id
stringlengths
9
13
submitter
stringlengths
4
48
authors
stringlengths
4
9.62k
title
stringlengths
4
343
comments
stringlengths
2
480
journal-ref
stringlengths
9
309
doi
stringlengths
12
138
report-no
stringclasses
277 values
categories
stringlengths
8
87
license
stringclasses
9 values
orig_abstract
stringlengths
27
3.76k
versions
listlengths
1
15
update_date
stringlengths
10
10
authors_parsed
listlengths
1
147
abstract
stringlengths
24
3.75k
q-bio/0309030
Amit Manwani
A. Manwani and C. Koch (California Institute of Technology, Pasadena)
Synaptic Transmission: An Information-Theoretic Perspective
7 pages, 4 figures, NIPS97 proceedings: neuroscience. Originally submitted to the neuro-sys archive which was never publicly announced (was 9809002)
Advances in Neural Information Processing Systems 10, Michael I. Jordan, Michael J. Kearns and Sara Solla (eds.), 1997
null
null
q-bio.NC
null
Here we analyze synaptic transmission from an information-theoretic perspective. We derive closed-form expressions for the lower-bounds on the capacity of a simple model of a cortical synapse under two explicit coding paradigms. Under the ``signal estimation'' paradigm, we assume the signal to be encoded in the mean firing rate of a Poisson neuron. The performance of an optimal linear estimator of the signal then provides a lower bound on the capacity for signal estimation. Under the ``signal detection'' paradigm, the presence or absence of the signal has to be detected. Performance of the optimal spike detector allows us to compute a lower bound on the capacity for signal detection. We find that single synapses (for empirically measured parameter values) transmit information poorly but significant improvement can be achieved with a small amount of redundancy.
[ { "created": "Tue, 22 Sep 1998 20:07:14 GMT", "version": "v1" } ]
2007-05-23
[ [ "Manwani", "A.", "", "California Institute of Technology, Pasadena" ], [ "Koch", "C.", "", "California Institute of Technology, Pasadena" ] ]
Here we analyze synaptic transmission from an information-theoretic perspective. We derive closed-form expressions for the lower-bounds on the capacity of a simple model of a cortical synapse under two explicit coding paradigms. Under the ``signal estimation'' paradigm, we assume the signal to be encoded in the mean firing rate of a Poisson neuron. The performance of an optimal linear estimator of the signal then provides a lower bound on the capacity for signal estimation. Under the ``signal detection'' paradigm, the presence or absence of the signal has to be detected. Performance of the optimal spike detector allows us to compute a lower bound on the capacity for signal detection. We find that single synapses (for empirically measured parameter values) transmit information poorly but significant improvement can be achieved with a small amount of redundancy.
2011.08308
Leah B. Shaw
Fangming Xu, Leah B. Shaw, Junping Shi, Romuald N. Lipcius
Impacts of density-dependent predation, cannibalism and fishing in a stage-structured population model of the blue crab in Chesapeake Bay
null
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The blue crab (Callinectes sapidus) is a dominant ecological species of high commercial value. Spawning stock and recruitment of the Chesapeake Bay population declined by 80% in the 1990s. After severe management actions were implemented in 2008, female abundance rebounded to pre-1994 levels and stabilized. The stepwise decline in the early 1990s, followed by a consistently low level of abundance for 15 y and a jump to high abundance after 2008, suggested the existence of alternative stable states. Alternatively, high fishing pressure combined with low recruitment in 1992 could have triggered a proportional decline in the population, followed by a population increase in 2008 due to rigorous management actions that reduced fishing. We evaluated these alternatives with a stage-structured dynamic population model using ordinary differential equations. In addition, stock assessment models assume that fishing and mortality are independent of density. Hence, we also investigated the role of density-dependent predation, cannibalism and fishing in blue crab population dynamics. We conclude that for the blue crab population in Chesapeake Bay: (1) bistable positive states are not likely with biologically realistic parameter values; (2) hyperbolic (depensatory) fishing will not produce extinction at the range of population densities observed in the bay; and (3) crabs can survive a higher fishing rate under the more realistic assumption of sigmoidal (density-dependent) predation and cannibalism than under constant (density-independent) predation and cannibalism. These collectively indicate that the blue crab population in Chesapeake Bay is resilient to a range of biotic and abiotic disturbances.
[ { "created": "Mon, 16 Nov 2020 22:13:30 GMT", "version": "v1" } ]
2020-11-18
[ [ "Xu", "Fangming", "" ], [ "Shaw", "Leah B.", "" ], [ "Shi", "Junping", "" ], [ "Lipcius", "Romuald N.", "" ] ]
The blue crab (Callinectes sapidus) is a dominant ecological species of high commercial value. Spawning stock and recruitment of the Chesapeake Bay population declined by 80% in the 1990s. After severe management actions were implemented in 2008, female abundance rebounded to pre-1994 levels and stabilized. The stepwise decline in the early 1990s, followed by a consistently low level of abundance for 15 y and a jump to high abundance after 2008, suggested the existence of alternative stable states. Alternatively, high fishing pressure combined with low recruitment in 1992 could have triggered a proportional decline in the population, followed by a population increase in 2008 due to rigorous management actions that reduced fishing. We evaluated these alternatives with a stage-structured dynamic population model using ordinary differential equations. In addition, stock assessment models assume that fishing and mortality are independent of density. Hence, we also investigated the role of density-dependent predation, cannibalism and fishing in blue crab population dynamics. We conclude that for the blue crab population in Chesapeake Bay: (1) bistable positive states are not likely with biologically realistic parameter values; (2) hyperbolic (depensatory) fishing will not produce extinction at the range of population densities observed in the bay; and (3) crabs can survive a higher fishing rate under the more realistic assumption of sigmoidal (density-dependent) predation and cannibalism than under constant (density-independent) predation and cannibalism. These collectively indicate that the blue crab population in Chesapeake Bay is resilient to a range of biotic and abiotic disturbances.
1911.10452
Toan T. Nguyen
Ly Hai Nguyen, Tuyen Thanh Tran, Lien Ngoc Thi Truong, Hanh Hong Mai, and Toan T. Nguyen
Overcharging of zinc ion in the structure of zinc finger protein is needed for DNA binding stability
33 pages, 9 figures, improved presentation
null
10.1021/acs.biochem.9b01055
null
q-bio.BM cond-mat.soft
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The zinc finger structure where a Zn2+ ion binds to 4 cysteine or histidine amino acids in a tetrahedral structure is very common motif of nucleic acid binding proteins. The corresponding interaction model is present in 3% of the genes of human genome. As a result, zinc finger has been shown to be extremely useful in various therapeutic and research capacities, as well as in biotechnology. In stable configuration, the cysteine amino acids are deprotonated and become negatively charged. This means the Zn2+ ion is overscreened by 4 cysteine charges (overcharged). It is question of whether this overcharged configuration is also stable when such negatively charged zinc finger binds to negatively charged DNA molecule. Using all atom molecular dynamics simulation up to microsecond range of an androgen receptor protein dimer, we investigate how the deprotonated state of cysteine influences its structure, dynamics, and function in binding o DNA molecules. Our results show that the deprotonated state of cysteine residues are essential for mechanical stabilization of the functional, folded conformation. Not only this state stabilizes the protein structure, it also stabilizes the protein-DNA binding complex. The differences in structural and energetic properties of the two (sequence-identical) monomers are also investigated showing the strong influence of DNA on the structure of zinc fingers upon complexation. Our result has potential impact on better molecular understanding of one of the most common classes of zinc fingers
[ { "created": "Sun, 24 Nov 2019 03:30:34 GMT", "version": "v1" }, { "created": "Sat, 22 Feb 2020 04:55:26 GMT", "version": "v2" } ]
2020-02-25
[ [ "Nguyen", "Ly Hai", "" ], [ "Tran", "Tuyen Thanh", "" ], [ "Truong", "Lien Ngoc Thi", "" ], [ "Mai", "Hanh Hong", "" ], [ "Nguyen", "Toan T.", "" ] ]
The zinc finger structure where a Zn2+ ion binds to 4 cysteine or histidine amino acids in a tetrahedral structure is very common motif of nucleic acid binding proteins. The corresponding interaction model is present in 3% of the genes of human genome. As a result, zinc finger has been shown to be extremely useful in various therapeutic and research capacities, as well as in biotechnology. In stable configuration, the cysteine amino acids are deprotonated and become negatively charged. This means the Zn2+ ion is overscreened by 4 cysteine charges (overcharged). It is question of whether this overcharged configuration is also stable when such negatively charged zinc finger binds to negatively charged DNA molecule. Using all atom molecular dynamics simulation up to microsecond range of an androgen receptor protein dimer, we investigate how the deprotonated state of cysteine influences its structure, dynamics, and function in binding o DNA molecules. Our results show that the deprotonated state of cysteine residues are essential for mechanical stabilization of the functional, folded conformation. Not only this state stabilizes the protein structure, it also stabilizes the protein-DNA binding complex. The differences in structural and energetic properties of the two (sequence-identical) monomers are also investigated showing the strong influence of DNA on the structure of zinc fingers upon complexation. Our result has potential impact on better molecular understanding of one of the most common classes of zinc fingers
1505.00775
Danko Nikolic
Danko Nikoli\'c
Only T3-AI can reach human-level intelligence: A variety argument
18 page, 6800 words, no figures
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The recently introduced theory of practopoiesis offers an account on how adaptive intelligent systems are organized. According to that theory biological agents adapt at three levels of organization and this structure applies also to our brains. This is referred to as tri-traversal theory of the organization of mind or for short, a T3-structure. To implement a similar T3-organization in an artificially intelligent agent, it is necessary to have multiple policies, as usually used as a concept in the theory of reinforcement learning. These policies have to form a hierarchy. We define adaptive practopoietic systems in terms of hierarchy of policies and calculate whether the total variety of behavior required by real-life conditions of an adult human can be satisfactorily accounted for by a traditional approach to artificial intelligence based on T2-agents, or whether a T3-agent is needed instead. We conclude that the complexity of real life can be dealt with appropriately only by a T3-agent.
[ { "created": "Sat, 2 May 2015 12:58:02 GMT", "version": "v1" }, { "created": "Thu, 16 Jul 2015 09:29:50 GMT", "version": "v2" } ]
2015-07-17
[ [ "Nikolić", "Danko", "" ] ]
The recently introduced theory of practopoiesis offers an account on how adaptive intelligent systems are organized. According to that theory biological agents adapt at three levels of organization and this structure applies also to our brains. This is referred to as tri-traversal theory of the organization of mind or for short, a T3-structure. To implement a similar T3-organization in an artificially intelligent agent, it is necessary to have multiple policies, as usually used as a concept in the theory of reinforcement learning. These policies have to form a hierarchy. We define adaptive practopoietic systems in terms of hierarchy of policies and calculate whether the total variety of behavior required by real-life conditions of an adult human can be satisfactorily accounted for by a traditional approach to artificial intelligence based on T2-agents, or whether a T3-agent is needed instead. We conclude that the complexity of real life can be dealt with appropriately only by a T3-agent.
1501.07854
Subhadip Raychaudhuri
Subhadip Raychaudhuri
Kinetic Monte Carlo study of the type1/type 2 choice in apoptosis elucidates selective killing of cancer cells under death ligand induction
31 pages, 11 figures
OJApo 4 (2015) 22-39
10.4236/ojapo.2015.41003
null
q-bio.CB physics.bio-ph
http://creativecommons.org/licenses/by/3.0/
Death ligand mediated apoptotic activation is a mode of programmed cell death that is widely used in cellular and physiological situations. Interest in studying death ligand induced apoptosis has increased due to the promising role of recombinant soluble forms of death ligands (mainly recombinant TRAIL) in anti-cancer therapy. A clear elucidation of how death ligands activate the type 1 and type 2 apoptotic pathways in healthy and cancer cells may help develop better chemotherapeutic strategies. In this work, we use kinetic Monte Carlo simulations to address the problem of type 1/ type 2 choice in death ligand mediated apoptosis of cancer cells. Our study provides insights into the activation of membrane proximal death module that results from complex interplay between death and decoy receptors. Relative abundance of death and decoy receptors was shown to be a key parameter for activation of the initiator caspases in the membrane module. Increased concentration of death ligands frequently increased the type 1 activation fraction in cancer cells, and, in certain cases changes the signaling phenotype from type 2 to type 1. Results of this study also indicate that inherent differences between cancer and healthy cells, such as in the membrane module, may allow robust activation of cancer cell apoptosis by death ligand induction. At the same time, large cell-to-cell variability through the type 2 pathway was shown to provide protection for healthy cells. Such elucidation of selective activation of apoptosis in cancer cells addresses a key question in cancer biology and cancer therapy.
[ { "created": "Fri, 30 Jan 2015 17:29:26 GMT", "version": "v1" } ]
2015-02-02
[ [ "Raychaudhuri", "Subhadip", "" ] ]
Death ligand mediated apoptotic activation is a mode of programmed cell death that is widely used in cellular and physiological situations. Interest in studying death ligand induced apoptosis has increased due to the promising role of recombinant soluble forms of death ligands (mainly recombinant TRAIL) in anti-cancer therapy. A clear elucidation of how death ligands activate the type 1 and type 2 apoptotic pathways in healthy and cancer cells may help develop better chemotherapeutic strategies. In this work, we use kinetic Monte Carlo simulations to address the problem of type 1/ type 2 choice in death ligand mediated apoptosis of cancer cells. Our study provides insights into the activation of membrane proximal death module that results from complex interplay between death and decoy receptors. Relative abundance of death and decoy receptors was shown to be a key parameter for activation of the initiator caspases in the membrane module. Increased concentration of death ligands frequently increased the type 1 activation fraction in cancer cells, and, in certain cases changes the signaling phenotype from type 2 to type 1. Results of this study also indicate that inherent differences between cancer and healthy cells, such as in the membrane module, may allow robust activation of cancer cell apoptosis by death ligand induction. At the same time, large cell-to-cell variability through the type 2 pathway was shown to provide protection for healthy cells. Such elucidation of selective activation of apoptosis in cancer cells addresses a key question in cancer biology and cancer therapy.
1705.07441
Alireza Alemi
Alireza Alemi and Alia Abbara
Exponential Capacity in an Autoencoder Neural Network with a Hidden Layer
3 figures, 14 pages
null
null
null
q-bio.NC cond-mat.dis-nn
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A fundamental aspect of limitations in learning any computation in neural architectures is characterizing their optimal capacities. An important, widely-used neural architecture is known as autoencoders where the network reconstructs the input at the output layer via a representation at a hidden layer. Even though capacities of several neural architectures have been addressed using statistical physics methods, the capacity of autoencoder neural networks is not well-explored. Here, we analytically show that an autoencoder network of binary neurons with a hidden layer can achieve a capacity that grows exponentially with network size. The network has fixed random weights encoding a set of dense input patterns into a dense, expanded (or \emph{overcomplete}) hidden layer representation. A set of learnable weights decodes the input patters at the output layer. We perform a mean-field approximation of the model to reduce the model to a perceptron problem with an input-output dependency. Carrying out Gardner's \emph{replica} calculation, we show that as the expansion ratio, defined as the number of hidden units over the number of input units, increases, the autoencoding capacity grows exponentially even when the sparseness or the coding level of the hidden layer representation is changed. The replica-symmetric solution is locally stable and is in good agreement with simulation results obtained using a local learning rule. In addition, the degree of symmetry between the encoding and decoding weights monotonically increases with the expansion ratio.
[ { "created": "Sun, 21 May 2017 12:13:42 GMT", "version": "v1" } ]
2017-05-23
[ [ "Alemi", "Alireza", "" ], [ "Abbara", "Alia", "" ] ]
A fundamental aspect of limitations in learning any computation in neural architectures is characterizing their optimal capacities. An important, widely-used neural architecture is known as autoencoders where the network reconstructs the input at the output layer via a representation at a hidden layer. Even though capacities of several neural architectures have been addressed using statistical physics methods, the capacity of autoencoder neural networks is not well-explored. Here, we analytically show that an autoencoder network of binary neurons with a hidden layer can achieve a capacity that grows exponentially with network size. The network has fixed random weights encoding a set of dense input patterns into a dense, expanded (or \emph{overcomplete}) hidden layer representation. A set of learnable weights decodes the input patters at the output layer. We perform a mean-field approximation of the model to reduce the model to a perceptron problem with an input-output dependency. Carrying out Gardner's \emph{replica} calculation, we show that as the expansion ratio, defined as the number of hidden units over the number of input units, increases, the autoencoding capacity grows exponentially even when the sparseness or the coding level of the hidden layer representation is changed. The replica-symmetric solution is locally stable and is in good agreement with simulation results obtained using a local learning rule. In addition, the degree of symmetry between the encoding and decoding weights monotonically increases with the expansion ratio.
2207.07274
Aaron Wang
Aaron Wang, Feng Li, Samantha Chiang, Jennifer Fulcher, Otto Yang, David Wong, Fang Wei
Machine Learning Prediction of COVID-19 Severity Levels From Salivaomics Data
null
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
The clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the strain of coronavirus that caused the COVID-19 pandemic, is broad, extending from asymptomatic infection to severe immunopulmonary reactions that, if not categorized properly, may be life-threatening. Researchers rate COVID-19 patients on a scale from 1 to 8 according to the severity level of COVID-19, 1 being healthy and 8 being extremely sick, based on a multitude of factors including number of clinic visits, days since the first sign of symptoms, and more. However, there are two issues with the current state of severity level designation. Firstly, there exists variation among researchers in determining these patient scores, which may lead to improper treatment. Secondly, researchers use a variety of metrics to determine patient severity level, including metrics involving plasma collection that require invasive procedures. This project aims to remedy both issues by introducing a machine learning framework that unifies severity level designations based on noninvasive saliva biomarkers. Our results show that we can successfully use machine learning on salivaomics data to predict the severity level of COVID-19 patients, indicating the presence of viral load using saliva biomarkers.
[ { "created": "Fri, 15 Jul 2022 03:45:40 GMT", "version": "v1" } ]
2022-07-18
[ [ "Wang", "Aaron", "" ], [ "Li", "Feng", "" ], [ "Chiang", "Samantha", "" ], [ "Fulcher", "Jennifer", "" ], [ "Yang", "Otto", "" ], [ "Wong", "David", "" ], [ "Wei", "Fang", "" ] ]
The clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the strain of coronavirus that caused the COVID-19 pandemic, is broad, extending from asymptomatic infection to severe immunopulmonary reactions that, if not categorized properly, may be life-threatening. Researchers rate COVID-19 patients on a scale from 1 to 8 according to the severity level of COVID-19, 1 being healthy and 8 being extremely sick, based on a multitude of factors including number of clinic visits, days since the first sign of symptoms, and more. However, there are two issues with the current state of severity level designation. Firstly, there exists variation among researchers in determining these patient scores, which may lead to improper treatment. Secondly, researchers use a variety of metrics to determine patient severity level, including metrics involving plasma collection that require invasive procedures. This project aims to remedy both issues by introducing a machine learning framework that unifies severity level designations based on noninvasive saliva biomarkers. Our results show that we can successfully use machine learning on salivaomics data to predict the severity level of COVID-19 patients, indicating the presence of viral load using saliva biomarkers.
1809.09700
Audrey Wong-Kee-You MA
Audrey M. B. Wong-Kee-You, John K. Tsotsos, and Scott A. Adler
Development of spatial suppression surrounding the focus of visual attention
null
null
null
null
q-bio.NC cs.CV
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The capacity to filter out irrelevant information from our environment is critical to efficient processing. Yet, during development, when building a knowledge base of the world is occurring, the ability to selectively allocate attentional resources is limited (e.g., Amso & Scerif, 2015). In adulthood, research has demonstrated that surrounding the spatial location of attentional focus is a suppressive field, resulting from top-down attention promoting the processing of relevant stimuli and inhibiting surrounding distractors (e.g., Hopf et al., 2006). It is not fully known, however, whether this phenomenon manifests in development. In the current study, we examined whether spatial suppression surrounding the focus of visual attention is exhibited in developmental age groups. Participants between 12 and 27 years of age exhibited spatial suppression surrounding their focus of visual attention. Their accuracy increased as a function of the separation distance between a spatially cued (and attended) target and a second target, suggesting that a ring of suppression surrounded the attended target. When a central cue was instead presented and therefore attention was no longer spatially cued, surround suppression was not observed, indicating that our initial findings of suppression were indeed related to the focus of attention. Attentional surround suppression was not observed in 8- to 11-years-olds, even with a longer spatial cue presentation time, demonstrating that the lack of the effect at these ages is not due to slowed attentional feedback processes. Our findings demonstrate that top-down attentional processes are still immature until approximately 12 years of age, and that they continue to be refined throughout adolescence, converging well with previous research on attentional development.
[ { "created": "Mon, 17 Sep 2018 01:35:56 GMT", "version": "v1" } ]
2018-09-27
[ [ "Wong-Kee-You", "Audrey M. B.", "" ], [ "Tsotsos", "John K.", "" ], [ "Adler", "Scott A.", "" ] ]
The capacity to filter out irrelevant information from our environment is critical to efficient processing. Yet, during development, when building a knowledge base of the world is occurring, the ability to selectively allocate attentional resources is limited (e.g., Amso & Scerif, 2015). In adulthood, research has demonstrated that surrounding the spatial location of attentional focus is a suppressive field, resulting from top-down attention promoting the processing of relevant stimuli and inhibiting surrounding distractors (e.g., Hopf et al., 2006). It is not fully known, however, whether this phenomenon manifests in development. In the current study, we examined whether spatial suppression surrounding the focus of visual attention is exhibited in developmental age groups. Participants between 12 and 27 years of age exhibited spatial suppression surrounding their focus of visual attention. Their accuracy increased as a function of the separation distance between a spatially cued (and attended) target and a second target, suggesting that a ring of suppression surrounded the attended target. When a central cue was instead presented and therefore attention was no longer spatially cued, surround suppression was not observed, indicating that our initial findings of suppression were indeed related to the focus of attention. Attentional surround suppression was not observed in 8- to 11-years-olds, even with a longer spatial cue presentation time, demonstrating that the lack of the effect at these ages is not due to slowed attentional feedback processes. Our findings demonstrate that top-down attentional processes are still immature until approximately 12 years of age, and that they continue to be refined throughout adolescence, converging well with previous research on attentional development.
1410.3951
Eleni Katifori
Carl D. Modes, Marcelo O. Magnasco, Eleni Katifori
Extracting Hidden Hierarchies in 3D Distribution Networks
null
Phys. Rev. X 6, 031009 (2016)
10.1103/PhysRevX.6.031009
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Natural and man-made transport webs are frequently dominated by dense sets of nested cycles. The architecture of these networks, as defined by the topology and edge weights, determines how efficiently the networks perform their function. Yet, the set of tools that can characterize such a weighted cycle-rich architecture in a physically relevant, mathematically compact way is sparse. In order to fill this void, we have developed a new algorithm that rests on an abstraction of the physical `tiling' in the case of a two dimensional network to an effective tiling of an abstract surface in space that the network may be thought to sit in. Generically these abstract surfaces are richer than the flat plane and as a result there are now two families of fundamental units that may aggregate upon cutting weakest links -- the plaquettes of the tiling and the longer `topological' cycles associated with the abstract surface itself. Upon sequential removal of the weakest links, as determined by the edge weight, neighboring plaquettes merge and a tree characterizing this merging process results. The properties of this characteristic tree can provide the physical and topological data required to describe the architecture of the network and to build physical models. The new algorithm can be used for automated phenotypic characterization of any weighted network whose structure is dominated by cycles, such as mammalian vasculature in the organs, the root networks of clonal colonies like quaking aspen, or the force networks in jammed granular matter.
[ { "created": "Wed, 15 Oct 2014 07:41:04 GMT", "version": "v1" } ]
2016-07-27
[ [ "Modes", "Carl D.", "" ], [ "Magnasco", "Marcelo O.", "" ], [ "Katifori", "Eleni", "" ] ]
Natural and man-made transport webs are frequently dominated by dense sets of nested cycles. The architecture of these networks, as defined by the topology and edge weights, determines how efficiently the networks perform their function. Yet, the set of tools that can characterize such a weighted cycle-rich architecture in a physically relevant, mathematically compact way is sparse. In order to fill this void, we have developed a new algorithm that rests on an abstraction of the physical `tiling' in the case of a two dimensional network to an effective tiling of an abstract surface in space that the network may be thought to sit in. Generically these abstract surfaces are richer than the flat plane and as a result there are now two families of fundamental units that may aggregate upon cutting weakest links -- the plaquettes of the tiling and the longer `topological' cycles associated with the abstract surface itself. Upon sequential removal of the weakest links, as determined by the edge weight, neighboring plaquettes merge and a tree characterizing this merging process results. The properties of this characteristic tree can provide the physical and topological data required to describe the architecture of the network and to build physical models. The new algorithm can be used for automated phenotypic characterization of any weighted network whose structure is dominated by cycles, such as mammalian vasculature in the organs, the root networks of clonal colonies like quaking aspen, or the force networks in jammed granular matter.
2310.19202
Xiong Xiong
Xiong Xiong, Ying Wang, Tianyuan Song, Jinguo Huang, Guixia Kang
Improved Motor Imagery Classification Using Adaptive Spatial Filters Based on Particle Swarm Optimization Algorithm
25 pages, 8 figures
null
null
null
q-bio.QM cs.LG eess.SP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
As a typical self-paced brain-computer interface (BCI) system, the motor imagery (MI) BCI has been widely applied in fields such as robot control, stroke rehabilitation, and assistance for patients with stroke or spinal cord injury. Many studies have focused on the traditional spatial filters obtained through the common spatial pattern (CSP) method. However, the CSP method can only obtain fixed spatial filters for specific input signals. Besides, CSP method only focuses on the variance difference of two types of electroencephalogram (EEG) signals, so the decoding ability of EEG signals is limited. To obtain more effective spatial filters for better extraction of spatial features that can improve classification to MI-EEG, this paper proposes an adaptive spatial filter solving method based on particle swarm optimization algorithm (PSO). A training and testing framework based on filter bank and spatial filters (FBCSP-ASP) is designed for MI EEG signal classification. Comparative experiments are conducted on two public datasets (2a and 2b) from BCI competition IV, which show the outstanding average recognition accuracy of FBCSP-ASP. The proposed method has achieved significant performance improvement on MI-BCI. The classification accuracy of the proposed method has reached 74.61% and 81.19% on datasets 2a and 2b, respectively. Compared with the baseline algorithm (FBCSP), the proposed algorithm improves 11.44% and 7.11% on two datasets respectively. Furthermore, the analysis based on mutual information, t-SNE and Shapley values further proves that ASP features have excellent decoding ability for MI-EEG signals, and explains the improvement of classification performance by the introduction of ASP features.
[ { "created": "Sun, 29 Oct 2023 23:53:37 GMT", "version": "v1" } ]
2023-10-31
[ [ "Xiong", "Xiong", "" ], [ "Wang", "Ying", "" ], [ "Song", "Tianyuan", "" ], [ "Huang", "Jinguo", "" ], [ "Kang", "Guixia", "" ] ]
As a typical self-paced brain-computer interface (BCI) system, the motor imagery (MI) BCI has been widely applied in fields such as robot control, stroke rehabilitation, and assistance for patients with stroke or spinal cord injury. Many studies have focused on the traditional spatial filters obtained through the common spatial pattern (CSP) method. However, the CSP method can only obtain fixed spatial filters for specific input signals. Besides, CSP method only focuses on the variance difference of two types of electroencephalogram (EEG) signals, so the decoding ability of EEG signals is limited. To obtain more effective spatial filters for better extraction of spatial features that can improve classification to MI-EEG, this paper proposes an adaptive spatial filter solving method based on particle swarm optimization algorithm (PSO). A training and testing framework based on filter bank and spatial filters (FBCSP-ASP) is designed for MI EEG signal classification. Comparative experiments are conducted on two public datasets (2a and 2b) from BCI competition IV, which show the outstanding average recognition accuracy of FBCSP-ASP. The proposed method has achieved significant performance improvement on MI-BCI. The classification accuracy of the proposed method has reached 74.61% and 81.19% on datasets 2a and 2b, respectively. Compared with the baseline algorithm (FBCSP), the proposed algorithm improves 11.44% and 7.11% on two datasets respectively. Furthermore, the analysis based on mutual information, t-SNE and Shapley values further proves that ASP features have excellent decoding ability for MI-EEG signals, and explains the improvement of classification performance by the introduction of ASP features.
2001.10614
Arti Ahluwalia Dr
Daniele Poli1, Giorgio Mattei, Nadia Ucciferri and Arti Ahluwalia
An integrated in vitro in silico approach for silver nanoparticle dosimetry in cell cultures
20 pages, including Supplementary Materials
null
null
null
q-bio.TO q-bio.QM
http://creativecommons.org/publicdomain/zero/1.0/
Potential human and environmental hazards resulting from the exposure of living organisms to silver nanoparticles (Ag NPs) have been the subject of intensive discussion in the last decade. Despite the growing use of Ag NPs in biomedical applications, a quantification of the toxic effects as a function of the total silver mass reaching cells (namely, target cell dose) is still needed. To provide a more accurate dose-response analysis, we propose a novel integrated approach combining well-established computational and experimental methodologies. We first used the particokinetic model (ISD3) proposed by Thomas and colleagues (2018) for providing experimental validation of computed Ag NP sedimentation in static-cuvette experiments. After validation, ISD3 was employed to predict the total mass of silver reaching human endothelial cells and hepatocytes cultured in 96 well plates. Cell viability measured after 24h of culture was then related to this target cell dose. Our results show that the dose perceived by the cell monolayer after 24 h of exposure is around 85% lower than the administered nominal media concentration. Therefore, accurate dosimetry considering particle characteristics and experimental conditions (e.g., time, size and shape of wells) should be employed for better interpreting effects induced by the amount of silver reaching cells.
[ { "created": "Tue, 7 Jan 2020 11:43:40 GMT", "version": "v1" } ]
2020-01-30
[ [ "Poli1", "Daniele", "" ], [ "Mattei", "Giorgio", "" ], [ "Ucciferri", "Nadia", "" ], [ "Ahluwalia", "Arti", "" ] ]
Potential human and environmental hazards resulting from the exposure of living organisms to silver nanoparticles (Ag NPs) have been the subject of intensive discussion in the last decade. Despite the growing use of Ag NPs in biomedical applications, a quantification of the toxic effects as a function of the total silver mass reaching cells (namely, target cell dose) is still needed. To provide a more accurate dose-response analysis, we propose a novel integrated approach combining well-established computational and experimental methodologies. We first used the particokinetic model (ISD3) proposed by Thomas and colleagues (2018) for providing experimental validation of computed Ag NP sedimentation in static-cuvette experiments. After validation, ISD3 was employed to predict the total mass of silver reaching human endothelial cells and hepatocytes cultured in 96 well plates. Cell viability measured after 24h of culture was then related to this target cell dose. Our results show that the dose perceived by the cell monolayer after 24 h of exposure is around 85% lower than the administered nominal media concentration. Therefore, accurate dosimetry considering particle characteristics and experimental conditions (e.g., time, size and shape of wells) should be employed for better interpreting effects induced by the amount of silver reaching cells.
