many tools exist that solve these equations numerically, they are often platform-specific. Further, there is a high barrier of entry to developing flexible platform-independent general-purpose code that supports hardware acceleration on modern computing architectures such as GPUs/TPUs and Distributed Platforms. TensorFlow is a Python-based open-source package designed for machine learning algorithms. However, it is also a scalable environment for a variety of computations, including solving differential equations using iterative algorithms such as Runge-Kutta methods. In this article and the accompanying tutorials, we present a simple exposition of numerical methods to solve ordinary differential equations using Python and TensorFlow. The tutorials consist of a series of Python notebooks that, over the course of five sessions, will lead novice programmers from writing programs to integrate simple one-dimensional ordinary differential equations using Python to solving a large system (1000's of differential equations) of coupled conductance-based neurons using a highly parallelized and scalable framework. Embedded with the tutorial is a physiologically realistic implementation of a network in the insect olfactory system. This system, consisting of multiple neuron and synapse types, can serve as a template to simulate other networks.
[ { "created": "Mon, 10 Jun 2019 13:01:57 GMT", "version": "v1" }, { "created": "Fri, 14 Jan 2022 06:54:26 GMT", "version": "v2" }, { "created": "Mon, 8 Aug 2022 15:21:13 GMT", "version": "v3" } ]
2022-08-09
[ [ "Mohanta", "Rishika", "" ], [ "Assisi", "Collins", "" ] ]
Biological neural networks are often modeled as systems of coupled, nonlinear, ordinary or partial differential equations. The number of differential equations used to model a network increases with the size of the network and the level of detail used to model individual neurons and synapses. As one scales up the size of the simulation, it becomes essential to utilize powerful computing platforms. While many tools exist that solve these equations numerically, they are often platform-specific. Further, there is a high barrier of entry to developing flexible platform-independent general-purpose code that supports hardware acceleration on modern computing architectures such as GPUs/TPUs and Distributed Platforms. TensorFlow is a Python-based open-source package designed for machine learning algorithms. However, it is also a scalable environment for a variety of computations, including solving differential equations using iterative algorithms such as Runge-Kutta methods. In this article and the accompanying tutorials, we present a simple exposition of numerical methods to solve ordinary differential equations using Python and TensorFlow. The tutorials consist of a series of Python notebooks that, over the course of five sessions, will lead novice programmers from writing programs to integrate simple one-dimensional ordinary differential equations using Python to solving a large system (1000's of differential equations) of coupled conductance-based neurons using a highly parallelized and scalable framework. Embedded with the tutorial is a physiologically realistic implementation of a network in the insect olfactory system. This system, consisting of multiple neuron and synapse types, can serve as a template to simulate other networks.
1707.08236
Youfang Cao
Youfang Cao, Anna Terebus, Jie Liang
State space truncation with quantified errors for accurate solutions to discrete Chemical Master Equation
41 pages, 6 figures
Bulletin of Mathematical Biology. 78 (2016) 617-661
10.1007/s11538-016-0149-1
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
The discrete chemical master equation (dCME) provides a general framework for studying stochasticity in mesoscopic reaction networks. Since its direct solution rapidly becomes intractable due to the increasing size of the state space, truncation of the state space is necessary for solving most dCMEs. It is therefore important to assess the consequences of state space truncations so errors can be quantified and minimized. Here we describe a novel method for state space truncation. By partitioning a reaction network into multiple molecular equivalence groups (MEG), we truncate the state space by limiting the total molecular copy numbers in each MEG. We further describe a theoretical framework for analysis of the truncation error in the steady state probability landscape using reflecting boundaries. By aggregating the state space based on the usage of a MEG and constructing an aggregated Markov process, we show that the truncation error of a MEG can be asymptotically bounded by the probability of states on the reflecting boundary of the MEG. Furthermore, truncating states of an arbitrary MEG will not undermine the estimated error of truncating any other MEGs. We then provide an error estimate for networks with multiple MEGs. To rapidly determine the appropriate size of an arbitrary MEG, we introduce an a priori method to estimate the upper bound of its truncation error, which can be rapidly computed from reaction rates, without costly trial solutions of the dCME. We show results of applying our methods to four stochastic networks. We demonstrate how truncation errors and steady state probability landscapes can be computed using different sizes of the MEG(s) and how the results validate out theories. Overall, the novel state space truncation and error analysis methods developed here can be used to ensure accurate direct solutions to the dCME for a large class of stochastic networks.
[ { "created": "Tue, 25 Jul 2017 21:58:30 GMT", "version": "v1" } ]
2017-07-27
[ [ "Cao", "Youfang", "" ], [ "Terebus", "Anna", "" ], [ "Liang", "Jie", "" ] ]
The discrete chemical master equation (dCME) provides a general framework for studying stochasticity in mesoscopic reaction networks. Since its direct solution rapidly becomes intractable due to the increasing size of the state space, truncation of the state space is necessary for solving most dCMEs. It is therefore important to assess the consequences of state space truncations so errors can be quantified and minimized. Here we describe a novel method for state space truncation. By partitioning a reaction network into multiple molecular equivalence groups (MEG), we truncate the state space by limiting the total molecular copy numbers in each MEG. We further describe a theoretical framework for analysis of the truncation error in the steady state probability landscape using reflecting boundaries. By aggregating the state space based on the usage of a MEG and constructing an aggregated Markov process, we show that the truncation error of a MEG can be asymptotically bounded by the probability of states on the reflecting boundary of the MEG. Furthermore, truncating states of an arbitrary MEG will not undermine the estimated error of truncating any other MEGs. We then provide an error estimate for networks with multiple MEGs. To rapidly determine the appropriate size of an arbitrary MEG, we introduce an a priori method to estimate the upper bound of its truncation error, which can be rapidly computed from reaction rates, without costly trial solutions of the dCME. We show results of applying our methods to four stochastic networks. We demonstrate how truncation errors and steady state probability landscapes can be computed using different sizes of the MEG(s) and how the results validate out theories. Overall, the novel state space truncation and error analysis methods developed here can be used to ensure accurate direct solutions to the dCME for a large class of stochastic networks.
1704.08583
Roberto Alamino
Roberto C. Alamino
A Model for Emergence of Multiple Anti-Microbial Resistance in a Petri Torus
7 pages, 7 figures
null
null
null
q-bio.PE cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This work introduces a new statistical physics lattice model of bacteria interacting with anti-microbial drugs that can reproduce qualitative features of resistance emergence and whose model parameters and outputs can be measured with controlled \textit{in vitro} experiments. The lattice is inhabited by agents modeled by Ising perceptrons. The results show the advantage of mixing drugs among the population compared to other treatment protocols.
[ { "created": "Tue, 25 Apr 2017 22:49:20 GMT", "version": "v1" }, { "created": "Tue, 16 May 2017 12:23:17 GMT", "version": "v2" } ]
2017-05-17
[ [ "Alamino", "Roberto C.", "" ] ]
This work introduces a new statistical physics lattice model of bacteria interacting with anti-microbial drugs that can reproduce qualitative features of resistance emergence and whose model parameters and outputs can be measured with controlled \textit{in vitro} experiments. The lattice is inhabited by agents modeled by Ising perceptrons. The results show the advantage of mixing drugs among the population compared to other treatment protocols.
