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2010.01758
Claudia Solis-Lemus
Claudia Solis-Lemus, Arrigo Coen, Cecile Ane
On the Identifiability of Phylogenetic Networks under a Pseudolikelihood model
null
null
null
null
q-bio.PE math.ST stat.TH
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The Tree of Life is the graphical structure that represents the evolutionary process from single-cell organisms at the origin of life to the vast biodiversity we see today. Reconstructing this tree from genomic sequences is challenging due to the variety of biological forces that shape the signal in the data, and many of those processes like incomplete lineage sorting and hybridization can produce confounding information. Here, we present the mathematical version of the identifiability proofs of phylogenetic networks under the pseudolikelihood model in SNaQ. We establish that the ability to detect different hybridization events depends on the number of nodes on the hybridization blob, with small blobs (corresponding to closely related species) being the hardest to be detected. Our work focuses on level-1 networks, but raises attention to the importance of identifiability studies on phylogenetic inference methods for broader classes of networks.
[ { "created": "Mon, 5 Oct 2020 03:28:25 GMT", "version": "v1" } ]
2020-10-06
[ [ "Solis-Lemus", "Claudia", "" ], [ "Coen", "Arrigo", "" ], [ "Ane", "Cecile", "" ] ]
The Tree of Life is the graphical structure that represents the evolutionary process from single-cell organisms at the origin of life to the vast biodiversity we see today. Reconstructing this tree from genomic sequences is challenging due to the variety of biological forces that shape the signal in the data, and many of those processes like incomplete lineage sorting and hybridization can produce confounding information. Here, we present the mathematical version of the identifiability proofs of phylogenetic networks under the pseudolikelihood model in SNaQ. We establish that the ability to detect different hybridization events depends on the number of nodes on the hybridization blob, with small blobs (corresponding to closely related species) being the hardest to be detected. Our work focuses on level-1 networks, but raises attention to the importance of identifiability studies on phylogenetic inference methods for broader classes of networks.
1804.04538
Priya Ranjan
Anju Mishra, Shanu Sharma, Sanjay Kumar, Priya Ranjan, and Amit Ujlayan
Automated Classification of Hand-grip action on Objects using Machine Learning
This is a report on an ongoing project
null
null
null
q-bio.NC cs.HC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Brain computer interface is the current area of research to provide assistance to disabled persons. To cope up with the growing needs of BCI applications, this paper presents an automated classification scheme for handgrip actions on objects by using Electroencephalography (EEG) data. The presented approach focuses on investigation of classifying correct and incorrect handgrip responses for objects by using EEG recorded patterns. The method starts with preprocessing of data, followed by extraction of relevant features from the epoch data in the form of discrete wavelet transform (DWT), and entropy measures. After computing feature vectors, artificial neural network classifiers used to classify the patterns into correct and incorrect handgrips on different objects. The proposed method was tested on real dataset, which contains EEG recordings from 14 persons. The results showed that the proposed approach is effective and may be useful to develop a variety of BCI based devices to control hand movements.
[ { "created": "Fri, 9 Mar 2018 11:51:43 GMT", "version": "v1" } ]
2018-04-13
[ [ "Mishra", "Anju", "" ], [ "Sharma", "Shanu", "" ], [ "Kumar", "Sanjay", "" ], [ "Ranjan", "Priya", "" ], [ "Ujlayan", "Amit", "" ] ]
Brain computer interface is the current area of research to provide assistance to disabled persons. To cope up with the growing needs of BCI applications, this paper presents an automated classification scheme for handgrip actions on objects by using Electroencephalography (EEG) data. The presented approach focuses on investigation of classifying correct and incorrect handgrip responses for objects by using EEG recorded patterns. The method starts with preprocessing of data, followed by extraction of relevant features from the epoch data in the form of discrete wavelet transform (DWT), and entropy measures. After computing feature vectors, artificial neural network classifiers used to classify the patterns into correct and incorrect handgrips on different objects. The proposed method was tested on real dataset, which contains EEG recordings from 14 persons. The results showed that the proposed approach is effective and may be useful to develop a variety of BCI based devices to control hand movements.
1003.5839
Arne Traulsen
Chaitanya S. Gokhale and Arne Traulsen
Evolutionary games in the multiverse
null
PNAS 107, 5500-5504 (2010)
10.1073/pnas.0912214107
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Evolutionary game dynamics of two players with two strategies has been studied in great detail. These games have been used to model many biologically relevant scenarios, ranging from social dilemmas in mammals to microbial diversity. Some of these games may in fact take place between a number of individuals and not just between two. Here, we address one-shot games with multiple players. As long as we have only two strategies, many results from two player games can be generalized to multiple players. For games with multiple players and more than two strategies, we show that statements derived for pairwise interactions do no longer hold. For two player games with any number of strategies there can be at most one isolated internal equilibrium. For any number of players $\boldsymbol{d}$ with any number of strategies n, there can be at most (d-1)^(n-1) isolated internal equilibria. Multiplayer games show a great dynamical complexity that cannot be captured based on pairwise interactions. Our results hold for any game and can easily be applied for specific cases, e.g. public goods games or multiplayer stag hunts.
[ { "created": "Tue, 30 Mar 2010 15:05:56 GMT", "version": "v1" } ]
2010-03-31
[ [ "Gokhale", "Chaitanya S.", "" ], [ "Traulsen", "Arne", "" ] ]
Evolutionary game dynamics of two players with two strategies has been studied in great detail. These games have been used to model many biologically relevant scenarios, ranging from social dilemmas in mammals to microbial diversity. Some of these games may in fact take place between a number of individuals and not just between two. Here, we address one-shot games with multiple players. As long as we have only two strategies, many results from two player games can be generalized to multiple players. For games with multiple players and more than two strategies, we show that statements derived for pairwise interactions do no longer hold. For two player games with any number of strategies there can be at most one isolated internal equilibrium. For any number of players $\boldsymbol{d}$ with any number of strategies n, there can be at most (d-1)^(n-1) isolated internal equilibria. Multiplayer games show a great dynamical complexity that cannot be captured based on pairwise interactions. Our results hold for any game and can easily be applied for specific cases, e.g. public goods games or multiplayer stag hunts.
1212.0662
Nicolas Perony
Nicolas Perony, Barbara K\"onig, and Frank Schweitzer
A stochastic model of social interaction in wild house mice
12 pages, 5 figures, 2 tables. Originally published in the Proceedings of the European Conference on Complex Systems 2010 (ECCS'10), Lisbon, September 13-17, 2010
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We investigate to what extent the interaction dynamics of a population of wild house mouse (Mus musculus domesticus) in their environment can be explained by a simple stochastic model. We use a Markov chain model to describe the transitions of mice in a discrete space of nestboxes, and implement a multi-agent simulation of the model. We find that some important features of our behavioural dataset can be reproduced using this simplified stochastic representation, and discuss the improvements that could be made to our model in order to increase the accuracy of its predictions. Our findings have implications for the understanding of the complexity underlying social behaviour in the animal kingdom and the cognitive requirements of such behaviour.
[ { "created": "Tue, 4 Dec 2012 10:07:56 GMT", "version": "v1" } ]
2012-12-05
[ [ "Perony", "Nicolas", "" ], [ "König", "Barbara", "" ], [ "Schweitzer", "Frank", "" ] ]
We investigate to what extent the interaction dynamics of a population of wild house mouse (Mus musculus domesticus) in their environment can be explained by a simple stochastic model. We use a Markov chain model to describe the transitions of mice in a discrete space of nestboxes, and implement a multi-agent simulation of the model. We find that some important features of our behavioural dataset can be reproduced using this simplified stochastic representation, and discuss the improvements that could be made to our model in order to increase the accuracy of its predictions. Our findings have implications for the understanding of the complexity underlying social behaviour in the animal kingdom and the cognitive requirements of such behaviour.
q-bio/0701009
Johannes Wollbold
Johannes Wollbold
Attribute Exploration of Discrete Temporal Transitions
Only the email address and reference have been replaced
In: Gely, A. et al.. Contributions to ICFCA 2007 - 5th International Conference on Formal Concept Analysis. Clermont-Ferrand 2007, 121-130
null
null
q-bio.QM cs.AI q-bio.MN
null
Discrete temporal transitions occur in a variety of domains, but this work is mainly motivated by applications in molecular biology: explaining and analyzing observed transcriptome and proteome time series by literature and database knowledge. The starting point of a formal concept analysis model is presented. The objects of a formal context are states of the interesting entities, and the attributes are the variable properties defining the current state (e.g. observed presence or absence of proteins). Temporal transitions assign a relation to the objects, defined by deterministic or non-deterministic transition rules between sets of pre- and postconditions. This relation can be generalized to its transitive closure, i.e. states are related if one results from the other by a transition sequence of arbitrary length. The focus of the work is the adaptation of the attribute exploration algorithm to such a relational context, so that questions concerning temporal dependencies can be asked during the exploration process and be answered from the computed stem base. Results are given for the abstract example of a game and a small gene regulatory network relevant to a biomedical question.