1911.04779
Annick Lesne
Julien Mozziconacci (LPTMC, MNHN), M\'elody Merle (LPTMC), Annick Lesne (LPTMC, IGMM)
The 3D genome shapes the regulatory code of developmental genes
Journal of Molecular Biology, Elsevier, 2019
null
10.1016/j.jmb.2019.10.017
null
q-bio.GN physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We revisit the notion of gene regulatory code in embryonic development in the light of recent findings about genome spatial organisation. By analogy with the genetic code, we posit that the concept of code can only be used if the corresponding adaptor can clearly be identified. An adaptor is here defined as an intermediary physical entity mediating the correspondence between codewords and objects in a gratuitous and evolvable way. In the context of the gene regulatory code, the encoded objects are the gene expression levels, while the concentrations of specific transcription factors in the cell nucleus provide the codewords. The notion of code is meaningful in the absence of direct physicochemical relationships between the objects and the codewords, when the mediation by an adaptor is required. We propose that a plausible adaptor for this code is the gene domain, that is, the genome segment delimited by topological insulators and comprising the gene and its enhancer regulatory sequences. We review recent evidences, based on genome-wide chromosome conformation capture experiments, showing that preferential contact domains found in metazoan genomes are the physical traces of gene domains. Accordingly, genome 3D folding plays a direct role in shaping the developmental gene regulatory code.
[ { "created": "Tue, 12 Nov 2019 10:36:56 GMT", "version": "v1" } ]
2019-11-13
[ [ "Mozziconacci", "Julien", "", "LPTMC, MNHN" ], [ "Merle", "Mélody", "", "LPTMC" ], [ "Lesne", "Annick", "", "LPTMC, IGMM" ] ]
We revisit the notion of gene regulatory code in embryonic development in the light of recent findings about genome spatial organisation. By analogy with the genetic code, we posit that the concept of code can only be used if the corresponding adaptor can clearly be identified. An adaptor is here defined as an intermediary physical entity mediating the correspondence between codewords and objects in a gratuitous and evolvable way. In the context of the gene regulatory code, the encoded objects are the gene expression levels, while the concentrations of specific transcription factors in the cell nucleus provide the codewords. The notion of code is meaningful in the absence of direct physicochemical relationships between the objects and the codewords, when the mediation by an adaptor is required. We propose that a plausible adaptor for this code is the gene domain, that is, the genome segment delimited by topological insulators and comprising the gene and its enhancer regulatory sequences. We review recent evidences, based on genome-wide chromosome conformation capture experiments, showing that preferential contact domains found in metazoan genomes are the physical traces of gene domains. Accordingly, genome 3D folding plays a direct role in shaping the developmental gene regulatory code.
1202.1223
Francesc Rossell\'o
Arnau Mir, Francesc Rossello, Lucia Rotger
A new balance index for phylogenetic trees
24 pages, 2 figures, preliminary version presented at the JBI 2012
Math. Biosc. 241 (2013) 125-136
10.1016/j.mbs.2012.10.005
null
q-bio.PE cs.DM q-bio.QM
http://creativecommons.org/licenses/publicdomain/
Several indices that measure the degree of balance of a rooted phylogenetic tree have been proposed so far in the literature. In this work we define and study a new index of this kind, which we call the total cophenetic index: the sum, over all pairs of different leaves, of the depth of their least common ancestor. This index makes sense for arbitrary trees, can be computed in linear time and it has a larger range of values and a greater resolution power than other indices like Colless' or Sackin's. We compute its maximum and minimum values for arbitrary and binary trees, as well as exact formulas for its expected value for binary trees under the Yule and the uniform models of evolution. As a byproduct of this study, we obtain an exact formula for the expected value of the Sackin index under the uniform model, a result that seems to be new in the literature.
[ { "created": "Mon, 6 Feb 2012 17:47:01 GMT", "version": "v1" } ]
2014-02-11
[ [ "Mir", "Arnau", "" ], [ "Rossello", "Francesc", "" ], [ "Rotger", "Lucia", "" ] ]
Several indices that measure the degree of balance of a rooted phylogenetic tree have been proposed so far in the literature. In this work we define and study a new index of this kind, which we call the total cophenetic index: the sum, over all pairs of different leaves, of the depth of their least common ancestor. This index makes sense for arbitrary trees, can be computed in linear time and it has a larger range of values and a greater resolution power than other indices like Colless' or Sackin's. We compute its maximum and minimum values for arbitrary and binary trees, as well as exact formulas for its expected value for binary trees under the Yule and the uniform models of evolution. As a byproduct of this study, we obtain an exact formula for the expected value of the Sackin index under the uniform model, a result that seems to be new in the literature.
0901.1851
Stefan Auer SA
Stefan Auer, Filip Meersman, Christopher M. Dobson, Michele Vendruscolo
Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates
14 pages, 4 figures
PLoS Comput Biol 4(11): e1000222 (2008)
10.1371/journal.pcbi.1000222
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention since it has been associated with neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate how the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Initially individual beta-sheets form with random orientations, which subsequently tend to align into protofilaments as their lengths increases. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.
[ { "created": "Tue, 13 Jan 2009 18:23:18 GMT", "version": "v1" }, { "created": "Wed, 14 Jan 2009 09:48:36 GMT", "version": "v2" } ]
2009-01-14
[ [ "Auer", "Stefan", "" ], [ "Meersman", "Filip", "" ], [ "Dobson", "Christopher M.", "" ], [ "Vendruscolo", "Michele", "" ] ]
The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention since it has been associated with neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate how the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Initially individual beta-sheets form with random orientations, which subsequently tend to align into protofilaments as their lengths increases. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.
2402.11657
Marius Brusselmans
Marius Brusselmans, Luiz Max Carvalho, Samuel L. Hong, Jiansi Gao, Frederick A. Matsen IV, Andrew Rambaut, Philippe Lemey, Marc A. Suchard, Gytis Dudas, and Guy Baele
On the importance of assessing topological convergence in Bayesian phylogenetic inference
null
null
null
null
q-bio.PE q-bio.GN q-bio.QM
http://creativecommons.org/licenses/by-sa/4.0/
Modern phylogenetics research is often performed within a Bayesian framework, using sampling algorithms such as Markov chain Monte Carlo (MCMC) to approximate the posterior distribution. These algorithms require careful evaluation of the quality of the generated samples. Within the field of phylogenetics, one frequently adopted diagnostic approach is to evaluate the effective sample size (ESS) and to investigate trace graphs of the sampled parameters. A major limitation of these approaches is that they are developed for continuous parameters and therefore incompatible with a crucial parameter in these inferences: the tree topology. Several recent advancements have aimed at extending these diagnostics to topological space. In this short reflection paper, we present a case study illustrating how these topological diagnostics can contain information not found in standard diagnostics, and how decisions regarding which of these diagnostics to compute can impact inferences regarding MCMC convergence and mixing. Given the major importance of detecting convergence and mixing issues in Bayesian phylogenetic analyses, the lack of a unified approach to this problem warrants further action, especially now that additional tools are becoming available to researchers.
[ { "created": "Sun, 18 Feb 2024 17:28:15 GMT", "version": "v1" } ]
2024-02-20
[ [ "Brusselmans", "Marius", "" ], [ "Carvalho", "Luiz Max", "" ], [ "Hong", "Samuel L.", "" ], [ "Gao", "Jiansi", "" ], [ "Matsen", "Frederick A.", "IV" ], [ "Rambaut", "Andrew", "" ], [ "Lemey", "Philippe", "" ], [ "Suchard", "Marc A.", "" ], [ "Dudas", "Gytis", "" ], [ "Baele", "Guy", "" ] ]
Modern phylogenetics research is often performed within a Bayesian framework, using sampling algorithms such as Markov chain Monte Carlo (MCMC) to approximate the posterior distribution. These algorithms require careful evaluation of the quality of the generated samples. Within the field of phylogenetics, one frequently adopted diagnostic approach is to evaluate the effective sample size (ESS) and to investigate trace graphs of the sampled parameters. A major limitation of these approaches is that they are developed for continuous parameters and therefore incompatible with a crucial parameter in these inferences: the tree topology. Several recent advancements have aimed at extending these diagnostics to topological space. In this short reflection paper, we present a case study illustrating how these topological diagnostics can contain information not found in standard diagnostics, and how decisions regarding which of these diagnostics to compute can impact inferences regarding MCMC convergence and mixing. Given the major importance of detecting convergence and mixing issues in Bayesian phylogenetic analyses, the lack of a unified approach to this problem warrants further action, especially now that additional tools are becoming available to researchers.
1407.3499
Anjan Dasgupta Prof.
Sufi O Raja and Anjan Kr Dasgupta
Instant Response of Live HeLa Cells to Static Magnetic Field and Its Magnetic Adaptation
17 pages 7 figures
null
null
null
q-bio.CB physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We report Static Magnetic Field (SMF) induced altered sub-cellular streaming, which retains even after withdrawal of the field. The observation is statistically validated by differential fluorescence recovery after photo-bleaching (FRAP) studies in presence and absence of SMF, recovery rate being higher in presence of SMF. This instant magneto-sensing by live cells can be explained by inherent diamagnetic susceptibility of cells and alternatively by spin recombination, e.g., by the radical pair mechanism. These arguments are however insufficient to explain the retention of the SMF effect even after field withdrawal. Typically, a relaxation time scale at least of the order of minutes is observed. This long duration of the SMF effect can be explained postulating a field induced coherence that is followed by decoherence after the field withdrawal. A related observation is the emergence of enhanced magnetic susceptibility of cells after magnetic pre-incubation. This implies onset of a new spin equilibrium state as a result of prolonged SMF incubation. Lastly, translation of such altered spin states to a cellular signal that leads to an altered sub-cellular streaming, probable intracellular machineries for this translation being discussed in the text.
[ { "created": "Sun, 13 Jul 2014 19:02:08 GMT", "version": "v1" } ]
2014-07-15
[ [ "Raja", "Sufi O", "" ], [ "Dasgupta", "Anjan Kr", "" ] ]
We report Static Magnetic Field (SMF) induced altered sub-cellular streaming, which retains even after withdrawal of the field. The observation is statistically validated by differential fluorescence recovery after photo-bleaching (FRAP) studies in presence and absence of SMF, recovery rate being higher in presence of SMF. This instant magneto-sensing by live cells can be explained by inherent diamagnetic susceptibility of cells and alternatively by spin recombination, e.g., by the radical pair mechanism. These arguments are however insufficient to explain the retention of the SMF effect even after field withdrawal. Typically, a relaxation time scale at least of the order of minutes is observed. This long duration of the SMF effect can be explained postulating a field induced coherence that is followed by decoherence after the field withdrawal. A related observation is the emergence of enhanced magnetic susceptibility of cells after magnetic pre-incubation. This implies onset of a new spin equilibrium state as a result of prolonged SMF incubation. Lastly, translation of such altered spin states to a cellular signal that leads to an altered sub-cellular streaming, probable intracellular machineries for this translation being discussed in the text.
2211.05469
Abhishek Senapati
Abhishek Senapati, Adam Mertel, Weronika Schlechte-Welnicz, Justin M. Calabrese
Estimating cross-border mobility from the difference in peak-timing: A case study in Poland-Germany border regions
Added Reference (Abdussalam et al. (2022) in Section 3
null
null
null
q-bio.PE physics.soc-ph
http://creativecommons.org/licenses/by/4.0/
Human mobility contributes to the fast spatio-temporal propagation of infectious diseases. During an outbreak, monitoring the infection situation on either side of an international border is very crucial as there is always a higher risk of disease importation associated with cross-border migration. Mechanistic models are effective tools to investigate the consequences of cross-border mobility on disease dynamics and help in designing effective control strategies. However, in practice, due to the unavailability of cross-border mobility data, it becomes difficult to propose reliable, model-based strategies. In this study, we propose a method for estimating cross-border mobility flux between any pair of regions that share an international border from the observed difference in the timing of the infection peak in each region. Assuming the underlying disease dynamics is governed by a Susceptible-Infected-Recovered (SIR) model, we employ stochastic simulations to obtain the maximum likelihood cross-border mobility estimate for any pair of regions where the difference in peak time can be measured. We then investigate how the estimate of cross-border mobility flux varies depending on the disease transmission rate, which is a key epidemiological parameter. We further show that the uncertainty in mobility flux estimates decreases for higher disease transmission rates and larger observed differences in peak timing. Finally, as a case study, we apply the method to some selected regions along the Poland-Germany border which are directly connected through multiple modes of transportation and quantify the cross-border fluxes from the COVID-19 cases data during the period $20^{\rm th}$ February $2021$ to $20^{\rm th}$ June $2021$.
[ { "created": "Thu, 10 Nov 2022 10:29:20 GMT", "version": "v1" }, { "created": "Fri, 11 Nov 2022 11:06:32 GMT", "version": "v2" } ]
2022-11-14
[ [ "Senapati", "Abhishek", "" ], [ "Mertel", "Adam", "" ], [ "Schlechte-Welnicz", "Weronika", "" ], [ "Calabrese", "Justin M.", "" ] ]
Human mobility contributes to the fast spatio-temporal propagation of infectious diseases. During an outbreak, monitoring the infection situation on either side of an international border is very crucial as there is always a higher risk of disease importation associated with cross-border migration. Mechanistic models are effective tools to investigate the consequences of cross-border mobility on disease dynamics and help in designing effective control strategies. However, in practice, due to the unavailability of cross-border mobility data, it becomes difficult to propose reliable, model-based strategies. In this study, we propose a method for estimating cross-border mobility flux between any pair of regions that share an international border from the observed difference in the timing of the infection peak in each region. Assuming the underlying disease dynamics is governed by a Susceptible-Infected-Recovered (SIR) model, we employ stochastic simulations to obtain the maximum likelihood cross-border mobility estimate for any pair of regions where the difference in peak time can be measured. We then investigate how the estimate of cross-border mobility flux varies depending on the disease transmission rate, which is a key epidemiological parameter. We further show that the uncertainty in mobility flux estimates decreases for higher disease transmission rates and larger observed differences in peak timing. Finally, as a case study, we apply the method to some selected regions along the Poland-Germany border which are directly connected through multiple modes of transportation and quantify the cross-border fluxes from the COVID-19 cases data during the period $20^{\rm th}$ February $2021$ to $20^{\rm th}$ June $2021$.
q-bio/0701039
Ryan Gutenkunst
Ryan N. Gutenkunst, Joshua J. Waterfall, Fergal P. Casey, Kevin S. Brown, Christopher R. Myers and James P. Sethna
Universally Sloppy Parameter Sensitivities in Systems Biology
Submitted to PLoS Computational Biology. Supplementary Information available in "Other Formats" bundle. Discussion slightly revised to add historical context
PLoS Comput Biol 3(10):e189 (2007)
10.1371/journal.pcbi.0030189
null
q-bio.QM q-bio.MN
null
Quantitative computational models play an increasingly important role in modern biology. Such models typically involve many free parameters, and assigning their values is often a substantial obstacle to model development. Directly measuring \emph{in vivo} biochemical parameters is difficult, and collectively fitting them to other data often yields large parameter uncertainties. Nevertheless, in earlier work we showed in a growth-factor-signaling model that collective fitting could yield well-constrained predictions, even when it left individual parameters very poorly constrained. We also showed that the model had a `sloppy' spectrum of parameter sensitivities, with eigenvalues roughly evenly distributed over many decades. Here we use a collection of models from the literature to test whether such sloppy spectra are common in systems biology. Strikingly, we find that every model we examine has a sloppy spectrum of sensitivities. We also test several consequences of this sloppiness for building predictive models. In particular, sloppiness suggests that collective fits to even large amounts of ideal time-series data will often leave many parameters poorly constrained. Tests over our model collection are consistent with this suggestion. This difficulty with collective fits may seem to argue for direct parameter measurements, but sloppiness also implies that such measurements must be formidably precise and complete to usefully constrain many model predictions. We confirm this implication in our signaling model. Our results suggest that sloppy sensitivity spectra are universal in systems biology models. The prevalence of sloppiness highlights the power of collective fits and suggests that modelers should focus on predictions rather than on parameters.
[ { "created": "Wed, 24 Jan 2007 19:12:58 GMT", "version": "v1" }, { "created": "Tue, 29 May 2007 19:53:33 GMT", "version": "v2" }, { "created": "Fri, 27 Jul 2007 18:43:41 GMT", "version": "v3" } ]
2011-11-09
[ [ "Gutenkunst", "Ryan N.", "" ], [ "Waterfall", "Joshua J.", "" ], [ "Casey", "Fergal P.", "" ], [ "Brown", "Kevin S.", "" ], [ "Myers", "Christopher R.", "" ], [ "Sethna", "James P.", "" ] ]
Quantitative computational models play an increasingly important role in modern biology. Such models typically involve many free parameters, and assigning their values is often a substantial obstacle to model development. Directly measuring \emph{in vivo} biochemical parameters is difficult, and collectively fitting them to other data often yields large parameter uncertainties. Nevertheless, in earlier work we showed in a growth-factor-signaling model that collective fitting could yield well-constrained predictions, even when it left individual parameters very poorly constrained. We also showed that the model had a `sloppy' spectrum of parameter sensitivities, with eigenvalues roughly evenly distributed over many decades. Here we use a collection of models from the literature to test whether such sloppy spectra are common in systems biology. Strikingly, we find that every model we examine has a sloppy spectrum of sensitivities. We also test several consequences of this sloppiness for building predictive models. In particular, sloppiness suggests that collective fits to even large amounts of ideal time-series data will often leave many parameters poorly constrained. Tests over our model collection are consistent with this suggestion. This difficulty with collective fits may seem to argue for direct parameter measurements, but sloppiness also implies that such measurements must be formidably precise and complete to usefully constrain many model predictions. We confirm this implication in our signaling model. Our results suggest that sloppy sensitivity spectra are universal in systems biology models. The prevalence of sloppiness highlights the power of collective fits and suggests that modelers should focus on predictions rather than on parameters.
2309.10823
Julian G\"oltz
Julian G\"oltz, Sebastian Billaudelle, Laura Kriener, Luca Blessing, Christian Pehle, Eric M\"uller, Johannes Schemmel, Mihai A. Petrovici
Gradient-based methods for spiking physical systems
2 page abstract, submitted to and accepted by the NNPC (International conference on neuromorphic, natural and physical computing)
null
null
null
q-bio.NC cs.NE
http://creativecommons.org/licenses/by/4.0/
Recent efforts have fostered significant progress towards deep learning in spiking networks, both theoretical and in silico. Here, we discuss several different approaches, including a tentative comparison of the results on BrainScaleS-2, and hint towards future such comparative studies.
[ { "created": "Tue, 29 Aug 2023 15:47:19 GMT", "version": "v1" } ]
2023-09-21
[ [ "Göltz", "Julian", "" ], [ "Billaudelle", "Sebastian", "" ], [ "Kriener", "Laura", "" ], [ "Blessing", "Luca", "" ], [ "Pehle", "Christian", "" ], [ "Müller", "Eric", "" ], [ "Schemmel", "Johannes", "" ], [ "Petrovici", "Mihai A.", "" ] ]
Recent efforts have fostered significant progress towards deep learning in spiking networks, both theoretical and in silico. Here, we discuss several different approaches, including a tentative comparison of the results on BrainScaleS-2, and hint towards future such comparative studies.
1809.02956
Amit Chattopadhyay
Ewa Grela, Michael Stich, Amit K Chattopadhyay
Epidemiological impact of waning immunization on a vaccinated population
Published version In EPJB has 11 pages (2-columned), 1 Table, 10 figures
null
10.1140/epjb/e2018-90136-3
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This is an epidemiological SIRV model based study that is designed to analyze the impact of vaccination in containing infection spread, in a 4-tiered population compartment comprised of susceptible, infected, recovered and vaccinated agents. While many models assume a lifelong protection through vaccination, we focus on the impact of waning immunization due to conversion of vaccinated and recovered agents back to susceptible ones. Two asymptotic states exist, the "disease-free equilibrium" and the "endemic equilibrium"; we express the transitions between these states as function of the vaccination and conversion rates using the basic reproduction number as a descriptor. We find that the vaccination of newborns and adults have different consequences in controlling epidemics. We also find that a decaying disease protection within the recovered sub-population is not sufficient to trigger an epidemic at the linear level. Our simulations focus on parameter sets that could model a disease with waning immunization like pertussis. For a diffusively coupled population, a transition to the endemic state can be initiated via the propagation of a traveling infection wave, described successfully within a Fisher-Kolmogorov framework.
[ { "created": "Sun, 9 Sep 2018 11:22:51 GMT", "version": "v1" } ]
2018-11-14
[ [ "Grela", "Ewa", "" ], [ "Stich", "Michael", "" ], [ "Chattopadhyay", "Amit K", "" ] ]
This is an epidemiological SIRV model based study that is designed to analyze the impact of vaccination in containing infection spread, in a 4-tiered population compartment comprised of susceptible, infected, recovered and vaccinated agents. While many models assume a lifelong protection through vaccination, we focus on the impact of waning immunization due to conversion of vaccinated and recovered agents back to susceptible ones. Two asymptotic states exist, the "disease-free equilibrium" and the "endemic equilibrium"; we express the transitions between these states as function of the vaccination and conversion rates using the basic reproduction number as a descriptor. We find that the vaccination of newborns and adults have different consequences in controlling epidemics. We also find that a decaying disease protection within the recovered sub-population is not sufficient to trigger an epidemic at the linear level. Our simulations focus on parameter sets that could model a disease with waning immunization like pertussis. For a diffusively coupled population, a transition to the endemic state can be initiated via the propagation of a traveling infection wave, described successfully within a Fisher-Kolmogorov framework.
2107.08530
Christopher Stock
Christopher H. Stock, Sarah E. Harvey, Samuel A. Ocko, Surya Ganguli
Synaptic balancing: a biologically plausible local learning rule that provably increases neural network noise robustness without sacrificing task performance
null
null
10.1371/journal.pcbi.1010418
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We introduce a novel, biologically plausible local learning rule that provably increases the robustness of neural dynamics to noise in nonlinear recurrent neural networks with homogeneous nonlinearities. Our learning rule achieves higher noise robustness without sacrificing performance on the task and without requiring any knowledge of the particular task. The plasticity dynamics -- an integrable dynamical system operating on the weights of the network -- maintains a multiplicity of conserved quantities, most notably the network's entire temporal map of input to output trajectories. The outcome of our learning rule is a synaptic balancing between the incoming and outgoing synapses of every neuron. This synaptic balancing rule is consistent with many known aspects of experimentally observed heterosynaptic plasticity, and moreover makes new experimentally testable predictions relating plasticity at the incoming and outgoing synapses of individual neurons. Overall, this work provides a novel, practical local learning rule that exactly preserves overall network function and, in doing so, provides new conceptual bridges between the disparate worlds of the neurobiology of heterosynaptic plasticity, the engineering of regularized noise-robust networks, and the mathematics of integrable Lax dynamical systems.
[ { "created": "Sun, 18 Jul 2021 20:15:43 GMT", "version": "v1" } ]
2022-10-12
[ [ "Stock", "Christopher H.", "" ], [ "Harvey", "Sarah E.", "" ], [ "Ocko", "Samuel A.", "" ], [ "Ganguli", "Surya", "" ] ]
We introduce a novel, biologically plausible local learning rule that provably increases the robustness of neural dynamics to noise in nonlinear recurrent neural networks with homogeneous nonlinearities. Our learning rule achieves higher noise robustness without sacrificing performance on the task and without requiring any knowledge of the particular task. The plasticity dynamics -- an integrable dynamical system operating on the weights of the network -- maintains a multiplicity of conserved quantities, most notably the network's entire temporal map of input to output trajectories. The outcome of our learning rule is a synaptic balancing between the incoming and outgoing synapses of every neuron. This synaptic balancing rule is consistent with many known aspects of experimentally observed heterosynaptic plasticity, and moreover makes new experimentally testable predictions relating plasticity at the incoming and outgoing synapses of individual neurons. Overall, this work provides a novel, practical local learning rule that exactly preserves overall network function and, in doing so, provides new conceptual bridges between the disparate worlds of the neurobiology of heterosynaptic plasticity, the engineering of regularized noise-robust networks, and the mathematics of integrable Lax dynamical systems.
1112.5026
Gasper Tkacik
Ga\v{s}per Tka\v{c}ik, Aleksandra M Walczak, William Bialek
Optimizing information flow in small genetic networks. III. A self-interacting gene
18 pages, 9 figures
Phys Rev E 85 (2012): 041903
10.1103/PhysRevE.85.041903
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Living cells must control the reading out or "expression" of information encoded in their genomes, and this regulation often is mediated by transcription factors--proteins that bind to DNA and either enhance or repress the expression of nearby genes. But the expression of transcription factor proteins is itself regulated, and many transcription factors regulate their own expression in addition to responding to other input signals. Here we analyze the simplest of such self-regulatory circuits, asking how parameters can be chosen to optimize information transmission from inputs to outputs in the steady state. Some nonzero level of self-regulation is almost always optimal, with self-activation dominant when transcription factor concentrations are low and self-repression dominant when concentrations are high. In steady state the optimal self-activation is never strong enough to induce bistability, although there is a limit in which the optimal parameters are very close to the critical point.
[ { "created": "Wed, 21 Dec 2011 14:14:30 GMT", "version": "v1" } ]
2013-08-01
[ [ "Tkačik", "Gašper", "" ], [ "Walczak", "Aleksandra M", "" ], [ "Bialek", "William", "" ] ]
Living cells must control the reading out or "expression" of information encoded in their genomes, and this regulation often is mediated by transcription factors--proteins that bind to DNA and either enhance or repress the expression of nearby genes. But the expression of transcription factor proteins is itself regulated, and many transcription factors regulate their own expression in addition to responding to other input signals. Here we analyze the simplest of such self-regulatory circuits, asking how parameters can be chosen to optimize information transmission from inputs to outputs in the steady state. Some nonzero level of self-regulation is almost always optimal, with self-activation dominant when transcription factor concentrations are low and self-repression dominant when concentrations are high. In steady state the optimal self-activation is never strong enough to induce bistability, although there is a limit in which the optimal parameters are very close to the critical point.
2303.16361
Thomas Parmer
Thomas Parmer, Luis M. Rocha
Dynamical Modularity in Automata Models of Biochemical Networks
42 pages, 7 figures; updated author information
null
null
null
q-bio.MN cs.CE
http://creativecommons.org/licenses/by/4.0/
Given the large size and complexity of most biochemical regulation and signaling networks, there is a non-trivial relationship between the micro-level logic of component interactions and the observed macro-dynamics. Here we address this issue by formalizing the existing concept of pathway modules, which are sequences of state updates that are guaranteed to occur (barring outside interference) in the dynamics of automata networks after the perturbation of a subset of driver nodes. We present a novel algorithm to automatically extract pathway modules from networks and we characterize the interactions that may take place between modules. This methodology uses only the causal logic of individual node variables (micro-dynamics) without the need to compute the dynamical landscape of the networks (macro-dynamics). Specifically, we identify complex modules, which maximize pathway length and require synergy between their components. This allows us to propose a new take on dynamical modularity that partitions complex networks into causal pathways of variables that are guaranteed to transition to specific states given a perturbation to a set of driver nodes. Thus, the same node variable can take part in distinct modules depending on the state it takes. Our measure of dynamical modularity of a network is then inversely proportional to the overlap among complex modules and maximal when complex modules are completely decouplable from one another in the network dynamics. We estimate dynamical modularity for several genetic regulatory networks, including the Drosophila melanogaster segment-polarity network. We discuss how identifying complex modules and the dynamical modularity portrait of networks explains the macro-dynamics of biological networks, such as uncovering the (more or less) decouplable building blocks of emergent computation (or collective behavior) in biochemical regulation and signaling.
[ { "created": "Wed, 29 Mar 2023 00:01:30 GMT", "version": "v1" }, { "created": "Mon, 17 Apr 2023 22:41:08 GMT", "version": "v2" } ]
2023-04-19
[ [ "Parmer", "Thomas", "" ], [ "Rocha", "Luis M.", "" ] ]
Given the large size and complexity of most biochemical regulation and signaling networks, there is a non-trivial relationship between the micro-level logic of component interactions and the observed macro-dynamics. Here we address this issue by formalizing the existing concept of pathway modules, which are sequences of state updates that are guaranteed to occur (barring outside interference) in the dynamics of automata networks after the perturbation of a subset of driver nodes. We present a novel algorithm to automatically extract pathway modules from networks and we characterize the interactions that may take place between modules. This methodology uses only the causal logic of individual node variables (micro-dynamics) without the need to compute the dynamical landscape of the networks (macro-dynamics). Specifically, we identify complex modules, which maximize pathway length and require synergy between their components. This allows us to propose a new take on dynamical modularity that partitions complex networks into causal pathways of variables that are guaranteed to transition to specific states given a perturbation to a set of driver nodes. Thus, the same node variable can take part in distinct modules depending on the state it takes. Our measure of dynamical modularity of a network is then inversely proportional to the overlap among complex modules and maximal when complex modules are completely decouplable from one another in the network dynamics. We estimate dynamical modularity for several genetic regulatory networks, including the Drosophila melanogaster segment-polarity network. We discuss how identifying complex modules and the dynamical modularity portrait of networks explains the macro-dynamics of biological networks, such as uncovering the (more or less) decouplable building blocks of emergent computation (or collective behavior) in biochemical regulation and signaling.
2403.14202
Hong-Li Zeng
Hong-Li Zeng, Cheng-Long Yang, Bo Jing, John Barton, Erik Aurell
Two fitness inference schemes compared using allele frequencies from 1,068,391 sequences sampled in the UK during the COVID-19 pandemic
10 pages, 6 figures
null
null
null
q-bio.PE q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Throughout the course of the SARS-CoV-2 pandemic, genetic variation has contributed to the spread and persistence of the virus. For example, various mutations have allowed SARS-CoV-2 to escape antibody neutralization or to bind more strongly to the receptors that it uses to enter human cells. Here, we compared two methods that estimate the fitness effects of viral mutations using the abundant sequence data gathered over the course of the pandemic. Both approaches are grounded in population genetics theory but with different assumptions. One approach, tQLE, features an epistatic fitness landscape and assumes that alleles are nearly in linkage equilibrium. Another approach, MPL, assumes a simple, additive fitness landscape, but allows for any level of correlation between alleles. We characterized differences in the distributions of fitness values inferred by each approach and in the ranks of fitness values that they assign to sequences across time. We find that in a large fraction of weeks the two methods are in good agreement as to their top-ranked sequences, i.e., as to which sequences observed that week are most fit. We also find that agreement between ranking of sequences varies with genetic unimodality in the population in a given week.