1602.07170
Pramod Shinde
Pramod Shinde, Alok Yadav, Aparna Rai and Sarika Jalan
Dissortativity and duplications in Oral cancer
null
The European Physical Journal B. 2015 Aug 1;88(8):1-7
10.1140/epjb/e2015-60426-5
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
More than 300,000 new cases worldwide are being diagnosed with oral cancer annually. Complexity of oral cancer renders designing drug targets very difficult. We analyse protein-protein interaction network for the normal and oral cancer tissue and detect crucial changes in the structural properties of the networks in terms of the interactions of the hub proteins and the degree-degree correlations. Further analysis of the spectra of both the networks, while exhibiting universal statistical behavior, manifest distinction in terms of the zero degeneracy, providing insight to the complexity of the underlying system.
[ { "created": "Tue, 23 Feb 2016 14:42:48 GMT", "version": "v1" } ]
2016-03-08
[ [ "Shinde", "Pramod", "" ], [ "Yadav", "Alok", "" ], [ "Rai", "Aparna", "" ], [ "Jalan", "Sarika", "" ] ]
More than 300,000 new cases worldwide are being diagnosed with oral cancer annually. Complexity of oral cancer renders designing drug targets very difficult. We analyse protein-protein interaction network for the normal and oral cancer tissue and detect crucial changes in the structural properties of the networks in terms of the interactions of the hub proteins and the degree-degree correlations. Further analysis of the spectra of both the networks, while exhibiting universal statistical behavior, manifest distinction in terms of the zero degeneracy, providing insight to the complexity of the underlying system.
1007.0622
Masahiro Anazawa
Masahiro Anazawa
Combined effect of successive competition periods on population dynamics
20 pages, 4 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This study investigates the effect of competition between individuals on population dynamics when they compete for different resources during different seasons or during different growth stages. Individuals are assumed to compete for a single resource during each of these periods according to one of the following competition types: scramble, contest, or an intermediate between the two. The effect of two successive competition periods is determined to be expressed by simple relations on products of two "transition matrices" for various sets of competition types for the two periods. In particular, for the scramble and contest competition combination, results vary widely depending on the order of the two competition types. Furthermore, the stability properties of derived population models as well as the effect of more than two successive competition periods are discussed.
[ { "created": "Mon, 5 Jul 2010 06:18:54 GMT", "version": "v1" } ]
2010-07-06
[ [ "Anazawa", "Masahiro", "" ] ]
This study investigates the effect of competition between individuals on population dynamics when they compete for different resources during different seasons or during different growth stages. Individuals are assumed to compete for a single resource during each of these periods according to one of the following competition types: scramble, contest, or an intermediate between the two. The effect of two successive competition periods is determined to be expressed by simple relations on products of two "transition matrices" for various sets of competition types for the two periods. In particular, for the scramble and contest competition combination, results vary widely depending on the order of the two competition types. Furthermore, the stability properties of derived population models as well as the effect of more than two successive competition periods are discussed.
2308.09558
Pelin Icer Baykal
Pelin Icer Baykal, Pawe{\l} P. {\L}abaj, Florian Markowetz, Lynn M. Schriml, Daniel J. Stekhoven, Serghei Mangul, Niko Beerenwinkel
Genomic reproducibility in the bioinformatics era
10 pages, 2 figures, 2 tables
null
null
null
q-bio.GN
http://creativecommons.org/licenses/by/4.0/
In biomedical research, validation of a new scientific discovery is tied to the reproducibility of its experimental results. However, in genomics, the definition and implementation of reproducibility still remain imprecise. Here, we argue that genomic reproducibility, defined as the ability of bioinformatics tools to maintain consistent genomics results across technical replicates, is key to generating scientific knowledge and enabling medical applications. We first discuss different concepts of reproducibility and then focus on reproducibility in the context of genomics, aiming to establish clear definitions of relevant terms. We then focus on the role of bioinformatics tools and their impact on genomic reproducibility and assess methods of evaluating bioinformatics tools in terms of genomic reproducibility. Lastly, we suggest best practices for enhancing genomic reproducibility, with an emphasis on assessing the performance of bioinformatics tools through rigorous testing across multiple technical replicates.
[ { "created": "Fri, 18 Aug 2023 13:43:36 GMT", "version": "v1" } ]
2023-08-21
[ [ "Baykal", "Pelin Icer", "" ], [ "Łabaj", "Paweł P.", "" ], [ "Markowetz", "Florian", "" ], [ "Schriml", "Lynn M.", "" ], [ "Stekhoven", "Daniel J.", "" ], [ "Mangul", "Serghei", "" ], [ "Beerenwinkel", "Niko", ...
In biomedical research, validation of a new scientific discovery is tied to the reproducibility of its experimental results. However, in genomics, the definition and implementation of reproducibility still remain imprecise. Here, we argue that genomic reproducibility, defined as the ability of bioinformatics tools to maintain consistent genomics results across technical replicates, is key to generating scientific knowledge and enabling medical applications. We first discuss different concepts of reproducibility and then focus on reproducibility in the context of genomics, aiming to establish clear definitions of relevant terms. We then focus on the role of bioinformatics tools and their impact on genomic reproducibility and assess methods of evaluating bioinformatics tools in terms of genomic reproducibility. Lastly, we suggest best practices for enhancing genomic reproducibility, with an emphasis on assessing the performance of bioinformatics tools through rigorous testing across multiple technical replicates.
1312.6660
Mariano Sigman
Ariel D Zylberberg, Luciano Paz, Pieter R Roelfsema, Stanislas Dehaene, Mariano Sigman
A neuronal device for the control of multi-step computations
13 pages, 6 figures
Papers in Physics 5, 050006 (2013)
10.4279/PIP.050006
null
q-bio.NC
http://creativecommons.org/licenses/by/3.0/
We describe the operation of a neuronal device which embodies the computational principles of the `paper-and-pencil' machine envisioned by Alan Turing. The network is based on principles of cortical organization. We develop a plausible solution to implement pointers and investigate how neuronal circuits may instantiate the basic operations involved in assigning a value to a variable (i.e., x=5), in determining whether two variables have the same value and in retrieving the value of a given variable to be accessible to other nodes of the network. We exemplify the collective function of the network in simplified arithmetic and problem solving (blocks-world) tasks.
[ { "created": "Tue, 10 Dec 2013 13:55:34 GMT", "version": "v1" } ]
2013-12-24
[ [ "Zylberberg", "Ariel D", "" ], [ "Paz", "Luciano", "" ], [ "Roelfsema", "Pieter R", "" ], [ "Dehaene", "Stanislas", "" ], [ "Sigman", "Mariano", "" ] ]
We describe the operation of a neuronal device which embodies the computational principles of the `paper-and-pencil' machine envisioned by Alan Turing. The network is based on principles of cortical organization. We develop a plausible solution to implement pointers and investigate how neuronal circuits may instantiate the basic operations involved in assigning a value to a variable (i.e., x=5), in determining whether two variables have the same value and in retrieving the value of a given variable to be accessible to other nodes of the network. We exemplify the collective function of the network in simplified arithmetic and problem solving (blocks-world) tasks.