[ { "created": "Thu, 4 Jan 2007 14:10:51 GMT", "version": "v1" }, { "created": "Tue, 18 Sep 2007 08:46:00 GMT", "version": "v2" } ]
2007-09-18
[ [ "Wollbold", "Johannes", "" ] ]
Discrete temporal transitions occur in a variety of domains, but this work is mainly motivated by applications in molecular biology: explaining and analyzing observed transcriptome and proteome time series by literature and database knowledge. The starting point of a formal concept analysis model is presented. The objects of a formal context are states of the interesting entities, and the attributes are the variable properties defining the current state (e.g. observed presence or absence of proteins). Temporal transitions assign a relation to the objects, defined by deterministic or non-deterministic transition rules between sets of pre- and postconditions. This relation can be generalized to its transitive closure, i.e. states are related if one results from the other by a transition sequence of arbitrary length. The focus of the work is the adaptation of the attribute exploration algorithm to such a relational context, so that questions concerning temporal dependencies can be asked during the exploration process and be answered from the computed stem base. Results are given for the abstract example of a game and a small gene regulatory network relevant to a biomedical question.
1810.06831
Andrew Francis
Michael Hendriksen and Andrew Francis
Lattice consensus: A partial order on phylogenetic trees that induces an associatively stable consensus method
The paper has an error in the proof of Theorem 5.3, and this affects 5.4, which is incorrect (there is a counterexample to the Theorem statement). As a consequence the results in Section 6 about a consensus method are vacuous. Some results in the paper stand, for instance the results in Sections 2, 3, 4, and 7
null
null
null
q-bio.PE math.CO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
There is a long tradition of the axiomatic study of consensus methods in phylogenetics that satisfy certain desirable properties. One recently-introduced property is associative stability, which is desirable because it confers a computational advantage, in that the consensus method only needs to be computed "pairwise". In this paper, we introduce a phylogenetic consensus method that satisfies this property, in addition to being "regular". The method is based on the introduction of a partial order on the set of rooted phylogenetic trees, itself based on the notion of a hierarchy-preserving map between trees. This partial order may be of independent interest. We call the method "lattice consensus", because it takes the unique maximal element in a lattice of trees defined by the partial order. Aside from being associatively stable, lattice consensus also satisfies the property of being Pareto on rooted triples, answering in the affirmative a question of Bryant et al (2017). We conclude the paper with an answer to another question of Bryant et al, showing that there is no regular extension stable consensus method for binary trees.
[ { "created": "Tue, 16 Oct 2018 06:26:40 GMT", "version": "v1" }, { "created": "Fri, 19 Oct 2018 07:14:08 GMT", "version": "v2" } ]
2018-10-22
[ [ "Hendriksen", "Michael", "" ], [ "Francis", "Andrew", "" ] ]
There is a long tradition of the axiomatic study of consensus methods in phylogenetics that satisfy certain desirable properties. One recently-introduced property is associative stability, which is desirable because it confers a computational advantage, in that the consensus method only needs to be computed "pairwise". In this paper, we introduce a phylogenetic consensus method that satisfies this property, in addition to being "regular". The method is based on the introduction of a partial order on the set of rooted phylogenetic trees, itself based on the notion of a hierarchy-preserving map between trees. This partial order may be of independent interest. We call the method "lattice consensus", because it takes the unique maximal element in a lattice of trees defined by the partial order. Aside from being associatively stable, lattice consensus also satisfies the property of being Pareto on rooted triples, answering in the affirmative a question of Bryant et al (2017). We conclude the paper with an answer to another question of Bryant et al, showing that there is no regular extension stable consensus method for binary trees.
2012.02246
Gabriel Schamberg
Gabriel Schamberg, Sourish Chakravarty, Taylor E. Baum, Emery N. Brown
Inferring neural dynamics during burst suppression using a neurophysiology-inspired switching state-space model
To appear in the proceedings of the 2020 IEEE Asilomar Conference on Signals, Systems, and Computers
null
null
null
q-bio.QM q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Burst suppression is an electroencephalography (EEG) pattern associated with profoundly inactivated brain states characterized by cerebral metabolic depression. Its distinctive feature is alternation between short temporal segments of near-isoelectric inactivity (suppressions) and relatively high-voltage activity (bursts). Prior modeling studies suggest that burst-suppression EEG is a manifestation of two alternating brain states associated with consumption (during a burst) and production (during a suppression) of adenosine triphosphate (ATP). This finding motivates us to infer latent states characterizing alternating brain states and underlying ATP kinetics from instantaneous power of multichannel EEG using a switching state-space model. Our model assumes Gaussian distributed data as a broadcast network manifestation of one of two global brain states. The two brain states are allowed to stochastically alternate with transition probabilities that depend on the instantaneous ATP level, which evolves according to first-order kinetics. The rate constants governing the ATP kinetics are allowed to vary as first-order autoregressive processes. Our latent state estimates are determined from data using a sequential Monte Carlo algorithm. Our neurophysiology-informed model not only provides unsupervised segmentation of multi-channel burst-suppression EEG but can also generate additional insights on the level of brain inactivation during anesthesia.
[ { "created": "Thu, 3 Dec 2020 20:30:46 GMT", "version": "v1" } ]
2020-12-07
[ [ "Schamberg", "Gabriel", "" ], [ "Chakravarty", "Sourish", "" ], [ "Baum", "Taylor E.", "" ], [ "Brown", "Emery N.", "" ] ]
Burst suppression is an electroencephalography (EEG) pattern associated with profoundly inactivated brain states characterized by cerebral metabolic depression. Its distinctive feature is alternation between short temporal segments of near-isoelectric inactivity (suppressions) and relatively high-voltage activity (bursts). Prior modeling studies suggest that burst-suppression EEG is a manifestation of two alternating brain states associated with consumption (during a burst) and production (during a suppression) of adenosine triphosphate (ATP). This finding motivates us to infer latent states characterizing alternating brain states and underlying ATP kinetics from instantaneous power of multichannel EEG using a switching state-space model. Our model assumes Gaussian distributed data as a broadcast network manifestation of one of two global brain states. The two brain states are allowed to stochastically alternate with transition probabilities that depend on the instantaneous ATP level, which evolves according to first-order kinetics. The rate constants governing the ATP kinetics are allowed to vary as first-order autoregressive processes. Our latent state estimates are determined from data using a sequential Monte Carlo algorithm. Our neurophysiology-informed model not only provides unsupervised segmentation of multi-channel burst-suppression EEG but can also generate additional insights on the level of brain inactivation during anesthesia.
2007.03157
Shiladitya Banerjee
Jake Cornwall Scoones, Deb Sankar Banerjee, Shiladitya Banerjee
Size-regulated symmetry breaking in reaction-diffusion models of developmental transitions
11 pages, 5 figures, Perspective Article
null
null
null
q-bio.TO nlin.PS physics.bio-ph
http://creativecommons.org/licenses/by/4.0/
The development of multicellular organisms proceeds through a series of morphogenetic and cell-state transitions, transforming homogeneous zygotes into complex adults by a process of self-organization. Many of these transitions are achieved by spontaneous symmetry breaking mechanisms, allowing cells and tissues to acquire pattern and polarity by virtue of local interactions without an upstream supply of information. The combined work of theory and experiment has elucidated how these systems break symmetry during developmental transitions. Given such transitions are multiple and their temporal ordering is crucial, an equally important question is how these developmental transitions are coordinated in time. Using a minimal mass-conserved substrate-depletion model for symmetry breaking as our case study, we elucidate mechanisms by which cells and tissues can couple reaction-diffusion driven symmetry breaking to the timing of developmental transitions, arguing that the dependence of patterning mode on system size may be a generic principle by which developing organisms measure time. By analyzing different regimes of our model, simulated on growing domains, we elaborate three distinct behaviours, allowing for clock-, timer-, or switch-like dynamics. By relating these behaviours to experimentally documented case studies of developmental timing, we provide a minimal conceptual framework to interrogate how developing organisms coordinate developmental transitions.
[ { "created": "Tue, 7 Jul 2020 01:29:09 GMT", "version": "v1" } ]
2020-07-08
[ [ "Scoones", "Jake Cornwall", "" ], [ "Banerjee", "Deb Sankar", "" ], [ "Banerjee", "Shiladitya", "" ] ]
The development of multicellular organisms proceeds through a series of morphogenetic and cell-state transitions, transforming homogeneous zygotes into complex adults by a process of self-organization. Many of these transitions are achieved by spontaneous symmetry breaking mechanisms, allowing cells and tissues to acquire pattern and polarity by virtue of local interactions without an upstream supply of information. The combined work of theory and experiment has elucidated how these systems break symmetry during developmental transitions. Given such transitions are multiple and their temporal ordering is crucial, an equally important question is how these developmental transitions are coordinated in time. Using a minimal mass-conserved substrate-depletion model for symmetry breaking as our case study, we elucidate mechanisms by which cells and tissues can couple reaction-diffusion driven symmetry breaking to the timing of developmental transitions, arguing that the dependence of patterning mode on system size may be a generic principle by which developing organisms measure time. By analyzing different regimes of our model, simulated on growing domains, we elaborate three distinct behaviours, allowing for clock-, timer-, or switch-like dynamics. By relating these behaviours to experimentally documented case studies of developmental timing, we provide a minimal conceptual framework to interrogate how developing organisms coordinate developmental transitions.