[ { "created": "Thu, 21 Mar 2024 07:54:11 GMT", "version": "v1" } ]
2024-03-22
[ [ "Zeng", "Hong-Li", "" ], [ "Yang", "Cheng-Long", "" ], [ "Jing", "Bo", "" ], [ "Barton", "John", "" ], [ "Aurell", "Erik", "" ] ]
Throughout the course of the SARS-CoV-2 pandemic, genetic variation has contributed to the spread and persistence of the virus. For example, various mutations have allowed SARS-CoV-2 to escape antibody neutralization or to bind more strongly to the receptors that it uses to enter human cells. Here, we compared two methods that estimate the fitness effects of viral mutations using the abundant sequence data gathered over the course of the pandemic. Both approaches are grounded in population genetics theory but with different assumptions. One approach, tQLE, features an epistatic fitness landscape and assumes that alleles are nearly in linkage equilibrium. Another approach, MPL, assumes a simple, additive fitness landscape, but allows for any level of correlation between alleles. We characterized differences in the distributions of fitness values inferred by each approach and in the ranks of fitness values that they assign to sequences across time. We find that in a large fraction of weeks the two methods are in good agreement as to their top-ranked sequences, i.e., as to which sequences observed that week are most fit. We also find that agreement between ranking of sequences varies with genetic unimodality in the population in a given week.
1911.00716
Martin Vasilev
Martin R. Vasilev, Victoria I. Adedeji, Calvin Laursen, Marcin Budka, Timothy J. Slattery
Do readers use character information when programming return-sweep saccades?
null
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
Reading saccades that occur within a single line of text are guided by the size of letters. However, readers occasionally need to make longer saccades (known as return-sweeps) that take their eyes from the end of one line of text to the beginning of the next. In this study, we tested whether return-sweep saccades are also guided by font size information and whether this guidance depends on visual acuity of the return-sweep target area. To do this, we manipulated the font size of letters (0.29 vs 0.39 deg. per character) and the length of the first line of text (16 vs 26 deg.). The larger font resulted in return-sweeps that landed further to the right of the line start and in a reduction of under-sweeps compared to the smaller font. This suggests that font size information is used when programming return-sweeps. Return-sweeps in the longer line condition landed further to the right of the line start and the proportion of under-sweeps increased compared to the short line condition. This likely reflects an increase in saccadic undershoot error with the increase in intended saccade size. Critically, there was no interaction between font size and line length. This suggests that when programming return-sweeps, the use of font size information does not depend on visual acuity at the saccade target. Instead, it appears that readers rely on global typographic properties of the text in order to maintain an optimal number of characters to the left of their first fixation on a new line.
[ { "created": "Sat, 2 Nov 2019 13:48:12 GMT", "version": "v1" }, { "created": "Tue, 14 Jul 2020 10:23:13 GMT", "version": "v2" }, { "created": "Tue, 5 Jan 2021 19:24:20 GMT", "version": "v3" } ]
2021-01-07
[ [ "Vasilev", "Martin R.", "" ], [ "Adedeji", "Victoria I.", "" ], [ "Laursen", "Calvin", "" ], [ "Budka", "Marcin", "" ], [ "Slattery", "Timothy J.", "" ] ]
Reading saccades that occur within a single line of text are guided by the size of letters. However, readers occasionally need to make longer saccades (known as return-sweeps) that take their eyes from the end of one line of text to the beginning of the next. In this study, we tested whether return-sweep saccades are also guided by font size information and whether this guidance depends on visual acuity of the return-sweep target area. To do this, we manipulated the font size of letters (0.29 vs 0.39 deg. per character) and the length of the first line of text (16 vs 26 deg.). The larger font resulted in return-sweeps that landed further to the right of the line start and in a reduction of under-sweeps compared to the smaller font. This suggests that font size information is used when programming return-sweeps. Return-sweeps in the longer line condition landed further to the right of the line start and the proportion of under-sweeps increased compared to the short line condition. This likely reflects an increase in saccadic undershoot error with the increase in intended saccade size. Critically, there was no interaction between font size and line length. This suggests that when programming return-sweeps, the use of font size information does not depend on visual acuity at the saccade target. Instead, it appears that readers rely on global typographic properties of the text in order to maintain an optimal number of characters to the left of their first fixation on a new line.
2306.03159
Julia Berezutskaya
Evan Canny, Mariska J. Vansteensel, Sandra M.A. van der Salm, Gernot R. M\"uller-Putz, Julia Berezutskaya
The feasibility of combining communication BCIs with FES for individuals with locked-in syndrome
null
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
Individuals with a locked-in state live with severe whole-body paralysis that limits their ability to communicate with family and loved ones. Recent advances in the brain-computer interface (BCI) technology have presented a potential alternative for these people to communicate by detecting neural activity associated with attempted hand or speech movements and translating the decoded intended movements to a control signal for a computer. A technique that could potentially enrich the communication capacity of BCIs is functional electrical stimulation (FES) of paralyzed limbs and face to restore body and facial movements of paralyzed individuals, allowing to add body language and facial expression to communication BCI utterances. Here, we review the current state of the art of existing BCI and FES work in people with paralysis of body and face and propose that a combined BCI-FES approach, which has already proved successful in several applications in stroke and spinal cord injury, can provide a novel promising mode of communication for locked-in individuals.
[ { "created": "Mon, 5 Jun 2023 18:12:31 GMT", "version": "v1" }, { "created": "Mon, 17 Jul 2023 09:48:16 GMT", "version": "v2" } ]
2023-07-18
[ [ "Canny", "Evan", "" ], [ "Vansteensel", "Mariska J.", "" ], [ "van der Salm", "Sandra M. A.", "" ], [ "Müller-Putz", "Gernot R.", "" ], [ "Berezutskaya", "Julia", "" ] ]
Individuals with a locked-in state live with severe whole-body paralysis that limits their ability to communicate with family and loved ones. Recent advances in the brain-computer interface (BCI) technology have presented a potential alternative for these people to communicate by detecting neural activity associated with attempted hand or speech movements and translating the decoded intended movements to a control signal for a computer. A technique that could potentially enrich the communication capacity of BCIs is functional electrical stimulation (FES) of paralyzed limbs and face to restore body and facial movements of paralyzed individuals, allowing to add body language and facial expression to communication BCI utterances. Here, we review the current state of the art of existing BCI and FES work in people with paralysis of body and face and propose that a combined BCI-FES approach, which has already proved successful in several applications in stroke and spinal cord injury, can provide a novel promising mode of communication for locked-in individuals.
1402.1805
Jonathan Potts
Jonathan R. Potts, Marie Auger-M\'eth\'e, Karl Mokross, Mark A. Lewis
A generalized residual technique for analyzing complex movement models using earth mover's distance
null
Methods in Ecology and Evolution (2014) 5:1012-1022
10.1111/2041-210X.12253
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
1. Complex systems of moving and interacting objects are ubiquitous in the natural and social sciences. Predicting their behavior often requires models that mimic these systems with sufficient accuracy, while accounting for their inherent stochasticity. Though tools exist to determine which of a set of candidate models is best relative to the others, there is currently no generic goodness-of-fit framework for testing how close the best model is to the real complex stochastic system. 2. We propose such a framework, using a novel application of the Earth mover's distance, also known as the Wasserstein metric. It is applicable to any stochastic process where the probability of the model's state at time $t$ is a function of the state at previous times. It generalizes the concept of a residual, often used to analyze 1D summary statistics, to situations where the complexity of the underlying model's probability distribution makes standard residual analysis too imprecise for practical use. 3. We give a scheme for testing the hypothesis that a model is an accurate description of a data set. We demonstrate the tractability and usefulness of our approach by application to animal movement models in complex, heterogeneous environments. We detail methods for visualizing results and extracting a variety of information on a given model's quality, such as whether there is any inherent bias in the model, or in which situations it is most accurate. We demonstrate our techniques by application to data on multi-species flocks of insectivore birds in the Amazon rainforest. 4. This work provides a usable toolkit to assess the quality of generic movement models of complex systems, in an absolute rather than a relative sense.
[ { "created": "Sat, 8 Feb 2014 00:55:29 GMT", "version": "v1" }, { "created": "Tue, 13 May 2014 14:29:22 GMT", "version": "v2" }, { "created": "Thu, 28 Aug 2014 21:29:59 GMT", "version": "v3" } ]
2014-12-02
[ [ "Potts", "Jonathan R.", "" ], [ "Auger-Méthé", "Marie", "" ], [ "Mokross", "Karl", "" ], [ "Lewis", "Mark A.", "" ] ]
1. Complex systems of moving and interacting objects are ubiquitous in the natural and social sciences. Predicting their behavior often requires models that mimic these systems with sufficient accuracy, while accounting for their inherent stochasticity. Though tools exist to determine which of a set of candidate models is best relative to the others, there is currently no generic goodness-of-fit framework for testing how close the best model is to the real complex stochastic system. 2. We propose such a framework, using a novel application of the Earth mover's distance, also known as the Wasserstein metric. It is applicable to any stochastic process where the probability of the model's state at time $t$ is a function of the state at previous times. It generalizes the concept of a residual, often used to analyze 1D summary statistics, to situations where the complexity of the underlying model's probability distribution makes standard residual analysis too imprecise for practical use. 3. We give a scheme for testing the hypothesis that a model is an accurate description of a data set. We demonstrate the tractability and usefulness of our approach by application to animal movement models in complex, heterogeneous environments. We detail methods for visualizing results and extracting a variety of information on a given model's quality, such as whether there is any inherent bias in the model, or in which situations it is most accurate. We demonstrate our techniques by application to data on multi-species flocks of insectivore birds in the Amazon rainforest. 4. This work provides a usable toolkit to assess the quality of generic movement models of complex systems, in an absolute rather than a relative sense.
2307.02171
K. Anton Feenstra
Jose Gavald\'a-Garci\'a, Bas Stringer, Olga Ivanova, Sanne Abeln, K. Anton Feenstra, Halima Mouhib
Data Resources for Structural Bioinformatics
editorial responsability: Sanne Abeln, K. Anton Feenstra, Halima Mouhib. This chapter is part of the book "Introduction to Protein Structural Bioinformatics". The Preface arXiv:1801.09442 contains links to all the (published) chapters. The update adds available arxiv hyperlinks for the chapters
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by/4.0/
While many good textbooks are available on Protein Structure, Molecular Simulations, Thermodynamics and Bioinformatics methods in general, there is no good introductory level book for the field of Structural Bioinformatics. This book aims to give an introduction into Structural Bioinformatics, which is where the previous topics meet to explore three dimensional protein structures through computational analysis. We provide an overview of existing computational techniques, to validate, simulate, predict and analyse protein structures. More importantly, it will aim to provide practical knowledge about how and when to use such techniques. We will consider proteins from three major vantage points: Protein structure quantification, Protein structure prediction, and Protein simulation & dynamics. Structural bioinformatics involves a variety of computational methods, all of which require input data. Typical inputs include protein structures and sequences, which are usually retrieved from a public or private database. This chapter introduces several key resources that make such data available, as well as a handful of tools that derive additional information from experimentally determined or computationally predicted protein structures and sequences.
[ { "created": "Wed, 5 Jul 2023 10:12:59 GMT", "version": "v1" }, { "created": "Thu, 6 Jul 2023 18:07:07 GMT", "version": "v2" } ]
2023-07-10
[ [ "Gavaldá-Garciá", "Jose", "" ], [ "Stringer", "Bas", "" ], [ "Ivanova", "Olga", "" ], [ "Abeln", "Sanne", "" ], [ "Feenstra", "K. Anton", "" ], [ "Mouhib", "Halima", "" ] ]
While many good textbooks are available on Protein Structure, Molecular Simulations, Thermodynamics and Bioinformatics methods in general, there is no good introductory level book for the field of Structural Bioinformatics. This book aims to give an introduction into Structural Bioinformatics, which is where the previous topics meet to explore three dimensional protein structures through computational analysis. We provide an overview of existing computational techniques, to validate, simulate, predict and analyse protein structures. More importantly, it will aim to provide practical knowledge about how and when to use such techniques. We will consider proteins from three major vantage points: Protein structure quantification, Protein structure prediction, and Protein simulation & dynamics. Structural bioinformatics involves a variety of computational methods, all of which require input data. Typical inputs include protein structures and sequences, which are usually retrieved from a public or private database. This chapter introduces several key resources that make such data available, as well as a handful of tools that derive additional information from experimentally determined or computationally predicted protein structures and sequences.
1805.02809
Daqing Guo
Yangsong Zhang, Erwei Yin, Fali Li, Yu Zhang, Toshihisa Tanaka, Qibin Zhao, Yan Cui, Peng Xu, Dezhong Yao, Daqing Guo
Two-stage frequency recognition method based on correlated component analysis for SSVEP-based BCI
10 pages, 10 figures, submitted to IEEE TNSRE
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Canonical correlation analysis (CCA) is a state-of-the-art method for frequency recognition in steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) systems. Various extended methods have been developed, and among such methods, a combination method of CCA and individual-template-based CCA (IT-CCA) has achieved excellent performance. However, CCA requires the canonical vectors to be orthogonal, which may not be a reasonable assumption for EEG analysis. In the current study, we propose using the correlated component analysis (CORRCA) rather than CCA to implement frequency recognition. CORRCA can relax the constraint of canonical vectors in CCA, and generate the same projection vector for two multichannel EEG signals. Furthermore, we propose a two-stage method based on the basic CORRCA method (termed TSCORRCA). Evaluated on a benchmark dataset of thirty-five subjects, the experimental results demonstrate that CORRCA significantly outperformed CCA, and TSCORRCA obtained the best performance among the compared methods. This study demonstrates that CORRCA-based methods have great potential for implementing high-performance SSVEP-based BCI systems.
[ { "created": "Tue, 8 May 2018 02:50:17 GMT", "version": "v1" }, { "created": "Tue, 12 Jun 2018 09:56:15 GMT", "version": "v2" }, { "created": "Sun, 1 Jul 2018 11:53:06 GMT", "version": "v3" } ]
2018-07-03
[ [ "Zhang", "Yangsong", "" ], [ "Yin", "Erwei", "" ], [ "Li", "Fali", "" ], [ "Zhang", "Yu", "" ], [ "Tanaka", "Toshihisa", "" ], [ "Zhao", "Qibin", "" ], [ "Cui", "Yan", "" ], [ "Xu", "Peng", "" ], [ "Yao", "Dezhong", "" ], [ "Guo", "Daqing", "" ] ]
Canonical correlation analysis (CCA) is a state-of-the-art method for frequency recognition in steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) systems. Various extended methods have been developed, and among such methods, a combination method of CCA and individual-template-based CCA (IT-CCA) has achieved excellent performance. However, CCA requires the canonical vectors to be orthogonal, which may not be a reasonable assumption for EEG analysis. In the current study, we propose using the correlated component analysis (CORRCA) rather than CCA to implement frequency recognition. CORRCA can relax the constraint of canonical vectors in CCA, and generate the same projection vector for two multichannel EEG signals. Furthermore, we propose a two-stage method based on the basic CORRCA method (termed TSCORRCA). Evaluated on a benchmark dataset of thirty-five subjects, the experimental results demonstrate that CORRCA significantly outperformed CCA, and TSCORRCA obtained the best performance among the compared methods. This study demonstrates that CORRCA-based methods have great potential for implementing high-performance SSVEP-based BCI systems.
1501.01603
Trilochan Bagarti
Trilochan Bagarti
Population extinction in an inhomogeneous host-pathogen model
Errors in the text are fixed, Fig.5 and 6 are corrected. 13 pages, 6 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We study inhomogeneous host-pathogen dynamics to model the global amphibian population extinction in a lake basin system. The lake basin system is modeled as quenched disorder. In this model we show that once the pathogen arrives at the lake basin it spreads from one lake to another, eventually spreading to the entire lake basin system in a wave like pattern. The extinction time has been found to depend on the steady state host population and pathogen growth rate. Linear estimate of the extinction time is computed. The steady state host population shows a threshold behavior in the interaction strength for a given growth rate.
[ { "created": "Thu, 18 Dec 2014 19:24:27 GMT", "version": "v1" }, { "created": "Sun, 1 Feb 2015 23:21:50 GMT", "version": "v2" } ]
2015-02-03
[ [ "Bagarti", "Trilochan", "" ] ]
We study inhomogeneous host-pathogen dynamics to model the global amphibian population extinction in a lake basin system. The lake basin system is modeled as quenched disorder. In this model we show that once the pathogen arrives at the lake basin it spreads from one lake to another, eventually spreading to the entire lake basin system in a wave like pattern. The extinction time has been found to depend on the steady state host population and pathogen growth rate. Linear estimate of the extinction time is computed. The steady state host population shows a threshold behavior in the interaction strength for a given growth rate.
1104.5583
Sarada Seetharaman
Kavita Jain and Sarada Seetharaman
Multiple adaptive substitutions during evolution in novel environments
null
Genetics 189, no. 3 1029-1043 (2011)
null
null
q-bio.PE cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We consider an asexual population under strong selection-weak mutation conditions evolving on rugged fitness landscapes with many local fitness peaks. Unlike the previous studies in which the initial fitness of the population is assumed to be high, here we start the adaptation process with a low fitness corresponding to a population in a stressful novel environment. For generic fitness distributions, using an analytic argument we find that the average number of steps to a local optimum varies logarithmically with the genotype sequence length and increases as the correlations amongst genotypic fitnesses increase. When the fitnesses are exponentially or uniformly distributed, using an evolution equation for the distribution of population fitness, we analytically calculate the fitness distribution of fixed beneficial mutations and the walk length distribution.
[ { "created": "Fri, 29 Apr 2011 09:45:18 GMT", "version": "v1" }, { "created": "Fri, 2 Sep 2011 11:50:52 GMT", "version": "v2" } ]
2011-11-18
[ [ "Jain", "Kavita", "" ], [ "Seetharaman", "Sarada", "" ] ]
We consider an asexual population under strong selection-weak mutation conditions evolving on rugged fitness landscapes with many local fitness peaks. Unlike the previous studies in which the initial fitness of the population is assumed to be high, here we start the adaptation process with a low fitness corresponding to a population in a stressful novel environment. For generic fitness distributions, using an analytic argument we find that the average number of steps to a local optimum varies logarithmically with the genotype sequence length and increases as the correlations amongst genotypic fitnesses increase. When the fitnesses are exponentially or uniformly distributed, using an evolution equation for the distribution of population fitness, we analytically calculate the fitness distribution of fixed beneficial mutations and the walk length distribution.
2101.02865
Julio Augusto Freyre-Gonz\'alez
Juan M. Escorcia-Rodr\'iguez, Andreas Tauch, and Julio A. Freyre-Gonz\'alez
Corynebacterium glutamicum regulation beyond transcription: Organizing principles and reconstruction of an extended regulatory network incorporating regulations mediated by small RNA and protein-protein interactions
32 pages, 4 figures, 1 supplementary material
null
null
null
q-bio.MN
http://creativecommons.org/licenses/by/4.0/
Corynebacterium glutamicum is a Gram-positive bacterium found in soil where the condition changes demand plasticity of the regulatory machinery. The study of such machinery at the global scale has been challenged by the lack of data integration. Here, we report three regulatory network models for C. glutamicum: strong (3040 interactions) constructed solely with regulations previously supported by directed experiments; all evidence (4665 interactions) containing the strong network, regulations previously supported by non-directed experiments, and protein-protein interactions with a direct effect on gene transcription; and sRNA (5222 interactions) containing the all evidence network and sRNA-mediated regulations. Compared to the previous version (2018), the strong and all evidence networks increased by 75 and 1225 interactions, respectively. We analyzed the system-level components of the three networks to identify how they differ and compared their structures against those for the networks of more than 40 species. The inclusion of the sRNAs regulations changed the proportions of the system-level components and increased the number of modules but decreased their size. The C. glutamicum regulatory structure contrasted with other bacterial regulatory networks. Finally, we used the strong networks of three model organisms to provide insights and future directions of the C. glutamicum regulatory network characterization.
[ { "created": "Fri, 8 Jan 2021 06:03:26 GMT", "version": "v1" } ]
2021-01-11
[ [ "Escorcia-Rodríguez", "Juan M.", "" ], [ "Tauch", "Andreas", "" ], [ "Freyre-González", "Julio A.", "" ] ]
Corynebacterium glutamicum is a Gram-positive bacterium found in soil where the condition changes demand plasticity of the regulatory machinery. The study of such machinery at the global scale has been challenged by the lack of data integration. Here, we report three regulatory network models for C. glutamicum: strong (3040 interactions) constructed solely with regulations previously supported by directed experiments; all evidence (4665 interactions) containing the strong network, regulations previously supported by non-directed experiments, and protein-protein interactions with a direct effect on gene transcription; and sRNA (5222 interactions) containing the all evidence network and sRNA-mediated regulations. Compared to the previous version (2018), the strong and all evidence networks increased by 75 and 1225 interactions, respectively. We analyzed the system-level components of the three networks to identify how they differ and compared their structures against those for the networks of more than 40 species. The inclusion of the sRNAs regulations changed the proportions of the system-level components and increased the number of modules but decreased their size. The C. glutamicum regulatory structure contrasted with other bacterial regulatory networks. Finally, we used the strong networks of three model organisms to provide insights and future directions of the C. glutamicum regulatory network characterization.
1511.02079
Salva Duran-Nebreda
Salva Duran-Nebreda, Adriano Bonforti, Raul Monta\~nez, Sergi Valverde and Ricard Sol\'e
Emergence of proto-organisms from bistable stochastic differentiation and adhesion
9 pages, 4 figures
null
null
null
q-bio.PE q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The rise of multicellularity in the early evolution of life represents a major challenge for evolutionary biology. Guidance for finding answers has emerged from disparate fields, from phylogenetics to modelling and synthetic biology, but little is known about the potential origins of multicellular aggregates before genetic programs took full control of developmental processes. Such aggregates should involve spatial organisation of differentiated cells and the modification of flows and concentrations of metabolites within well defined boundaries. Here we show that, in an environment where limited nutrients and toxic metabolites are introduced, a population of cells capable of stochastic differentiation and differential adhesion can develop into multicellular aggregates with a complex internal structure. The morphospace of possible patterns is shown to be very rich, including proto-organisms that display a high degree of organisational complexity, far beyond simple heterogeneous populations of cells. Our findings reveal that there is a potentially enormous richness of organismal complexity between simple mixed cooperators and embodied living organisms.
[ { "created": "Fri, 6 Nov 2015 13:59:03 GMT", "version": "v1" } ]
2015-11-09
[ [ "Duran-Nebreda", "Salva", "" ], [ "Bonforti", "Adriano", "" ], [ "Montañez", "Raul", "" ], [ "Valverde", "Sergi", "" ], [ "Solé", "Ricard", "" ] ]
The rise of multicellularity in the early evolution of life represents a major challenge for evolutionary biology. Guidance for finding answers has emerged from disparate fields, from phylogenetics to modelling and synthetic biology, but little is known about the potential origins of multicellular aggregates before genetic programs took full control of developmental processes. Such aggregates should involve spatial organisation of differentiated cells and the modification of flows and concentrations of metabolites within well defined boundaries. Here we show that, in an environment where limited nutrients and toxic metabolites are introduced, a population of cells capable of stochastic differentiation and differential adhesion can develop into multicellular aggregates with a complex internal structure. The morphospace of possible patterns is shown to be very rich, including proto-organisms that display a high degree of organisational complexity, far beyond simple heterogeneous populations of cells. Our findings reveal that there is a potentially enormous richness of organismal complexity between simple mixed cooperators and embodied living organisms.
2207.07912
Eric Wong
Eric C. Wong
A Reservoir Model of Explicit Human Intelligence
8 pages
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by-nc-sa/4.0/
A fundamental feature of human intelligence is that we accumulate and transfer knowledge as a society and across generations. We describe here a network architecture for the human brain that may support this feature and suggest that two key innovations were the ability to consider an offline model of the world, and the use of language to record and communicate knowledge within this model. We propose that these two innovations, together with pre-existing mechanisms for associative learning, allowed us to develop a conceptually simple associative network that operates like a reservoir of attractors and can learn in a rapid, flexible, and robust manner. We hypothesize that explicit human intelligence is based primarily on this type of network, which works in conjunction with older and likely more complex deep networks that perform sensory, motor, and other implicit forms of processing.
[ { "created": "Wed, 6 Jul 2022 04:08:58 GMT", "version": "v1" } ]
2022-07-19
[ [ "Wong", "Eric C.", "" ] ]
A fundamental feature of human intelligence is that we accumulate and transfer knowledge as a society and across generations. We describe here a network architecture for the human brain that may support this feature and suggest that two key innovations were the ability to consider an offline model of the world, and the use of language to record and communicate knowledge within this model. We propose that these two innovations, together with pre-existing mechanisms for associative learning, allowed us to develop a conceptually simple associative network that operates like a reservoir of attractors and can learn in a rapid, flexible, and robust manner. We hypothesize that explicit human intelligence is based primarily on this type of network, which works in conjunction with older and likely more complex deep networks that perform sensory, motor, and other implicit forms of processing.
1805.05322
Konstantin Blyuss
F. Fatehi Chenar, Y.N. Kyrychko, K.B. Blyuss
Mathematical model of immune response to hepatitis B
24 pages, 10 figures
J. Theor. Biol. 447, 98-110 (2018)
10.1016/j.jtbi.2018.03.025
null
q-bio.PE nlin.CD
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A new detailed mathematical model for dynamics of immune response to hepatitis B is proposed, which takes into account contributions from innate and adaptive immune responses, as well as cytokines. Stability analysis of different steady states is performed to identify parameter regions where the model exhibits clearance of infection, maintenance of a chronic infection, or periodic oscillations. Effects of nucleoside analogues and interferon treatments are analysed, and the critical drug efficiency is determined.
[ { "created": "Fri, 11 May 2018 20:08:19 GMT", "version": "v1" } ]
2018-05-16
[ [ "Chenar", "F. Fatehi", "" ], [ "Kyrychko", "Y. N.", "" ], [ "Blyuss", "K. B.", "" ] ]
A new detailed mathematical model for dynamics of immune response to hepatitis B is proposed, which takes into account contributions from innate and adaptive immune responses, as well as cytokines. Stability analysis of different steady states is performed to identify parameter regions where the model exhibits clearance of infection, maintenance of a chronic infection, or periodic oscillations. Effects of nucleoside analogues and interferon treatments are analysed, and the critical drug efficiency is determined.
2112.10575
David Graff
David E. Graff and Connor W. Coley
pyscreener: A Python Wrapper for Computational Docking Software
null
null
10.21105/joss.03950
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
pyscreener is a Python library that seeks to alleviate the challenges of large-scale structure-based design using computational docking. It provides a simple and uniform interface that is agnostic to the backend docking engine with which to calculate the docking score of a given molecule in a specified active site. Additionally, pyscreener features first-class support for task distribution, allowing users to seamlessly scale their code from a local, multi-core setup to a large, heterogeneous resource allocation.
[ { "created": "Fri, 17 Dec 2021 17:40:47 GMT", "version": "v1" } ]
2022-05-05
[ [ "Graff", "David E.", "" ], [ "Coley", "Connor W.", "" ] ]
pyscreener is a Python library that seeks to alleviate the challenges of large-scale structure-based design using computational docking. It provides a simple and uniform interface that is agnostic to the backend docking engine with which to calculate the docking score of a given molecule in a specified active site. Additionally, pyscreener features first-class support for task distribution, allowing users to seamlessly scale their code from a local, multi-core setup to a large, heterogeneous resource allocation.
q-bio/0609002
Stuart Borrett
Stuart R. Borrett, Brian D. Fath, Bernard C. Patten
Functional Integration of Ecological Networks through Pathway Proliferation
29 pages, 2 figures, 3 tables, Submitted to Journal of Theoretical Biology
Journal of Theoretical Biology 245: 98-111
10.1016/j.jtbi.2006.09.024
null
q-bio.PE q-bio.QM
null
Large-scale structural patterns commonly occur in network models of complex systems including a skewed node degree distribution and small-world topology. These patterns suggest common organizational constraints and similar functional consequences. Here, we investigate a structural pattern termed pathway proliferation. Previous research enumerating pathways that link species determined that as pathway length increases, the number of pathways tends to increase without bound. We hypothesize that this pathway proliferation influences the flow of energy, matter, and information in ecosystems. In this paper, we clarify the pathway proliferation concept, introduce a measure of the node--node proliferation rate, describe factors influencing the rate, and characterize it in 17 large empirical food-webs. During this investigation, we uncovered a modular organization within these systems. Over half of the food-webs were composed of one or more subgroups that were strongly connected internally, but weakly connected to the rest of the system. Further, these modules had distinct proliferation rates. We conclude that pathway proliferation in ecological networks reveals subgroups of species that will be functionally integrated through cyclic indirect effects.
[ { "created": "Sat, 2 Sep 2006 20:10:32 GMT", "version": "v1" } ]
2011-04-04
[ [ "Borrett", "Stuart R.", "" ], [ "Fath", "Brian D.", "" ], [ "Patten", "Bernard C.", "" ] ]
Large-scale structural patterns commonly occur in network models of complex systems including a skewed node degree distribution and small-world topology. These patterns suggest common organizational constraints and similar functional consequences. Here, we investigate a structural pattern termed pathway proliferation. Previous research enumerating pathways that link species determined that as pathway length increases, the number of pathways tends to increase without bound. We hypothesize that this pathway proliferation influences the flow of energy, matter, and information in ecosystems. In this paper, we clarify the pathway proliferation concept, introduce a measure of the node--node proliferation rate, describe factors influencing the rate, and characterize it in 17 large empirical food-webs. During this investigation, we uncovered a modular organization within these systems. Over half of the food-webs were composed of one or more subgroups that were strongly connected internally, but weakly connected to the rest of the system. Further, these modules had distinct proliferation rates. We conclude that pathway proliferation in ecological networks reveals subgroups of species that will be functionally integrated through cyclic indirect effects.
1607.04463
Marzia Di Filippo
M. Di Filippo, C. Damiani, R. Colombo, D. Pescini, G. Mauri
Constraint-based modeling and simulation of cell populations
null
null
null
null
q-bio.QM q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The intratumor heterogeneity has been recognized to characterize cancer cells impairing the efficacy of cancer treatments. We here propose an extension of constraint-based modeling approach in order to simulate metabolism of cell populations with the aim to provide a more complete characterization of these systems, especially focusing on the relationships among their components. We tested our methodology by using a toy-model and taking into account the main metabolic pathways involved in cancer metabolic rewiring. This toy-model is used as individual to construct a population model characterized by multiple interacting individuals, all having the same topology and stoichiometry, and sharing the same nutrients supply. We observed that, in our population, cancer cells cooperate with each other to reach a common objective, but without necessarily having the same metabolic traits. We also noticed that the heterogeneity emerging from the population model is due to the mismatch between the objective of the individual members and the objective of the entire population.