1710.10641
Qifan Yang
Qifan Yang, Gennady V. Roshchupkin, Wiro J. Niessen, Sarah E. Medland, Alyssa H. Zhu, Paul M. Thompson, Neda Jahanshad
A Fast, Accurate Two-Step Linear Mixed Model for Genetic Analysis Applied to Repeat MRI Measurements
2017 Neural Information Processing Systems (NeurIPS) BigNeuro Workshop
null
null
null
q-bio.QM stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Large-scale biobanks are being collected around the world in efforts to better understand human health and risk factors for disease. They often survey hundreds of thousands of individuals, combining questionnaires with clinical, genetic, demographic, and imaging assessments; some of this data may be collected longitudinally. Genetic associations analysis of such datasets requires methods to properly handle relatedness, population structure and other types of biases introduced by confounders. Most popular and accurate approaches rely on linear mixed model (LMM) algorithms, which are iterative and computational complexity of each iteration scales by the square of the sample size, slowing the pace of discoveries (up to several days for single trait analysis), and, furthermore, limiting the use of repeat phenotypic measurements. Here, we describe our new, non-iterative, much faster and accurate Two-Step Linear Mixed Model (Two-Step LMM) approach, that has a computational complexity that scales linearly with sample size. We show that the first step retains accurate estimates of the heritability (the proportion of the trait variance explained by additive genetic factors), even when increasingly complex genetic relationships between individuals are modeled. Second step provides a faster framework to obtain the effect sizes of covariates in regression model. We applied Two-Step LMM to real data from the UK Biobank, which recently released genotyping information and processed MRI data from 9,725 individuals. We used the left and right hippocampus volume (HV) as repeated measures, and observed increased and more accurate heritability estimation, consistent with simulations.
[ { "created": "Sun, 29 Oct 2017 16:24:40 GMT", "version": "v1" }, { "created": "Thu, 7 Dec 2017 13:07:09 GMT", "version": "v2" }, { "created": "Fri, 15 Feb 2019 01:42:45 GMT", "version": "v3" }, { "created": "Fri, 15 Mar 2019 19:01:43 GMT", "version": "v4" } ]
2019-03-19
[ [ "Yang", "Qifan", "" ], [ "Roshchupkin", "Gennady V.", "" ], [ "Niessen", "Wiro J.", "" ], [ "Medland", "Sarah E.", "" ], [ "Zhu", "Alyssa H.", "" ], [ "Thompson", "Paul M.", "" ], [ "Jahanshad", "Neda", "" ...
Large-scale biobanks are being collected around the world in efforts to better understand human health and risk factors for disease. They often survey hundreds of thousands of individuals, combining questionnaires with clinical, genetic, demographic, and imaging assessments; some of this data may be collected longitudinally. Genetic associations analysis of such datasets requires methods to properly handle relatedness, population structure and other types of biases introduced by confounders. Most popular and accurate approaches rely on linear mixed model (LMM) algorithms, which are iterative and computational complexity of each iteration scales by the square of the sample size, slowing the pace of discoveries (up to several days for single trait analysis), and, furthermore, limiting the use of repeat phenotypic measurements. Here, we describe our new, non-iterative, much faster and accurate Two-Step Linear Mixed Model (Two-Step LMM) approach, that has a computational complexity that scales linearly with sample size. We show that the first step retains accurate estimates of the heritability (the proportion of the trait variance explained by additive genetic factors), even when increasingly complex genetic relationships between individuals are modeled. Second step provides a faster framework to obtain the effect sizes of covariates in regression model. We applied Two-Step LMM to real data from the UK Biobank, which recently released genotyping information and processed MRI data from 9,725 individuals. We used the left and right hippocampus volume (HV) as repeated measures, and observed increased and more accurate heritability estimation, consistent with simulations.
2011.04415
Fernando Antoneli Jr
Jo\~ao Luiz de Oliveira Madeira, Fernando Antoneli
Homeostasis in Networks with Multiple Input Nodes and Robustness in Bacterial Chemotaxis
64 pages, 9 figures. Substantial revision with rearrangement of sections
null
null
null
q-bio.MN math.DS physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A biological system achieve homeostasis when there is a regulated quantity that is maintained within a narrow range of values. Here we consider homeostasis as a phenomenon of network dynamics. In this context, we improve a general theory for the analysis of homeostasis in network dynamical systems with distinguished input and output nodes, called `input-output networks'. The theory allows one to define `homeostasis types' of a given network in a `model independent' fashion, in the sense that the classification depends on the network topology rather than on the specific model equations. Each `homeostasis type' represents a possible mechanism for generating homeostasis and is associated with a suitable `subnetwork motif' of the original network. Our contribution is an extension of the theory to the case of networks with multiple input nodes. To showcase our theory, we apply it to bacterial chemotaxis, a paradigm for homeostasis in biochemical systems. By considering a representative model of Escherichia coli chemotaxis, we verify that the corresponding abstract network has multiple input nodes. Thus showing that our extension of the theory allows for the inclusion of an important class of models that were previously out of reach. Moreover, from our abstract point of view, the occurrence of homeostasis in the studied model is caused by a new mechanism, called input counterweight homeostasis. This new homeostasis mechanism was discovered in the course of our investigation and is generated by a balancing between the several input nodes of the network -- therefore, it requires the existence of at least two input nodes to occur. Finally, the framework developed here allows one to formalize a notion of `robustness' of homeostasis based on the concept of `genericity' from the theory dynamical systems. We discuss how this kind of robustness of homeostasis appears in the chemotaxis model.
[ { "created": "Thu, 5 Nov 2020 21:28:51 GMT", "version": "v1" }, { "created": "Fri, 16 Apr 2021 17:06:03 GMT", "version": "v2" }, { "created": "Tue, 25 Jan 2022 17:53:30 GMT", "version": "v3" } ]
2024-05-08
[ [ "Madeira", "João Luiz de Oliveira", "" ], [ "Antoneli", "Fernando", "" ] ]
A biological system achieve homeostasis when there is a regulated quantity that is maintained within a narrow range of values. Here we consider homeostasis as a phenomenon of network dynamics. In this context, we improve a general theory for the analysis of homeostasis in network dynamical systems with distinguished input and output nodes, called `input-output networks'. The theory allows one to define `homeostasis types' of a given network in a `model independent' fashion, in the sense that the classification depends on the network topology rather than on the specific model equations. Each `homeostasis type' represents a possible mechanism for generating homeostasis and is associated with a suitable `subnetwork motif' of the original network. Our contribution is an extension of the theory to the case of networks with multiple input nodes. To showcase our theory, we apply it to bacterial chemotaxis, a paradigm for homeostasis in biochemical systems. By considering a representative model of Escherichia coli chemotaxis, we verify that the corresponding abstract network has multiple input nodes. Thus showing that our extension of the theory allows for the inclusion of an important class of models that were previously out of reach. Moreover, from our abstract point of view, the occurrence of homeostasis in the studied model is caused by a new mechanism, called input counterweight homeostasis. This new homeostasis mechanism was discovered in the course of our investigation and is generated by a balancing between the several input nodes of the network -- therefore, it requires the existence of at least two input nodes to occur. Finally, the framework developed here allows one to formalize a notion of `robustness' of homeostasis based on the concept of `genericity' from the theory dynamical systems. We discuss how this kind of robustness of homeostasis appears in the chemotaxis model.