2308.05685
Netta Haroush
Netta Haroush, Michal Levo, Eric Wieschaus and Thomas Gregor
Functional analysis of a gene locus in response to non-canonical combinations of transcription factors
null
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Transcription factor combinations determine gene locus activity and thereby cell identity. However, the precise link between concentrations of such activating transcription factors and target-gene activity is ambiguous. Here we investigate this link for the gap gene dependent activation of the even-skipped (eve) locus in the Drosophila embryo. We simultaneously measure the spatiotemporal gap gene concentrations in hemizygous and homozygous gap mutants, and link these to eve activity. Although changes in expression extend well beyond the genetically manipulated gene, nearly all expression alternations approximate the canonical combinations of activating levels in wild-type, sometimes necessitating pattern shifts. Expression levels that diverge from the wild-type repertoire still drive locus activation. Specific stripes in the homozygous mutants show partial penetrance, justifying their renown variable phenotypes. However, all eve stripes appear at highly reproducible positions, even though a broader span of gap gene expression levels activates eve. Our results suggest a correction capacity of the gap gene network and set constraints on the activity of multi-enhancer gene loci.
[ { "created": "Thu, 10 Aug 2023 16:38:59 GMT", "version": "v1" } ]
2023-08-11
[ [ "Haroush", "Netta", "" ], [ "Levo", "Michal", "" ], [ "Wieschaus", "Eric", "" ], [ "Gregor", "Thomas", "" ] ]
Transcription factor combinations determine gene locus activity and thereby cell identity. However, the precise link between concentrations of such activating transcription factors and target-gene activity is ambiguous. Here we investigate this link for the gap gene dependent activation of the even-skipped (eve) locus in the Drosophila embryo. We simultaneously measure the spatiotemporal gap gene concentrations in hemizygous and homozygous gap mutants, and link these to eve activity. Although changes in expression extend well beyond the genetically manipulated gene, nearly all expression alternations approximate the canonical combinations of activating levels in wild-type, sometimes necessitating pattern shifts. Expression levels that diverge from the wild-type repertoire still drive locus activation. Specific stripes in the homozygous mutants show partial penetrance, justifying their renown variable phenotypes. However, all eve stripes appear at highly reproducible positions, even though a broader span of gap gene expression levels activates eve. Our results suggest a correction capacity of the gap gene network and set constraints on the activity of multi-enhancer gene loci.
1602.05177
Olivier Sperandio
G Moroy (UMR S973, UP7), O Sperandio (UMR S973, UP7), S Rielland (UMR S973, UP7), S Khemka (LBPA), K Druart (UMR S973, UP7), D. Goyal (LBPA), D. Perahia (LBPA), M. A. Miteva (UMR S973, UP7)
Sampling of conformational ensemble for virtual screening using molecular dynamics simulations and normal mode analysis
null
Future Medicinal Chemistry, 2015, 7 (17), pp.2317-2331
10.4155/fmc.15.150
null
q-bio.QM q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Aim: Molecular dynamics simulations and normal mode analysis are well-established approaches to generate receptor conformational ensembles (RCEs) for ligand docking and virtual screening. Here, we report new fast molecular dynamics-based and normal mode analysis-based protocols combined with conformational pocket classifications to efficiently generate RCEs. Materials \& methods: We assessed our protocols on two well-characterized protein targets showing local active site flexibility, dihydrofolate reductase and large collective movements, CDK2. The performance of the RCEs was validated by distinguishing known ligands of dihydrofolate reductase and CDK2 among a dataset of diverse chemical decoys. Results \& discussion: Our results show that different simulation protocols can be efficient for generation of RCEs depending on different kind of protein flexibility.
[ { "created": "Tue, 16 Feb 2016 20:42:10 GMT", "version": "v1" } ]
2016-02-17
[ [ "Moroy", "G", "", "UMR S973, UP7" ], [ "Sperandio", "O", "", "UMR S973, UP7" ], [ "Rielland", "S", "", "UMR\n S973, UP7" ], [ "Khemka", "S", "", "LBPA" ], [ "Druart", "K", "", "UMR S973, UP7" ], [ "Goyal", "D.", "", "LBPA" ], [ "Perahia", "D.", "", "LBPA" ], [ "Miteva", "M. A.", "", "UMR S973, UP7" ] ]
Aim: Molecular dynamics simulations and normal mode analysis are well-established approaches to generate receptor conformational ensembles (RCEs) for ligand docking and virtual screening. Here, we report new fast molecular dynamics-based and normal mode analysis-based protocols combined with conformational pocket classifications to efficiently generate RCEs. Materials \& methods: We assessed our protocols on two well-characterized protein targets showing local active site flexibility, dihydrofolate reductase and large collective movements, CDK2. The performance of the RCEs was validated by distinguishing known ligands of dihydrofolate reductase and CDK2 among a dataset of diverse chemical decoys. Results \& discussion: Our results show that different simulation protocols can be efficient for generation of RCEs depending on different kind of protein flexibility.
2310.13598
Laurent Gatto
Samuel Gr\'egoire and Christophe Vanderaa and S\'ebastien Pyr dit Ruys and Gabriel Mazzucchelli and Christopher Kune and Didier Vertommen and Laurent Gatto
Standardised workflow for mass spectrometry-based single-cell proteomics data processing and analysis using the scp package
null
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by-sa/4.0/
Mass spectrometry (MS) based single-cell proteomics (SCP) explores cellular heterogeneity by focusing on the functional effectors of the cells - proteins. However, extracting meaningful biological information from MS data is far from trivial, especially with single cells. Currently, data analysis workflows are substantially different from one research team to another. Moreover,it is difficult to evaluate pipelines as ground truths are missing. Our team has developed the R/Bioconductor package called scp to provide a standardised framework for SCP data analysis. It relies on the widely used QFeatures and SingleCellExperiment data structures. In addition, we used a design containing cell lines mixed in known proportions to generate controlled variability for data analysis benchmarking. In this work, we provide a flexible data analysis protocol for SCP data using the scp package together with comprehensive explanations at each step of the processing. Our main steps are quality control on the feature and cell level, aggregation of the raw data into peptides and proteins, normalisation and batch correction. We validate our workflow using our ground truth data set. We illustrate how to use this modular, standardised framework and highlight some crucial steps.
[ { "created": "Fri, 20 Oct 2023 15:46:51 GMT", "version": "v1" }, { "created": "Wed, 13 Dec 2023 16:47:50 GMT", "version": "v2" } ]
2023-12-14
[ [ "Grégoire", "Samuel", "" ], [ "Vanderaa", "Christophe", "" ], [ "Ruys", "Sébastien Pyr dit", "" ], [ "Mazzucchelli", "Gabriel", "" ], [ "Kune", "Christopher", "" ], [ "Vertommen", "Didier", "" ], [ "Gatto", "Laurent", "" ] ]
Mass spectrometry (MS) based single-cell proteomics (SCP) explores cellular heterogeneity by focusing on the functional effectors of the cells - proteins. However, extracting meaningful biological information from MS data is far from trivial, especially with single cells. Currently, data analysis workflows are substantially different from one research team to another. Moreover,it is difficult to evaluate pipelines as ground truths are missing. Our team has developed the R/Bioconductor package called scp to provide a standardised framework for SCP data analysis. It relies on the widely used QFeatures and SingleCellExperiment data structures. In addition, we used a design containing cell lines mixed in known proportions to generate controlled variability for data analysis benchmarking. In this work, we provide a flexible data analysis protocol for SCP data using the scp package together with comprehensive explanations at each step of the processing. Our main steps are quality control on the feature and cell level, aggregation of the raw data into peptides and proteins, normalisation and batch correction. We validate our workflow using our ground truth data set. We illustrate how to use this modular, standardised framework and highlight some crucial steps.
2012.03720
Leon Avery
Leon Avery, Brian Ingalls, Catherine Dumur, Alexander Artyukhin
A Keller-Segel model for C elegans L1 aggregation
null
null
10.1371/journal.pcbi.1009231
null
q-bio.MN q-bio.QM
http://creativecommons.org/licenses/by-sa/4.0/
We describe a mathematical model for the aggregation of starved first-stage C elegans larvae (L1s). We propose that starved L1s produce and respond chemotactically to two labile diffusible chemical signals, a short-range attractant and a longer range repellent. This model takes the mathematical form of three coupled partial differential equations, one that describes the movement of the worms and one for each of the chemical signals. Numerical solution of these equations produced a pattern of aggregates that resembled that of worm aggregates observed in experiments. We also describe the identification of a sensory receptor gene, srh-2, whose expression is induced under conditions that promote L1 aggregation. Worms whose srh-2 gene has been knocked out form irregularly shaped aggregates. Our model suggests this phenotype may be explained by the mutant worms slowing their movement more quickly than the wild type.