[ { "created": "Fri, 15 Jul 2016 11:18:36 GMT", "version": "v1" } ]
2016-07-18
[ [ "Di Filippo", "M.", "" ], [ "Damiani", "C.", "" ], [ "Colombo", "R.", "" ], [ "Pescini", "D.", "" ], [ "Mauri", "G.", "" ] ]
The intratumor heterogeneity has been recognized to characterize cancer cells impairing the efficacy of cancer treatments. We here propose an extension of constraint-based modeling approach in order to simulate metabolism of cell populations with the aim to provide a more complete characterization of these systems, especially focusing on the relationships among their components. We tested our methodology by using a toy-model and taking into account the main metabolic pathways involved in cancer metabolic rewiring. This toy-model is used as individual to construct a population model characterized by multiple interacting individuals, all having the same topology and stoichiometry, and sharing the same nutrients supply. We observed that, in our population, cancer cells cooperate with each other to reach a common objective, but without necessarily having the same metabolic traits. We also noticed that the heterogeneity emerging from the population model is due to the mismatch between the objective of the individual members and the objective of the entire population.
2301.02433
Norichika Ogata
Norichika Ogata
The Growing Liberality Observed in Primary Animal and Plant Cultures is Common to the Social Amoeba
2 pages, 1 figure
null
null
null
q-bio.CB
http://creativecommons.org/licenses/by-nc-nd/4.0/
Tissue culture environment liberates cells from ordinary laws of multi-cellular organisms. This liberation enables cells several behaviors, such as proliferation, dedifferentiation, acquisition of pluripotency, immortalization, and reprogramming. Recently, the quantitative value of cellular dedifferentiation and differentiation was defined as liberality, which is measurable as Shannon entropy of numerical transcriptome data and Lempel-Zip complexity of nucleotide sequence transcriptome data. The increasing liberality induced by the culture environment had first been observed in animal cells and had reconfirmed in plant cells. The phenomena may be common across the kingdom, also in a social amoeba. We measured the liberality of the social amoeba which disaggregated from multicellular aggregates and transferred into a liquid medium.
[ { "created": "Fri, 6 Jan 2023 09:36:52 GMT", "version": "v1" } ]
2023-01-09
[ [ "Ogata", "Norichika", "" ] ]
Tissue culture environment liberates cells from ordinary laws of multi-cellular organisms. This liberation enables cells several behaviors, such as proliferation, dedifferentiation, acquisition of pluripotency, immortalization, and reprogramming. Recently, the quantitative value of cellular dedifferentiation and differentiation was defined as liberality, which is measurable as Shannon entropy of numerical transcriptome data and Lempel-Zip complexity of nucleotide sequence transcriptome data. The increasing liberality induced by the culture environment had first been observed in animal cells and had reconfirmed in plant cells. The phenomena may be common across the kingdom, also in a social amoeba. We measured the liberality of the social amoeba which disaggregated from multicellular aggregates and transferred into a liquid medium.
1811.09366
Shulu Feng
Shulu Feng, Richard A. Friesner
Prediction of Cytochrome P450-Mediated Metabolism Using a Combination of QSAR Derived Reactivity and Induced Fit Docking
null
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Prediction of metabolism in cytochrome P450s remains to be a crucial yet challenging topic in discovering and designing drugs, agrochemicals and nutritional supplements. The problem is challenging because the rate of P450 metabolism depends upon both the intrinsic chemical reactivity of the site and the protein-ligand geometry that is energetically accessible in the active site of a given P450 isozyme. We have addressed this problem using a two-level screening system. The first level implements an empirical QSAR-based scoring function employing the local chemical motifs to characterize the intrinsic reactivity. The second level uses molecular docking and molecular mechanics to account for the geometrical effects, including induced-fit effects in the protein which can be very important in P450 interactions with ligands. This approach has achieved high accuracy for both the P450 3A4 and 2D6 isoforms. In identifying at least one metabolic site in the top two ranked positions, the prediction rate can reach as high as 92.7% for the test set of isoform 3A4. For the 2D6 isoform, 100% accuracy is achieved on this basic evaluation metric, and, because this active site is considerably smaller and more selective than 3A4, very high precision is attained for full prediction of all metabolic sites. The method also requires considerably less CPU time than our previous efforts, which involved a large number of expensive simulations for each ligand to be evaluated. After screening using the empirical score function, only a few best candidates are left for each ligand, making the number of necessary estimations in the second level very small, which significantly reduces the computation time.
[ { "created": "Fri, 23 Nov 2018 05:44:38 GMT", "version": "v1" } ]
2018-11-26
[ [ "Feng", "Shulu", "" ], [ "Friesner", "Richard A.", "" ] ]
Prediction of metabolism in cytochrome P450s remains to be a crucial yet challenging topic in discovering and designing drugs, agrochemicals and nutritional supplements. The problem is challenging because the rate of P450 metabolism depends upon both the intrinsic chemical reactivity of the site and the protein-ligand geometry that is energetically accessible in the active site of a given P450 isozyme. We have addressed this problem using a two-level screening system. The first level implements an empirical QSAR-based scoring function employing the local chemical motifs to characterize the intrinsic reactivity. The second level uses molecular docking and molecular mechanics to account for the geometrical effects, including induced-fit effects in the protein which can be very important in P450 interactions with ligands. This approach has achieved high accuracy for both the P450 3A4 and 2D6 isoforms. In identifying at least one metabolic site in the top two ranked positions, the prediction rate can reach as high as 92.7% for the test set of isoform 3A4. For the 2D6 isoform, 100% accuracy is achieved on this basic evaluation metric, and, because this active site is considerably smaller and more selective than 3A4, very high precision is attained for full prediction of all metabolic sites. The method also requires considerably less CPU time than our previous efforts, which involved a large number of expensive simulations for each ligand to be evaluated. After screening using the empirical score function, only a few best candidates are left for each ligand, making the number of necessary estimations in the second level very small, which significantly reduces the computation time.
1007.0471
Dalibor Stys
Dalibor Stys
Technical performance and interpretation of physical experiment in problems of cell biology
23 pages
null
null
null
q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The lecture summarises main results of my team over last five years in the field of technical experiment design and interpretation of results of experiments for cell bi-ology. I introduce the theoretical concept of the experiment, based mainly on ideqas of stochastic systems theory, and confront it with general ideas of systems theory. In the next part I introduce available experiments and discuss their information con-tent. Namely, I show that light microscopy may be designed to give resolution com-parable to that of electron microscopy and that may be used for experiments using living cells. I show avenues to objective analysis of cell behavior observation. I pro-pose new microscope design, which shall combine advantages of all methods, and steps to be taken to build a model of living cells with predictive power for practical use
[ { "created": "Sat, 3 Jul 2010 06:46:37 GMT", "version": "v1" } ]
2010-07-06
[ [ "Stys", "Dalibor", "" ] ]
The lecture summarises main results of my team over last five years in the field of technical experiment design and interpretation of results of experiments for cell bi-ology. I introduce the theoretical concept of the experiment, based mainly on ideqas of stochastic systems theory, and confront it with general ideas of systems theory. In the next part I introduce available experiments and discuss their information con-tent. Namely, I show that light microscopy may be designed to give resolution com-parable to that of electron microscopy and that may be used for experiments using living cells. I show avenues to objective analysis of cell behavior observation. I pro-pose new microscope design, which shall combine advantages of all methods, and steps to be taken to build a model of living cells with predictive power for practical use
1311.3769
Thierry Rabilloud
Thierry Rabilloud (LCBM)
When 2D is not enough, go for an extra dimension
null
PROTEOMICS 13, 14 (2013) 2065-8
10.1002/pmic.201300215
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The use of an extra SDS separation in a different buffer system provide a technique for deconvoluting 2D gel spots made of several proteins (Colignon et al. Proteomics, 2013, 13, 2077-2082). This technique keeps the quantitative analysis of the protein amounts and combines it with a strongly improved identification process by mass spectrometry, removing identification ambiguities in most cases. In some favorable cases, posttranslational variants can be separated by this procedure. This versatile and easy to use technique is anticipated to be a very valuable addition to the toolbox used in 2D gel-based proteomics.
[ { "created": "Fri, 15 Nov 2013 08:39:25 GMT", "version": "v1" } ]
2013-11-18
[ [ "Rabilloud", "Thierry", "", "LCBM" ] ]
The use of an extra SDS separation in a different buffer system provide a technique for deconvoluting 2D gel spots made of several proteins (Colignon et al. Proteomics, 2013, 13, 2077-2082). This technique keeps the quantitative analysis of the protein amounts and combines it with a strongly improved identification process by mass spectrometry, removing identification ambiguities in most cases. In some favorable cases, posttranslational variants can be separated by this procedure. This versatile and easy to use technique is anticipated to be a very valuable addition to the toolbox used in 2D gel-based proteomics.
2211.16742
Bozhen Hu
Bozhen Hu, Jun Xia, Jiangbin Zheng, Cheng Tan, Yufei Huang, Yongjie Xu, Stan Z. Li
Protein Language Models and Structure Prediction: Connection and Progression
null
null
null
null
q-bio.QM cs.AI cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The prediction of protein structures from sequences is an important task for function prediction, drug design, and related biological processes understanding. Recent advances have proved the power of language models (LMs) in processing the protein sequence databases, which inherit the advantages of attention networks and capture useful information in learning representations for proteins. The past two years have witnessed remarkable success in tertiary protein structure prediction (PSP), including evolution-based and single-sequence-based PSP. It seems that instead of using energy-based models and sampling procedures, protein language model (pLM)-based pipelines have emerged as mainstream paradigms in PSP. Despite the fruitful progress, the PSP community needs a systematic and up-to-date survey to help bridge the gap between LMs in the natural language processing (NLP) and PSP domains and introduce their methodologies, advancements and practical applications. To this end, in this paper, we first introduce the similarities between protein and human languages that allow LMs extended to pLMs, and applied to protein databases. Then, we systematically review recent advances in LMs and pLMs from the perspectives of network architectures, pre-training strategies, applications, and commonly-used protein databases. Next, different types of methods for PSP are discussed, particularly how the pLM-based architectures function in the process of protein folding. Finally, we identify challenges faced by the PSP community and foresee promising research directions along with the advances of pLMs. This survey aims to be a hands-on guide for researchers to understand PSP methods, develop pLMs and tackle challenging problems in this field for practical purposes.
[ { "created": "Wed, 30 Nov 2022 04:58:54 GMT", "version": "v1" } ]
2022-12-01
[ [ "Hu", "Bozhen", "" ], [ "Xia", "Jun", "" ], [ "Zheng", "Jiangbin", "" ], [ "Tan", "Cheng", "" ], [ "Huang", "Yufei", "" ], [ "Xu", "Yongjie", "" ], [ "Li", "Stan Z.", "" ] ]
The prediction of protein structures from sequences is an important task for function prediction, drug design, and related biological processes understanding. Recent advances have proved the power of language models (LMs) in processing the protein sequence databases, which inherit the advantages of attention networks and capture useful information in learning representations for proteins. The past two years have witnessed remarkable success in tertiary protein structure prediction (PSP), including evolution-based and single-sequence-based PSP. It seems that instead of using energy-based models and sampling procedures, protein language model (pLM)-based pipelines have emerged as mainstream paradigms in PSP. Despite the fruitful progress, the PSP community needs a systematic and up-to-date survey to help bridge the gap between LMs in the natural language processing (NLP) and PSP domains and introduce their methodologies, advancements and practical applications. To this end, in this paper, we first introduce the similarities between protein and human languages that allow LMs extended to pLMs, and applied to protein databases. Then, we systematically review recent advances in LMs and pLMs from the perspectives of network architectures, pre-training strategies, applications, and commonly-used protein databases. Next, different types of methods for PSP are discussed, particularly how the pLM-based architectures function in the process of protein folding. Finally, we identify challenges faced by the PSP community and foresee promising research directions along with the advances of pLMs. This survey aims to be a hands-on guide for researchers to understand PSP methods, develop pLMs and tackle challenging problems in this field for practical purposes.
1503.01104
Alexander Alemi
Alexander A. Alemi, Matthew Bierbaum, Christopher R. Myers, James P. Sethna
You Can Run, You Can Hide: The Epidemiology and Statistical Mechanics of Zombies
13 pages, 13 figures
Phys. Rev. E 92, 052801 (2015)
10.1103/PhysRevE.92.052801
null
q-bio.PE physics.pop-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We use a popular fictional disease, zombies, in order to introduce techniques used in modern epidemiology modelling, and ideas and techniques used in the numerical study of critical phenomena. We consider variants of zombie models, from fully connected continuous time dynamics to a full scale exact stochastic dynamic simulation of a zombie outbreak on the continental United States. Along the way, we offer a closed form analytical expression for the fully connected differential equation, and demonstrate that the single person per site two dimensional square lattice version of zombies lies in the percolation universality class. We end with a quantitative study of the full scale US outbreak, including the average susceptibility of different geographical regions.
[ { "created": "Wed, 4 Mar 2015 00:36:09 GMT", "version": "v1" }, { "created": "Thu, 5 Mar 2015 03:24:37 GMT", "version": "v2" }, { "created": "Thu, 4 Jun 2015 19:26:09 GMT", "version": "v3" } ]
2016-06-14
[ [ "Alemi", "Alexander A.", "" ], [ "Bierbaum", "Matthew", "" ], [ "Myers", "Christopher R.", "" ], [ "Sethna", "James P.", "" ] ]
We use a popular fictional disease, zombies, in order to introduce techniques used in modern epidemiology modelling, and ideas and techniques used in the numerical study of critical phenomena. We consider variants of zombie models, from fully connected continuous time dynamics to a full scale exact stochastic dynamic simulation of a zombie outbreak on the continental United States. Along the way, we offer a closed form analytical expression for the fully connected differential equation, and demonstrate that the single person per site two dimensional square lattice version of zombies lies in the percolation universality class. We end with a quantitative study of the full scale US outbreak, including the average susceptibility of different geographical regions.
2210.09666
Nen Saito
Yuji Omachi, Nen Saito, and Chikara Furusawa
Rare-Event Sampling Analysis Uncovers the Fitness Landscape of the Genetic Code
8 pages, 3 figures
null
10.1371/journal.pcbi.1011034
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The genetic code refers to a rule that maps 64 codons to 20 amino acids. Nearly all organisms, with few exceptions, share the same genetic code, the standard genetic code (SGC). While it remains unclear why this universal code has arisen and been maintained during evolution, it may have been preserved under selection pressure. Theoretical studies comparing the SGC and numerically created hypothetical random genetic codes have suggested that the SGC has been subject to strong selection pressure for being robust against translation errors. However, these prior studies have searched for random genetic codes in only a small subspace of the possible code space due to limitations in computation time. Thus, how the genetic code has evolved, and the characteristics of the genetic code fitness landscape, remain unclear. By applying multicanonical Monte Carlo, an efficient rare-event sampling method, we efficiently sampled random codes from a much broader random ensemble of genetic codes than in previous studies, estimating that only one out of every $10^{20}$ random codes is more robust than the SGC. This estimate is significantly smaller than the previous estimate, one in a million. We also characterized the fitness landscape of the genetic code that has four major fitness peaks, one of which includes the SGC. Furthermore, genetic algorithm analysis revealed that evolution under such a multi-peaked fitness landscape could be strongly biased toward a narrow peak, in an evolutionary path-dependent manner.
[ { "created": "Tue, 18 Oct 2022 08:08:45 GMT", "version": "v1" } ]
2023-05-10
[ [ "Omachi", "Yuji", "" ], [ "Saito", "Nen", "" ], [ "Furusawa", "Chikara", "" ] ]
The genetic code refers to a rule that maps 64 codons to 20 amino acids. Nearly all organisms, with few exceptions, share the same genetic code, the standard genetic code (SGC). While it remains unclear why this universal code has arisen and been maintained during evolution, it may have been preserved under selection pressure. Theoretical studies comparing the SGC and numerically created hypothetical random genetic codes have suggested that the SGC has been subject to strong selection pressure for being robust against translation errors. However, these prior studies have searched for random genetic codes in only a small subspace of the possible code space due to limitations in computation time. Thus, how the genetic code has evolved, and the characteristics of the genetic code fitness landscape, remain unclear. By applying multicanonical Monte Carlo, an efficient rare-event sampling method, we efficiently sampled random codes from a much broader random ensemble of genetic codes than in previous studies, estimating that only one out of every $10^{20}$ random codes is more robust than the SGC. This estimate is significantly smaller than the previous estimate, one in a million. We also characterized the fitness landscape of the genetic code that has four major fitness peaks, one of which includes the SGC. Furthermore, genetic algorithm analysis revealed that evolution under such a multi-peaked fitness landscape could be strongly biased toward a narrow peak, in an evolutionary path-dependent manner.
2407.19851
Li Chen
Guozhong Zheng, Jiqiang Zhang, Shengfeng Deng, Weiran Cai, Li Chen
Evolution of cooperation in the public goods game with Q-learning
16 pages, 12 figures, comments are appreciated
null
null
null
q-bio.PE cond-mat.stat-mech nlin.AO
http://creativecommons.org/licenses/by/4.0/
Recent paradigm shifts from imitation learning to reinforcement learning (RL) is shown to be productive in understanding human behaviors. In the RL paradigm, individuals search for optimal strategies through interaction with the environment to make decisions. This implies that gathering, processing, and utilizing information from their surroundings are crucial. However, existing studies typically study pairwise games such as the prisoners' dilemma and employ a self-regarding setup, where individuals play against one opponent based solely on their own strategies, neglecting the environmental information. In this work, we investigate the evolution of cooperation with the multiplayer game -- the public goods game using the Q-learning algorithm by leveraging the environmental information. Specifically, the decision-making of players is based upon the cooperation information in their neighborhood. Our results show that cooperation is more likely to emerge compared to the case of imitation learning by using Fermi rule. Of particular interest is the observation of an anomalous non-monotonic dependence which is revealed when voluntary participation is further introduced. The analysis of the Q-table explains the mechanisms behind the cooperation evolution. Our findings indicate the fundamental role of environment information in the RL paradigm to understand the evolution of cooperation, and human behaviors in general.
[ { "created": "Mon, 29 Jul 2024 10:09:07 GMT", "version": "v1" } ]
2024-07-30
[ [ "Zheng", "Guozhong", "" ], [ "Zhang", "Jiqiang", "" ], [ "Deng", "Shengfeng", "" ], [ "Cai", "Weiran", "" ], [ "Chen", "Li", "" ] ]
Recent paradigm shifts from imitation learning to reinforcement learning (RL) is shown to be productive in understanding human behaviors. In the RL paradigm, individuals search for optimal strategies through interaction with the environment to make decisions. This implies that gathering, processing, and utilizing information from their surroundings are crucial. However, existing studies typically study pairwise games such as the prisoners' dilemma and employ a self-regarding setup, where individuals play against one opponent based solely on their own strategies, neglecting the environmental information. In this work, we investigate the evolution of cooperation with the multiplayer game -- the public goods game using the Q-learning algorithm by leveraging the environmental information. Specifically, the decision-making of players is based upon the cooperation information in their neighborhood. Our results show that cooperation is more likely to emerge compared to the case of imitation learning by using Fermi rule. Of particular interest is the observation of an anomalous non-monotonic dependence which is revealed when voluntary participation is further introduced. The analysis of the Q-table explains the mechanisms behind the cooperation evolution. Our findings indicate the fundamental role of environment information in the RL paradigm to understand the evolution of cooperation, and human behaviors in general.
1610.02308
Henning Dickten
Henning Dickten and Klaus Lehnertz
Identifying delayed directional couplings with symbolic transfer entropy
null
Phys. Rev. E 90, 062706 (2014)
10.1103/PhysRevE.90.062706
null
q-bio.NC nlin.CD physics.comp-ph physics.data-an physics.med-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We propose a straightforward extension of symbolic transfer entropy to enable the investigation of delayed directional relationships between coupled dynamical systems from time series. Analyzing time series from chaotic model systems, we demonstrate the applicability and limitations of our approach. Our findings obtained from applying our method to infer delayed directed interactions in the human epileptic brain underline the importance of our approach for improving the construction of functional network structures from data.
[ { "created": "Thu, 6 Oct 2016 12:56:27 GMT", "version": "v1" } ]
2016-10-10
[ [ "Dickten", "Henning", "" ], [ "Lehnertz", "Klaus", "" ] ]
We propose a straightforward extension of symbolic transfer entropy to enable the investigation of delayed directional relationships between coupled dynamical systems from time series. Analyzing time series from chaotic model systems, we demonstrate the applicability and limitations of our approach. Our findings obtained from applying our method to infer delayed directed interactions in the human epileptic brain underline the importance of our approach for improving the construction of functional network structures from data.
1103.4339
Andrii Mironchenko
Andrii Mironchenko and Jan Kozlowski
Optimal allocation patterns and optimal seed mass of a perennial plant
null
null
null
null
q-bio.PE cs.SY math.OC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present a novel optimal allocation model for perennial plants, in which assimilates are not allocated directly to vegetative or reproductive parts but instead go first to a storage compartment from where they are then optimally redistributed. We do not restrict considerations purely to periods favourable for photosynthesis, as it was done in published models of perennial species, but analyse the whole life period of a perennial plant. As a result, we obtain the general scheme of perennial plant development, for which annual and monocarpic strategies are special cases. We not only re-derive predictions from several previous optimal allocation models, but also obtain more information about plants' strategies during transitions between favourable and unfavourable seasons. One of the model's predictions is that a plant can begin to re-establish vegetative tissues from storage, some time before the beginning of favourable conditions, which in turn allows for better production potential when conditions become better. By means of numerical examples we show that annual plants with single or multiple reproduction periods, monocarps, evergreen perennials and polycarpic perennials can be studied successfully with the help of our unified model. Finally, we build a bridge between optimal allocation models and models describing trade-offs between size and the number of seeds: a modelled plant can control the distribution of not only allocated carbohydrates but also seed size. We provide sufficient conditions for the optimality of producing the smallest and largest seeds possible.
[ { "created": "Tue, 22 Mar 2011 18:25:16 GMT", "version": "v1" }, { "created": "Tue, 9 Oct 2012 12:50:57 GMT", "version": "v2" }, { "created": "Mon, 30 Sep 2013 16:12:26 GMT", "version": "v3" } ]
2013-10-01
[ [ "Mironchenko", "Andrii", "" ], [ "Kozlowski", "Jan", "" ] ]
We present a novel optimal allocation model for perennial plants, in which assimilates are not allocated directly to vegetative or reproductive parts but instead go first to a storage compartment from where they are then optimally redistributed. We do not restrict considerations purely to periods favourable for photosynthesis, as it was done in published models of perennial species, but analyse the whole life period of a perennial plant. As a result, we obtain the general scheme of perennial plant development, for which annual and monocarpic strategies are special cases. We not only re-derive predictions from several previous optimal allocation models, but also obtain more information about plants' strategies during transitions between favourable and unfavourable seasons. One of the model's predictions is that a plant can begin to re-establish vegetative tissues from storage, some time before the beginning of favourable conditions, which in turn allows for better production potential when conditions become better. By means of numerical examples we show that annual plants with single or multiple reproduction periods, monocarps, evergreen perennials and polycarpic perennials can be studied successfully with the help of our unified model. Finally, we build a bridge between optimal allocation models and models describing trade-offs between size and the number of seeds: a modelled plant can control the distribution of not only allocated carbohydrates but also seed size. We provide sufficient conditions for the optimality of producing the smallest and largest seeds possible.
1105.4961
Mikko Tuomi
Mikko Tuomi, Jussi Rasinm\"aki, Anna Repo, Pekka Vanhala, Jari Liski
Soil carbon model Yasso07 graphical user interface
15 pages, 1 figure. Accepted for publication in Environmental Modelling and Software
null
null
null
q-bio.QM physics.geo-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this article, we present a graphical user interface software for the litter decomposition and soil carbon model Yasso07 and an overview of the principles and formulae it is based on. The software can be used to test the model and use it in simple applications. Yasso07 is applicable to upland soils of different ecosystems worldwide, because it has been developed using data covering the global climate conditions and representing various ecosystem types. As input information, Yasso07 requires data on litter input to soil, climate conditions, and land-use change if any. The model predictions are given as probability densities representing the uncertainties in the parameter values of the model and those in the input data - the user interface calculates these densities using a built-in Monte Carlo simulation.
[ { "created": "Wed, 25 May 2011 08:18:07 GMT", "version": "v1" } ]
2011-05-26
[ [ "Tuomi", "Mikko", "" ], [ "Rasinmäki", "Jussi", "" ], [ "Repo", "Anna", "" ], [ "Vanhala", "Pekka", "" ], [ "Liski", "Jari", "" ] ]
In this article, we present a graphical user interface software for the litter decomposition and soil carbon model Yasso07 and an overview of the principles and formulae it is based on. The software can be used to test the model and use it in simple applications. Yasso07 is applicable to upland soils of different ecosystems worldwide, because it has been developed using data covering the global climate conditions and representing various ecosystem types. As input information, Yasso07 requires data on litter input to soil, climate conditions, and land-use change if any. The model predictions are given as probability densities representing the uncertainties in the parameter values of the model and those in the input data - the user interface calculates these densities using a built-in Monte Carlo simulation.
1611.06973
Seymour Knowles-Barley
Seymour Knowles-Barley, Verena Kaynig, Thouis Ray Jones, Alyssa Wilson, Joshua Morgan, Dongil Lee, Daniel Berger, Narayanan Kasthuri, Jeff W. Lichtman, Hanspeter Pfister
RhoanaNet Pipeline: Dense Automatic Neural Annotation
13 pages, 4 figures
null
null
null
q-bio.NC cs.CV
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Reconstructing a synaptic wiring diagram, or connectome, from electron microscopy (EM) images of brain tissue currently requires many hours of manual annotation or proofreading (Kasthuri and Lichtman, 2010; Lichtman and Sanes, 2008; Seung, 2009). The desire to reconstruct ever larger and more complex networks has pushed the collection of ever larger EM datasets. A cubic millimeter of raw imaging data would take up 1 PB of storage and present an annotation project that would be impractical without relying heavily on automatic segmentation methods. The RhoanaNet image processing pipeline was developed to automatically segment large volumes of EM data and ease the burden of manual proofreading and annotation. Based on (Kaynig et al., 2015), we updated every stage of the software pipeline to provide better throughput performance and higher quality segmentation results. We used state of the art deep learning techniques to generate improved membrane probability maps, and Gala (Nunez-Iglesias et al., 2014) was used to agglomerate 2D segments into 3D objects. We applied the RhoanaNet pipeline to four densely annotated EM datasets, two from mouse cortex, one from cerebellum and one from mouse lateral geniculate nucleus (LGN). All training and test data is made available for benchmark comparisons. The best segmentation results obtained gave $V^\text{Info}_\text{F-score}$ scores of 0.9054 and 09182 for the cortex datasets, 0.9438 for LGN, and 0.9150 for Cerebellum. The RhoanaNet pipeline is open source software. All source code, training data, test data, and annotations for all four benchmark datasets are available at www.rhoana.org.
[ { "created": "Mon, 21 Nov 2016 19:48:29 GMT", "version": "v1" } ]
2016-11-22
[ [ "Knowles-Barley", "Seymour", "" ], [ "Kaynig", "Verena", "" ], [ "Jones", "Thouis Ray", "" ], [ "Wilson", "Alyssa", "" ], [ "Morgan", "Joshua", "" ], [ "Lee", "Dongil", "" ], [ "Berger", "Daniel", "" ], [ "Kasthuri", "Narayanan", "" ], [ "Lichtman", "Jeff W.", "" ], [ "Pfister", "Hanspeter", "" ] ]
Reconstructing a synaptic wiring diagram, or connectome, from electron microscopy (EM) images of brain tissue currently requires many hours of manual annotation or proofreading (Kasthuri and Lichtman, 2010; Lichtman and Sanes, 2008; Seung, 2009). The desire to reconstruct ever larger and more complex networks has pushed the collection of ever larger EM datasets. A cubic millimeter of raw imaging data would take up 1 PB of storage and present an annotation project that would be impractical without relying heavily on automatic segmentation methods. The RhoanaNet image processing pipeline was developed to automatically segment large volumes of EM data and ease the burden of manual proofreading and annotation. Based on (Kaynig et al., 2015), we updated every stage of the software pipeline to provide better throughput performance and higher quality segmentation results. We used state of the art deep learning techniques to generate improved membrane probability maps, and Gala (Nunez-Iglesias et al., 2014) was used to agglomerate 2D segments into 3D objects. We applied the RhoanaNet pipeline to four densely annotated EM datasets, two from mouse cortex, one from cerebellum and one from mouse lateral geniculate nucleus (LGN). All training and test data is made available for benchmark comparisons. The best segmentation results obtained gave $V^\text{Info}_\text{F-score}$ scores of 0.9054 and 09182 for the cortex datasets, 0.9438 for LGN, and 0.9150 for Cerebellum. The RhoanaNet pipeline is open source software. All source code, training data, test data, and annotations for all four benchmark datasets are available at www.rhoana.org.
0811.1005
Michel Gauthier
Michel G. Gauthier, Gary W. Slater
Non-driven polymer translocation through a nanopore: computational evidence that the escape and relaxation processes are coupled
null
null
10.1103/PhysRevE.79.021802
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Most of the theoretical models describing the translocation of a polymer chain through a nanopore use the hypothesis that the polymer is always relaxed during the complete process. In other words, models generally assume that the characteristic relaxation time of the chain is small enough compared to the translocation time that non-equilibrium molecular conformations can be ignored. In this paper, we use Molecular Dynamics simulations to directly test this hypothesis by looking at the escape time of unbiased polymer chains starting with different initial conditions. We find that the translocation process is not quite in equilibrium for the systems studied, even though the translocation time tau is about 10 times larger than the relaxation time tau_r. Our most striking result is the observation that the last half of the chain escapes in less than ~12% of the total escape time, which implies that there is a large acceleration of the chain at the end of its escape from the channel.
[ { "created": "Thu, 6 Nov 2008 17:47:45 GMT", "version": "v1" } ]
2009-11-13
[ [ "Gauthier", "Michel G.", "" ], [ "Slater", "Gary W.", "" ] ]
Most of the theoretical models describing the translocation of a polymer chain through a nanopore use the hypothesis that the polymer is always relaxed during the complete process. In other words, models generally assume that the characteristic relaxation time of the chain is small enough compared to the translocation time that non-equilibrium molecular conformations can be ignored. In this paper, we use Molecular Dynamics simulations to directly test this hypothesis by looking at the escape time of unbiased polymer chains starting with different initial conditions. We find that the translocation process is not quite in equilibrium for the systems studied, even though the translocation time tau is about 10 times larger than the relaxation time tau_r. Our most striking result is the observation that the last half of the chain escapes in less than ~12% of the total escape time, which implies that there is a large acceleration of the chain at the end of its escape from the channel.