1610.03653
Ugo Bardi
Ilaria Perissi, Ugo Bardi, Toufic El Asmar, Alessandro Lavacchi
Dynamic patterns of overexploitation in fisheries
23 pages, 9 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Understanding overfishing phenomenon and regulating fishing quotas is a major global challenge for the 21st Century both in terms of providing food for humankind and to preserve the oceans ecosystems. However, fishing is a complex economic activity, affected not just by overfishing but also by such factors as pollution, technology, financial factors and more. For this reason, it is often difficult to state with complete certainty that overfishing is the cause of the decline of a fishery. In this study, we developed a simple dynamic model based on the earlier, well-known Lotka-Volterra model or Prey-Predator model. To describe exploitation patterns, we assume that the fish stock and the fishing industry are coupled stock variables in the model and they dynamically affect each other, with the fishing yield proportional to both the fishing capital and the fish stock. The model is based on the concept that the fishing industry acts as the predator of the resource and that its growth and subsequent decline is directly related to the abundance of the fish stock. If the model can be fit historical data relative to specific fisheries, then it is a strong indication that the fishing industry is strongly affected by the magnitude of the fish stock and that, in particular, the decline of the yield and the decline of the stock are linked to each other. The model does not pretend to be a general description of the fishing industry in all its varied forms; however, the data reported here show that the model can indeed qualitatively describe several historical case of the collapse of fisheries. The model can also be used as a qualitative guide to understand the behavior of several other fisheries. These result indicate that one of the main factors causing the present crisis of the world's fisheries is the overexploitation of the fish stocks.
[ { "created": "Wed, 12 Oct 2016 09:53:39 GMT", "version": "v1" }, { "created": "Wed, 26 Oct 2016 15:28:52 GMT", "version": "v2" } ]
2016-10-27
[ [ "Perissi", "Ilaria", "" ], [ "Bardi", "Ugo", "" ], [ "Asmar", "Toufic El", "" ], [ "Lavacchi", "Alessandro", "" ] ]
Understanding overfishing phenomenon and regulating fishing quotas is a major global challenge for the 21st Century both in terms of providing food for humankind and to preserve the oceans ecosystems. However, fishing is a complex economic activity, affected not just by overfishing but also by such factors as pollution, technology, financial factors and more. For this reason, it is often difficult to state with complete certainty that overfishing is the cause of the decline of a fishery. In this study, we developed a simple dynamic model based on the earlier, well-known Lotka-Volterra model or Prey-Predator model. To describe exploitation patterns, we assume that the fish stock and the fishing industry are coupled stock variables in the model and they dynamically affect each other, with the fishing yield proportional to both the fishing capital and the fish stock. The model is based on the concept that the fishing industry acts as the predator of the resource and that its growth and subsequent decline is directly related to the abundance of the fish stock. If the model can be fit historical data relative to specific fisheries, then it is a strong indication that the fishing industry is strongly affected by the magnitude of the fish stock and that, in particular, the decline of the yield and the decline of the stock are linked to each other. The model does not pretend to be a general description of the fishing industry in all its varied forms; however, the data reported here show that the model can indeed qualitatively describe several historical case of the collapse of fisheries. The model can also be used as a qualitative guide to understand the behavior of several other fisheries. These result indicate that one of the main factors causing the present crisis of the world's fisheries is the overexploitation of the fish stocks.
1206.0560
Alberto Mazzoni
Alberto Mazzoni, Nikos K. Logothetis and Stefano Panzeri
The information content of Local Field Potentials: experiments and models
To appear in Quian Quiroga and Panzeri (Eds) Principles of Neural Coding, CRC Press, 2012
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The LFPs is a broadband signal that captures variations of neural population activity over a wide range of time scales. The range of time scales available in LFPs is particularly interesting from the neural coding point of view because it opens up the possibility to investigate whether there are privileged time scales for information processing, a question that has been hotly debated over the last one or two decades.It is possible that information is represented by only a small number of specific frequency ranges, each carrying a separate contribution to the information representation. To shed light on this issue, it is important to quantify the information content of each frequency range of neural activity, and understand which ranges carry complementary or similar information.
[ { "created": "Mon, 4 Jun 2012 09:35:41 GMT", "version": "v1" } ]
2012-06-05
[ [ "Mazzoni", "Alberto", "" ], [ "Logothetis", "Nikos K.", "" ], [ "Panzeri", "Stefano", "" ] ]
The LFPs is a broadband signal that captures variations of neural population activity over a wide range of time scales. The range of time scales available in LFPs is particularly interesting from the neural coding point of view because it opens up the possibility to investigate whether there are privileged time scales for information processing, a question that has been hotly debated over the last one or two decades.It is possible that information is represented by only a small number of specific frequency ranges, each carrying a separate contribution to the information representation. To shed light on this issue, it is important to quantify the information content of each frequency range of neural activity, and understand which ranges carry complementary or similar information.
1608.04935
Mahmoud Hassan
Mahmoud Hassan, Isabelle Merlet, Ahmad Mheich, Aya Kabbara, Arnaud Biraben, Anca Nica and Fabrice Wendling
Identification of interictal epileptic networks from dense-EEG
30 pages, 5 figures
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Epilepsy is a network disease. The epileptic network usually involves spatially distributed brain regions. In this context, noninvasive M/EEG source connectivity is an emerging technique to identify functional brain networks at cortical level from noninvasive recordings. In this paper, we analyze the effect of the two key factors involved in EEG source connectivity processing: i) the algorithm used in the solution of the EEG inverse problem and ii) the method used in the estimation of the functional connectivity. We evaluate four inverse solutions algorithms and four connectivity measures on data simulated from a combined biophysical/physiological model to generate realistic interictal epileptic spikes reflected in scalp EEG. We use a new network-based similarity index (SI) to compare between the network identified by each of the inverse/connectivity combination and the original network generated in the model. The method will be also applied on real data recorded from one epileptic patient who underwent a full presurgical evaluation for drug-resistant focal epilepsy. In simulated data, results revealed that the selection of the inverse/connectivity combination has a significant impact on the identified networks. Results suggested that nonlinear methods for measuring the connectivity are more efficient than the linear one. The wMNE inverse solution showed higher performance than dSPM, cMEM and sLORETA. In real data, the combination (wMNE/PLV) led to a very good matching between the interictal epileptic network identified from noninvasive EEG recordings and the network obtained from connectivity analysis of intracerebral EEG recordings. These results suggest that source connectivity method, when appropriately configured, is able to extract highly relevant diagnostic information about networks involved in interictal epileptic spikes from non-invasive dense-EEG data.
[ { "created": "Wed, 17 Aug 2016 12:07:14 GMT", "version": "v1" } ]
2016-08-18
[ [ "Hassan", "Mahmoud", "" ], [ "Merlet", "Isabelle", "" ], [ "Mheich", "Ahmad", "" ], [ "Kabbara", "Aya", "" ], [ "Biraben", "Arnaud", "" ], [ "Nica", "Anca", "" ], [ "Wendling", "Fabrice", "" ] ]
Epilepsy is a network disease. The epileptic network usually involves spatially distributed brain regions. In this context, noninvasive M/EEG source connectivity is an emerging technique to identify functional brain networks at cortical level from noninvasive recordings. In this paper, we analyze the effect of the two key factors involved in EEG source connectivity processing: i) the algorithm used in the solution of the EEG inverse problem and ii) the method used in the estimation of the functional connectivity. We evaluate four inverse solutions algorithms and four connectivity measures on data simulated from a combined biophysical/physiological model to generate realistic interictal epileptic spikes reflected in scalp EEG. We use a new network-based similarity index (SI) to compare between the network identified by each of the inverse/connectivity combination and the original network generated in the model. The method will be also applied on real data recorded from one epileptic patient who underwent a full presurgical evaluation for drug-resistant focal epilepsy. In simulated data, results revealed that the selection of the inverse/connectivity combination has a significant impact on the identified networks. Results suggested that nonlinear methods for measuring the connectivity are more efficient than the linear one. The wMNE inverse solution showed higher performance than dSPM, cMEM and sLORETA. In real data, the combination (wMNE/PLV) led to a very good matching between the interictal epileptic network identified from noninvasive EEG recordings and the network obtained from connectivity analysis of intracerebral EEG recordings. These results suggest that source connectivity method, when appropriately configured, is able to extract highly relevant diagnostic information about networks involved in interictal epileptic spikes from non-invasive dense-EEG data.