[ { "created": "Fri, 4 Dec 2020 17:27:23 GMT", "version": "v1" }, { "created": "Fri, 7 May 2021 16:03:43 GMT", "version": "v2" } ]
2021-09-15
[ [ "Avery", "Leon", "" ], [ "Ingalls", "Brian", "" ], [ "Dumur", "Catherine", "" ], [ "Artyukhin", "Alexander", "" ] ]
We describe a mathematical model for the aggregation of starved first-stage C elegans larvae (L1s). We propose that starved L1s produce and respond chemotactically to two labile diffusible chemical signals, a short-range attractant and a longer range repellent. This model takes the mathematical form of three coupled partial differential equations, one that describes the movement of the worms and one for each of the chemical signals. Numerical solution of these equations produced a pattern of aggregates that resembled that of worm aggregates observed in experiments. We also describe the identification of a sensory receptor gene, srh-2, whose expression is induced under conditions that promote L1 aggregation. Worms whose srh-2 gene has been knocked out form irregularly shaped aggregates. Our model suggests this phenotype may be explained by the mutant worms slowing their movement more quickly than the wild type.
1111.2019
Santiago Ra\'ul Doyle
Santiago R. Doyle, Florencia Carusela, Sebasti\'an Guala and Fernando Momo
A null model for testing thermodynamic optimization in ecological systems
null
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Several authors have hypothesized that ecological systems are subject to thermodynamic optimization, which, if proven correct, could represent a long sought general principle of organization in ecology. Although there have been recent advances, this still remains as an unresolved topic, and ecologists lack a general method to test thermodynamic optimization hypotheses in specific systems. Here we present a general, novel approach that allows generating a null model for testing thermodynamic optimization on ecological systems. We first describe the general methodology, which is based in the analysis of a parametrized mathematical model of the system and the explicit consideration of constraints. Next we present an application example to an animal population using a general age-structured population model and physiological parameters from the literature. We finalize discussing the relevance of this work in the context of the current state of ecology, and implications for the further development of a thermodynamic ecological theory.
[ { "created": "Tue, 8 Nov 2011 19:14:37 GMT", "version": "v1" } ]
2011-11-09
[ [ "Doyle", "Santiago R.", "" ], [ "Carusela", "Florencia", "" ], [ "Guala", "Sebastián", "" ], [ "Momo", "Fernando", "" ] ]
Several authors have hypothesized that ecological systems are subject to thermodynamic optimization, which, if proven correct, could represent a long sought general principle of organization in ecology. Although there have been recent advances, this still remains as an unresolved topic, and ecologists lack a general method to test thermodynamic optimization hypotheses in specific systems. Here we present a general, novel approach that allows generating a null model for testing thermodynamic optimization on ecological systems. We first describe the general methodology, which is based in the analysis of a parametrized mathematical model of the system and the explicit consideration of constraints. Next we present an application example to an animal population using a general age-structured population model and physiological parameters from the literature. We finalize discussing the relevance of this work in the context of the current state of ecology, and implications for the further development of a thermodynamic ecological theory.
2102.00002
Elvira Di Nardo Prof.
A. Buonocore, A. Di Crescenzo, E. Di Nardo
Input-output behaviour of a model neuron with alternating drift
null
BioSystems (2002) 67, 27-34
10.1016/S0303-2647(02)00060-6
null
q-bio.NC math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The input-output behaviour of the Wiener neuronal model subject to alternating input is studied under the assumption that the effect of such an input is to make the drift itself of an alternating type. Firing densities and related statistics are obtained via simulations of the sample-paths of the process in the following three cases: the drift changes occur during random periods characterized by (i) exponential distribution, (ii) Erlang distribution with a preassigned shape parameter, and (iii) deterministic distribution. The obtained results are compared with those holding for the Wiener neuronal model subject to sinusoidal input
[ { "created": "Sun, 31 Jan 2021 16:30:22 GMT", "version": "v1" } ]
2021-02-02
[ [ "Buonocore", "A.", "" ], [ "Di Crescenzo", "A.", "" ], [ "Di Nardo", "E.", "" ] ]
The input-output behaviour of the Wiener neuronal model subject to alternating input is studied under the assumption that the effect of such an input is to make the drift itself of an alternating type. Firing densities and related statistics are obtained via simulations of the sample-paths of the process in the following three cases: the drift changes occur during random periods characterized by (i) exponential distribution, (ii) Erlang distribution with a preassigned shape parameter, and (iii) deterministic distribution. The obtained results are compared with those holding for the Wiener neuronal model subject to sinusoidal input
0801.3675
Paolo Ribeca
Paolo Ribeca and Emanuele Raineri
Faster exact Markovian probability functions for motif occurrences: a DFA-only approach
18 pages, 7 figures and 2 tables
null
10.1093/bioinformatics/btn525
null
q-bio.GN q-bio.QM
null
Background: The computation of the statistical properties of motif occurrences has an obviously relevant practical application: for example, patterns that are significantly over- or under-represented in the genome are interesting candidates for biological roles. However, the problem is computationally hard; as a result, virtually all the existing pipelines use fast but approximate scoring functions, in spite of the fact that they have been shown to systematically produce incorrect results. A few interesting exact approaches are known, but they are very slow and hence not practical in the case of realistic sequences. Results: We give an exact solution, solely based on deterministic finite-state automata (DFAs), to the problem of finding not only the p-value, but the whole relevant part of the Markovian probability distribution function of a motif in a biological sequence. In particular, the time complexity of the algorithm in the most interesting regimes is far better than that of Nuel (2006), which was the fastest similar exact algorithm known to date; in many cases, even approximate methods are outperformed. Conclusions: DFAs are a standard tool of computer science for the study of patterns, but so far they have been sparingly used in the study of biological motifs. Previous works do propose algorithms involving automata, but there they are used respectively as a first step to build a Finite Markov Chain Imbedding (FMCI), or to write a generating function: whereas we only rely on the concept of DFA to perform the calculations. This innovative approach can realistically be used for exact statistical studies of very long genomes and protein sequences, as we illustrate with some examples on the scale of the human genome.
[ { "created": "Thu, 24 Jan 2008 15:39:48 GMT", "version": "v1" } ]
2021-11-01
[ [ "Ribeca", "Paolo", "" ], [ "Raineri", "Emanuele", "" ] ]
Background: The computation of the statistical properties of motif occurrences has an obviously relevant practical application: for example, patterns that are significantly over- or under-represented in the genome are interesting candidates for biological roles. However, the problem is computationally hard; as a result, virtually all the existing pipelines use fast but approximate scoring functions, in spite of the fact that they have been shown to systematically produce incorrect results. A few interesting exact approaches are known, but they are very slow and hence not practical in the case of realistic sequences. Results: We give an exact solution, solely based on deterministic finite-state automata (DFAs), to the problem of finding not only the p-value, but the whole relevant part of the Markovian probability distribution function of a motif in a biological sequence. In particular, the time complexity of the algorithm in the most interesting regimes is far better than that of Nuel (2006), which was the fastest similar exact algorithm known to date; in many cases, even approximate methods are outperformed. Conclusions: DFAs are a standard tool of computer science for the study of patterns, but so far they have been sparingly used in the study of biological motifs. Previous works do propose algorithms involving automata, but there they are used respectively as a first step to build a Finite Markov Chain Imbedding (FMCI), or to write a generating function: whereas we only rely on the concept of DFA to perform the calculations. This innovative approach can realistically be used for exact statistical studies of very long genomes and protein sequences, as we illustrate with some examples on the scale of the human genome.
1112.3640
Christopher L. Henley
Hanrong Chen, C. L. Henley, and B. Xu
Propagating left/right asymmetry in the zebrafish embryo: one-dimensional model
13 pages, 5 figures
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
During embryonic development in vertebrates, left-right (L/R) asymmetry is reliably generated by a conserved mechanism: a L/R asymmetric signal is transmitted from the embryonic node to other parts of the embryo by the L/R asymmetric expression and diffusion of the TGF-$\beta$ related proteins Nodal and Lefty via propagating gene expression fronts in the lateral plate mesoderm (LPM) and midline. In zebrafish embryos, Nodal and Lefty expression can only occur along 3 narrow stripes that express the co-receptor \emph{one-eyed pinhead} (oep): Nodal along stripes in the left and right LPM, and Lefty along the midline. In wild-type embryos, Nodal is only expressed in the left LPM but not the right, because of inhibition by Lefty from the midline; however, bilateral Nodal expression occurs in loss-of-handedness mutants. A two-dimensional model of the zebrafish embryo predicts this loss of L/R asymmetry in oep mutants \cite{henley-xu-burdine}. In this paper, we simplify this two-dimensional picture to a one-dimensional model of Nodal and Lefty front propagation along the oep-expressing stripes. We represent Nodal and Lefty production by step functions that turn on when a linear function of Nodal and Lefty densities crosses a threshold. We do a parameter exploration of front propagation behavior, and find the existence of \emph{pinned} intervals, along which the linear function underlying production is pinned to the threshold. Finally, we find parameter regimes for which spatially uniform oscillating solutions are possible.