0706.3684
Pete Donnell
Pete Donnell, Murad Banaji and Stephen Baigent
Stability in generic mitochondrial models
22 pages, 1 figure. Submitted to Mathematical Biosciences
null
null
null
q-bio.QM q-bio.SC
null
In this paper, we use a variety of mathematical techniques to explore existence, local stability, and global stability of equilibria in abstract models of mitochondrial metabolism. The class of models constructed is defined by the biological description of the system, with minimal mathematical assumptions. The key features are an electron transport chain coupled to a process of charge translocation across a membrane. In the absence of charge translocation these models have previously been shown to behave in a very simple manner with a single, globally stable equilibrium. We show that with charge translocation the conclusion about a unique equilibrium remains true, but local and global stability do not necessarily follow. In sufficiently low dimensions - i.e. for short electron transport chains - it is possible to make claims about local and global stability of the equilibrium. On the other hand, for longer chains, these general claims are no longer valid. Some particular conditions which ensure stability of the equilibrium for chains of arbitrary length are presented.
[ { "created": "Mon, 25 Jun 2007 17:55:06 GMT", "version": "v1" } ]
2007-06-26
[ [ "Donnell", "Pete", "" ], [ "Banaji", "Murad", "" ], [ "Baigent", "Stephen", "" ] ]
In this paper, we use a variety of mathematical techniques to explore existence, local stability, and global stability of equilibria in abstract models of mitochondrial metabolism. The class of models constructed is defined by the biological description of the system, with minimal mathematical assumptions. The key features are an electron transport chain coupled to a process of charge translocation across a membrane. In the absence of charge translocation these models have previously been shown to behave in a very simple manner with a single, globally stable equilibrium. We show that with charge translocation the conclusion about a unique equilibrium remains true, but local and global stability do not necessarily follow. In sufficiently low dimensions - i.e. for short electron transport chains - it is possible to make claims about local and global stability of the equilibrium. On the other hand, for longer chains, these general claims are no longer valid. Some particular conditions which ensure stability of the equilibrium for chains of arbitrary length are presented.
1006.0408
Franziska Hinkelmann
Franziska Hinkelmann, David Murrugarra, Abdul Salam Jarrah, Reinhard Laubenbacher
A Mathematical Framework for Agent Based Models of Complex Biological Networks
To appear in Bulletin of Mathematical Biology
null
10.1007/S11538-010-9582-8
null
q-bio.QM cs.MA physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Agent-based modeling and simulation is a useful method to study biological phenomena in a wide range of fields, from molecular biology to ecology. Since there is currently no agreed-upon standard way to specify such models it is not always easy to use published models. Also, since model descriptions are not usually given in mathematical terms, it is difficult to bring mathematical analysis tools to bear, so that models are typically studied through simulation. In order to address this issue, Grimm et al. proposed a protocol for model specification, the so-called ODD protocol, which provides a standard way to describe models. This paper proposes an addition to the ODD protocol which allows the description of an agent-based model as a dynamical system, which provides access to computational and theoretical tools for its analysis. The mathematical framework is that of algebraic models, that is, time-discrete dynamical systems with algebraic structure. It is shown by way of several examples how this mathematical specification can help with model analysis.
[ { "created": "Wed, 2 Jun 2010 14:39:31 GMT", "version": "v1" }, { "created": "Wed, 7 Jul 2010 02:29:09 GMT", "version": "v2" }, { "created": "Fri, 9 Jul 2010 00:46:57 GMT", "version": "v3" }, { "created": "Sat, 28 Aug 2010 17:58:04 GMT", "version": "v4" }, { "created": "Thu, 9 Sep 2010 16:24:07 GMT", "version": "v5" } ]
2010-10-14
[ [ "Hinkelmann", "Franziska", "" ], [ "Murrugarra", "David", "" ], [ "Jarrah", "Abdul Salam", "" ], [ "Laubenbacher", "Reinhard", "" ] ]
Agent-based modeling and simulation is a useful method to study biological phenomena in a wide range of fields, from molecular biology to ecology. Since there is currently no agreed-upon standard way to specify such models it is not always easy to use published models. Also, since model descriptions are not usually given in mathematical terms, it is difficult to bring mathematical analysis tools to bear, so that models are typically studied through simulation. In order to address this issue, Grimm et al. proposed a protocol for model specification, the so-called ODD protocol, which provides a standard way to describe models. This paper proposes an addition to the ODD protocol which allows the description of an agent-based model as a dynamical system, which provides access to computational and theoretical tools for its analysis. The mathematical framework is that of algebraic models, that is, time-discrete dynamical systems with algebraic structure. It is shown by way of several examples how this mathematical specification can help with model analysis.
1505.06658
Yasunori Aoki
Yasunori Aoki, Monika Sundqvist, Andrew C. Hooker and Peter Gennemark
PopED lite: an optimal design software for preclinical pharmacokinetic and pharmacodynamic studies
Submitted to Computer Methods and Programs in Biomedicine
null
null
null
q-bio.QM stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Optimal experimental design approaches are seldom used in pre-clinical drug discovery. Main reasons for this lack of use are that available software tools require relatively high insight in optimal design theory, and that the design-execution cycle of in vivo experiments is short, making time-consuming optimizations infeasible. We present the publicly available software PopED lite in order to increase the use of optimal design in pre-clinical drug discovery. PopED lite is designed to be simple, fast and intuitive. Simple, to give many users access to basic optimal design calculations. Fast, to fit the short design-execution cycle and allow interactive experimental design (test one design, discuss proposed design, test another design, etc). Intuitive, so that the input to and output from the software can easily be understood by users without knowledge of the theory of optimal design. In this way, PopED lite is highly useful in practice and complements existing tools. Key functionality of PopED lite is demonstrated by three case studies from real drug discovery projects.
[ { "created": "Mon, 25 May 2015 15:07:44 GMT", "version": "v1" } ]
2015-05-26
[ [ "Aoki", "Yasunori", "" ], [ "Sundqvist", "Monika", "" ], [ "Hooker", "Andrew C.", "" ], [ "Gennemark", "Peter", "" ] ]
Optimal experimental design approaches are seldom used in pre-clinical drug discovery. Main reasons for this lack of use are that available software tools require relatively high insight in optimal design theory, and that the design-execution cycle of in vivo experiments is short, making time-consuming optimizations infeasible. We present the publicly available software PopED lite in order to increase the use of optimal design in pre-clinical drug discovery. PopED lite is designed to be simple, fast and intuitive. Simple, to give many users access to basic optimal design calculations. Fast, to fit the short design-execution cycle and allow interactive experimental design (test one design, discuss proposed design, test another design, etc). Intuitive, so that the input to and output from the software can easily be understood by users without knowledge of the theory of optimal design. In this way, PopED lite is highly useful in practice and complements existing tools. Key functionality of PopED lite is demonstrated by three case studies from real drug discovery projects.
1603.04955
Stephen Pankavich
Paul Diaz, Paul Constantine, Kelsey Kalmbach, Eric Jones, and Stephen Pankavich
A Modified SEIR Model for the Spread of Ebola in Western Africa and Metrics for Resource Allocation
28 pages, 9 figures
null
null
null
q-bio.PE math.NA
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A modified, deterministic SEIR model is developed for the 2014 Ebola epidemic occurring in the West African nations of Guinea, Liberia, and Sierra Leone. The model describes the dynamical interaction of susceptible and infected populations, while accounting for the effects of hospitalization and the spread of disease through interactions with deceased, but infectious, individuals. Using data from the World Health Organization (WHO), parameters within the model are fit to recent estimates of infected and deceased cases from each nation. The model is then analyzed using these parameter values. Finally, several metrics are proposed to determine which of these nations is in greatest need of additional resources to combat the spread of infection. These include local and global sensitivity metrics of both the infected population and the basic reproduction number with respect to rates of hospitalization and proper burial.
[ { "created": "Wed, 16 Mar 2016 04:15:58 GMT", "version": "v1" }, { "created": "Sat, 22 Oct 2016 20:56:51 GMT", "version": "v2" }, { "created": "Sat, 19 Nov 2016 07:33:42 GMT", "version": "v3" } ]
2016-11-22
[ [ "Diaz", "Paul", "" ], [ "Constantine", "Paul", "" ], [ "Kalmbach", "Kelsey", "" ], [ "Jones", "Eric", "" ], [ "Pankavich", "Stephen", "" ] ]
A modified, deterministic SEIR model is developed for the 2014 Ebola epidemic occurring in the West African nations of Guinea, Liberia, and Sierra Leone. The model describes the dynamical interaction of susceptible and infected populations, while accounting for the effects of hospitalization and the spread of disease through interactions with deceased, but infectious, individuals. Using data from the World Health Organization (WHO), parameters within the model are fit to recent estimates of infected and deceased cases from each nation. The model is then analyzed using these parameter values. Finally, several metrics are proposed to determine which of these nations is in greatest need of additional resources to combat the spread of infection. These include local and global sensitivity metrics of both the infected population and the basic reproduction number with respect to rates of hospitalization and proper burial.
1508.03796
Michael Margaliot
Alon Raveh and Yoram Zarai and Michael Margaliot and Tamir Tuller
Ribosome Flow Model on a Ring
arXiv admin note: substantial text overlap with arXiv:1406.7248
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The asymmetric simple exclusion process (ASEP) is an important model from statistical physics describing particles that hop randomly from one site to the next along an ordered lattice of sites, but only if the next site is empty. ASEP has been used to model and analyze numerous multiagent systems with local interactions including the flow of ribosomes along the mRNA strand. In ASEP with periodic boundary conditions a particle that hops from the last site returns to the first one. The mean field approximation of this model is referred to as the ribosome flow model on a ring (RFMR). The RFMR may be used to model both synthetic and endogenous gene expression regimes. We analyze the RFMR using the theory of monotone dynamical systems. We show that it admits a continuum of equilibrium points and that every trajectory converges to an equilibrium point. Furthermore, we show that it entrains to periodic transition rates between the sites. We describe the implications of the analysis results to understanding and engineering cyclic mRNA translation in-vitro and in-vivo.
[ { "created": "Sun, 16 Aug 2015 07:33:50 GMT", "version": "v1" } ]
2015-08-18
[ [ "Raveh", "Alon", "" ], [ "Zarai", "Yoram", "" ], [ "Margaliot", "Michael", "" ], [ "Tuller", "Tamir", "" ] ]
The asymmetric simple exclusion process (ASEP) is an important model from statistical physics describing particles that hop randomly from one site to the next along an ordered lattice of sites, but only if the next site is empty. ASEP has been used to model and analyze numerous multiagent systems with local interactions including the flow of ribosomes along the mRNA strand. In ASEP with periodic boundary conditions a particle that hops from the last site returns to the first one. The mean field approximation of this model is referred to as the ribosome flow model on a ring (RFMR). The RFMR may be used to model both synthetic and endogenous gene expression regimes. We analyze the RFMR using the theory of monotone dynamical systems. We show that it admits a continuum of equilibrium points and that every trajectory converges to an equilibrium point. Furthermore, we show that it entrains to periodic transition rates between the sites. We describe the implications of the analysis results to understanding and engineering cyclic mRNA translation in-vitro and in-vivo.
1501.02664
Burak Erman
Burak Erman
Effects of ligand binding upon flexibility of proteins
6 pages, 3 figures
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Binding of a ligand on a protein changes the flexibility of certain parts of the protein, which directly affects its function. These changes are not the same at each point, some parts become more flexible and some others become stiffer. Here, an equation is derived that gives the stiffness map for proteins. The model is based on correlations of fluctuations of pairs of points that need to be evaluated by molecular dynamics simulations. The model is also cast in terms of the Gaussian Network Model and changes of stiffness upon dimerization of AKT1 are evaluated as an example.
[ { "created": "Mon, 12 Jan 2015 14:40:31 GMT", "version": "v1" } ]
2015-01-13
[ [ "Erman", "Burak", "" ] ]
Binding of a ligand on a protein changes the flexibility of certain parts of the protein, which directly affects its function. These changes are not the same at each point, some parts become more flexible and some others become stiffer. Here, an equation is derived that gives the stiffness map for proteins. The model is based on correlations of fluctuations of pairs of points that need to be evaluated by molecular dynamics simulations. The model is also cast in terms of the Gaussian Network Model and changes of stiffness upon dimerization of AKT1 are evaluated as an example.
1308.0655
Daniel McGlinn
Daniel J. McGlinn, Xiao Xiao, Ethan P. White
An empirical evaluation of four variants of a universal species-area relationship
main text: 20 pages, 2 tables, 3 figures
null
null
null
q-bio.QM q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The Maximum Entropy Theory of Ecology (METE) predicts a universal species-area relationship (SAR) that can be fully characterized using only the total abundance (N) and species richness (S) at a single spatial scale. This theory has shown promise for characterizing scale dependence in the SAR. However, there are currently four different approaches to applying METE to predict the SAR and it is unclear which approach should be used due to a lack of empirical evaluation. Specifically, METE can be applied recursively or a non-recursively and can use either a theoretical or observed species-abundance distribution (SAD). We compared the four different combinations of approaches using empirical data from 16 datasets containing over 1000 species and 300,000 individual trees and herbs. In general, METE accurately downscaled the SAR (R^2> 0.94), but the recursive approach consistently under-predicted richness, and METEs accuracy did not depend strongly on using the observed or predicted SAD. This suggests that best approach to scaling diversity using METE is to use a combination of non-recursive scaling and the theoretical abundance distribution, which allows predictions to be made across a broad range of spatial scales with only knowledge of the species richness and total abundance at a single scale.
[ { "created": "Sat, 3 Aug 2013 03:15:48 GMT", "version": "v1" }, { "created": "Fri, 8 Nov 2013 23:08:15 GMT", "version": "v2" } ]
2013-11-12
[ [ "McGlinn", "Daniel J.", "" ], [ "Xiao", "Xiao", "" ], [ "White", "Ethan P.", "" ] ]
The Maximum Entropy Theory of Ecology (METE) predicts a universal species-area relationship (SAR) that can be fully characterized using only the total abundance (N) and species richness (S) at a single spatial scale. This theory has shown promise for characterizing scale dependence in the SAR. However, there are currently four different approaches to applying METE to predict the SAR and it is unclear which approach should be used due to a lack of empirical evaluation. Specifically, METE can be applied recursively or a non-recursively and can use either a theoretical or observed species-abundance distribution (SAD). We compared the four different combinations of approaches using empirical data from 16 datasets containing over 1000 species and 300,000 individual trees and herbs. In general, METE accurately downscaled the SAR (R^2> 0.94), but the recursive approach consistently under-predicted richness, and METEs accuracy did not depend strongly on using the observed or predicted SAD. This suggests that best approach to scaling diversity using METE is to use a combination of non-recursive scaling and the theoretical abundance distribution, which allows predictions to be made across a broad range of spatial scales with only knowledge of the species richness and total abundance at a single scale.
2006.14575
Subhas Khajanchi Dr.
Subhas Khajanchi, Kankan Sarkar
Forecasting the daily and cumulative number of cases for the COVID-19 pandemic in India
18 Pages, 7 Figures
null
10.1063/5.0016240
null
q-bio.PE physics.soc-ph
http://creativecommons.org/licenses/by/4.0/
The ongoing novel coronavirus epidemic has been announced a pandemic by the World Health Organization on March 11, 2020, and the Govt. of India has declared a nationwide lockdown from March 25, 2020, to prevent community transmission of COVID-19. Due to absence of specific antivirals or vaccine, mathematical modeling play an important role to better understand the disease dynamics and designing strategies to control rapidly spreading infectious diseases. In our study, we developed a new compartmental model that explains the transmission dynamics of COVID-19. We calibrated our proposed model with daily COVID-19 data for the four Indian provinces, namely Jharkhand, Gujarat, Andhra Pradesh, and Chandigarh. We study the qualitative properties of the model including feasible equilibria and their stability with respect to the basic reproduction number $\mathcal{R}_0$. The disease-free equilibrium becomes stable and the endemic equilibrium becomes unstable when the recovery rate of infected individuals increased but if the disease transmission rate remains higher then the endemic equilibrium always remain stable. For the estimated model parameters, $\mathcal{R}_0 >1$ for all the four provinces, which suggests the significant outbreak of COVID-19. Short-time prediction shows the increasing trend of daily and cumulative cases of COVID-19 for the four provinces of India.
[ { "created": "Thu, 25 Jun 2020 17:20:34 GMT", "version": "v1" } ]
2020-08-26
[ [ "Khajanchi", "Subhas", "" ], [ "Sarkar", "Kankan", "" ] ]
The ongoing novel coronavirus epidemic has been announced a pandemic by the World Health Organization on March 11, 2020, and the Govt. of India has declared a nationwide lockdown from March 25, 2020, to prevent community transmission of COVID-19. Due to absence of specific antivirals or vaccine, mathematical modeling play an important role to better understand the disease dynamics and designing strategies to control rapidly spreading infectious diseases. In our study, we developed a new compartmental model that explains the transmission dynamics of COVID-19. We calibrated our proposed model with daily COVID-19 data for the four Indian provinces, namely Jharkhand, Gujarat, Andhra Pradesh, and Chandigarh. We study the qualitative properties of the model including feasible equilibria and their stability with respect to the basic reproduction number $\mathcal{R}_0$. The disease-free equilibrium becomes stable and the endemic equilibrium becomes unstable when the recovery rate of infected individuals increased but if the disease transmission rate remains higher then the endemic equilibrium always remain stable. For the estimated model parameters, $\mathcal{R}_0 >1$ for all the four provinces, which suggests the significant outbreak of COVID-19. Short-time prediction shows the increasing trend of daily and cumulative cases of COVID-19 for the four provinces of India.
1401.5589
Stephen Odaibo
Stephen G. Odaibo
The Gabor-Einstein Wavelet: A Model for the Receptive Fields of V1 to MT Neurons
40 pages, 13 Figures. We presented a portion of this work in various parts at the National Medical Association's 111th Annual Convention and Scientific Assembly in Toronto Ontario, Canada (Jul. 2013); at the 23rd Annual Washington Retina Symposium in Washington D.C., U.S.A. (Oct. 2013); and at the Society for Neuroscience's 43rd Annual Meeting in San Diego California, U.S.A. (Nov. 2013)
null
null
null
q-bio.NC cs.CV physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Our visual system is astonishingly efficient at detecting moving objects. This process is mediated by the neurons which connect the primary visual cortex (V1) to the middle temporal (MT) area. Interestingly, since Kuffler's pioneering experiments on retinal ganglion cells, mathematical models have been vital for advancing our understanding of the receptive fields of visual neurons. However, existing models were not designed to describe the most salient attributes of the highly specialized neurons in the V1 to MT motion processing stream; and they have not been able to do so. Here, we introduce the Gabor-Einstein wavelet, a new family of functions for representing the receptive fields of V1 to MT neurons. We show that the way space and time are mixed in the visual cortex is analogous to the way they are mixed in the special theory of relativity (STR). Hence we constrained the Gabor-Einstein model by requiring: (i) relativistic-invariance of the wave carrier, and (ii) the minimum possible number of parameters. From these two constraints, the sinc function emerged as a natural descriptor of the wave carrier. The particular distribution of lowpass to bandpass temporal frequency filtering properties of V1 to MT neurons (Foster et al 1985; DeAngelis et al 1993b; Hawken et al 1996) is clearly explained by the Gabor-Einstein basis. Furthermore, it does so in a manner innately representative of the motion-processing stream's neuronal hierarchy. Our analysis and computer simulations show that the distribution of temporal frequency filtering properties along the motion processing stream is a direct effect of the way the brain jointly encodes space and time. We uncovered this fundamental link by demonstrating that analogous mathematical structures underlie STR and joint cortical spacetime encoding. This link will provide new physiological insights into how the brain represents visual information.
[ { "created": "Wed, 22 Jan 2014 08:48:53 GMT", "version": "v1" } ]
2014-01-23
[ [ "Odaibo", "Stephen G.", "" ] ]
Our visual system is astonishingly efficient at detecting moving objects. This process is mediated by the neurons which connect the primary visual cortex (V1) to the middle temporal (MT) area. Interestingly, since Kuffler's pioneering experiments on retinal ganglion cells, mathematical models have been vital for advancing our understanding of the receptive fields of visual neurons. However, existing models were not designed to describe the most salient attributes of the highly specialized neurons in the V1 to MT motion processing stream; and they have not been able to do so. Here, we introduce the Gabor-Einstein wavelet, a new family of functions for representing the receptive fields of V1 to MT neurons. We show that the way space and time are mixed in the visual cortex is analogous to the way they are mixed in the special theory of relativity (STR). Hence we constrained the Gabor-Einstein model by requiring: (i) relativistic-invariance of the wave carrier, and (ii) the minimum possible number of parameters. From these two constraints, the sinc function emerged as a natural descriptor of the wave carrier. The particular distribution of lowpass to bandpass temporal frequency filtering properties of V1 to MT neurons (Foster et al 1985; DeAngelis et al 1993b; Hawken et al 1996) is clearly explained by the Gabor-Einstein basis. Furthermore, it does so in a manner innately representative of the motion-processing stream's neuronal hierarchy. Our analysis and computer simulations show that the distribution of temporal frequency filtering properties along the motion processing stream is a direct effect of the way the brain jointly encodes space and time. We uncovered this fundamental link by demonstrating that analogous mathematical structures underlie STR and joint cortical spacetime encoding. This link will provide new physiological insights into how the brain represents visual information.
2404.08023
Zeyu Zhang
Zeyu Zhang, Yuanshen Zhao, Jingxian Duan, Yaou Liu, Hairong Zheng, Dong Liang, Zhenyu Zhang and Zhi-Cheng Li
Pathology-genomic fusion via biologically informed cross-modality graph learning for survival analysis
null
null
null
null
q-bio.QM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The diagnosis and prognosis of cancer are typically based on multi-modal clinical data, including histology images and genomic data, due to the complex pathogenesis and high heterogeneity. Despite the advancements in digital pathology and high-throughput genome sequencing, establishing effective multi-modal fusion models for survival prediction and revealing the potential association between histopathology and transcriptomics remains challenging. In this paper, we propose Pathology-Genome Heterogeneous Graph (PGHG) that integrates whole slide images (WSI) and bulk RNA-Seq expression data with heterogeneous graph neural network for cancer survival analysis. The PGHG consists of biological knowledge-guided representation learning network and pathology-genome heterogeneous graph. The representation learning network utilizes the biological prior knowledge of intra-modal and inter-modal data associations to guide the feature extraction. The node features of each modality are updated through attention-based graph learning strategy. Unimodal features and bi-modal fused features are extracted via attention pooling module and then used for survival prediction. We evaluate the model on low-grade gliomas, glioblastoma, and kidney renal papillary cell carcinoma datasets from the Cancer Genome Atlas (TCGA) and the First Affiliated Hospital of Zhengzhou University (FAHZU). Extensive experimental results demonstrate that the proposed method outperforms both unimodal and other multi-modal fusion models. For demonstrating the model interpretability, we also visualize the attention heatmap of pathological images and utilize integrated gradient algorithm to identify important tissue structure, biological pathways and key genes.
[ { "created": "Thu, 11 Apr 2024 09:07:40 GMT", "version": "v1" } ]
2024-04-15
[ [ "Zhang", "Zeyu", "" ], [ "Zhao", "Yuanshen", "" ], [ "Duan", "Jingxian", "" ], [ "Liu", "Yaou", "" ], [ "Zheng", "Hairong", "" ], [ "Liang", "Dong", "" ], [ "Zhang", "Zhenyu", "" ], [ "Li", "Zhi-Cheng", "" ] ]
The diagnosis and prognosis of cancer are typically based on multi-modal clinical data, including histology images and genomic data, due to the complex pathogenesis and high heterogeneity. Despite the advancements in digital pathology and high-throughput genome sequencing, establishing effective multi-modal fusion models for survival prediction and revealing the potential association between histopathology and transcriptomics remains challenging. In this paper, we propose Pathology-Genome Heterogeneous Graph (PGHG) that integrates whole slide images (WSI) and bulk RNA-Seq expression data with heterogeneous graph neural network for cancer survival analysis. The PGHG consists of biological knowledge-guided representation learning network and pathology-genome heterogeneous graph. The representation learning network utilizes the biological prior knowledge of intra-modal and inter-modal data associations to guide the feature extraction. The node features of each modality are updated through attention-based graph learning strategy. Unimodal features and bi-modal fused features are extracted via attention pooling module and then used for survival prediction. We evaluate the model on low-grade gliomas, glioblastoma, and kidney renal papillary cell carcinoma datasets from the Cancer Genome Atlas (TCGA) and the First Affiliated Hospital of Zhengzhou University (FAHZU). Extensive experimental results demonstrate that the proposed method outperforms both unimodal and other multi-modal fusion models. For demonstrating the model interpretability, we also visualize the attention heatmap of pathological images and utilize integrated gradient algorithm to identify important tissue structure, biological pathways and key genes.
1608.03467
Laurens Michiels Van Kessenich
L. Michiels van Kessenich, L. de Arcangelis and H. J. Herrmann
Synaptic plasticity and neuronal refractory time cause scaling behaviour of neuronal avalanches
9 pages, 4 figures, to be published in Scientific Reports
null
null
null
q-bio.NC nlin.AO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Neuronal avalanches measured in vitro and in vivo in different cortical networks consistently exhibit power law behaviour for the size and duration distributions with exponents typical for a mean field self-organized branching process. These exponents are also recovered in neuronal network simulations implementing various neuronal dynamics on different network topologies. They can therefore be considered a very robust feature of spontaneous neuronal activity. Interestingly, this scaling behaviour is also observed on regular lattices in finite dimensions, which raises the question about the origin of the mean field behaviour observed experimentally. In this study we provide an answer to this open question by investigating the effect of activity dependent plasticity in combination with the neuronal refractory time in a neuronal network. Results show that the refractory time hinders backward avalanches forcing a directed propagation. Hebbian plastic adaptation plays the role of sculpting these directed avalanche patterns into the topology of the network slowly changing it into a branched structure where loops are marginal.
[ { "created": "Wed, 10 Aug 2016 13:37:04 GMT", "version": "v1" } ]
2016-08-12
[ [ "van Kessenich", "L. Michiels", "" ], [ "de Arcangelis", "L.", "" ], [ "Herrmann", "H. J.", "" ] ]
Neuronal avalanches measured in vitro and in vivo in different cortical networks consistently exhibit power law behaviour for the size and duration distributions with exponents typical for a mean field self-organized branching process. These exponents are also recovered in neuronal network simulations implementing various neuronal dynamics on different network topologies. They can therefore be considered a very robust feature of spontaneous neuronal activity. Interestingly, this scaling behaviour is also observed on regular lattices in finite dimensions, which raises the question about the origin of the mean field behaviour observed experimentally. In this study we provide an answer to this open question by investigating the effect of activity dependent plasticity in combination with the neuronal refractory time in a neuronal network. Results show that the refractory time hinders backward avalanches forcing a directed propagation. Hebbian plastic adaptation plays the role of sculpting these directed avalanche patterns into the topology of the network slowly changing it into a branched structure where loops are marginal.
1904.10394
Urmimala Dey
Urmimala Dey, Archisman Ghosh, Syed Abbas, A Taraphder and Madhumita Roy
Cell damage and mitigation in Swiss albino mice: experiment and modelling
null
Alexandria Engineering Journal 59, 1345-1357 (2020)
10.1016/j.aej.2020.03.001
null
q-bio.TO q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Chronic exposure to inorganic arsenic is a potential cause of carcinogenesis. It elicits its potential by generation of ROS, leading to DNA, protein and lipid damage. Therefore, the deleterious effect of arsenic can be mitigated by quenching ROS using antioxidants. There is a homology between the protein coding regions of mice and human. Effect of these alterations in human can be mimicked in mice. Therefore to understand the underlying mechanism of arsenic toxicity and its amelioration by black tea, studies have been conducted in mice model. Long term exposure to iAs leads to tumour growth, which has been found to be alleviated by black tea. Observations reveal that black tea has two salutary effects on the growth of tumour: the rate of growth of damaged cells was appreciably reduced and an early saturation of the level of damage is achieved. To take the experimental findings further, the experimental data have been modelled with simple dynamical equations. The curves obtained from \textit{in vivo} studies have been fitted with the data obtained from the model. The corresponding steady states and their stabilities are analyzed.
[ { "created": "Fri, 5 Apr 2019 17:10:00 GMT", "version": "v1" } ]
2020-06-23
[ [ "Dey", "Urmimala", "" ], [ "Ghosh", "Archisman", "" ], [ "Abbas", "Syed", "" ], [ "Taraphder", "A", "" ], [ "Roy", "Madhumita", "" ] ]
Chronic exposure to inorganic arsenic is a potential cause of carcinogenesis. It elicits its potential by generation of ROS, leading to DNA, protein and lipid damage. Therefore, the deleterious effect of arsenic can be mitigated by quenching ROS using antioxidants. There is a homology between the protein coding regions of mice and human. Effect of these alterations in human can be mimicked in mice. Therefore to understand the underlying mechanism of arsenic toxicity and its amelioration by black tea, studies have been conducted in mice model. Long term exposure to iAs leads to tumour growth, which has been found to be alleviated by black tea. Observations reveal that black tea has two salutary effects on the growth of tumour: the rate of growth of damaged cells was appreciably reduced and an early saturation of the level of damage is achieved. To take the experimental findings further, the experimental data have been modelled with simple dynamical equations. The curves obtained from \textit{in vivo} studies have been fitted with the data obtained from the model. The corresponding steady states and their stabilities are analyzed.
1803.09727
Jie Ren
Jie Ren, Xin Bai, Yang Young Lu, Kujin Tang, Ying Wang, Gesine Reinert, Fengzhu Sun
Alignment-Free Sequence Analysis and Applications
null
null
null
null
q-bio.QM q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Genome and metagenome comparisons based on large amounts of next-generation sequencing (NGS) data pose significant challenges for alignment-based approaches due to the huge data size and the relatively short length of the reads. Alignment-free approaches based on the counts of word patterns in NGS data do not depend on the complete genome and are generally computationally efficient. Thus, they contribute significantly to genome and metagenome comparison. Recently, novel statistical approaches have been developed for the comparison of both long and shotgun sequences. These approaches have been applied to many problems including the comparison of gene regulatory regions, genome sequences, metagenomes, binning contigs in metagenomic data, identification of virus-host interactions, and detection of horizontal gene transfers. We provide an updated review of these applications and other related developments of word-count based approaches for alignment-free sequence analysis.
[ { "created": "Mon, 26 Mar 2018 17:31:11 GMT", "version": "v1" } ]
2018-03-28
[ [ "Ren", "Jie", "" ], [ "Bai", "Xin", "" ], [ "Lu", "Yang Young", "" ], [ "Tang", "Kujin", "" ], [ "Wang", "Ying", "" ], [ "Reinert", "Gesine", "" ], [ "Sun", "Fengzhu", "" ] ]
Genome and metagenome comparisons based on large amounts of next-generation sequencing (NGS) data pose significant challenges for alignment-based approaches due to the huge data size and the relatively short length of the reads. Alignment-free approaches based on the counts of word patterns in NGS data do not depend on the complete genome and are generally computationally efficient. Thus, they contribute significantly to genome and metagenome comparison. Recently, novel statistical approaches have been developed for the comparison of both long and shotgun sequences. These approaches have been applied to many problems including the comparison of gene regulatory regions, genome sequences, metagenomes, binning contigs in metagenomic data, identification of virus-host interactions, and detection of horizontal gene transfers. We provide an updated review of these applications and other related developments of word-count based approaches for alignment-free sequence analysis.