1803.05012
Ryan Suderman
Ryan Suderman, G. Matthew Fricke, William S. Hlavacek
Using RuleBuilder to graphically define and visualize BioNetGen-language patterns and reaction rules
19 pages, 3 figures
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
RuleBuilder is a tool for drawing graphs that can be represented by the BioNetGen language (BNGL), which is used to formulate mathematical, rule-based models of biochemical systems. BNGL provides an intuitive plain-text, or string, representation of such systems, which is based on a graphical formalism. Reactions are defined in terms of graph-rewriting rules that specify the necessary intrinsic properties of the reactants, a transformation, and a rate law. Rules may also contain contextual constraints that restrict application of the rule. In some cases, the specification of contextual constraints can be verbose, making a rule difficult to read. RuleBuilder is designed to ease the task of reading and writing individual reaction rules, as well as individual BNGL patterns similar to those found in rules. The software assists in the reading of existing models by converting BNGL strings of interest into a graph-based representation composed of nodes and edges. RuleBuilder also enables the user to construct de novo a visual representation of BNGL strings using drawing tools available in its interface. As objects are added to the drawing canvas, the corresponding BNGL string is generated on the fly, and objects are similarly drawn on the fly as BNGL strings are entered into the application. RuleBuilder thus facilitates construction and interpretation of rule-based models.
[ { "created": "Tue, 13 Mar 2018 19:07:26 GMT", "version": "v1" } ]
2018-03-15
[ [ "Suderman", "Ryan", "" ], [ "Fricke", "G. Matthew", "" ], [ "Hlavacek", "William S.", "" ] ]
RuleBuilder is a tool for drawing graphs that can be represented by the BioNetGen language (BNGL), which is used to formulate mathematical, rule-based models of biochemical systems. BNGL provides an intuitive plain-text, or string, representation of such systems, which is based on a graphical formalism. Reactions are defined in terms of graph-rewriting rules that specify the necessary intrinsic properties of the reactants, a transformation, and a rate law. Rules may also contain contextual constraints that restrict application of the rule. In some cases, the specification of contextual constraints can be verbose, making a rule difficult to read. RuleBuilder is designed to ease the task of reading and writing individual reaction rules, as well as individual BNGL patterns similar to those found in rules. The software assists in the reading of existing models by converting BNGL strings of interest into a graph-based representation composed of nodes and edges. RuleBuilder also enables the user to construct de novo a visual representation of BNGL strings using drawing tools available in its interface. As objects are added to the drawing canvas, the corresponding BNGL string is generated on the fly, and objects are similarly drawn on the fly as BNGL strings are entered into the application. RuleBuilder thus facilitates construction and interpretation of rule-based models.
1605.07222
Vadim N. Biktashev
D. Hornung, V. N. Biktashev, N. F. Otani, T. K. Shajahan, T. Baig, S. Berg, S. Han, V. Krinsky, S. Luther
Mechanisms of vortices termination in the cardiac muscle
7 pages, 6 figures, as accepted to Royal Society Open Science
Roy Soc Open Science, 4: 170024, 2017
10.1007/s00285-013-0669-3
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We propose a solution to a long standing problem: how to terminate multiple vortices in the heart, when the locations of their cores and their critical time windows are unknown. We scan the phases of all pinned vortices in parallel with electric field pulses (E-pulses). We specify a condition on pacing parameters that guarantees termination of one vortex. For more than one vortex with significantly different frequencies, the success of scanning depends on chance, and all vortices are terminated with a success rate of less than one. We found that a similar mechanism terminates also a free (not pinned) vortex. A series of about 500 experiments with termination of ventricular fibrillation by E-pulses in pig isolated hearts is evidence that pinned vortices, hidden from direct observation, are significant in fibrillation. These results form a physical basis needed for the creation of new effective low energy defibrillation methods based on the termination of vortices underlying fibrillation.
[ { "created": "Mon, 23 May 2016 22:11:22 GMT", "version": "v1" }, { "created": "Fri, 27 May 2016 11:11:51 GMT", "version": "v2" }, { "created": "Mon, 13 Feb 2017 20:37:30 GMT", "version": "v3" }, { "created": "Wed, 15 Feb 2017 14:15:11 GMT", "version": "v4" } ]
2017-09-26
[ [ "Hornung", "D.", "" ], [ "Biktashev", "V. N.", "" ], [ "Otani", "N. F.", "" ], [ "Shajahan", "T. K.", "" ], [ "Baig", "T.", "" ], [ "Berg", "S.", "" ], [ "Han", "S.", "" ], [ "Krinsky", "V.", ...
We propose a solution to a long standing problem: how to terminate multiple vortices in the heart, when the locations of their cores and their critical time windows are unknown. We scan the phases of all pinned vortices in parallel with electric field pulses (E-pulses). We specify a condition on pacing parameters that guarantees termination of one vortex. For more than one vortex with significantly different frequencies, the success of scanning depends on chance, and all vortices are terminated with a success rate of less than one. We found that a similar mechanism terminates also a free (not pinned) vortex. A series of about 500 experiments with termination of ventricular fibrillation by E-pulses in pig isolated hearts is evidence that pinned vortices, hidden from direct observation, are significant in fibrillation. These results form a physical basis needed for the creation of new effective low energy defibrillation methods based on the termination of vortices underlying fibrillation.
2106.16059
Thomas Shultz
Thomas R Shultz, Ardavan S Nobandegani
A Computational Model of Infant Learning and Reasoning with Probabilities
To be published in Psychological Review
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Recent experiments reveal that 6- to 12-month-old infants can learn probabilities and reason with them. In this work, we present a novel computational system called Neural Probability Learner and Sampler (NPLS) that learns and reasons with probabilities, providing a computationally sufficient mechanism to explain infant probabilistic learning and inference. In 24 computer simulations, NPLS simulations show how probability distributions can emerge naturally from neural-network learning of event sequences, providing a novel explanation of infant probabilistic learning and reasoning. Three mathematical proofs show how and why NPLS simulates the infant results so accurately. The results are situated in relation to seven other active research lines. This work provides an effective way to integrate Bayesian and neural-network approaches to cognition.