[ { "created": "Thu, 15 Dec 2011 20:29:10 GMT", "version": "v1" } ]
2011-12-16
[ [ "Chen", "Hanrong", "" ], [ "Henley", "C. L.", "" ], [ "Xu", "B.", "" ] ]
During embryonic development in vertebrates, left-right (L/R) asymmetry is reliably generated by a conserved mechanism: a L/R asymmetric signal is transmitted from the embryonic node to other parts of the embryo by the L/R asymmetric expression and diffusion of the TGF-$\beta$ related proteins Nodal and Lefty via propagating gene expression fronts in the lateral plate mesoderm (LPM) and midline. In zebrafish embryos, Nodal and Lefty expression can only occur along 3 narrow stripes that express the co-receptor \emph{one-eyed pinhead} (oep): Nodal along stripes in the left and right LPM, and Lefty along the midline. In wild-type embryos, Nodal is only expressed in the left LPM but not the right, because of inhibition by Lefty from the midline; however, bilateral Nodal expression occurs in loss-of-handedness mutants. A two-dimensional model of the zebrafish embryo predicts this loss of L/R asymmetry in oep mutants \cite{henley-xu-burdine}. In this paper, we simplify this two-dimensional picture to a one-dimensional model of Nodal and Lefty front propagation along the oep-expressing stripes. We represent Nodal and Lefty production by step functions that turn on when a linear function of Nodal and Lefty densities crosses a threshold. We do a parameter exploration of front propagation behavior, and find the existence of \emph{pinned} intervals, along which the linear function underlying production is pinned to the threshold. Finally, we find parameter regimes for which spatially uniform oscillating solutions are possible.
1311.5517
Helene Hill
Joel H Pitt and Helene Z Hill
Statistical Detection of Potentially Fabricated Data
31 pages of text including 2 figures, 3 tables and an Appendix containing the mathematical derivation of a model for detecting and quantifying the probability for the occurrence of the average of 3 counts as one of those counts. 166 pages of raw data that were used in the analyses
null
null
null
q-bio.QM stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Scientific fraud is an increasingly vexing problem. Many current programs for fraud detection focus on image manipulation, while techniques for detection based on anomalous patterns that may be discoverable in the underlying numerical data get much less attention, even though these techniques are often easy to apply. We employed three such techniques in a case study in which we considered data sets from several hundred experiments. We compared patterns in the data sets from one research teaching specialist (RTS), to those of 9 other members of the same laboratory and from 3 outside laboratories. Application of two conventional statistical tests and a newly developed test for anomalous patterns in the triplicate data commonly produced in such research to various data sets reported by the RTS resulted in repeated rejection of the hypotheses (often at p-levels well below 0.001) that anomalous patterns in his data may have occurred by chance. This analysis emphasizes the importance of access to raw data that form the bases of publications, reports and grant applications in order to evaluate the correctness of the conclusions, as well as the utility of methods for detecting anomalous, especially fabricated, numerical results.
[ { "created": "Thu, 21 Nov 2013 19:03:55 GMT", "version": "v1" } ]
2013-11-22
[ [ "Pitt", "Joel H", "" ], [ "Hill", "Helene Z", "" ] ]
Scientific fraud is an increasingly vexing problem. Many current programs for fraud detection focus on image manipulation, while techniques for detection based on anomalous patterns that may be discoverable in the underlying numerical data get much less attention, even though these techniques are often easy to apply. We employed three such techniques in a case study in which we considered data sets from several hundred experiments. We compared patterns in the data sets from one research teaching specialist (RTS), to those of 9 other members of the same laboratory and from 3 outside laboratories. Application of two conventional statistical tests and a newly developed test for anomalous patterns in the triplicate data commonly produced in such research to various data sets reported by the RTS resulted in repeated rejection of the hypotheses (often at p-levels well below 0.001) that anomalous patterns in his data may have occurred by chance. This analysis emphasizes the importance of access to raw data that form the bases of publications, reports and grant applications in order to evaluate the correctness of the conclusions, as well as the utility of methods for detecting anomalous, especially fabricated, numerical results.
2302.12455
Eitan Lerner
Evelyn Ploetz, Benjamin Ambrose, Anders Barth, Richard B\"orner, Felix Erichson, Achillefs N. Kapanidis, Harold D. Kim, Marcia Levitus, Timothy M. Lohman, Abhishek Mazumder, David S. Rueda, Fabio D. Steffen, Thorben Cordes, Steven W. Magennis and Eitan Lerner
A new twist on PIFE: photoisomerisation-related fluorescence enhancement
No Comments
null
10.1088/2050-6120/acfb58
null
q-bio.BM q-bio.QM
http://creativecommons.org/licenses/by-nc-nd/4.0/
PIFE was first used as an acronym for protein-induced fluorescence enhancement, which refers to the increase in fluorescence observed upon the interaction of a fluorophore, such as a cyanine, with a protein. This fluorescence enhancement is due to changes in the rate of cis/trans photoisomerisation. It is clear now that this mechanism is generally applicable to interactions with any biomolecule and, in this review, we propose that PIFE is thereby renamed according to its fundamental working principle as photoisomerisation-related fluorescence enhancement, keeping the PIFE acronym intact. We discuss the photochemistry of cyanine fluorophores, the mechanism of PIFE, its advantages and limitations, and recent approaches to turn PIFE into a quantitative assay. We provide an overview of its current applications to different biomolecules and discuss potential future uses, including the study of protein-protein interactions, protein-ligand interactions and conformational changes in biomolecules.
[ { "created": "Fri, 24 Feb 2023 05:11:25 GMT", "version": "v1" }, { "created": "Mon, 10 Jul 2023 10:01:48 GMT", "version": "v2" } ]
2023-10-24
[ [ "Ploetz", "Evelyn", "" ], [ "Ambrose", "Benjamin", "" ], [ "Barth", "Anders", "" ], [ "Börner", "Richard", "" ], [ "Erichson", "Felix", "" ], [ "Kapanidis", "Achillefs N.", "" ], [ "Kim", "Harold D.", "" ], [ "Levitus", "Marcia", "" ], [ "Lohman", "Timothy M.", "" ], [ "Mazumder", "Abhishek", "" ], [ "Rueda", "David S.", "" ], [ "Steffen", "Fabio D.", "" ], [ "Cordes", "Thorben", "" ], [ "Magennis", "Steven W.", "" ], [ "Lerner", "Eitan", "" ] ]
PIFE was first used as an acronym for protein-induced fluorescence enhancement, which refers to the increase in fluorescence observed upon the interaction of a fluorophore, such as a cyanine, with a protein. This fluorescence enhancement is due to changes in the rate of cis/trans photoisomerisation. It is clear now that this mechanism is generally applicable to interactions with any biomolecule and, in this review, we propose that PIFE is thereby renamed according to its fundamental working principle as photoisomerisation-related fluorescence enhancement, keeping the PIFE acronym intact. We discuss the photochemistry of cyanine fluorophores, the mechanism of PIFE, its advantages and limitations, and recent approaches to turn PIFE into a quantitative assay. We provide an overview of its current applications to different biomolecules and discuss potential future uses, including the study of protein-protein interactions, protein-ligand interactions and conformational changes in biomolecules.
1305.4354
Steven Frank
Steven A. Frank
Natural selection. VII. History and interpretation of kin selection theory
null
null
10.1111/jeb.12131
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Kin selection theory is a kind of causal analysis. The initial form of kin selection ascribed cause to costs, benefits, and genetic relatedness. The theory then slowly developed a deeper and more sophisticated approach to partitioning the causes of social evolution. Controversy followed because causal analysis inevitably attracts opposing views. It is always possible to separate total effects into different component causes. Alternative causal schemes emphasize different aspects of a problem, reflecting the distinct goals, interests, and biases of different perspectives. For example, group selection is a particular causal scheme with certain advantages and significant limitations. Ultimately, to use kin selection theory to analyze natural patterns and to understand the history of debates over different approaches, one must follow the underlying history of causal analysis. This article describes the history of kin selection theory, with emphasis on how the causal perspective improved through the study of key patterns of natural history, such as dispersal and sex ratio, and through a unified approach to demographic and social processes. Independent historical developments in the multivariate analysis of quantitative traits merged with the causal analysis of social evolution by kin selection.
[ { "created": "Sun, 19 May 2013 12:18:53 GMT", "version": "v1" } ]
2014-06-18
[ [ "Frank", "Steven A.", "" ] ]
Kin selection theory is a kind of causal analysis. The initial form of kin selection ascribed cause to costs, benefits, and genetic relatedness. The theory then slowly developed a deeper and more sophisticated approach to partitioning the causes of social evolution. Controversy followed because causal analysis inevitably attracts opposing views. It is always possible to separate total effects into different component causes. Alternative causal schemes emphasize different aspects of a problem, reflecting the distinct goals, interests, and biases of different perspectives. For example, group selection is a particular causal scheme with certain advantages and significant limitations. Ultimately, to use kin selection theory to analyze natural patterns and to understand the history of debates over different approaches, one must follow the underlying history of causal analysis. This article describes the history of kin selection theory, with emphasis on how the causal perspective improved through the study of key patterns of natural history, such as dispersal and sex ratio, and through a unified approach to demographic and social processes. Independent historical developments in the multivariate analysis of quantitative traits merged with the causal analysis of social evolution by kin selection.