1509.04602
Aristides Moustakas
Aristides Moustakas and Matthew R. Evans
Regional and temporal characteristics of bovine tuberculosis of cattle in Great Britain
(in press) Stochastic Environmental Research and Risk Assessment (2015)
null
null
null
q-bio.PE stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Bovine tuberculosis (TB) is a chronic disease in cattle that causes a serious food security challenge to the agricultural industry in terms of dairy and meat production. In GB, Scotland has had a risk based surveillance testing policy under which high risk herds are tested frequently, and in Sept 2009 was officially declared as TB free. Wales have had an annual or more frequent testing policy for all cattle herds since Jan 2010, while in England several herds are still tested every 4 years except some high TB prevalence areas where annual testing is applied. Time series analysis using publicly available data for total tests on herds, total cattle slaughtered, new herd incidents, and herds not TB free, were analysed globally for GB and locally for the constituent regions of Wales, Scotland, West, North, and East England. After detecting trends over time, underlying regional differences were compared with the testing policies in the region. Total cattle slaughtered are decreasing in Wales, Scotland and West England, but increasing in the North and East English regions. New herd incidents, i.e., disease incidence, are decreasing in Wales, Scotland, West English region, but increasing in North and East English regions. Herds not TB free, are increasing in West, North, and East English regions, while they are decreasing in Wales and Scotland. Total cattle slaughtered were positively correlated with total tests in the West, North, and East English regions, with high slopes of regression. There was no correlation between total cattle slaughtered and total tests on herds in Wales indicating that herds are tested frequent enough in order to detect all likely cases and so control TB. The main conclusion of the analysis conducted here is that more frequent testing is leading to lower TB infections in cattle both in terms of TB prevalence as well as TB incidence.
[ { "created": "Tue, 15 Sep 2015 15:29:41 GMT", "version": "v1" } ]
2015-09-16
[ [ "Moustakas", "Aristides", "" ], [ "Evans", "Matthew R.", "" ] ]
Bovine tuberculosis (TB) is a chronic disease in cattle that causes a serious food security challenge to the agricultural industry in terms of dairy and meat production. In GB, Scotland has had a risk based surveillance testing policy under which high risk herds are tested frequently, and in Sept 2009 was officially declared as TB free. Wales have had an annual or more frequent testing policy for all cattle herds since Jan 2010, while in England several herds are still tested every 4 years except some high TB prevalence areas where annual testing is applied. Time series analysis using publicly available data for total tests on herds, total cattle slaughtered, new herd incidents, and herds not TB free, were analysed globally for GB and locally for the constituent regions of Wales, Scotland, West, North, and East England. After detecting trends over time, underlying regional differences were compared with the testing policies in the region. Total cattle slaughtered are decreasing in Wales, Scotland and West England, but increasing in the North and East English regions. New herd incidents, i.e., disease incidence, are decreasing in Wales, Scotland, West English region, but increasing in North and East English regions. Herds not TB free, are increasing in West, North, and East English regions, while they are decreasing in Wales and Scotland. Total cattle slaughtered were positively correlated with total tests in the West, North, and East English regions, with high slopes of regression. There was no correlation between total cattle slaughtered and total tests on herds in Wales indicating that herds are tested frequent enough in order to detect all likely cases and so control TB. The main conclusion of the analysis conducted here is that more frequent testing is leading to lower TB infections in cattle both in terms of TB prevalence as well as TB incidence.
2004.01710
Andreas Kamilaris
Eleni Kamilari, Dimitrios A. Anagnostopoulos, Photis Papademas, Andreas Kamilaris, Dimitris Tsaltas
Characterizing Halloumi cheese bacterial communities through metagenomic analysis
null
LWT (2020): 109298
10.1016/j.lwt.2020.109298
null
q-bio.GN cs.CY
http://creativecommons.org/licenses/by/4.0/
Halloumi is a semi hard cheese produced in Cyprus for centuries and its popularity has significantly risen over the past years. High throughput sequencing (HTS) was applied in the present research to characterize traditional Cyprus Halloumi bacterial diversity. Eighteen samples made by different milk mixtures and produced in different areas of the country were analyzed, to reveal that Halloumi microbiome was mainly comprised by lactic acid bacteria (LAB), including Lactobacillus, Leuconostoc, and Pediococcus, as well as halophilic bacteria, such as Marinilactibacillus and Halomonas. Additionally, spore forming bacteria and spoilage bacteria, were also detected. Halloumi produced with the traditional method, had significantly richer bacterial diversity compared to Halloumi produced with the industrial method. Variations detected among the bacterial communities highlight the contribution of the initial microbiome that existed in milk and survived pasteurization, as well as factors associated with Halloumi manufacturing conditions, in the final microbiota composition shaping. Identification and characterization of Halloumi microbiome provides an additional, useful tool to characterize its typicity and probably safeguard it from fraud products that may appear in the market. Also, it may assist producers to further improve its quality and guarantee consumers safety.
[ { "created": "Fri, 3 Apr 2020 14:09:26 GMT", "version": "v1" } ]
2020-04-07
[ [ "Kamilari", "Eleni", "" ], [ "Anagnostopoulos", "Dimitrios A.", "" ], [ "Papademas", "Photis", "" ], [ "Kamilaris", "Andreas", "" ], [ "Tsaltas", "Dimitris", "" ] ]
Halloumi is a semi hard cheese produced in Cyprus for centuries and its popularity has significantly risen over the past years. High throughput sequencing (HTS) was applied in the present research to characterize traditional Cyprus Halloumi bacterial diversity. Eighteen samples made by different milk mixtures and produced in different areas of the country were analyzed, to reveal that Halloumi microbiome was mainly comprised by lactic acid bacteria (LAB), including Lactobacillus, Leuconostoc, and Pediococcus, as well as halophilic bacteria, such as Marinilactibacillus and Halomonas. Additionally, spore forming bacteria and spoilage bacteria, were also detected. Halloumi produced with the traditional method, had significantly richer bacterial diversity compared to Halloumi produced with the industrial method. Variations detected among the bacterial communities highlight the contribution of the initial microbiome that existed in milk and survived pasteurization, as well as factors associated with Halloumi manufacturing conditions, in the final microbiota composition shaping. Identification and characterization of Halloumi microbiome provides an additional, useful tool to characterize its typicity and probably safeguard it from fraud products that may appear in the market. Also, it may assist producers to further improve its quality and guarantee consumers safety.
1809.03961
Santiago Schnell
Justin Eilertsen, Wylie Stroberg and Santiago Schnell
Characteristic, completion or matching timescales? An analysis of temporary boundaries in enzyme kinetics
35 pages, 11 figures
Journal of Theoretical Biology, Volume 481, 21 November 2019, Pages 28-43
10.1016/j.jtbi.2019.01.005
null
q-bio.QM math.DS
http://creativecommons.org/licenses/by/4.0/
Scaling analysis exploiting timescale separation has been one of the most important techniques in the quantitative analysis of nonlinear dynamical systems in mathematical and theoretical biology. In the case of enzyme catalyzed reactions, it is often overlooked that the characteristic timescales used for the scaling the rate equations are not ideal for determining when concentrations and reaction rates reach their maximum values. In this work, we first illustrate this point by considering the classic example of the single-enzyme, single-substrate Michaelis--Menten reaction mechanism. We then extend this analysis to a more complicated reaction mechanism, the auxiliary enzyme reaction, in which a substrate is converted to product in two sequential enzyme-catalyzed reactions. In this case, depending on the ordering of the relevant timescales, several dynamic regimes can emerge. In addition to the characteristic timescales for these regimes, we derive matching timescales that determine (approximately) when the transitions from initial fast transient to steady-state kinetics occurs. The approach presented here is applicable to a wide range of singular perturbation problems in nonlinear dynamical systems.
[ { "created": "Tue, 11 Sep 2018 15:10:10 GMT", "version": "v1" }, { "created": "Wed, 2 Jan 2019 19:53:12 GMT", "version": "v2" } ]
2023-03-21
[ [ "Eilertsen", "Justin", "" ], [ "Stroberg", "Wylie", "" ], [ "Schnell", "Santiago", "" ] ]
Scaling analysis exploiting timescale separation has been one of the most important techniques in the quantitative analysis of nonlinear dynamical systems in mathematical and theoretical biology. In the case of enzyme catalyzed reactions, it is often overlooked that the characteristic timescales used for the scaling the rate equations are not ideal for determining when concentrations and reaction rates reach their maximum values. In this work, we first illustrate this point by considering the classic example of the single-enzyme, single-substrate Michaelis--Menten reaction mechanism. We then extend this analysis to a more complicated reaction mechanism, the auxiliary enzyme reaction, in which a substrate is converted to product in two sequential enzyme-catalyzed reactions. In this case, depending on the ordering of the relevant timescales, several dynamic regimes can emerge. In addition to the characteristic timescales for these regimes, we derive matching timescales that determine (approximately) when the transitions from initial fast transient to steady-state kinetics occurs. The approach presented here is applicable to a wide range of singular perturbation problems in nonlinear dynamical systems.
q-bio/0402014
Alan McKane
Christopher Quince, Paul Higgs and Alan McKane
Topological structure and interaction strengths in model food webs
43 pages, 15 figures
null
null
null
q-bio.PE cond-mat.stat-mech
null
We report the results of carrying out a large number of simulations on a coevolutionary model of multispecies communities. A wide range of parameter values were investigated which allowed a rather complete picture of the change in behaviour of the model as these parameters were varied to be built up. Our main interest was in the nature of the community food webs constructed via the simulations. We identify the range of parameter values which give rise to realistic food webs and give arguments which allow some of the structure which is found to be understood in an intuitive way. Since the webs are evolved according to the rules of the model, the strengths of the predator-prey links are not determined a priori, and emerge from the process of constructing the web. We measure the distribution of these link strengths, and find that there are a large number of weak links, in agreement with recent suggestions. We also review some of the data on food webs available in the literature, and make some tentative comparisons with our results. The difficulties of making such comparisons and the possible future developments of the model are also briefly discussed.
[ { "created": "Sat, 7 Feb 2004 14:45:15 GMT", "version": "v1" } ]
2007-05-23
[ [ "Quince", "Christopher", "" ], [ "Higgs", "Paul", "" ], [ "McKane", "Alan", "" ] ]
We report the results of carrying out a large number of simulations on a coevolutionary model of multispecies communities. A wide range of parameter values were investigated which allowed a rather complete picture of the change in behaviour of the model as these parameters were varied to be built up. Our main interest was in the nature of the community food webs constructed via the simulations. We identify the range of parameter values which give rise to realistic food webs and give arguments which allow some of the structure which is found to be understood in an intuitive way. Since the webs are evolved according to the rules of the model, the strengths of the predator-prey links are not determined a priori, and emerge from the process of constructing the web. We measure the distribution of these link strengths, and find that there are a large number of weak links, in agreement with recent suggestions. We also review some of the data on food webs available in the literature, and make some tentative comparisons with our results. The difficulties of making such comparisons and the possible future developments of the model are also briefly discussed.
0706.0163
Alexander K. Vidybida
Alexander K. Vidybida
Output Stream of Binding Neuron with Feedback
Version #1: 4 pages, 5 figures, manuscript submitted to Biological Cybernetics. Version #2 (this version): added 3 pages of new text with additional analytical and numerical calculations, 2 more figures, 11 more references, added Discussion section
Eur. Phys. J. B 65, 577-584 (2008); Eur. Phys. J. B 69, 313 (2009)
10.1140/epjb/e2008-00360-1
null
q-bio.NC q-bio.OT
null
The binding neuron model is inspired by numerical simulation of Hodgkin-Huxley-type point neuron, as well as by the leaky integrate-and-fire model. In the binding neuron, the trace of an input is remembered for a fixed period of time after which it disappears completely. This is in the contrast with the above two models, where the postsynaptic potentials decay exponentially and can be forgotten only after triggering. The finiteness of memory in the binding neuron allows one to construct fast recurrent networks for computer modeling. Recently, the finiteness is utilized for exact mathematical description of the output stochastic process if the binding neuron is driven with the Poissonian input stream. In this paper, the simplest networking is considered for binding neuron. Namely, it is expected that every output spike of single neuron is immediately fed into its input. For this construction, externally fed with Poissonian stream, the output stream is characterized in terms of interspike interval probability density distribution if the binding neuron has threshold 2. For higher thresholds, the distribution is calculated numerically. The distributions are compared with those found for binding neuron without feedback, and for leaky integrator. Sample distributions for leaky integrator with feedback are calculated numerically as well. It is oncluded that even the simplest networking can radically alter spikng statistics. Information condensation at the level of single neuron is discussed.
[ { "created": "Fri, 1 Jun 2007 14:20:19 GMT", "version": "v1" }, { "created": "Tue, 25 Sep 2007 15:00:26 GMT", "version": "v2" } ]
2011-07-20
[ [ "Vidybida", "Alexander K.", "" ] ]
The binding neuron model is inspired by numerical simulation of Hodgkin-Huxley-type point neuron, as well as by the leaky integrate-and-fire model. In the binding neuron, the trace of an input is remembered for a fixed period of time after which it disappears completely. This is in the contrast with the above two models, where the postsynaptic potentials decay exponentially and can be forgotten only after triggering. The finiteness of memory in the binding neuron allows one to construct fast recurrent networks for computer modeling. Recently, the finiteness is utilized for exact mathematical description of the output stochastic process if the binding neuron is driven with the Poissonian input stream. In this paper, the simplest networking is considered for binding neuron. Namely, it is expected that every output spike of single neuron is immediately fed into its input. For this construction, externally fed with Poissonian stream, the output stream is characterized in terms of interspike interval probability density distribution if the binding neuron has threshold 2. For higher thresholds, the distribution is calculated numerically. The distributions are compared with those found for binding neuron without feedback, and for leaky integrator. Sample distributions for leaky integrator with feedback are calculated numerically as well. It is oncluded that even the simplest networking can radically alter spikng statistics. Information condensation at the level of single neuron is discussed.
1211.6611
Marcelo Briones
Danielle C. F. Silva, Richard C. Silva, Renata C. Ferreira and Marcelo R. S. Briones
Examining marginal sequence similarities between bacterial type III secretion system and Trypanosoma cruzi surface proteins: Horizontal gene transfer or convergent evolution?
40 pages, 9 figures, 6 tables
null
null
null
q-bio.PE q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The cell invasion mechanism of Trypanosoma cruzi has similarities with some intracellular bacterial taxa especially regarding calcium mobilization. This mechanism is not observed in other trypanosomatids, suggesting that the molecules involved in this type of cell invasion were a product of (1) acquired by horizontal gene transfer; (2) secondary loss in the other trypanosomatid lineages of the mechanism inherited since the bifurcation Bacteria-Neomura (1.9 billion to 900 million years ago) or (3) de novo evolution from non-homologous proteins via convergent evolution. Similar to T. cruzi, several bacterial genera require increased host cell cytosolic calcium for intracellular invasion. Among intracellular bacteria, the mechanism of host cell invasion of genus Salmonella is the most similar to T. cruzi. The invasion of Salmonella occurs by contact with the host's cell surface and is mediated by the type III secretion system (T3SS) that promotes the contact-dependent translocation of effector proteins directly into host's cell cytoplasm. Here we provide evidence of distant sequence similarities and structurally conserved domains between T. cruzi and Salmonella spp T3SS proteins. Exhaustive database searches were directed to a wide range of intracellular bacteria and trypanosomatids, exploring sequence patterns for comparison of structural similarities and Bayesian phylogenies. Based on our data we hypothesize that T. cruzi acquired genes for calcium mobilization mediated invasion by ancient horizontal gene transfer from ancestral Salmonella lineages.
[ { "created": "Wed, 28 Nov 2012 14:35:37 GMT", "version": "v1" } ]
2012-11-29
[ [ "Silva", "Danielle C. F.", "" ], [ "Silva", "Richard C.", "" ], [ "Ferreira", "Renata C.", "" ], [ "Briones", "Marcelo R. S.", "" ] ]
The cell invasion mechanism of Trypanosoma cruzi has similarities with some intracellular bacterial taxa especially regarding calcium mobilization. This mechanism is not observed in other trypanosomatids, suggesting that the molecules involved in this type of cell invasion were a product of (1) acquired by horizontal gene transfer; (2) secondary loss in the other trypanosomatid lineages of the mechanism inherited since the bifurcation Bacteria-Neomura (1.9 billion to 900 million years ago) or (3) de novo evolution from non-homologous proteins via convergent evolution. Similar to T. cruzi, several bacterial genera require increased host cell cytosolic calcium for intracellular invasion. Among intracellular bacteria, the mechanism of host cell invasion of genus Salmonella is the most similar to T. cruzi. The invasion of Salmonella occurs by contact with the host's cell surface and is mediated by the type III secretion system (T3SS) that promotes the contact-dependent translocation of effector proteins directly into host's cell cytoplasm. Here we provide evidence of distant sequence similarities and structurally conserved domains between T. cruzi and Salmonella spp T3SS proteins. Exhaustive database searches were directed to a wide range of intracellular bacteria and trypanosomatids, exploring sequence patterns for comparison of structural similarities and Bayesian phylogenies. Based on our data we hypothesize that T. cruzi acquired genes for calcium mobilization mediated invasion by ancient horizontal gene transfer from ancestral Salmonella lineages.
2211.10422
Sam Sinai
Lauren Berk Wheelock, Stephen Malina, Jeffrey Gerold, Sam Sinai
Forecasting labels under distribution-shift for machine-guided sequence design
15 pages, 3 figures, to appear in MLCB-PMLR proceedings, oral presentation at MLCB 2022 and LMLR 2022
null
null
null
q-bio.QM cs.LG math.OC q-bio.BM
http://creativecommons.org/licenses/by/4.0/
The ability to design and optimize biological sequences with specific functionalities would unlock enormous value in technology and healthcare. In recent years, machine learning-guided sequence design has progressed this goal significantly, though validating designed sequences in the lab or clinic takes many months and substantial labor. It is therefore valuable to assess the likelihood that a designed set contains sequences of the desired quality (which often lies outside the label distribution in our training data) before committing resources to an experiment. Forecasting, a prominent concept in many domains where feedback can be delayed (e.g. elections), has not been used or studied in the context of sequence design. Here we propose a method to guide decision-making that forecasts the performance of high-throughput libraries (e.g. containing $10^5$ unique variants) based on estimates provided by models, providing a posterior for the distribution of labels in the library. We show that our method outperforms baselines that naively use model scores to estimate library performance, which are the only tool available today for this purpose.
[ { "created": "Fri, 18 Nov 2022 18:35:50 GMT", "version": "v1" } ]
2022-11-21
[ [ "Wheelock", "Lauren Berk", "" ], [ "Malina", "Stephen", "" ], [ "Gerold", "Jeffrey", "" ], [ "Sinai", "Sam", "" ] ]
The ability to design and optimize biological sequences with specific functionalities would unlock enormous value in technology and healthcare. In recent years, machine learning-guided sequence design has progressed this goal significantly, though validating designed sequences in the lab or clinic takes many months and substantial labor. It is therefore valuable to assess the likelihood that a designed set contains sequences of the desired quality (which often lies outside the label distribution in our training data) before committing resources to an experiment. Forecasting, a prominent concept in many domains where feedback can be delayed (e.g. elections), has not been used or studied in the context of sequence design. Here we propose a method to guide decision-making that forecasts the performance of high-throughput libraries (e.g. containing $10^5$ unique variants) based on estimates provided by models, providing a posterior for the distribution of labels in the library. We show that our method outperforms baselines that naively use model scores to estimate library performance, which are the only tool available today for this purpose.
1508.02309
Keith Lidke
Peter K. Relich, Mark J. Olah, Patrick J. Cutler, Keith A. Lidke
Estimation of the Diffusion Constant from Intermittent Trajectories with Variable Position Uncertainties
2 figures: 6 plots
Phys. Rev. E 93, 042401 (2016)
10.1103/PhysRevE.93.042401
null
q-bio.SC
http://creativecommons.org/licenses/by/4.0/
The movement of a particle described by Brownian motion is quantified by a single parameter, $D$, the diffusion constant. The estimation of $D$ from a discrete sequence of noisy observations is a fundamental problem in biological single particle tracking experiments since it can report on the environment and/or the state of the particle itself via hydrodynamic radius. Here we present a method to estimate $D$ that takes into account several effects that occur in practice, that are important for correct estimation of $D$, and that have hitherto not been combined together for estimation of $D$. These effects are motion blur from finite integration time of the camera, intermittent trajectories, and time-dependent localization uncertainty. Our estimation procedure, a maximum likelihood estimation, follows directly from the likelihood expression for a discretely observed Brownian trajectory that explicitly includes these effects. The manuscript begins with the formulation of the likelihood expression and then presents three methods to find the exact solution. Each method has its own advantages in either computational robustness, theoretical insight, or the estimation of hidden variables. We then compare our estimator to previously published estimators using a squared log loss function to demonstrate the benefit of including these effects.
[ { "created": "Mon, 10 Aug 2015 16:22:56 GMT", "version": "v1" }, { "created": "Fri, 21 Aug 2015 11:46:32 GMT", "version": "v2" } ]
2016-04-13
[ [ "Relich", "Peter K.", "" ], [ "Olah", "Mark J.", "" ], [ "Cutler", "Patrick J.", "" ], [ "Lidke", "Keith A.", "" ] ]
The movement of a particle described by Brownian motion is quantified by a single parameter, $D$, the diffusion constant. The estimation of $D$ from a discrete sequence of noisy observations is a fundamental problem in biological single particle tracking experiments since it can report on the environment and/or the state of the particle itself via hydrodynamic radius. Here we present a method to estimate $D$ that takes into account several effects that occur in practice, that are important for correct estimation of $D$, and that have hitherto not been combined together for estimation of $D$. These effects are motion blur from finite integration time of the camera, intermittent trajectories, and time-dependent localization uncertainty. Our estimation procedure, a maximum likelihood estimation, follows directly from the likelihood expression for a discretely observed Brownian trajectory that explicitly includes these effects. The manuscript begins with the formulation of the likelihood expression and then presents three methods to find the exact solution. Each method has its own advantages in either computational robustness, theoretical insight, or the estimation of hidden variables. We then compare our estimator to previously published estimators using a squared log loss function to demonstrate the benefit of including these effects.
2109.03183
Katharina Huber
Andrew Francis and Katharina T. Huber and Vincent Moulton and Taoyang Wu
Encoding and ordering X-cactuses
null
null
null
null
q-bio.PE math.CO
http://creativecommons.org/licenses/by-nc-nd/4.0/
Phylogenetic networks are a generalization of evolutionary or phylogenetic trees that are commonly used to represent the evolution of species which cross with one another. A special type of phylogenetic network is an {\em $X$-cactus}, which is essentially a cactus graph in which all vertices with degree less than three are labelled by at least one element from a set $X$ of species. In this paper, we present a way to {\em encode} $X$-cactuses in terms of certain collections of partitions of $X$ that naturally arise from $X$-cactuses. Using this encoding, we also introduce a partial order on the set of $X$-cactuses (up to isomorphism), and derive some structural properties of the resulting partially ordered set. This includes an analysis of some properties of its least upper and greatest lower bounds. Our results not only extend some fundamental properties of phylogenetic trees to $X$-cactuses, but also provides a new approach to solving topical problems in phylogenetic network theory such as deriving consensus networks.
[ { "created": "Tue, 7 Sep 2021 16:28:08 GMT", "version": "v1" } ]
2021-09-08
[ [ "Francis", "Andrew", "" ], [ "Huber", "Katharina T.", "" ], [ "Moulton", "Vincent", "" ], [ "Wu", "Taoyang", "" ] ]
Phylogenetic networks are a generalization of evolutionary or phylogenetic trees that are commonly used to represent the evolution of species which cross with one another. A special type of phylogenetic network is an {\em $X$-cactus}, which is essentially a cactus graph in which all vertices with degree less than three are labelled by at least one element from a set $X$ of species. In this paper, we present a way to {\em encode} $X$-cactuses in terms of certain collections of partitions of $X$ that naturally arise from $X$-cactuses. Using this encoding, we also introduce a partial order on the set of $X$-cactuses (up to isomorphism), and derive some structural properties of the resulting partially ordered set. This includes an analysis of some properties of its least upper and greatest lower bounds. Our results not only extend some fundamental properties of phylogenetic trees to $X$-cactuses, but also provides a new approach to solving topical problems in phylogenetic network theory such as deriving consensus networks.
0908.2827
Nicola Fameli
Nicola Fameli, Kuo-Hsing Kuo, Cornelis van Breemen
A model for the generation of localized transient Na+ elevations in vascular smooth muscle
16 pages, 9 figures; an abridged version submitted for publication
Biochem Biophys Res Commun 389, 461-465 (2009)
10.1016/j.bbrc.2009.08.166
null
q-bio.QM q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present a stochastic computational model to study the mechanism of signalling between a source and a target ionic transporter, both localized on the plasma membrane (PM) and in intracellular nanometre-scale subplasmalemmal signalling compartments comprising the PM, the sarcoplasmic reticulum (SR), Ca2+ and Na+ transporters, and the intervening cytosol. We refer to these compartments, sometimes called junctions, as cytoplasmic nanospaces or nanodomains. In the chain of events leading to Ca2+ influx for SR reloading during asynchronous Ca2+ waves in vascular smooth muscle (VSM), the physical and functional link between non-selective cation channels (NSCC) and Na+/Ca2+ exchangers (NCX) needs to be elucidated in view of two recent findings: the identification of the transient receptor potential canonical channel 6 (TRPC6) as a crucial NSCC in VSM cells and the observation of localized cytosolic [Na+] transients following purinergic stimulation of these cells. Having previously helped clarify the Ca2+ signalling step between NCX and SERCA behind SR Ca2+ refilling, this quantitative approach now allows us to model the upstream linkage of NSCC and NCX. We have implemented a random walk (RW) Monte Carlo (MC) model with simulations mimicking a Na+ diffusion process originating at the NSCC within PM-SR junctions. The model calculates the average [Na+] in the nanospace and also produces [Na+] profiles as a function of distance from the Na+ source. Our results highlight the necessity of a strategic juxtaposition of the relevant signalling channels as well as other physical structures within the nanospaces to permit adequate [Na+] build-up to provoke NCX reversal and Ca2+ influx to refill the SR.
[ { "created": "Wed, 19 Aug 2009 22:55:49 GMT", "version": "v1" } ]
2009-10-22
[ [ "Fameli", "Nicola", "" ], [ "Kuo", "Kuo-Hsing", "" ], [ "van Breemen", "Cornelis", "" ] ]
We present a stochastic computational model to study the mechanism of signalling between a source and a target ionic transporter, both localized on the plasma membrane (PM) and in intracellular nanometre-scale subplasmalemmal signalling compartments comprising the PM, the sarcoplasmic reticulum (SR), Ca2+ and Na+ transporters, and the intervening cytosol. We refer to these compartments, sometimes called junctions, as cytoplasmic nanospaces or nanodomains. In the chain of events leading to Ca2+ influx for SR reloading during asynchronous Ca2+ waves in vascular smooth muscle (VSM), the physical and functional link between non-selective cation channels (NSCC) and Na+/Ca2+ exchangers (NCX) needs to be elucidated in view of two recent findings: the identification of the transient receptor potential canonical channel 6 (TRPC6) as a crucial NSCC in VSM cells and the observation of localized cytosolic [Na+] transients following purinergic stimulation of these cells. Having previously helped clarify the Ca2+ signalling step between NCX and SERCA behind SR Ca2+ refilling, this quantitative approach now allows us to model the upstream linkage of NSCC and NCX. We have implemented a random walk (RW) Monte Carlo (MC) model with simulations mimicking a Na+ diffusion process originating at the NSCC within PM-SR junctions. The model calculates the average [Na+] in the nanospace and also produces [Na+] profiles as a function of distance from the Na+ source. Our results highlight the necessity of a strategic juxtaposition of the relevant signalling channels as well as other physical structures within the nanospaces to permit adequate [Na+] build-up to provoke NCX reversal and Ca2+ influx to refill the SR.
1104.3783
Aldo Di Biasio
Aldo Di Biasio, Elena Agliari, Adriano Barra and Raffaella Burioni
Mean-field cooperativity in chemical kinetics
25 pages, 4 figures
Theoretical Chemistry Accounts (2012)
10.1007/s00214-012-1104-3
null
q-bio.QM cond-mat.stat-mech physics.chem-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We consider cooperative reactions and we study the effects of the interaction strength among the system components on the reaction rate, hence realizing a connection between microscopic and macroscopic observables. Our approach is based on statistical mechanics models and it is developed analytically via mean-field techniques. First of all, we show that, when the coupling strength is set positive, the model is able to consistently recover all the various cooperative measures previously introduced, hence obtaining a single unifying framework. Furthermore, we introduce a criterion to discriminate between weak and strong cooperativity, based on a measure of "susceptibility". We also properly extend the model in order to account for multiple attachments phenomena: this is realized by incorporating within the model $p$-body interactions, whose non-trivial cooperative capability is investigated too.
[ { "created": "Tue, 19 Apr 2011 15:45:35 GMT", "version": "v1" } ]
2012-06-07
[ [ "Di Biasio", "Aldo", "" ], [ "Agliari", "Elena", "" ], [ "Barra", "Adriano", "" ], [ "Burioni", "Raffaella", "" ] ]
We consider cooperative reactions and we study the effects of the interaction strength among the system components on the reaction rate, hence realizing a connection between microscopic and macroscopic observables. Our approach is based on statistical mechanics models and it is developed analytically via mean-field techniques. First of all, we show that, when the coupling strength is set positive, the model is able to consistently recover all the various cooperative measures previously introduced, hence obtaining a single unifying framework. Furthermore, we introduce a criterion to discriminate between weak and strong cooperativity, based on a measure of "susceptibility". We also properly extend the model in order to account for multiple attachments phenomena: this is realized by incorporating within the model $p$-body interactions, whose non-trivial cooperative capability is investigated too.
2011.08902
Marisol Salgado-Albarran
Marisol Salgado-Albarran, Erick I. Navarro-Delgado, Aylin Del Moral-Morales, Nicolas Alcaraz, Jan Baumbach, Rodrigo Gonzalez-Barrios, Ernesto Soto-Reyes
Comparative transcriptome analysis reveals key epigenetic targets in SARS-CoV-2 infection
33 pages, 2 tables, 5 figures, 4 supplementary figures
null
10.1038/s41540-021-00181-x
null
q-bio.MN
http://creativecommons.org/licenses/by/4.0/
COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that have therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.
[ { "created": "Tue, 17 Nov 2020 19:40:19 GMT", "version": "v1" } ]
2021-05-27
[ [ "Salgado-Albarran", "Marisol", "" ], [ "Navarro-Delgado", "Erick I.", "" ], [ "Del Moral-Morales", "Aylin", "" ], [ "Alcaraz", "Nicolas", "" ], [ "Baumbach", "Jan", "" ], [ "Gonzalez-Barrios", "Rodrigo", "" ], [ "Soto-Reyes", "Ernesto", "" ] ]
COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that have therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.