[ { "created": "Wed, 30 Jun 2021 13:34:37 GMT", "version": "v1" } ]
2021-07-01
[ [ "Shultz", "Thomas R", "" ], [ "Nobandegani", "Ardavan S", "" ] ]
Recent experiments reveal that 6- to 12-month-old infants can learn probabilities and reason with them. In this work, we present a novel computational system called Neural Probability Learner and Sampler (NPLS) that learns and reasons with probabilities, providing a computationally sufficient mechanism to explain infant probabilistic learning and inference. In 24 computer simulations, NPLS simulations show how probability distributions can emerge naturally from neural-network learning of event sequences, providing a novel explanation of infant probabilistic learning and reasoning. Three mathematical proofs show how and why NPLS simulates the infant results so accurately. The results are situated in relation to seven other active research lines. This work provides an effective way to integrate Bayesian and neural-network approaches to cognition.
1306.2258
Konstantin Berlin
Konstantin Berlin, Nail A. Gumerov, Ramani Duraiswami, David Fushman
Performance of a GPU-based Direct Summation Algorithm for Computation of Small Angle Scattering Profile
null
null
null
null
q-bio.BM cs.DC physics.comp-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Small Angle Scattering (SAS) of X-rays or neutrons is an experimental technique that provides valuable structural information for biological macromolecules under physiological conditions and with no limitation on the molecular size. In order to refine molecular structure against experimental SAS data, ab initio prediction of the scattering profile must be recomputed hundreds of thousands of times, which involves the computation of the sinc kernel over all pairs of atoms in a molecule. The quadratic computational complexity of predicting the SAS profile limits the size of the molecules and and has been a major impediment for integration of SAS data into structure refinement protocols. In order to significantly speed up prediction of the SAS profile we present a general purpose graphical processing unit (GPU) algorithm, written in OpenCL, for the summation of the sinc kernel (Debye summation) over all pairs of atoms. This program is an order of magnitude faster than a parallel CPU algorithm, and faster than an FMM-like approximation method for certain input domains. We show that our algorithm is currently the fastest method for performing SAS computation for small and medium size molecules (around 50000 atoms or less). This algorithm is critical for quick and accurate SAS profile computation of elongated structures, such as DNA, RNA, and sparsely spaced pseudo-atom molecules.
[ { "created": "Mon, 10 Jun 2013 17:44:17 GMT", "version": "v1" } ]
2013-06-11
[ [ "Berlin", "Konstantin", "" ], [ "Gumerov", "Nail A.", "" ], [ "Duraiswami", "Ramani", "" ], [ "Fushman", "David", "" ] ]
Small Angle Scattering (SAS) of X-rays or neutrons is an experimental technique that provides valuable structural information for biological macromolecules under physiological conditions and with no limitation on the molecular size. In order to refine molecular structure against experimental SAS data, ab initio prediction of the scattering profile must be recomputed hundreds of thousands of times, which involves the computation of the sinc kernel over all pairs of atoms in a molecule. The quadratic computational complexity of predicting the SAS profile limits the size of the molecules and and has been a major impediment for integration of SAS data into structure refinement protocols. In order to significantly speed up prediction of the SAS profile we present a general purpose graphical processing unit (GPU) algorithm, written in OpenCL, for the summation of the sinc kernel (Debye summation) over all pairs of atoms. This program is an order of magnitude faster than a parallel CPU algorithm, and faster than an FMM-like approximation method for certain input domains. We show that our algorithm is currently the fastest method for performing SAS computation for small and medium size molecules (around 50000 atoms or less). This algorithm is critical for quick and accurate SAS profile computation of elongated structures, such as DNA, RNA, and sparsely spaced pseudo-atom molecules.
1301.1031
Kaushik Majumdar
Kaushik Majumdar, Pradeep D. Prasad and Shailesh Verma
Synchronization Implies Seizure or Seizure Implies Synchronization?
22 pages, 6 figures and 5 tables
null
null
null
q-bio.NC q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Epileptic seizures are considered as abnormally hypersynchronous neuronal activities of the brain. Do hypersynchronous neuronal activities in a brain region lead to seizure or the hypersynchronous activities take place due to the progression of the seizure? We have examined the ECoG signals of 21 epileptic patients consisting of 87 focal-onset seizures by three different measures namely, phase synchronization, amplitude correlation and simultaneous occurrence of peaks and troughs. Each of the measures indicates that for a majority of the focal-onset seizures, synchronization or correlation or simultaneity occurs towards the end of the seizure or even after the offset rather than at the onset or in the beginning or during the progression of the seizure. We also have outlined how extracellular acidosis caused due to the seizure in the focal zone can induce synchrony in the seizure generating network. This implies synchronization is an effect rather than the cause of a significant number of pharmacologically intractable focal-onset seizures. Since all the seizures that we have tested belong to the pharmacologically intractable class, their termination through more coherent neuronal activities may lead to new and effective ways of discovery and testing of drugs.
[ { "created": "Sun, 6 Jan 2013 17:39:51 GMT", "version": "v1" } ]
2013-01-08
[ [ "Majumdar", "Kaushik", "" ], [ "Prasad", "Pradeep D.", "" ], [ "Verma", "Shailesh", "" ] ]
Epileptic seizures are considered as abnormally hypersynchronous neuronal activities of the brain. Do hypersynchronous neuronal activities in a brain region lead to seizure or the hypersynchronous activities take place due to the progression of the seizure? We have examined the ECoG signals of 21 epileptic patients consisting of 87 focal-onset seizures by three different measures namely, phase synchronization, amplitude correlation and simultaneous occurrence of peaks and troughs. Each of the measures indicates that for a majority of the focal-onset seizures, synchronization or correlation or simultaneity occurs towards the end of the seizure or even after the offset rather than at the onset or in the beginning or during the progression of the seizure. We also have outlined how extracellular acidosis caused due to the seizure in the focal zone can induce synchrony in the seizure generating network. This implies synchronization is an effect rather than the cause of a significant number of pharmacologically intractable focal-onset seizures. Since all the seizures that we have tested belong to the pharmacologically intractable class, their termination through more coherent neuronal activities may lead to new and effective ways of discovery and testing of drugs.
1410.3456
Juven C. Wang
Juven Wang, Jiunn-Wei Chen
Gene-Mating Dynamic Evolution Theory I: Fundamental assumptions, exactly solvable models and analytic solutions
32 pages, 15 figures, 6 tables. (Work completed in 2006 and reported in 2014.) See Tables and Figures for a summary of key results, sequel arXiv:1502.07741. Blood type data of world ethnic groups from: http://www.bloodbook.com/world-abo.html and https://www.human-abo.org/. v3: Refinement, to appear on Theory in Biosciences - Springer
Theory in Biosciences 139, 105-134, Springer Nature (2020)
10.1007/s12064-020-00309-3
null
q-bio.PE nlin.CD physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Fundamental properties of macroscopic gene-mating dynamic evolutionary systems are investigated. We focus on a single locus, any number of alleles in a two-gender dioecious population, for a large class of systems within population genetics. Our governing equations are time-dependent differential equations labeled by a set of genotype frequencies. Our equations are uniquely derived from 4 assumptions within any population: (1) a closed system; (2) average-and-random mating process (mean-field behavior); (3) Mendelian inheritance; (4) exponential growth/death. Although our equations are nonlinear with time-evolutionary dynamics, we have obtained an exact analytic time-dependent solution and an exactly solvable model. From the phenomenological viewpoint, any initial parameter of genotype frequencies of a closed system will eventually approach a stable fixed point. Under time evolution, we show (1) the monotonic behavior of genotype frequencies, (2) any genotype or allele that appears in the population will never become extinct, (3) the Hardy-Weinberg law, and (4) the global stability without chaos in the parameter space. To demonstrate the experimental evidence for our theory, as an example, we show a mapping from the data of blood type genotype frequencies of world ethnic groups to our stable fixed-point solutions. This fixed-point Hardy-Weinberg manifold, attracting any initial point in any Euclidean fiber bounded within the genotype frequency space to the fixed point where this fiber is attached. The stable base manifold and its attached fibers form a fiber bundle, which fills in the whole genotype frequency space completely. We can define the genetic distance of two populations as their geodesic distance on the equilibrium manifold. The modification of our theory under the process of natural selection and mutation is addressed.