1409.4404
Almaz Mustafin
Almaz Mustafin
Awakened oscillations in coupled consumer-resource pairs
31 pages, 8 figures 2 tables, 48 references
Journal of Applied Mathematics 2014 (2014), Article ID 561958, pages 1-20
10.1155/2014/561958
null
q-bio.PE nlin.AO physics.optics
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The paper concerns two interacting consumer-resource pairs based on chemostat-like equations under the assumption that the dynamics of the resource is considerably slower than that of the consumer. The presence of two different time scales enables to carry out a fairly complete analysis of the problem. This is done by treating consumers and resources in the coupled system as fast-scale and slow-scale variables respectively and subsequently considering developments in phase planes of these variables, fast and slow, as if they are independent. When uncoupled, each pair has unique asymptotically stable steady state and no self-sustained oscillatory behavior (although damped oscillations about the equilibrium are admitted). When the consumer-resource pairs are weakly coupled through direct reciprocal inhibition of consumers, the whole system exhibits self-sustained relaxation oscillations with a period that can be significantly longer than intrinsic relaxation time of either pair. It is shown that the model equations adequately describe locally linked consumer-resource systems of quite different nature: living populations under interspecific interference competition and lasers coupled via their cavity losses.
[ { "created": "Sun, 14 Sep 2014 07:32:22 GMT", "version": "v1" } ]
2014-09-17
[ [ "Mustafin", "Almaz", "" ] ]
The paper concerns two interacting consumer-resource pairs based on chemostat-like equations under the assumption that the dynamics of the resource is considerably slower than that of the consumer. The presence of two different time scales enables to carry out a fairly complete analysis of the problem. This is done by treating consumers and resources in the coupled system as fast-scale and slow-scale variables respectively and subsequently considering developments in phase planes of these variables, fast and slow, as if they are independent. When uncoupled, each pair has unique asymptotically stable steady state and no self-sustained oscillatory behavior (although damped oscillations about the equilibrium are admitted). When the consumer-resource pairs are weakly coupled through direct reciprocal inhibition of consumers, the whole system exhibits self-sustained relaxation oscillations with a period that can be significantly longer than intrinsic relaxation time of either pair. It is shown that the model equations adequately describe locally linked consumer-resource systems of quite different nature: living populations under interspecific interference competition and lasers coupled via their cavity losses.
2012.00281
Muriel Gros-Balthazard
Muriel Gros-Balthazard and Jonathan M. Flowers
A brief history of the origin of domesticated date palms
null
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
The study of the origins of crops is of interest from both a fundamental evolutionary understanding viewpoint, and from an applied agricultural technology perspective. The date palm (Phoenix dactylifera L.) is the iconic fruit crop of hot and arid regions of North Africa and the Middle East, producing sugar-rich fruits, known as dates. There are many different cultivars each with distinctive fruit traits, and there are many wild Phoenix species too, which in total form a complex of related species. The understanding of plant domestication involves multiple disciplines, including phylogeography, population genetics and archaeology. In the past decade, they have prompted new discoveries on the evolutionary history of date palm, but a complete understanding of its origins remains to be elucidated, along with the genetic architecture of its domestication syndrome. In this chapter, we review the current state of the art regarding the origins of the domesticated date palm. We first discuss whether date palms are domesticated, and highlight how they diverge from their wild Phoenix relatives. We then outline patterns in the population genetic and archaeobotanical data, and review different models for the origins of domesticated date palms by highlighting sources of evidence that are either consistent or inconsistent with each model. We then review the process of date palm domestication, and emphasize the human activities that have prompted its domestication. We particularly focus on the evolution of fruit traits.
[ { "created": "Tue, 1 Dec 2020 05:40:54 GMT", "version": "v1" } ]
2020-12-02
[ [ "Gros-Balthazard", "Muriel", "" ], [ "Flowers", "Jonathan M.", "" ] ]
The study of the origins of crops is of interest from both a fundamental evolutionary understanding viewpoint, and from an applied agricultural technology perspective. The date palm (Phoenix dactylifera L.) is the iconic fruit crop of hot and arid regions of North Africa and the Middle East, producing sugar-rich fruits, known as dates. There are many different cultivars each with distinctive fruit traits, and there are many wild Phoenix species too, which in total form a complex of related species. The understanding of plant domestication involves multiple disciplines, including phylogeography, population genetics and archaeology. In the past decade, they have prompted new discoveries on the evolutionary history of date palm, but a complete understanding of its origins remains to be elucidated, along with the genetic architecture of its domestication syndrome. In this chapter, we review the current state of the art regarding the origins of the domesticated date palm. We first discuss whether date palms are domesticated, and highlight how they diverge from their wild Phoenix relatives. We then outline patterns in the population genetic and archaeobotanical data, and review different models for the origins of domesticated date palms by highlighting sources of evidence that are either consistent or inconsistent with each model. We then review the process of date palm domestication, and emphasize the human activities that have prompted its domestication. We particularly focus on the evolution of fruit traits.
0903.4168
Satoru Hayasaka
Satoru Hayasaka, Paul J. Laurienti
Degree distributions in mesoscopic and macroscopic functional brain networks
null
null
null
null
q-bio.NC q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We investigated the degree distribution of brain networks extracted from functional magnetic resonance imaging of the human brain. In particular, the distributions are compared between macroscopic brain networks using region-based nodes and mesoscopic brain networks using voxel-based nodes. We found that the distribution from these networks follow the same family of distributions and represent a continuum of exponentially truncated power law distributions.
[ { "created": "Tue, 24 Mar 2009 19:42:36 GMT", "version": "v1" } ]
2009-03-25
[ [ "Hayasaka", "Satoru", "" ], [ "Laurienti", "Paul J.", "" ] ]
We investigated the degree distribution of brain networks extracted from functional magnetic resonance imaging of the human brain. In particular, the distributions are compared between macroscopic brain networks using region-based nodes and mesoscopic brain networks using voxel-based nodes. We found that the distribution from these networks follow the same family of distributions and represent a continuum of exponentially truncated power law distributions.
2101.08211
Xinwei Yu
Xinwei Yu, Matthew S. Creamer, Francesco Randi, Anuj K. Sharma, Scott W. Linderman, Andrew M. Leifer
Fast deep learning correspondence for neuron tracking and identification in C.elegans using synthetic training
5 figures
eLife 2021;10:e66410
10.7554/eLife.66410
null
q-bio.QM cs.CV q-bio.NC
http://creativecommons.org/licenses/by-nc-nd/4.0/
We present an automated method to track and identify neurons in C. elegans, called "fast Deep Learning Correspondence" or fDLC, based on the transformer network architecture. The model is trained once on empirically derived synthetic data and then predicts neural correspondence across held-out real animals via transfer learning. The same pre-trained model both tracks neurons across time and identifies corresponding neurons across individuals. Performance is evaluated against hand-annotated datasets, including NeuroPAL [1]. Using only position information, the method achieves 80.0% accuracy at tracking neurons within an individual and 65.8% accuracy at identifying neurons across individuals. Accuracy is even higher on a published dataset [2]. Accuracy reaches 76.5% when using color information from NeuroPAL. Unlike previous methods, fDLC does not require straightening or transforming the animal into a canonical coordinate system. The method is fast and predicts correspondence in 10 ms making it suitable for future real-time applications.
[ { "created": "Wed, 20 Jan 2021 16:46:37 GMT", "version": "v1" } ]
2021-07-16
[ [ "Yu", "Xinwei", "" ], [ "Creamer", "Matthew S.", "" ], [ "Randi", "Francesco", "" ], [ "Sharma", "Anuj K.", "" ], [ "Linderman", "Scott W.", "" ], [ "Leifer", "Andrew M.", "" ] ]
We present an automated method to track and identify neurons in C. elegans, called "fast Deep Learning Correspondence" or fDLC, based on the transformer network architecture. The model is trained once on empirically derived synthetic data and then predicts neural correspondence across held-out real animals via transfer learning. The same pre-trained model both tracks neurons across time and identifies corresponding neurons across individuals. Performance is evaluated against hand-annotated datasets, including NeuroPAL [1]. Using only position information, the method achieves 80.0% accuracy at tracking neurons within an individual and 65.8% accuracy at identifying neurons across individuals. Accuracy is even higher on a published dataset [2]. Accuracy reaches 76.5% when using color information from NeuroPAL. Unlike previous methods, fDLC does not require straightening or transforming the animal into a canonical coordinate system. The method is fast and predicts correspondence in 10 ms making it suitable for future real-time applications.
q-bio/0508040
Chih-Yuan Tseng
Hung-I Pai, Chih-Yuan Tseng and HC Lee
Identifying Biomagnetic Sources in the Brain by the Maximum Entropy Approach
8 pages, 8 figures. Presented at 25th International Workshop on Bayesian Inference and Maximum Entropy Methods in Science and Engineering, San Jose, CA, USA Aug 7-12, 2005
p. 527 in "Bayesian Inference and Maximum Entropy Methods in Science and Engineering" ed. by K. H. Knuth, A. E. Abbda, R. D. Moriss, and J. P. Castle (A.I.P. Vol. 803, 2005)
10.1063/1.2149834
null
q-bio.NC q-bio.QM
null
Magnetoencephalographic (MEG) measurements record magnetic fields generated from neurons while information is being processed in the brain. The inverse problem of identifying sources of biomagnetic fields and deducing their intensities from MEG measurements is ill-posed when the number of field detectors is far less than the number of sources. This problem is less severe if there is already a reasonable prior knowledge in the form of a distribution in the intensity of source activation. In this case the problem of identifying and deducing source intensities may be transformed to one of using the MEG data to update a prior distribution to a posterior distribution. Here we report on some work done using the maximum entropy method (ME) as an updating tool. Specifically, we propose an implementation of the ME method in cases when the prior contain almost no knowledge of source activation. Two examples are studied, in which part of motor cortex is activated with uniform and varying intensities, respectively.