1604.06713
Luca Ferretti
Luca Ferretti, Alexander Klassmann, Emanuele Raineri, Thomas Wiehe, Sebastian E. Ramos-Onsins, Guillaume Achaz
The expected neutral frequency spectrum of linked sites
26 pages, 5 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present an exact, closed expression for the expected neutral Site Frequency Spectrum for two neutral sites, 2-SFS, without recombination. This spectrum is the immediate extension of the well known single site $\theta/f$ neutral SFS. Similar formulae are also provided for the case of the expected SFS of sites that are linked to a focal neutral mutation of known frequency. Formulae for finite samples are obtained by coalescent methods and remarkably simple expressions are derived for the SFS of a large population, which are also solutions of the multi-allelic Kolmogorov equations. Besides the general interest of these new spectra, they relate to interesting biological cases such as structural variants and introgressions. As an example, we present the expected neutral frequency spectrum of regions with a chromosomal inversion.
[ { "created": "Fri, 22 Apr 2016 15:28:33 GMT", "version": "v1" }, { "created": "Mon, 9 Jan 2017 19:22:48 GMT", "version": "v2" } ]
2017-01-11
[ [ "Ferretti", "Luca", "" ], [ "Klassmann", "Alexander", "" ], [ "Raineri", "Emanuele", "" ], [ "Wiehe", "Thomas", "" ], [ "Ramos-Onsins", "Sebastian E.", "" ], [ "Achaz", "Guillaume", "" ] ]
We present an exact, closed expression for the expected neutral Site Frequency Spectrum for two neutral sites, 2-SFS, without recombination. This spectrum is the immediate extension of the well known single site $\theta/f$ neutral SFS. Similar formulae are also provided for the case of the expected SFS of sites that are linked to a focal neutral mutation of known frequency. Formulae for finite samples are obtained by coalescent methods and remarkably simple expressions are derived for the SFS of a large population, which are also solutions of the multi-allelic Kolmogorov equations. Besides the general interest of these new spectra, they relate to interesting biological cases such as structural variants and introgressions. As an example, we present the expected neutral frequency spectrum of regions with a chromosomal inversion.
0912.3057
Maurizio De Pitta'
Maurizio De Pitta` (1), Mati Goldberg (1), Vladislav Volman (2 and 3), Hugues Berry (4) and Eshel Ben-Jacob (1 and 2) ((1) School of Physics and Astronomy, Tel Aviv University, Israel, (2) Center for Theoretical Biological Physics, UCSD, La Jolla, CA, USA, (3) Computational Neurobiology Lab, The Salk Institute, La Jolla, CA, USA, (4) Project-Team Alchemy, INRIA Saclay, Orsay, France)
Glutamate regulation of calcium and IP3 oscillating and pulsating dynamics in astrocytes
42 pages, 16 figures, 1 table. Figure filenames mirror figure order in the paper. Ending "S" in figure filenames stands for "Supplementary Figure". This article was selected by the Faculty of 1000 Biology: "Genevieve Dupont: Faculty of 1000 Biology, 4 Sep 2009" at http://www.f1000biology.com/article/id/1163674/evaluation
J. Biol. Phys. 35(4) (2009) 383-411
10.1007/s10867-009-9155-y
null
q-bio.NC q-bio.MN q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Recent years have witnessed an increasing interest in neuron-glia communication. This interest stems from the realization that glia participates in cognitive functions and information processing and is involved in many brain disorders and neurodegenerative diseases. An important process in neuron-glia communications is astrocyte encoding of synaptic information transfer: the modulation of intracellular calcium dynamics in astrocytes in response to synaptic activity. Here, we derive and investigate a concise mathematical model for glutamate-induced astrocytic intracellular Ca2+ dynamics that captures the essential biochemical features of the regulatory pathway of inositol 1,4,5-trisphosphate (IP3). Starting from the well-known two-state Li-Rinzel model for calcium-induced-calcium release, we incorporate the regulation of the IP3 production and phosphorylation. Doing so we extended it to a three-state model (referred as the G-ChI model), that could account for Ca2+ oscillations triggered by endogenous IP3 metabolism as well as by IP3 production by external glutamate signals. Compared to previous similar models, our three-state models include a more realistic description of the IP3 production and degradation pathways, lumping together their essential nonlinearities within a concise formulation. Using bifurcation analysis and time simulations, we demonstrate the existence of new putative dynamical features. The cross-couplings between IP3 and Ca2+ pathways endows the system with self-consistent oscillator properties and favor mixed frequency-amplitude encoding modes over pure amplitude modulation ones. These and additional results of our model are in general agreement with available experimental data and may have important implications on the role of astrocytes in the synaptic transfer of information.
[ { "created": "Wed, 16 Dec 2009 05:51:55 GMT", "version": "v1" } ]
2009-12-17
[ [ "De Pitta`", "Maurizio", "", "2 and 3" ], [ "Goldberg", "Mati", "", "2 and 3" ], [ "Volman", "Vladislav", "", "2 and 3" ], [ "Berry", "Hugues", "", "1 and 2" ], [ "Ben-Jacob", "Eshel", "", "1 and 2" ] ]
Recent years have witnessed an increasing interest in neuron-glia communication. This interest stems from the realization that glia participates in cognitive functions and information processing and is involved in many brain disorders and neurodegenerative diseases. An important process in neuron-glia communications is astrocyte encoding of synaptic information transfer: the modulation of intracellular calcium dynamics in astrocytes in response to synaptic activity. Here, we derive and investigate a concise mathematical model for glutamate-induced astrocytic intracellular Ca2+ dynamics that captures the essential biochemical features of the regulatory pathway of inositol 1,4,5-trisphosphate (IP3). Starting from the well-known two-state Li-Rinzel model for calcium-induced-calcium release, we incorporate the regulation of the IP3 production and phosphorylation. Doing so we extended it to a three-state model (referred as the G-ChI model), that could account for Ca2+ oscillations triggered by endogenous IP3 metabolism as well as by IP3 production by external glutamate signals. Compared to previous similar models, our three-state models include a more realistic description of the IP3 production and degradation pathways, lumping together their essential nonlinearities within a concise formulation. Using bifurcation analysis and time simulations, we demonstrate the existence of new putative dynamical features. The cross-couplings between IP3 and Ca2+ pathways endows the system with self-consistent oscillator properties and favor mixed frequency-amplitude encoding modes over pure amplitude modulation ones. These and additional results of our model are in general agreement with available experimental data and may have important implications on the role of astrocytes in the synaptic transfer of information.
2406.01648
Craig McKenzie
Craig I. McKenzie
Consciousness defined: requirements for biological and artificial general intelligence
16 pages, 1 figure, 2 tables, 74 references
null
null
null
q-bio.NC cs.AI
http://creativecommons.org/licenses/by-nc-sa/4.0/
Consciousness is notoriously hard to define with objective terms. An objective definition of consciousness is critically needed so that we might accurately understand how consciousness and resultant choice behaviour may arise in biological or artificial systems. Many theories have integrated neurobiological and psychological research to explain how consciousness might arise, but few, if any, outline what is fundamentally required to generate consciousness. To identify such requirements, I examine current theories of consciousness and corresponding scientific research to generate a new definition of consciousness from first principles. Critically, consciousness is the apparatus that provides the ability to make decisions, but it is not defined by the decision itself. As such, a definition of consciousness does not require choice behaviour or an explicit awareness of temporality despite both being well-characterised outcomes of conscious thought. Rather, requirements for consciousness include: at least some capability for perception, a memory for the storage of such perceptual information which in turn provides a framework for an imagination with which a sense of self can be capable of making decisions based on possible and desired futures. Thought experiments and observable neurological phenomena demonstrate that these components are fundamentally required of consciousness, whereby the loss of any one component removes the capability for conscious thought. Identifying these requirements provides a new definition for consciousness by which we can objectively determine consciousness in any conceivable agent, such as non-human animals and artificially intelligent systems.
[ { "created": "Mon, 3 Jun 2024 14:20:56 GMT", "version": "v1" } ]
2024-06-05
[ [ "McKenzie", "Craig I.", "" ] ]
Consciousness is notoriously hard to define with objective terms. An objective definition of consciousness is critically needed so that we might accurately understand how consciousness and resultant choice behaviour may arise in biological or artificial systems. Many theories have integrated neurobiological and psychological research to explain how consciousness might arise, but few, if any, outline what is fundamentally required to generate consciousness. To identify such requirements, I examine current theories of consciousness and corresponding scientific research to generate a new definition of consciousness from first principles. Critically, consciousness is the apparatus that provides the ability to make decisions, but it is not defined by the decision itself. As such, a definition of consciousness does not require choice behaviour or an explicit awareness of temporality despite both being well-characterised outcomes of conscious thought. Rather, requirements for consciousness include: at least some capability for perception, a memory for the storage of such perceptual information which in turn provides a framework for an imagination with which a sense of self can be capable of making decisions based on possible and desired futures. Thought experiments and observable neurological phenomena demonstrate that these components are fundamentally required of consciousness, whereby the loss of any one component removes the capability for conscious thought. Identifying these requirements provides a new definition for consciousness by which we can objectively determine consciousness in any conceivable agent, such as non-human animals and artificially intelligent systems.
2102.04296
Jacob Bradley
Jacob R. Bradley and Timothy I. Cannings
Data-driven design of targeted gene panels for estimating immunotherapy biomarkers
21 pages, 10 figures
null
null
null
q-bio.GN stat.AP
http://creativecommons.org/licenses/by/4.0/
We introduce a novel data-driven framework for the design of targeted gene panels for estimating exome-wide biomarkers in cancer immunotherapy. Our first goal is to develop a generative model for the profile of mutation across the exome, which allows for gene- and variant type-dependent mutation rates. Based on this model, we then propose a new procedure for estimating biomarkers such as tumour mutation burden and tumour indel nurden. Our approach allows the practitioner to select a targeted gene panel of a prespecified size, and then construct an estimator that only depends on the selected genes. Alternatively, the practitioner may apply our method to make predictions based on an existing gene panel, or to augment a gene panel to a given size. We demonstrate the excellent performance of our proposal using data from three non-small cell lung cancer studies, as well as data from six other cancer types.
[ { "created": "Mon, 8 Feb 2021 16:03:05 GMT", "version": "v1" }, { "created": "Tue, 9 Feb 2021 13:48:47 GMT", "version": "v2" }, { "created": "Thu, 3 Feb 2022 18:50:48 GMT", "version": "v3" } ]
2022-02-04
[ [ "Bradley", "Jacob R.", "" ], [ "Cannings", "Timothy I.", "" ] ]
We introduce a novel data-driven framework for the design of targeted gene panels for estimating exome-wide biomarkers in cancer immunotherapy. Our first goal is to develop a generative model for the profile of mutation across the exome, which allows for gene- and variant type-dependent mutation rates. Based on this model, we then propose a new procedure for estimating biomarkers such as tumour mutation burden and tumour indel nurden. Our approach allows the practitioner to select a targeted gene panel of a prespecified size, and then construct an estimator that only depends on the selected genes. Alternatively, the practitioner may apply our method to make predictions based on an existing gene panel, or to augment a gene panel to a given size. We demonstrate the excellent performance of our proposal using data from three non-small cell lung cancer studies, as well as data from six other cancer types.
2212.05064
Jianing Xi
Jianing Xi, Zhen Deng, Yang Liu, Qian Wang, Wen Shi
Integrating multi-type aberrations from DNA and RNA through dynamic mapping gene space for subtype-specific breast cancer driver discovery
14 pages, 5 figures, 1 table
null
10.7717/peerj.14843
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Driver event discovery is a crucial demand for breast cancer diagnosis and therapy. Especially, discovering subtype-specificity of drivers can prompt the personalized biomarker discovery and precision treatment of cancer patients. still, most of the existing computational driver discovery studies mainly exploit the information from DNA aberrations and gene interactions. Notably, cancer driver events would occur due to not only DNA aberrations but also RNA alternations, but integrating multi-type aberrations from both DNA and RNA is still a challenging task for breast cancer drivers. On the one hand, the data formats of different aberration types also differ from each other, known as data format incompatibility. One the other hand, different types of aberrations demonstrate distinct patterns across samples, known as aberration type heterogeneity. To promote the integrated analysis of subtype-specific breast cancer drivers, we design a "splicing-and-fusing" framework to address the issues of data format incompatibility and aberration type heterogeneity respectively. To overcome the data format incompatibility, the "splicing-step" employs a knowledge graph structure to connect multi-type aberrations from the DNA and RNA data into a unified formation. To tackle the aberration type heterogeneity, the "fusing-step" adopts a dynamic mapping gene space integration approach to represent the multi-type information by vectorized profiles. The experiments also demonstrate the advantages of our approach in both the integration of multi-type aberrations from DNA and RNA and the discovery of subtype-specific breast cancer drivers. In summary, our "splicing-and-fusing" framework with knowledge graph connection and dynamic mapping gene space fusion of multi-type aberrations data from DNA and RNA can successfully discover potential breast cancer drivers with subtype-specificity indication.
[ { "created": "Fri, 9 Dec 2022 16:53:46 GMT", "version": "v1" } ]
2023-02-06
[ [ "Xi", "Jianing", "" ], [ "Deng", "Zhen", "" ], [ "Liu", "Yang", "" ], [ "Wang", "Qian", "" ], [ "Shi", "Wen", "" ] ]
Driver event discovery is a crucial demand for breast cancer diagnosis and therapy. Especially, discovering subtype-specificity of drivers can prompt the personalized biomarker discovery and precision treatment of cancer patients. still, most of the existing computational driver discovery studies mainly exploit the information from DNA aberrations and gene interactions. Notably, cancer driver events would occur due to not only DNA aberrations but also RNA alternations, but integrating multi-type aberrations from both DNA and RNA is still a challenging task for breast cancer drivers. On the one hand, the data formats of different aberration types also differ from each other, known as data format incompatibility. One the other hand, different types of aberrations demonstrate distinct patterns across samples, known as aberration type heterogeneity. To promote the integrated analysis of subtype-specific breast cancer drivers, we design a "splicing-and-fusing" framework to address the issues of data format incompatibility and aberration type heterogeneity respectively. To overcome the data format incompatibility, the "splicing-step" employs a knowledge graph structure to connect multi-type aberrations from the DNA and RNA data into a unified formation. To tackle the aberration type heterogeneity, the "fusing-step" adopts a dynamic mapping gene space integration approach to represent the multi-type information by vectorized profiles. The experiments also demonstrate the advantages of our approach in both the integration of multi-type aberrations from DNA and RNA and the discovery of subtype-specific breast cancer drivers. In summary, our "splicing-and-fusing" framework with knowledge graph connection and dynamic mapping gene space fusion of multi-type aberrations data from DNA and RNA can successfully discover potential breast cancer drivers with subtype-specificity indication.
0906.2504
Chiu Fan Lee
Chiu Fan Lee
Isotropic-nematic phase transition in amyloid fibrilization
Typos corrected
Physical Review E 80, 031902 (2009)
10.1103/PhysRevE.80.031902
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We carry out a theoretical study on the isotropic-nematic phase transition and phase separation in amyloid fibril solutions. Borrowing the thermodynamic model employed in the study of cylindrical micelles, we investigate the variations in the fibril length distribution and phase behavior with respect to changes in the protein concentration, fibril's rigidity, and binding energy. We then relate our theoretical findings to the nematic ordering observed in Hen Lysozyme fibril solution.
[ { "created": "Sat, 13 Jun 2009 21:36:05 GMT", "version": "v1" }, { "created": "Wed, 17 Jun 2009 19:12:03 GMT", "version": "v2" }, { "created": "Tue, 11 Aug 2009 14:10:35 GMT", "version": "v3" } ]
2009-09-10
[ [ "Lee", "Chiu Fan", "" ] ]
We carry out a theoretical study on the isotropic-nematic phase transition and phase separation in amyloid fibril solutions. Borrowing the thermodynamic model employed in the study of cylindrical micelles, we investigate the variations in the fibril length distribution and phase behavior with respect to changes in the protein concentration, fibril's rigidity, and binding energy. We then relate our theoretical findings to the nematic ordering observed in Hen Lysozyme fibril solution.
q-bio/0411018
Christof Aegerter
Tinri Aegerter-Wilmsen, Christof M. Aegerter and Ton Bisseling
Model for the robust establishment of precise proportions in the early Drosophila embryo
20 pages, 2 figures, accepted for publication in J. theor. Biol
null
null
null
q-bio.CB
null
During embryonic development, a spatial pattern is formed in which proportions are established precisely. As an early pattern formation step in Drosophila embryos, an anterior-posterior gradient of Bicoid (Bcd) induces hunchback (hb) expression (Driever et al. 1989; Tautz et al. 1988). In contrast to the Bcd gradient, the Hb profile includes information about the scale of the embryo. Furthermore, the resulting hb expression pattern shows a much lower embryo-to-embryo variability than the Bcd gradient (Houchmandzadeh et al. 2002). An additional graded posterior repressing activity could theoretically account for the observed scaling. However, we show that such a model cannot produce the observed precision in the Hb boundary, such that a fundamentally different mechanism must be at work. We describe and simulate a model that can account for the observed precise generation of the scaled Hb profile in a highly robust manner. The proposed mechanism includes Staufen (Stau), an RNA binding protein that appears essential to precision scaling (Houchmandzadeh et al. 2002). In the model, Stau is released from both ends of the embryo and relocalises hb RNA by increasing its mobility. This leads to an effective transport of hb away from the respective Stau sources. The balance between these opposing effects then gives rise to scaling and precision. Considering the biological importance of robust precision scaling and the simplicity of the model, the same principle may be employed more often during development.
[ { "created": "Thu, 4 Nov 2004 12:52:55 GMT", "version": "v1" } ]
2007-05-23
[ [ "Aegerter-Wilmsen", "Tinri", "" ], [ "Aegerter", "Christof M.", "" ], [ "Bisseling", "Ton", "" ] ]
During embryonic development, a spatial pattern is formed in which proportions are established precisely. As an early pattern formation step in Drosophila embryos, an anterior-posterior gradient of Bicoid (Bcd) induces hunchback (hb) expression (Driever et al. 1989; Tautz et al. 1988). In contrast to the Bcd gradient, the Hb profile includes information about the scale of the embryo. Furthermore, the resulting hb expression pattern shows a much lower embryo-to-embryo variability than the Bcd gradient (Houchmandzadeh et al. 2002). An additional graded posterior repressing activity could theoretically account for the observed scaling. However, we show that such a model cannot produce the observed precision in the Hb boundary, such that a fundamentally different mechanism must be at work. We describe and simulate a model that can account for the observed precise generation of the scaled Hb profile in a highly robust manner. The proposed mechanism includes Staufen (Stau), an RNA binding protein that appears essential to precision scaling (Houchmandzadeh et al. 2002). In the model, Stau is released from both ends of the embryo and relocalises hb RNA by increasing its mobility. This leads to an effective transport of hb away from the respective Stau sources. The balance between these opposing effects then gives rise to scaling and precision. Considering the biological importance of robust precision scaling and the simplicity of the model, the same principle may be employed more often during development.
1011.0241
Christopher Hillar
Guy Isely, Christopher J. Hillar, Friedrich T. Sommer
Deciphering subsampled data: adaptive compressive sampling as a principle of brain communication
9 pages, NIPS 2010
null
null
null
q-bio.NC q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A new algorithm is proposed for a) unsupervised learning of sparse representations from subsampled measurements and b) estimating the parameters required for linearly reconstructing signals from the sparse codes. We verify that the new algorithm performs efficient data compression on par with the recent method of compressive sampling. Further, we demonstrate that the algorithm performs robustly when stacked in several stages or when applied in undercomplete or overcomplete situations. The new algorithm can explain how neural populations in the brain that receive subsampled input through fiber bottlenecks are able to form coherent response properties.
[ { "created": "Mon, 1 Nov 2010 03:23:52 GMT", "version": "v1" } ]
2010-11-02
[ [ "Isely", "Guy", "" ], [ "Hillar", "Christopher J.", "" ], [ "Sommer", "Friedrich T.", "" ] ]
A new algorithm is proposed for a) unsupervised learning of sparse representations from subsampled measurements and b) estimating the parameters required for linearly reconstructing signals from the sparse codes. We verify that the new algorithm performs efficient data compression on par with the recent method of compressive sampling. Further, we demonstrate that the algorithm performs robustly when stacked in several stages or when applied in undercomplete or overcomplete situations. The new algorithm can explain how neural populations in the brain that receive subsampled input through fiber bottlenecks are able to form coherent response properties.
1702.03474
Cheng Ly
Andrea K. Barreiro, Cheng Ly
Practical Approximation Method for Firing Rate Models of Coupled Neural Networks with Correlated Inputs
15 pages, 7 figures
Phys. Rev. E 96, 022413 (2017)
10.1103/PhysRevE.96.022413
null
q-bio.NC q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Rapid experimental advances now enable simultaneous electrophysiological recording of neural activity at single-cell resolution across large regions of the nervous system. Models of this neural network activity will necessarily increase in size and complexity, thus increasing the computational cost of simulating them and the challenge of analyzing them. Here we present a novel method to approximate the activity and firing statistics of a general firing rate network model (of Wilson-Cowan type) subject to noisy correlated background inputs. The method requires solving a system of transcendental equations and is fast compared to Monte Carlo simulations of coupled stochastic differential equations. We implement the method with several examples of coupled neural networks and show that the results are quantitatively accurate even with moderate coupling strengths and an appreciable amount of heterogeneity in many parameters. This work should be useful for investigating how various neural attributes qualitatively effect the spiking statistics of coupled neural networks. Matlab code implementing the method is freely available at GitHub (\url{http://github.com/chengly70/FiringRateModReduction}).
[ { "created": "Sun, 12 Feb 2017 00:52:12 GMT", "version": "v1" }, { "created": "Thu, 29 Jun 2017 12:07:20 GMT", "version": "v2" }, { "created": "Fri, 4 Aug 2017 16:22:00 GMT", "version": "v3" }, { "created": "Fri, 29 Sep 2017 11:57:42 GMT", "version": "v4" } ]
2017-10-02
[ [ "Barreiro", "Andrea K.", "" ], [ "Ly", "Cheng", "" ] ]
Rapid experimental advances now enable simultaneous electrophysiological recording of neural activity at single-cell resolution across large regions of the nervous system. Models of this neural network activity will necessarily increase in size and complexity, thus increasing the computational cost of simulating them and the challenge of analyzing them. Here we present a novel method to approximate the activity and firing statistics of a general firing rate network model (of Wilson-Cowan type) subject to noisy correlated background inputs. The method requires solving a system of transcendental equations and is fast compared to Monte Carlo simulations of coupled stochastic differential equations. We implement the method with several examples of coupled neural networks and show that the results are quantitatively accurate even with moderate coupling strengths and an appreciable amount of heterogeneity in many parameters. This work should be useful for investigating how various neural attributes qualitatively effect the spiking statistics of coupled neural networks. Matlab code implementing the method is freely available at GitHub (\url{http://github.com/chengly70/FiringRateModReduction}).
1603.01880
Jannis Schuecker
Jannis Schuecker, Sven Goedeke and Moritz Helias
Optimal sequence memory in driven random networks
null
Phys. Rev. X 8, 041029 (2018)
10.1103/PhysRevX.8.041029
null
q-bio.NC nlin.CD
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Autonomous randomly coupled neural networks display a transition to chaos at a critical coupling strength. We here investigate the effect of a time-varying input on the onset of chaos and the resulting consequences for information processing. Dynamic mean-field theory yields the statistics of the activity, the maximum Lyapunov exponent, and the memory capacity of the network. We find an exact condition that determines the transition from stable to chaotic dynamics and the sequential memory capacity in closed form. The input suppresses chaos by a dynamic mechanism, shifting the transition to significantly larger coupling strengths than predicted by local stability analysis. Beyond linear stability, a regime of coexistent locally expansive, but non-chaotic dynamics emerges that optimizes the capacity of the network to store sequential input.
[ { "created": "Sun, 6 Mar 2016 21:21:03 GMT", "version": "v1" }, { "created": "Tue, 14 Jun 2016 16:29:48 GMT", "version": "v2" }, { "created": "Fri, 22 Sep 2017 17:22:28 GMT", "version": "v3" } ]
2018-11-21
[ [ "Schuecker", "Jannis", "" ], [ "Goedeke", "Sven", "" ], [ "Helias", "Moritz", "" ] ]
Autonomous randomly coupled neural networks display a transition to chaos at a critical coupling strength. We here investigate the effect of a time-varying input on the onset of chaos and the resulting consequences for information processing. Dynamic mean-field theory yields the statistics of the activity, the maximum Lyapunov exponent, and the memory capacity of the network. We find an exact condition that determines the transition from stable to chaotic dynamics and the sequential memory capacity in closed form. The input suppresses chaos by a dynamic mechanism, shifting the transition to significantly larger coupling strengths than predicted by local stability analysis. Beyond linear stability, a regime of coexistent locally expansive, but non-chaotic dynamics emerges that optimizes the capacity of the network to store sequential input.
2311.12917
Ethan Kulman
E. Kulman, R. Kuang, Q. Morris
Orchard: building large cancer phylogenies using stochastic combinatorial search
null
null
null
null
q-bio.PE cs.AI cs.LG
http://creativecommons.org/licenses/by/4.0/
Phylogenies depicting the evolutionary history of genetically heterogeneous subpopulations of cells from the same cancer, i.e., cancer phylogenies, offer valuable insights about cancer development and guide treatment strategies. Many methods exist that reconstruct cancer phylogenies using point mutations detected with bulk DNA sequencing. However, these methods become inaccurate when reconstructing phylogenies with more than 30 mutations, or, in some cases, fail to recover a phylogeny altogether. Here, we introduce Orchard, a cancer phylogeny reconstruction algorithm that is fast and accurate using up to 1000 mutations. Orchard samples without replacement from a factorized approximation of the posterior distribution over phylogenies, a novel result derived in this paper. Each factor in this approximate posterior corresponds to a conditional distribution for adding a new mutation to a partially built phylogeny. Orchard optimizes each factor sequentially, generating a sequence of incrementally larger phylogenies that ultimately culminate in a complete tree containing all mutations. Our evaluations demonstrate that Orchard outperforms state-of-the-art cancer phylogeny reconstruction methods in reconstructing more plausible phylogenies across 90 simulated cancers and 14 B-progenitor acute lymphoblastic leukemias (B-ALLs). Remarkably, Orchard accurately reconstructs cancer phylogenies using up to 1,000 mutations. Additionally, we demonstrate that the large and accurate phylogenies reconstructed by Orchard are useful for identifying patterns of somatic mutations and genetic variations among distinct cancer cell subpopulations.
[ { "created": "Tue, 21 Nov 2023 18:25:23 GMT", "version": "v1" }, { "created": "Wed, 10 Jul 2024 00:32:49 GMT", "version": "v2" } ]
2024-07-11
[ [ "Kulman", "E.", "" ], [ "Kuang", "R.", "" ], [ "Morris", "Q.", "" ] ]
Phylogenies depicting the evolutionary history of genetically heterogeneous subpopulations of cells from the same cancer, i.e., cancer phylogenies, offer valuable insights about cancer development and guide treatment strategies. Many methods exist that reconstruct cancer phylogenies using point mutations detected with bulk DNA sequencing. However, these methods become inaccurate when reconstructing phylogenies with more than 30 mutations, or, in some cases, fail to recover a phylogeny altogether. Here, we introduce Orchard, a cancer phylogeny reconstruction algorithm that is fast and accurate using up to 1000 mutations. Orchard samples without replacement from a factorized approximation of the posterior distribution over phylogenies, a novel result derived in this paper. Each factor in this approximate posterior corresponds to a conditional distribution for adding a new mutation to a partially built phylogeny. Orchard optimizes each factor sequentially, generating a sequence of incrementally larger phylogenies that ultimately culminate in a complete tree containing all mutations. Our evaluations demonstrate that Orchard outperforms state-of-the-art cancer phylogeny reconstruction methods in reconstructing more plausible phylogenies across 90 simulated cancers and 14 B-progenitor acute lymphoblastic leukemias (B-ALLs). Remarkably, Orchard accurately reconstructs cancer phylogenies using up to 1,000 mutations. Additionally, we demonstrate that the large and accurate phylogenies reconstructed by Orchard are useful for identifying patterns of somatic mutations and genetic variations among distinct cancer cell subpopulations.
2010.07417
Adriaan-Alexander Ludl
Adriaan-Alexander Ludl and Tom Michoel
Comparison between instrumental variable and mediation-based methods for reconstructing causal gene networks in yeast
null
Molecular Omics, 2021,17, 241-251
10.1039/D0MO00140F
null
q-bio.MN q-bio.GN stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Causal gene networks model the flow of information within a cell, but reconstructing them from omics data is challenging because correlation does not imply causation. Combining genomics and transcriptomics data from a segregating population allows to orient the direction of causality between gene expression traits using genomic variants. Instrumental-variable methods (IV) use a local expression quantitative trait locus (eQTL) as a randomized instrument for a gene's expression level, and assign target genes based on distal eQTL associations. Mediation-based methods (ME) additionally require that distal eQTL associations are mediated by the source gene. Here we used Findr, a software providing uniform implementations of IV, ME, and coexpression-based methods, a recent dataset of 1,012 segregants from a cross between two budding yeast strains, and the YEASTRACT database of known transcriptional interactions to compare causal gene network inference methods. We found that causal inference methods result in a significant overlap with the ground-truth, whereas coexpression did not perform better than random. A subsampling analysis revealed that the performance of ME decreases at large sample sizes, due to a loss of sensitivity when residual correlations become significant. IV methods contain false positive predictions, due to genomic linkage between eQTL instruments. IV and ME methods also have complementary roles for identifying causal genes underlying transcriptional hotspots. IV methods correctly predicted STB5 targets for a hotspot centred on the transcription factor STB5, whereas ME failed due to Stb5p auto-regulating its own expression. ME suggests a new candidate gene, DNM1, for a hotspot on Chr XII, where IV methods could not distinguish between multiple genes located within the hotspot.
[ { "created": "Wed, 14 Oct 2020 22:02:23 GMT", "version": "v1" }, { "created": "Wed, 18 Nov 2020 22:21:57 GMT", "version": "v2" } ]
2021-10-29
[ [ "Ludl", "Adriaan-Alexander", "" ], [ "Michoel", "Tom", "" ] ]
Causal gene networks model the flow of information within a cell, but reconstructing them from omics data is challenging because correlation does not imply causation. Combining genomics and transcriptomics data from a segregating population allows to orient the direction of causality between gene expression traits using genomic variants. Instrumental-variable methods (IV) use a local expression quantitative trait locus (eQTL) as a randomized instrument for a gene's expression level, and assign target genes based on distal eQTL associations. Mediation-based methods (ME) additionally require that distal eQTL associations are mediated by the source gene. Here we used Findr, a software providing uniform implementations of IV, ME, and coexpression-based methods, a recent dataset of 1,012 segregants from a cross between two budding yeast strains, and the YEASTRACT database of known transcriptional interactions to compare causal gene network inference methods. We found that causal inference methods result in a significant overlap with the ground-truth, whereas coexpression did not perform better than random. A subsampling analysis revealed that the performance of ME decreases at large sample sizes, due to a loss of sensitivity when residual correlations become significant. IV methods contain false positive predictions, due to genomic linkage between eQTL instruments. IV and ME methods also have complementary roles for identifying causal genes underlying transcriptional hotspots. IV methods correctly predicted STB5 targets for a hotspot centred on the transcription factor STB5, whereas ME failed due to Stb5p auto-regulating its own expression. ME suggests a new candidate gene, DNM1, for a hotspot on Chr XII, where IV methods could not distinguish between multiple genes located within the hotspot.