[ { "created": "Mon, 13 Oct 2014 19:58:20 GMT", "version": "v1" }, { "created": "Thu, 8 Jan 2015 18:44:54 GMT", "version": "v2" }, { "created": "Mon, 13 Jan 2020 03:00:00 GMT", "version": "v3" } ]
2020-07-22
[ [ "Wang", "Juven", "" ], [ "Chen", "Jiunn-Wei", "" ] ]
Fundamental properties of macroscopic gene-mating dynamic evolutionary systems are investigated. We focus on a single locus, any number of alleles in a two-gender dioecious population, for a large class of systems within population genetics. Our governing equations are time-dependent differential equations labeled by a set of genotype frequencies. Our equations are uniquely derived from 4 assumptions within any population: (1) a closed system; (2) average-and-random mating process (mean-field behavior); (3) Mendelian inheritance; (4) exponential growth/death. Although our equations are nonlinear with time-evolutionary dynamics, we have obtained an exact analytic time-dependent solution and an exactly solvable model. From the phenomenological viewpoint, any initial parameter of genotype frequencies of a closed system will eventually approach a stable fixed point. Under time evolution, we show (1) the monotonic behavior of genotype frequencies, (2) any genotype or allele that appears in the population will never become extinct, (3) the Hardy-Weinberg law, and (4) the global stability without chaos in the parameter space. To demonstrate the experimental evidence for our theory, as an example, we show a mapping from the data of blood type genotype frequencies of world ethnic groups to our stable fixed-point solutions. This fixed-point Hardy-Weinberg manifold, attracting any initial point in any Euclidean fiber bounded within the genotype frequency space to the fixed point where this fiber is attached. The stable base manifold and its attached fibers form a fiber bundle, which fills in the whole genotype frequency space completely. We can define the genetic distance of two populations as their geodesic distance on the equilibrium manifold. The modification of our theory under the process of natural selection and mutation is addressed.
2101.03163
Elham Ghazizadeh Ms
Elham Ghazizadeh, ShiNung Ching
Slow manifolds in recurrent networks encode working memory efficiently and robustly
null
null
10.1371/journal.pcbi.1009366
null
q-bio.NC cs.AI
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Working memory is a cognitive function involving the storage and manipulation of latent information over brief intervals of time, thus making it crucial for context-dependent computation. Here, we use a top-down modeling approach to examine network-level mechanisms of working memory, an enigmatic issue and central topic of study in neuroscience and machine intelligence. We train thousands of recurrent neural networks on a working memory task and then perform dynamical systems analysis on the ensuing optimized networks, wherein we find that four distinct dynamical mechanisms can emerge. In particular, we show the prevalence of a mechanism in which memories are encoded along slow stable manifolds in the network state space, leading to a phasic neuronal activation profile during memory periods. In contrast to mechanisms in which memories are directly encoded at stable attractors, these networks naturally forget stimuli over time. Despite this seeming functional disadvantage, they are more efficient in terms of how they leverage their attractor landscape and paradoxically, are considerably more robust to noise. Our results provide new dynamical hypotheses regarding how working memory function is encoded in both natural and artificial neural networks.
[ { "created": "Fri, 8 Jan 2021 18:47:02 GMT", "version": "v1" } ]
2021-11-17
[ [ "Ghazizadeh", "Elham", "" ], [ "Ching", "ShiNung", "" ] ]
Working memory is a cognitive function involving the storage and manipulation of latent information over brief intervals of time, thus making it crucial for context-dependent computation. Here, we use a top-down modeling approach to examine network-level mechanisms of working memory, an enigmatic issue and central topic of study in neuroscience and machine intelligence. We train thousands of recurrent neural networks on a working memory task and then perform dynamical systems analysis on the ensuing optimized networks, wherein we find that four distinct dynamical mechanisms can emerge. In particular, we show the prevalence of a mechanism in which memories are encoded along slow stable manifolds in the network state space, leading to a phasic neuronal activation profile during memory periods. In contrast to mechanisms in which memories are directly encoded at stable attractors, these networks naturally forget stimuli over time. Despite this seeming functional disadvantage, they are more efficient in terms of how they leverage their attractor landscape and paradoxically, are considerably more robust to noise. Our results provide new dynamical hypotheses regarding how working memory function is encoded in both natural and artificial neural networks.
2003.11363
Federico Zullo
Federico Zullo
Some numerical observations about the COVID-19 epidemic in Italy
This is versione n. 2. A section and two figures have been added 12 pages, 9 figures
null
null
null
q-bio.PE math.DS physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We give some numerical observations on the total number of infected by the SARS-CoV-2 in Italy. The analysis is based on a tanh formula involving two parameters. A polynomial correlation between the parameters gives an upper bound for the time of the peak of new infected. A numerical indicator of the temporal variability of the upper bound is introduced. The result and the possibility to extend the analysis to other countries are discussed in the conclusions.
[ { "created": "Wed, 25 Mar 2020 12:31:01 GMT", "version": "v1" }, { "created": "Sat, 11 Apr 2020 18:21:49 GMT", "version": "v2" } ]
2020-04-14
[ [ "Zullo", "Federico", "" ] ]
We give some numerical observations on the total number of infected by the SARS-CoV-2 in Italy. The analysis is based on a tanh formula involving two parameters. A polynomial correlation between the parameters gives an upper bound for the time of the peak of new infected. A numerical indicator of the temporal variability of the upper bound is introduced. The result and the possibility to extend the analysis to other countries are discussed in the conclusions.
1311.1120
Cory McLean
Eric Y. Durand and Nicholas Eriksson and Cory Y. McLean
Reducing pervasive false positive identical-by-descent segments detected by large-scale pedigree analysis
35 pages, 16 figures
null
null
null
q-bio.PE q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Analysis of genomic segments shared identical-by-descent (IBD) between individuals is fundamental to many genetic applications, from demographic inference to estimating the heritability of diseases, but IBD detection accuracy in non-simulated data is largely unknown. In principle, it can be evaluated using known pedigrees, as IBD segments are by definition inherited without recombination down a family tree. We extracted 25,432 genotyped European individuals containing 2,952 father-mother-child trios from the 23andMe, Inc. dataset. We then used GERMLINE, a widely used IBD detection method, to detect IBD segments within this cohort. Exploiting known familial relationships, we identified a false positive rate over 67% for 2-4 centiMorgan (cM) segments, in sharp contrast with accuracies reported in simulated data at these sizes. Nearly all false positives arose from the allowance of haplotype switch errors when detecting IBD, a necessity for retrieving long (> 6 cM) segments in the presence of imperfect phasing. We introduce HaploScore, a novel, computationally efficient metric that scores IBD segments proportional to the number of switch errors they contain. Applying HaploScore filtering to the IBD data at a precision of 0.8 produced a 13-fold increase in recall when compared to length-based filtering. We replicate the false IBD findings and demonstrate the generalizability of HaploScore to alternative data sources using an independent cohort of 555 European individuals from the 1000 Genomes project. HaploScore can improve the accuracy of segments reported by any IBD detection method, provided that estimates of the genotyping error rate and switch error rate are available.