[ { "created": "Mon, 29 Aug 2005 03:21:25 GMT", "version": "v1" } ]
2009-11-11
[ [ "Pai", "Hung-I", "" ], [ "Tseng", "Chih-Yuan", "" ], [ "Lee", "HC", "" ] ]
Magnetoencephalographic (MEG) measurements record magnetic fields generated from neurons while information is being processed in the brain. The inverse problem of identifying sources of biomagnetic fields and deducing their intensities from MEG measurements is ill-posed when the number of field detectors is far less than the number of sources. This problem is less severe if there is already a reasonable prior knowledge in the form of a distribution in the intensity of source activation. In this case the problem of identifying and deducing source intensities may be transformed to one of using the MEG data to update a prior distribution to a posterior distribution. Here we report on some work done using the maximum entropy method (ME) as an updating tool. Specifically, we propose an implementation of the ME method in cases when the prior contain almost no knowledge of source activation. Two examples are studied, in which part of motor cortex is activated with uniform and varying intensities, respectively.
1612.05463
Thomas Gueudr\'e PhD
Thomas Gueudr\'e
Growth over time-correlated disorder: a spectral approach to Mean-field
10 pages + Appendix
Phys. Rev. E 95, 042134 (2017)
10.1103/PhysRevE.95.042134
null
q-bio.PE cond-mat.dis-nn cond-mat.stat-mech physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We generalize a model of growth over a disordered environment, to a large class of It\=o processes. In particular, we study how the microscopic properties of the noise influence the macroscopic growth rate. The present model can account for growth processes in large dimensions, and provides a bed to understand better the trade-off between exploration and exploitation. An additional mapping to the Schr\"ordinger equation readily provides a set of disorders for which this model can be solved exactly. This mean-field approach exhibits interesting features, such as a freezing transition and an optimal point of growth, that can be studied in details, and gives yet another explanation for the occurrence of the $\textit{Zipf law}$ in complex, well-connected systems.
[ { "created": "Fri, 16 Dec 2016 13:38:24 GMT", "version": "v1" } ]
2017-04-26
[ [ "Gueudré", "Thomas", "" ] ]
We generalize a model of growth over a disordered environment, to a large class of It\=o processes. In particular, we study how the microscopic properties of the noise influence the macroscopic growth rate. The present model can account for growth processes in large dimensions, and provides a bed to understand better the trade-off between exploration and exploitation. An additional mapping to the Schr\"ordinger equation readily provides a set of disorders for which this model can be solved exactly. This mean-field approach exhibits interesting features, such as a freezing transition and an optimal point of growth, that can be studied in details, and gives yet another explanation for the occurrence of the $\textit{Zipf law}$ in complex, well-connected systems.
2402.18583
Ling Yang
Zhilin Huang, Ling Yang, Zaixi Zhang, Xiangxin Zhou, Yu Bao, Xiawu Zheng, Yuwei Yang, Yu Wang, Wenming Yang
Binding-Adaptive Diffusion Models for Structure-Based Drug Design
Accepted by AAAI 2024. Project: https://github.com/YangLing0818/BindDM
null
null
null
q-bio.BM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to capture the essential protein-ligand interactions exactly in 3D space for molecular generation. To address this problem, we propose a novel framework, namely Binding-Adaptive Diffusion Models (BindDM). In BindDM, we adaptively extract subcomplex, the essential part of binding sites responsible for protein-ligand interactions. Then the selected protein-ligand subcomplex is processed with SE(3)-equivariant neural networks, and transmitted back to each atom of the complex for augmenting the target-aware 3D molecule diffusion generation with binding interaction information. We iterate this hierarchical complex-subcomplex process with cross-hierarchy interaction node for adequately fusing global binding context between the complex and its corresponding subcomplex. Empirical studies on the CrossDocked2020 dataset show BindDM can generate molecules with more realistic 3D structures and higher binding affinities towards the protein targets, with up to -5.92 Avg. Vina Score, while maintaining proper molecular properties. Our code is available at https://github.com/YangLing0818/BindDM
[ { "created": "Mon, 15 Jan 2024 00:34:00 GMT", "version": "v1" } ]
2024-03-01
[ [ "Huang", "Zhilin", "" ], [ "Yang", "Ling", "" ], [ "Zhang", "Zaixi", "" ], [ "Zhou", "Xiangxin", "" ], [ "Bao", "Yu", "" ], [ "Zheng", "Xiawu", "" ], [ "Yang", "Yuwei", "" ], [ "Wang", "Yu", "" ], [ "Yang", "Wenming", "" ] ]
Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to capture the essential protein-ligand interactions exactly in 3D space for molecular generation. To address this problem, we propose a novel framework, namely Binding-Adaptive Diffusion Models (BindDM). In BindDM, we adaptively extract subcomplex, the essential part of binding sites responsible for protein-ligand interactions. Then the selected protein-ligand subcomplex is processed with SE(3)-equivariant neural networks, and transmitted back to each atom of the complex for augmenting the target-aware 3D molecule diffusion generation with binding interaction information. We iterate this hierarchical complex-subcomplex process with cross-hierarchy interaction node for adequately fusing global binding context between the complex and its corresponding subcomplex. Empirical studies on the CrossDocked2020 dataset show BindDM can generate molecules with more realistic 3D structures and higher binding affinities towards the protein targets, with up to -5.92 Avg. Vina Score, while maintaining proper molecular properties. Our code is available at https://github.com/YangLing0818/BindDM
2110.14602
Vitaly Vanchurin
Vitaly Vanchurin, Yuri I. Wolf, Mikhail I. Katsnelson, Eugene V. Koonin
Towards a Theory of Evolution as Multilevel Learning
29 pages, 3 figures
null
10.1073/pnas.2120037119
null
q-bio.PE cond-mat.dis-nn cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We apply the theory of learning to physically renormalizable systems in an attempt to develop a theory of biological evolution, including the origin of life, as multilevel learning. We formulate seven fundamental principles of evolution that appear to be necessary and sufficient to render a universe observable and show that they entail the major features of biological evolution, including replication and natural selection. These principles also follow naturally from the theory of learning. We formulate the theory of evolution using the mathematical framework of neural networks, which provides for detailed analysis of evolutionary phenomena. To demonstrate the potential of the proposed theoretical framework, we derive a generalized version of the Central Dogma of molecular biology by analyzing the flow of information during learning (back-propagation) and predicting (forward-propagation) the environment by evolving organisms. The more complex evolutionary phenomena, such as major transitions in evolution, in particular, the origin of life, have to be analyzed in the thermodynamic limit, which is described in detail in the accompanying paper.
[ { "created": "Wed, 27 Oct 2021 17:21:16 GMT", "version": "v1" } ]
2022-10-12
[ [ "Vanchurin", "Vitaly", "" ], [ "Wolf", "Yuri I.", "" ], [ "Katsnelson", "Mikhail I.", "" ], [ "Koonin", "Eugene V.", "" ] ]
We apply the theory of learning to physically renormalizable systems in an attempt to develop a theory of biological evolution, including the origin of life, as multilevel learning. We formulate seven fundamental principles of evolution that appear to be necessary and sufficient to render a universe observable and show that they entail the major features of biological evolution, including replication and natural selection. These principles also follow naturally from the theory of learning. We formulate the theory of evolution using the mathematical framework of neural networks, which provides for detailed analysis of evolutionary phenomena. To demonstrate the potential of the proposed theoretical framework, we derive a generalized version of the Central Dogma of molecular biology by analyzing the flow of information during learning (back-propagation) and predicting (forward-propagation) the environment by evolving organisms. The more complex evolutionary phenomena, such as major transitions in evolution, in particular, the origin of life, have to be analyzed in the thermodynamic limit, which is described in detail in the accompanying paper.