1807.04788
Ethan Romero-Severson
Dmitry Gromov, Ingo Bulla, Ethan Obie Romero-Severson
Systematic evaluation of the population-level effects of alternative treatment strategies on the basic reproduction number
null
null
10.1016/j.jtbi.2018.11.029
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
An approach to estimate the influence of the treatment-type controls on the basic reproduction number, R 0 , is proposed and elaborated. The presented approach allows one to estimate the effect of a given treatment strategy or to compare a number of different treatment strategies on the basic reproduction number. All our results are valid for sufficiently small values of the control. However, in many cases it is possible to extend this analysis to larger values of the control as was illustrated by examples.
[ { "created": "Thu, 12 Jul 2018 18:54:32 GMT", "version": "v1" } ]
2023-05-30
[ [ "Gromov", "Dmitry", "" ], [ "Bulla", "Ingo", "" ], [ "Romero-Severson", "Ethan Obie", "" ] ]
An approach to estimate the influence of the treatment-type controls on the basic reproduction number, R 0 , is proposed and elaborated. The presented approach allows one to estimate the effect of a given treatment strategy or to compare a number of different treatment strategies on the basic reproduction number. All our results are valid for sufficiently small values of the control. However, in many cases it is possible to extend this analysis to larger values of the control as was illustrated by examples.
2010.09483
Jeremy Georges-Filteau
Jeremy Georges-Filteau, Richard C. Hamelin and Mathieu Blanchette
Mycorrhiza: Genotype Assignment usingPhylogenetic Networks
null
Bioinformatics, Volume 36, Issue 1, 1 January 2020
10.1093/bioinformatics/btz476
null
q-bio.QM cs.LG q-bio.GN q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Motivation The genotype assignment problem consists of predicting, from the genotype of an individual, which of a known set of populations it originated from. The problem arises in a variety of contexts, including wildlife forensics, invasive species detection and biodiversity monitoring. Existing approaches perform well under ideal conditions but are sensitive to a variety of common violations of the assumptions they rely on. Results In this article, we introduce Mycorrhiza, a machine learning approach for the genotype assignment problem. Our algorithm makes use of phylogenetic networks to engineer features that encode the evolutionary relationships among samples. Those features are then used as input to a Random Forests classifier. The classification accuracy was assessed on multiple published empirical SNP, microsatellite or consensus sequence datasets with wide ranges of size, geographical distribution and population structure and on simulated datasets. It compared favorably against widely used assessment tests or mixture analysis methods such as STRUCTURE and Admixture, and against another machine-learning based approach using principal component analysis for dimensionality reduction. Mycorrhiza yields particularly significant gains on datasets with a large average fixation index (FST) or deviation from the Hardy-Weinberg equilibrium. Moreover, the phylogenetic network approach estimates mixture proportions with good accuracy.
[ { "created": "Wed, 14 Oct 2020 02:36:27 GMT", "version": "v1" } ]
2020-10-20
[ [ "Georges-Filteau", "Jeremy", "" ], [ "Hamelin", "Richard C.", "" ], [ "Blanchette", "Mathieu", "" ] ]
Motivation The genotype assignment problem consists of predicting, from the genotype of an individual, which of a known set of populations it originated from. The problem arises in a variety of contexts, including wildlife forensics, invasive species detection and biodiversity monitoring. Existing approaches perform well under ideal conditions but are sensitive to a variety of common violations of the assumptions they rely on. Results In this article, we introduce Mycorrhiza, a machine learning approach for the genotype assignment problem. Our algorithm makes use of phylogenetic networks to engineer features that encode the evolutionary relationships among samples. Those features are then used as input to a Random Forests classifier. The classification accuracy was assessed on multiple published empirical SNP, microsatellite or consensus sequence datasets with wide ranges of size, geographical distribution and population structure and on simulated datasets. It compared favorably against widely used assessment tests or mixture analysis methods such as STRUCTURE and Admixture, and against another machine-learning based approach using principal component analysis for dimensionality reduction. Mycorrhiza yields particularly significant gains on datasets with a large average fixation index (FST) or deviation from the Hardy-Weinberg equilibrium. Moreover, the phylogenetic network approach estimates mixture proportions with good accuracy.
1206.4386
Liane Gabora
Liane Gabora
An Evolutionary Framework for Culture: Selectionism versus Communal Exchange
18 pages; 2 tables and 11 figures embedded in text
Physics of Life Reviews, 10(2), 117-145 (2013)
10.1016/j.plrev.2013.03.006
null
q-bio.PE nlin.AO q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Dawkins' replicator-based conception of evolution has led to widespread mis-application selectionism across the social sciences because it does not address the paradox that inspired the theory of natural selection in the first place: how do organisms accumulate change when traits acquired over their lifetime are obliterated? This is addressed by von Neumann's concept of a self-replicating automaton (SRA). A SRA consists of a self-assembly code that is used in two distinct ways: (1) actively deciphered during development to construct a self-similar replicant, and (2) passively copied to the replicant to ensure that it can reproduce. Information that is acquired over a lifetime is not transmitted to offspring, whereas information that is inherited during copying is transmitted. In cultural evolution there is no mechanism for discarding acquired change. Acquired change can accumulate orders of magnitude faster than, and quickly overwhelm, inherited change due to differential replication of variants in response to selection. This prohibits a selectionist but not an evolutionary framework for culture. Recent work on the origin of life suggests that early life evolved through a non-Darwinian process referred to as communal exchange that does not involve a self-assembly code, and that natural selection emerged from this more haphazard, ancestral evolutionary process. It is proposed that communal exchange provides a more appropriate evolutionary framework for culture than selectionism. This is supported by a computational model of cultural evolution and a network-based program for documenting material cultural history, and it is consistent with high levels of human cooperation.
[ { "created": "Wed, 20 Jun 2012 05:38:06 GMT", "version": "v1" }, { "created": "Fri, 2 Aug 2013 17:06:46 GMT", "version": "v2" }, { "created": "Sun, 30 Jun 2019 01:51:37 GMT", "version": "v3" } ]
2019-07-02
[ [ "Gabora", "Liane", "" ] ]
Dawkins' replicator-based conception of evolution has led to widespread mis-application selectionism across the social sciences because it does not address the paradox that inspired the theory of natural selection in the first place: how do organisms accumulate change when traits acquired over their lifetime are obliterated? This is addressed by von Neumann's concept of a self-replicating automaton (SRA). A SRA consists of a self-assembly code that is used in two distinct ways: (1) actively deciphered during development to construct a self-similar replicant, and (2) passively copied to the replicant to ensure that it can reproduce. Information that is acquired over a lifetime is not transmitted to offspring, whereas information that is inherited during copying is transmitted. In cultural evolution there is no mechanism for discarding acquired change. Acquired change can accumulate orders of magnitude faster than, and quickly overwhelm, inherited change due to differential replication of variants in response to selection. This prohibits a selectionist but not an evolutionary framework for culture. Recent work on the origin of life suggests that early life evolved through a non-Darwinian process referred to as communal exchange that does not involve a self-assembly code, and that natural selection emerged from this more haphazard, ancestral evolutionary process. It is proposed that communal exchange provides a more appropriate evolutionary framework for culture than selectionism. This is supported by a computational model of cultural evolution and a network-based program for documenting material cultural history, and it is consistent with high levels of human cooperation.
1607.05386
Jin Xu
Dong-Ho Park, Taegeun Song, Danh-Tai Hoang, Jin Xu, Junghyo Jo
A Local Counter-Regulatory Motif Modulates the Global Phase of Hormonal Oscillations
null
null
10.1038/s41598-017-01806-0
null
q-bio.TO
http://creativecommons.org/licenses/by-nc-nd/4.0/
Counter-regulatory elements maintain dynamic equilibrium ubiquitously in living systems. The most prominent example, which is critical to mammalian survival, is that of pancreatic {\alpha} and {\beta} cells producing glucagon and insulin for glucose homeostasis. These cells are not found in a single gland but are dispersed in multiple micro-organs known as the islets of Langerhans. Within an islet, these two reciprocal cell types interact with each other and with an additional cell type: the {\delta} cell. By testing all possible motifs governing the interactions of these three cell types, we found that a unique set of positive/negative intra-islet interactions between different islet cell types functions not only to reduce the superficially wasteful zero-sum action of glucagon and insulin but also to enhance/suppress the synchronization of hormone secretions between islets under high/normal glucose conditions. This anti-symmetric interaction motif confers effective controllability for network (de)synchronization.
[ { "created": "Tue, 19 Jul 2016 02:58:20 GMT", "version": "v1" }, { "created": "Tue, 13 Feb 2024 01:10:55 GMT", "version": "v2" } ]
2024-02-14
[ [ "Park", "Dong-Ho", "" ], [ "Song", "Taegeun", "" ], [ "Hoang", "Danh-Tai", "" ], [ "Xu", "Jin", "" ], [ "Jo", "Junghyo", "" ] ]
Counter-regulatory elements maintain dynamic equilibrium ubiquitously in living systems. The most prominent example, which is critical to mammalian survival, is that of pancreatic {\alpha} and {\beta} cells producing glucagon and insulin for glucose homeostasis. These cells are not found in a single gland but are dispersed in multiple micro-organs known as the islets of Langerhans. Within an islet, these two reciprocal cell types interact with each other and with an additional cell type: the {\delta} cell. By testing all possible motifs governing the interactions of these three cell types, we found that a unique set of positive/negative intra-islet interactions between different islet cell types functions not only to reduce the superficially wasteful zero-sum action of glucagon and insulin but also to enhance/suppress the synchronization of hormone secretions between islets under high/normal glucose conditions. This anti-symmetric interaction motif confers effective controllability for network (de)synchronization.
2310.04463
Siyuan Guo
Siyuan Guo and Jihong Guan and Shuigeng Zhou
Diffusing on Two Levels and Optimizing for Multiple Properties: A Novel Approach to Generating Molecules with Desirable Properties
null
null
null
null
q-bio.BM cs.AI cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In the past decade, Artificial Intelligence driven drug design and discovery has been a hot research topic, where an important branch is molecule generation by generative models, from GAN-based models and VAE-based models to the latest diffusion-based models. However, most existing models pursue only the basic properties like validity and uniqueness of the generated molecules, a few go further to explicitly optimize one single important molecular property (e.g. QED or PlogP), which makes most generated molecules little usefulness in practice. In this paper, we present a novel approach to generating molecules with desirable properties, which expands the diffusion model framework with multiple innovative designs. The novelty is two-fold. On the one hand, considering that the structures of molecules are complex and diverse, and molecular properties are usually determined by some substructures (e.g. pharmacophores), we propose to perform diffusion on two structural levels: molecules and molecular fragments respectively, with which a mixed Gaussian distribution is obtained for the reverse diffusion process. To get desirable molecular fragments, we develop a novel electronic effect based fragmentation method. On the other hand, we introduce two ways to explicitly optimize multiple molecular properties under the diffusion model framework. First, as potential drug molecules must be chemically valid, we optimize molecular validity by an energy-guidance function. Second, since potential drug molecules should be desirable in various properties, we employ a multi-objective mechanism to optimize multiple molecular properties simultaneously. Extensive experiments with two benchmark datasets QM9 and ZINC250k show that the molecules generated by our proposed method have better validity, uniqueness, novelty, Fr\'echet ChemNet Distance (FCD), QED, and PlogP than those generated by current SOTA models.
[ { "created": "Thu, 5 Oct 2023 11:43:21 GMT", "version": "v1" } ]
2023-10-10
[ [ "Guo", "Siyuan", "" ], [ "Guan", "Jihong", "" ], [ "Zhou", "Shuigeng", "" ] ]
In the past decade, Artificial Intelligence driven drug design and discovery has been a hot research topic, where an important branch is molecule generation by generative models, from GAN-based models and VAE-based models to the latest diffusion-based models. However, most existing models pursue only the basic properties like validity and uniqueness of the generated molecules, a few go further to explicitly optimize one single important molecular property (e.g. QED or PlogP), which makes most generated molecules little usefulness in practice. In this paper, we present a novel approach to generating molecules with desirable properties, which expands the diffusion model framework with multiple innovative designs. The novelty is two-fold. On the one hand, considering that the structures of molecules are complex and diverse, and molecular properties are usually determined by some substructures (e.g. pharmacophores), we propose to perform diffusion on two structural levels: molecules and molecular fragments respectively, with which a mixed Gaussian distribution is obtained for the reverse diffusion process. To get desirable molecular fragments, we develop a novel electronic effect based fragmentation method. On the other hand, we introduce two ways to explicitly optimize multiple molecular properties under the diffusion model framework. First, as potential drug molecules must be chemically valid, we optimize molecular validity by an energy-guidance function. Second, since potential drug molecules should be desirable in various properties, we employ a multi-objective mechanism to optimize multiple molecular properties simultaneously. Extensive experiments with two benchmark datasets QM9 and ZINC250k show that the molecules generated by our proposed method have better validity, uniqueness, novelty, Fr\'echet ChemNet Distance (FCD), QED, and PlogP than those generated by current SOTA models.
1105.4387
Kazuhiro Takemoto
Kazuhiro Takemoto
Global architecture of metabolite distributions across species and its formation mechanisms
14 pages, 5 figures
Biosystems 100, 8 (2010)
10.1016/j.biosystems.2009.12.002
null
q-bio.PE physics.data-an
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Living organisms produce metabolites of many types via their metabolisms. Especially, flavonoids, a kind of secondary metabolites, of plant species are interesting examples. Since plant species are believed to have specific flavonoids with respect to diverse environment, elucidation of design principles of metabolite distributions across plant species is important to understand metabolite diversity and plant evolution. In the previous work, we found heterogeneous connectivity in metabolite distributions, and proposed a simple model to explain a possible origin of heterogeneous connectivity. In this paper, we show further structural properties in the metabolite distribution among families inspired by analogy with plant-animal mutualistic networks: nested structure and modular structure. An earlier model represents that these structural properties in bipartite relationships are determined based on traits of elements and external factors. However, we find that the architecture of metabolite distributions is described by simple evolution processes without trait-based mechanisms by comparison between our model and the earlier model. Our model can better predict nested structure and modular structure in addition to heterogeneous connectivity both qualitatively and quantitatively. This finding implies an alternative possible origin of these structural properties, and suggests simpler formation mechanisms of metabolite distributions across plant species than expected.
[ { "created": "Mon, 23 May 2011 02:16:23 GMT", "version": "v1" } ]
2015-03-19
[ [ "Takemoto", "Kazuhiro", "" ] ]
Living organisms produce metabolites of many types via their metabolisms. Especially, flavonoids, a kind of secondary metabolites, of plant species are interesting examples. Since plant species are believed to have specific flavonoids with respect to diverse environment, elucidation of design principles of metabolite distributions across plant species is important to understand metabolite diversity and plant evolution. In the previous work, we found heterogeneous connectivity in metabolite distributions, and proposed a simple model to explain a possible origin of heterogeneous connectivity. In this paper, we show further structural properties in the metabolite distribution among families inspired by analogy with plant-animal mutualistic networks: nested structure and modular structure. An earlier model represents that these structural properties in bipartite relationships are determined based on traits of elements and external factors. However, we find that the architecture of metabolite distributions is described by simple evolution processes without trait-based mechanisms by comparison between our model and the earlier model. Our model can better predict nested structure and modular structure in addition to heterogeneous connectivity both qualitatively and quantitatively. This finding implies an alternative possible origin of these structural properties, and suggests simpler formation mechanisms of metabolite distributions across plant species than expected.
1301.4298
Shuji Ishihara
S. Ishihara, K. Sugimura, S.J. Cox, I. Bonnet, Y. Bellaiche, and F. Graner
Comparative study of non-invasive force and stress inference methods in tissue
12 pages, 8 figures, EPJ E: Topical issue on "Physical constraints on morphogenesis and evolution"
null
null
null
q-bio.QM cond-mat.soft q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In the course of animal development, the shape of tissue emerges in part from mechanical and biochemical interactions between cells. Measuring stress in tissue is essential for studying morphogenesis and its physical constraints. Experimental measurements of stress reported thus far have been invasive, indirect, or local. One theoretical approach is force inference from cell shapes and connectivity, which is non-invasive, can provide a space-time map of stress and relies on prefactors. Here, to validate force- inference methods, we performed a comparative study of them. Three force-inference methods, which differ in their approach of treating indefiniteness in an inverse problem between cell shapes and forces, were tested by using two artificial and two experimental data sets. Our results using different datasets consistently indicate that our Bayesian force inference, by which cell-junction tensions and cell pressures are simultaneously estimated, performs best in terms of accuracy and robustness. Moreover, by measuring the stress anisotropy and relaxation, we cross-validated the force inference and the global annular ablation of tissue, each of which relies on different prefactors. A practical choice of force-inference methods in distinct systems of interest is discussed.
[ { "created": "Fri, 18 Jan 2013 05:12:51 GMT", "version": "v1" } ]
2013-01-21
[ [ "Ishihara", "S.", "" ], [ "Sugimura", "K.", "" ], [ "Cox", "S. J.", "" ], [ "Bonnet", "I.", "" ], [ "Bellaiche", "Y.", "" ], [ "Graner", "F.", "" ] ]
In the course of animal development, the shape of tissue emerges in part from mechanical and biochemical interactions between cells. Measuring stress in tissue is essential for studying morphogenesis and its physical constraints. Experimental measurements of stress reported thus far have been invasive, indirect, or local. One theoretical approach is force inference from cell shapes and connectivity, which is non-invasive, can provide a space-time map of stress and relies on prefactors. Here, to validate force- inference methods, we performed a comparative study of them. Three force-inference methods, which differ in their approach of treating indefiniteness in an inverse problem between cell shapes and forces, were tested by using two artificial and two experimental data sets. Our results using different datasets consistently indicate that our Bayesian force inference, by which cell-junction tensions and cell pressures are simultaneously estimated, performs best in terms of accuracy and robustness. Moreover, by measuring the stress anisotropy and relaxation, we cross-validated the force inference and the global annular ablation of tissue, each of which relies on different prefactors. A practical choice of force-inference methods in distinct systems of interest is discussed.
1702.08421
Ines Samengo Dr.
Ines Samengo
The role of the observer in goal-directed behavior
11 pages, 5 figures. Essay submitted to FQXi
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In goal-directed behavior, a large number of possible initial states end up in the pursued goal. The accompanying information loss implies that goal-oriented behavior is in one-to-one correspondence with an open subsystem whose entropy decreases in time. Yet ultimately, the laws of physics are reversible, so systems capable of yielding goal-directed behavior must transfer the information about initial conditions to other degrees of freedom outside the boundaries of the agent. To operate steadily, they must consume ordered degrees of freedom provided as input, and be dispensed of disordered outputs that act as wastes from the point of view of the aimed objective. Here I argue that a physical system may or may not display goal-directed behavior depending on what exactly is defined as the agent. The borders of the agent must be carefully tailored so as to entail the appropriate information balance sheet. In this game, observers play the role of tailors: They design agents by setting the limits of the system of interest. Brain-guided subjects perform this creative observation task naturally, implying that the observation of goal-oriented behavior is a goal-oriented behavior in itself. Minds evolved to cut out pieces of reality and endow them with intentionality, because ascribing intentionality is an efficient way of modeling the world, and making predictions. One most remarkable agent of whom we have indisputable evidence of its goal-pursuing attitude is the self. Notably, this agent is simultaneously the subject and the object of observation.
[ { "created": "Mon, 27 Feb 2017 18:27:48 GMT", "version": "v1" } ]
2017-02-28
[ [ "Samengo", "Ines", "" ] ]
In goal-directed behavior, a large number of possible initial states end up in the pursued goal. The accompanying information loss implies that goal-oriented behavior is in one-to-one correspondence with an open subsystem whose entropy decreases in time. Yet ultimately, the laws of physics are reversible, so systems capable of yielding goal-directed behavior must transfer the information about initial conditions to other degrees of freedom outside the boundaries of the agent. To operate steadily, they must consume ordered degrees of freedom provided as input, and be dispensed of disordered outputs that act as wastes from the point of view of the aimed objective. Here I argue that a physical system may or may not display goal-directed behavior depending on what exactly is defined as the agent. The borders of the agent must be carefully tailored so as to entail the appropriate information balance sheet. In this game, observers play the role of tailors: They design agents by setting the limits of the system of interest. Brain-guided subjects perform this creative observation task naturally, implying that the observation of goal-oriented behavior is a goal-oriented behavior in itself. Minds evolved to cut out pieces of reality and endow them with intentionality, because ascribing intentionality is an efficient way of modeling the world, and making predictions. One most remarkable agent of whom we have indisputable evidence of its goal-pursuing attitude is the self. Notably, this agent is simultaneously the subject and the object of observation.
2408.01528
KongFatt Wong-Lin
Abdoreza Asadpour and KongFatt Wong-Lin
Can multivariate Granger causality detect directed connectivity of a multistable and dynamic biological decision network model?
null
null
null
null
q-bio.NC cs.LG cs.NE math.DS
http://creativecommons.org/licenses/by-nc-sa/4.0/
Extracting causal connections can advance interpretable AI and machine learning. Granger causality (GC) is a robust statistical method for estimating directed influences (DC) between signals. While GC has been widely applied to analysing neuronal signals in biological neural networks and other domains, its application to complex, nonlinear, and multistable neural networks is less explored. In this study, we applied time-domain multi-variate Granger causality (MVGC) to the time series neural activity of all nodes in a trained multistable biologically based decision neural network model with real-time decision uncertainty monitoring. Our analysis demonstrated that challenging two-choice decisions, where input signals could be closely matched, and the appropriate application of fine-grained sliding time windows, could readily reveal the original model's DC. Furthermore, the identified DC varied based on whether the network had correct or error decisions. Integrating the identified DC from different decision outcomes recovered most of the original model's architecture, despite some spurious and missing connectivity. This approach could be used as an initial exploration to enhance the interpretability and transparency of dynamic multistable and nonlinear biological or AI systems by revealing causal connections throughout different phases of neural network dynamics and outcomes.
[ { "created": "Fri, 2 Aug 2024 18:40:15 GMT", "version": "v1" } ]
2024-08-06
[ [ "Asadpour", "Abdoreza", "" ], [ "Wong-Lin", "KongFatt", "" ] ]
Extracting causal connections can advance interpretable AI and machine learning. Granger causality (GC) is a robust statistical method for estimating directed influences (DC) between signals. While GC has been widely applied to analysing neuronal signals in biological neural networks and other domains, its application to complex, nonlinear, and multistable neural networks is less explored. In this study, we applied time-domain multi-variate Granger causality (MVGC) to the time series neural activity of all nodes in a trained multistable biologically based decision neural network model with real-time decision uncertainty monitoring. Our analysis demonstrated that challenging two-choice decisions, where input signals could be closely matched, and the appropriate application of fine-grained sliding time windows, could readily reveal the original model's DC. Furthermore, the identified DC varied based on whether the network had correct or error decisions. Integrating the identified DC from different decision outcomes recovered most of the original model's architecture, despite some spurious and missing connectivity. This approach could be used as an initial exploration to enhance the interpretability and transparency of dynamic multistable and nonlinear biological or AI systems by revealing causal connections throughout different phases of neural network dynamics and outcomes.
1407.1333
Lennaert van Veen
Lennaert van Veen and Kevin Green
Periodic solutions to a mean-field model for electrocortical activity
9 pages, 5 figures
null
10.1140/epjst/e2014-02311-y
null
q-bio.NC nlin.PS physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We consider a continuum model of electrical signals in the human cortex, which takes the form of a system of semilinear, hyperbolic partial differential equations for the inhibitory and excitatory membrane potentials and the synaptic inputs. The coupling of these components is represented by sigmoidal and quadratic nonlinearities. We consider these equations on a square domain with periodic boundary conditions, in the vicinity of the primary transition from a stable equilibrium to time-periodic motion through an equivariant Hopf bifurcation. We compute part of a family of standing wave solutions, emanating from this point.
[ { "created": "Fri, 4 Jul 2014 21:24:53 GMT", "version": "v1" } ]
2015-06-22
[ [ "van Veen", "Lennaert", "" ], [ "Green", "Kevin", "" ] ]
We consider a continuum model of electrical signals in the human cortex, which takes the form of a system of semilinear, hyperbolic partial differential equations for the inhibitory and excitatory membrane potentials and the synaptic inputs. The coupling of these components is represented by sigmoidal and quadratic nonlinearities. We consider these equations on a square domain with periodic boundary conditions, in the vicinity of the primary transition from a stable equilibrium to time-periodic motion through an equivariant Hopf bifurcation. We compute part of a family of standing wave solutions, emanating from this point.
2205.02365
Joshua Stevenson
Joshua Stevenson, Barbara Holland, Michael Charleston, Jeremy Sumner
Evaluation of the relative performance of the subflattenings method for phylogenetic inference
21 pages, 13 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The algebraic properties of flattenings and subflattenings provide direct methods for identifying edges in the true phylogeny -- and by extension the complete tree -- using pattern counts from a sequence alignment. The relatively small number of possible internal edges among a set of taxa (compared to the number of binary trees) makes these methods attractive, however more could be done to evaluate their effectiveness for inferring phylogenetic trees. This is the case particularly for subflattenings, and our work makes progress in this area. We introduce software for constructing and evaluating subflattenings for splits, utilising a number of methods to make computing subflattenings more tractable. We then present the results of simulations we have performed in order to compare the effectiveness of subflattenings to that of flattenings in terms of split score distributions, and susceptibility to possible biases. We find that subflattenings perform similarly to flattenings in terms of the distribution of split scores on the trees we examined, but may be less affected by bias arising from both split size/balance and long branch attraction. These insights are useful for developing effective algorithms to utilise these tools for the purpose of inferring phylogenetic trees.
[ { "created": "Wed, 4 May 2022 23:57:04 GMT", "version": "v1" } ]
2022-05-06
[ [ "Stevenson", "Joshua", "" ], [ "Holland", "Barbara", "" ], [ "Charleston", "Michael", "" ], [ "Sumner", "Jeremy", "" ] ]
The algebraic properties of flattenings and subflattenings provide direct methods for identifying edges in the true phylogeny -- and by extension the complete tree -- using pattern counts from a sequence alignment. The relatively small number of possible internal edges among a set of taxa (compared to the number of binary trees) makes these methods attractive, however more could be done to evaluate their effectiveness for inferring phylogenetic trees. This is the case particularly for subflattenings, and our work makes progress in this area. We introduce software for constructing and evaluating subflattenings for splits, utilising a number of methods to make computing subflattenings more tractable. We then present the results of simulations we have performed in order to compare the effectiveness of subflattenings to that of flattenings in terms of split score distributions, and susceptibility to possible biases. We find that subflattenings perform similarly to flattenings in terms of the distribution of split scores on the trees we examined, but may be less affected by bias arising from both split size/balance and long branch attraction. These insights are useful for developing effective algorithms to utilise these tools for the purpose of inferring phylogenetic trees.
2403.15685
Iheanyi Okonko Okonko
David Nwachukwu, Edith Nnenna Oketah, Chineze Helen Ugwu, Hope Chioma Innocent-Adiele, Chisom Chimbundum Adim, Euslar Nnenna Onu, Ann Onyinyechi Chukwu, Grace Aghaji Nwankwo, Mary Uche Igwe, Phillip O. Okerentugba and Iheanyi Omezuruike Okonko
Semi-Quantitative Analysis and Seroepidemiological Evidence of Past Dengue Virus Infection among HIV-infected patients in Onitsha, Anambra State, Nigeria
null
null
null
null
q-bio.PE q-bio.QM
http://creativecommons.org/licenses/by-nc-nd/4.0/
Despite its endemic nature as well as the recent outbreaks, information on the opportunistic DENV in Anambra state has been sparse. This study thus aimed to give seroepidemiological evidence of past dengue virus infection among HIV-infected patients in Onitsha, Anambra State, Nigeria. Plasma from 94 HIV-infected patients who were attending Saint Charles Borromeo Hospital, Onitsha in Anambra State, Nigeria was tested for IgG antibodies specific to the dengue virus by IgG ELISA assay. The prevalence of past dengue virus infection was 61.7% (n = 58/94). This study showed age group 0-15 years (77.30%), female gender (65.1%), married (63.9%) and no formal level (100.0 %) as the highest seropositivity among the study participants. In terms of immunological and virological markers, greater IgG seroprevalence was observed in individuals with a viral load of <40 copies/ml (64.0%) and a CD4 count of >350 cells/ul (63.2%). The high IgG seropositivity of Dengue Virus (DENV) among HIV-infected individuals on Onitsha is cause for concern.
[ { "created": "Sat, 23 Mar 2024 02:21:50 GMT", "version": "v1" } ]
2024-03-26
[ [ "Nwachukwu", "David", "" ], [ "Oketah", "Edith Nnenna", "" ], [ "Ugwu", "Chineze Helen", "" ], [ "Innocent-Adiele", "Hope Chioma", "" ], [ "Adim", "Chisom Chimbundum", "" ], [ "Onu", "Euslar Nnenna", "" ], [ "Chukwu", "Ann Onyinyechi", "" ], [ "Nwankwo", "Grace Aghaji", "" ], [ "Igwe", "Mary Uche", "" ], [ "Okerentugba", "Phillip O.", "" ], [ "Okonko", "Iheanyi Omezuruike", "" ] ]
Despite its endemic nature as well as the recent outbreaks, information on the opportunistic DENV in Anambra state has been sparse. This study thus aimed to give seroepidemiological evidence of past dengue virus infection among HIV-infected patients in Onitsha, Anambra State, Nigeria. Plasma from 94 HIV-infected patients who were attending Saint Charles Borromeo Hospital, Onitsha in Anambra State, Nigeria was tested for IgG antibodies specific to the dengue virus by IgG ELISA assay. The prevalence of past dengue virus infection was 61.7% (n = 58/94). This study showed age group 0-15 years (77.30%), female gender (65.1%), married (63.9%) and no formal level (100.0 %) as the highest seropositivity among the study participants. In terms of immunological and virological markers, greater IgG seroprevalence was observed in individuals with a viral load of <40 copies/ml (64.0%) and a CD4 count of >350 cells/ul (63.2%). The high IgG seropositivity of Dengue Virus (DENV) among HIV-infected individuals on Onitsha is cause for concern.