[ { "created": "Tue, 5 Nov 2013 17:01:48 GMT", "version": "v1" }, { "created": "Fri, 7 Feb 2014 23:31:47 GMT", "version": "v2" } ]
2014-02-11
[ [ "Durand", "Eric Y.", "" ], [ "Eriksson", "Nicholas", "" ], [ "McLean", "Cory Y.", "" ] ]
Analysis of genomic segments shared identical-by-descent (IBD) between individuals is fundamental to many genetic applications, from demographic inference to estimating the heritability of diseases, but IBD detection accuracy in non-simulated data is largely unknown. In principle, it can be evaluated using known pedigrees, as IBD segments are by definition inherited without recombination down a family tree. We extracted 25,432 genotyped European individuals containing 2,952 father-mother-child trios from the 23andMe, Inc. dataset. We then used GERMLINE, a widely used IBD detection method, to detect IBD segments within this cohort. Exploiting known familial relationships, we identified a false positive rate over 67% for 2-4 centiMorgan (cM) segments, in sharp contrast with accuracies reported in simulated data at these sizes. Nearly all false positives arose from the allowance of haplotype switch errors when detecting IBD, a necessity for retrieving long (> 6 cM) segments in the presence of imperfect phasing. We introduce HaploScore, a novel, computationally efficient metric that scores IBD segments proportional to the number of switch errors they contain. Applying HaploScore filtering to the IBD data at a precision of 0.8 produced a 13-fold increase in recall when compared to length-based filtering. We replicate the false IBD findings and demonstrate the generalizability of HaploScore to alternative data sources using an independent cohort of 555 European individuals from the 1000 Genomes project. HaploScore can improve the accuracy of segments reported by any IBD detection method, provided that estimates of the genotyping error rate and switch error rate are available.
0807.3002
Su-Chan Park
J. Arjan G. M. de Visser, Su-Chan Park, and Joachim Krug
Exploring the effect of sex on an empirical fitness landscape
null
American Naturalist 174 (2009) S15-S30 (with substantial revisions)
null
null
q-bio.PE cond-mat.dis-nn
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The nature of epistasis has important consequences for the evolutionary significance of sex and recombination. Recent efforts to find negative epistasis as source of negative linkage disequilibrium and associated long-term sex advantage have yielded little support. Sign epistasis, where the sign of the fitness effects of alleles varies across genetic backgrounds, is responsible for ruggedness of the fitness landscape with implications for the evolution of sex that have been largely unexplored. Here, we describe fitness landscapes for two sets of strains of the asexual fungus \emph{Aspergillus niger} involving all combinations of five mutations. We find that $\sim 30$% of the single-mutation fitness effects are positive despite their negative effect in the wild-type strain, and that several local fitness maxima and minima are present. We then compare adaptation of sexual and asexual populations on these empirical fitness landscapes using simulations. The results show a general disadvantage of sex on these rugged landscapes, caused by the break down by recombination of genotypes escaping from local peaks. Sex facilitates escape from a local peak only for some parameter values on one landscape, indicating its dependence on the landscape's topography. We discuss possible reasons for the discrepancy between our results and the reports of faster adaptation of sexual populations.
[ { "created": "Fri, 18 Jul 2008 16:15:31 GMT", "version": "v1" } ]
2009-10-02
[ [ "de Visser", "J. Arjan G. M.", "" ], [ "Park", "Su-Chan", "" ], [ "Krug", "Joachim", "" ] ]
The nature of epistasis has important consequences for the evolutionary significance of sex and recombination. Recent efforts to find negative epistasis as source of negative linkage disequilibrium and associated long-term sex advantage have yielded little support. Sign epistasis, where the sign of the fitness effects of alleles varies across genetic backgrounds, is responsible for ruggedness of the fitness landscape with implications for the evolution of sex that have been largely unexplored. Here, we describe fitness landscapes for two sets of strains of the asexual fungus \emph{Aspergillus niger} involving all combinations of five mutations. We find that $\sim 30$% of the single-mutation fitness effects are positive despite their negative effect in the wild-type strain, and that several local fitness maxima and minima are present. We then compare adaptation of sexual and asexual populations on these empirical fitness landscapes using simulations. The results show a general disadvantage of sex on these rugged landscapes, caused by the break down by recombination of genotypes escaping from local peaks. Sex facilitates escape from a local peak only for some parameter values on one landscape, indicating its dependence on the landscape's topography. We discuss possible reasons for the discrepancy between our results and the reports of faster adaptation of sexual populations.
1803.00643
Ran Darshan
Ran Darshan, Carl van Vreeswijk and David Hansel
How strong are correlations in strongly recurrent neuronal networks?
null
Phys. Rev. X 8, 031072 (2018)
10.1103/PhysRevX.8.031072
null
q-bio.NC cond-mat.dis-nn nlin.CD physics.bio-ph
http://creativecommons.org/licenses/by-sa/4.0/
Cross-correlations in the activity in neural networks are commonly used to characterize their dynamical states and their anatomical and functional organizations. Yet, how these latter network features affect the spatiotemporal structure of the correlations in recurrent networks is not fully understood. Here, we develop a general theory for the emergence of correlated neuronal activity from the dynamics in strongly recurrent networks consisting of several populations of binary neurons. We apply this theory to the case in which the connectivity depends on the anatomical or functional distance between the neurons. We establish the architectural conditions under which the system settles into a dynamical state where correlations are strong, highly robust and spatially modulated. We show that such strong correlations arise if the network exhibits an effective feedforward structure. We establish how this feedforward structure determines the way correlations scale with the network size and the degree of the connectivity. In networks lacking an effective feedforward structure correlations are extremely small and only weakly depend on the number of connections per neuron. Our work shows how strong correlations can be consistent with highly irregular activity in recurrent networks, two key features of neuronal dynamics in the central nervous system.
[ { "created": "Thu, 1 Mar 2018 21:51:39 GMT", "version": "v1" } ]
2018-09-26
[ [ "Darshan", "Ran", "" ], [ "van Vreeswijk", "Carl", "" ], [ "Hansel", "David", "" ] ]
Cross-correlations in the activity in neural networks are commonly used to characterize their dynamical states and their anatomical and functional organizations. Yet, how these latter network features affect the spatiotemporal structure of the correlations in recurrent networks is not fully understood. Here, we develop a general theory for the emergence of correlated neuronal activity from the dynamics in strongly recurrent networks consisting of several populations of binary neurons. We apply this theory to the case in which the connectivity depends on the anatomical or functional distance between the neurons. We establish the architectural conditions under which the system settles into a dynamical state where correlations are strong, highly robust and spatially modulated. We show that such strong correlations arise if the network exhibits an effective feedforward structure. We establish how this feedforward structure determines the way correlations scale with the network size and the degree of the connectivity. In networks lacking an effective feedforward structure correlations are extremely small and only weakly depend on the number of connections per neuron. Our work shows how strong correlations can be consistent with highly irregular activity in recurrent networks, two key features of neuronal dynamics in the central nervous system.