1308.6240
Wentian Li
Wentian Li, Jan Freudenberg, Pedro Miramontes
Diminishing Return for Increased Mappability with Longer Sequencing Reads: Implications of the k-mer Distributions in the Human Genome
5 figures
BMC Bioinformatics, 15:2 (2014)
10.1186/1471-2105-15-2
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The amount of non-unique sequence (non-singletons) in a genome directly affects the difficulty of read alignment to a reference assembly for high throughput-sequencing data. Although a greater length increases the chance for reads being uniquely mapped to the reference genome, a quantitative analysis of the influence of read lengths on mappability has been lacking. To address this question, we evaluate the k-mer distribution of the human reference genome. The k-mer frequency is determined for k ranging from 20 to 1000 basepairs. We use the proportion of non-singleton k-mers to evaluate the mappability of reads for a corresponding read length. We observe that the proportion of non-singletons decreases slowly with increasing k, and can be fitted by piecewise power-law functions with different exponents at different k ranges. A faster decay at smaller values for k indicates more limited gains for read lengths > 200 basepairs. The frequency distributions of k-mers exhibit long tails in a power-law-like trend, and rank frequency plots exhibit a concave Zipf's curve. The location of the most frequent 1000-mers comprises 172 kilobase-ranged regions, including four large stretches on chromosomes 1 and X, containing genes with biomedical implications. Even the read length 1000 would be insufficient to reliably sequence these specific regions.
[ { "created": "Wed, 28 Aug 2013 18:14:47 GMT", "version": "v1" } ]
2017-03-03
[ [ "Li", "Wentian", "" ], [ "Freudenberg", "Jan", "" ], [ "Miramontes", "Pedro", "" ] ]
The amount of non-unique sequence (non-singletons) in a genome directly affects the difficulty of read alignment to a reference assembly for high throughput-sequencing data. Although a greater length increases the chance for reads being uniquely mapped to the reference genome, a quantitative analysis of the influence of read lengths on mappability has been lacking. To address this question, we evaluate the k-mer distribution of the human reference genome. The k-mer frequency is determined for k ranging from 20 to 1000 basepairs. We use the proportion of non-singleton k-mers to evaluate the mappability of reads for a corresponding read length. We observe that the proportion of non-singletons decreases slowly with increasing k, and can be fitted by piecewise power-law functions with different exponents at different k ranges. A faster decay at smaller values for k indicates more limited gains for read lengths > 200 basepairs. The frequency distributions of k-mers exhibit long tails in a power-law-like trend, and rank frequency plots exhibit a concave Zipf's curve. The location of the most frequent 1000-mers comprises 172 kilobase-ranged regions, including four large stretches on chromosomes 1 and X, containing genes with biomedical implications. Even the read length 1000 would be insufficient to reliably sequence these specific regions.
2302.04338
Viren Shah
Viren Shah, Justin Womack, Anthony E. Zamora, Scott S. Terhune, and Ranjan K. Dash
Simulating the Evolution of Signaling Signatures during CART-Cell -- Tumor Cell Interactions
null
null
null
null
q-bio.MN
http://creativecommons.org/licenses/by/4.0/
Immunotherapies have been proven to have significant therapeutic efficacy in the treatment of cancer. The last decade has seen adoptive cell therapies, such as chimeric antigen receptor T-cell (CART-cell) therapy, gain FDA approval against specific cancers. Additionally, there are numerous clinical trials ongoing investigating additional designs and targets. Nevertheless, despite the excitement and promising potential of CART-cell therapy, response rates to therapy vary greatly between studies, patients, and cancers. There remains an unmet need to develop computational frameworks that more accurately predict CART-cell function and clinical efficacy. Here we present a coarse-grained model simulated with logical rules that demonstrates the evolution of signaling signatures following the inter-action between CART-cells and tumor cells and allows for in silico based prediction of CART-cell functionality prior to experimentation.
[ { "created": "Wed, 8 Feb 2023 21:10:58 GMT", "version": "v1" } ]
2023-02-10
[ [ "Shah", "Viren", "" ], [ "Womack", "Justin", "" ], [ "Zamora", "Anthony E.", "" ], [ "Terhune", "Scott S.", "" ], [ "Dash", "Ranjan K.", "" ] ]
Immunotherapies have been proven to have significant therapeutic efficacy in the treatment of cancer. The last decade has seen adoptive cell therapies, such as chimeric antigen receptor T-cell (CART-cell) therapy, gain FDA approval against specific cancers. Additionally, there are numerous clinical trials ongoing investigating additional designs and targets. Nevertheless, despite the excitement and promising potential of CART-cell therapy, response rates to therapy vary greatly between studies, patients, and cancers. There remains an unmet need to develop computational frameworks that more accurately predict CART-cell function and clinical efficacy. Here we present a coarse-grained model simulated with logical rules that demonstrates the evolution of signaling signatures following the inter-action between CART-cells and tumor cells and allows for in silico based prediction of CART-cell functionality prior to experimentation.
0801.0253
William Bialek
Greg J. Stephens and William Bialek
Toward a statistical mechanics of four letter words
null
null
10.1103/PhysRevE.81.066119
null
q-bio.NC cs.CL physics.data-an physics.soc-ph
null
We consider words as a network of interacting letters, and approximate the probability distribution of states taken on by this network. Despite the intuition that the rules of English spelling are highly combinatorial (and arbitrary), we find that maximum entropy models consistent with pairwise correlations among letters provide a surprisingly good approximation to the full statistics of four letter words, capturing ~92% of the multi-information among letters and even "discovering" real words that were not represented in the data from which the pairwise correlations were estimated. The maximum entropy model defines an energy landscape on the space of possible words, and local minima in this landscape account for nearly two-thirds of words used in written English.
[ { "created": "Mon, 31 Dec 2007 23:51:51 GMT", "version": "v1" } ]
2013-05-29
[ [ "Stephens", "Greg J.", "" ], [ "Bialek", "William", "" ] ]
We consider words as a network of interacting letters, and approximate the probability distribution of states taken on by this network. Despite the intuition that the rules of English spelling are highly combinatorial (and arbitrary), we find that maximum entropy models consistent with pairwise correlations among letters provide a surprisingly good approximation to the full statistics of four letter words, capturing ~92% of the multi-information among letters and even "discovering" real words that were not represented in the data from which the pairwise correlations were estimated. The maximum entropy model defines an energy landscape on the space of possible words, and local minima in this landscape account for nearly two-thirds of words used in written English.
1011.2939
Bob Eisenberg
Bob Eisenberg
From Structure to Function in Open Ionic Channels
Nearly final version of publication
Journal of Membrane Biol. 171, 1-24 (1999)
10.1007/s002329900554
null
q-bio.BM cond-mat.soft math-ph math.MP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We consider a simple working hypothesis that all permeation properties of open ionic channels can be predicted by understanding electrodiffusion in fixed structures, without invoking conformation changes, or changes in chemical bonds. We know, of course, that ions can bind to specific protein structures, and that this binding is not easily described by the traditional electrostatic equations of physics textbooks, that describe average electric fields, the so-called `mean field'. The question is which specific properties can be explained just by mean field electrostatics and which cannot. I believe the best way to uncover the specific chemical properties of channels is to invoke them as little as possible, seeking to explain with mean field electrostatics first. Then, when phenomena appear that cannot be described that way, by the mean field alone, we turn to chemically specific explanations, seeking the appropriate tools (of electrochemistry, Langevin, or molecular dynamics, for example) to understand them. In this spirit, we turn now to the structure of open ionic channels, apply the laws of electrodiffusion to them, and see how many of their properties we can predict just that way.
[ { "created": "Fri, 12 Nov 2010 15:10:07 GMT", "version": "v1" } ]
2015-03-17
[ [ "Eisenberg", "Bob", "" ] ]
We consider a simple working hypothesis that all permeation properties of open ionic channels can be predicted by understanding electrodiffusion in fixed structures, without invoking conformation changes, or changes in chemical bonds. We know, of course, that ions can bind to specific protein structures, and that this binding is not easily described by the traditional electrostatic equations of physics textbooks, that describe average electric fields, the so-called `mean field'. The question is which specific properties can be explained just by mean field electrostatics and which cannot. I believe the best way to uncover the specific chemical properties of channels is to invoke them as little as possible, seeking to explain with mean field electrostatics first. Then, when phenomena appear that cannot be described that way, by the mean field alone, we turn to chemically specific explanations, seeking the appropriate tools (of electrochemistry, Langevin, or molecular dynamics, for example) to understand them. In this spirit, we turn now to the structure of open ionic channels, apply the laws of electrodiffusion to them, and see how many of their properties we can predict just that way.
2312.15055
Kexuan Li
Kexuan Li
Deep Learning for Efficient GWAS Feature Selection
null
null
null
null
q-bio.GN cs.LG stat.ME
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Genome-Wide Association Studies (GWAS) face unique challenges in the era of big genomics data, particularly when dealing with ultra-high-dimensional datasets where the number of genetic features significantly exceeds the available samples. This paper introduces an extension to the feature selection methodology proposed by Mirzaei et al. (2020), specifically tailored to tackle the intricacies associated with ultra-high-dimensional GWAS data. Our extended approach enhances the original method by introducing a Frobenius norm penalty into the student network, augmenting its capacity to adapt to scenarios characterized by a multitude of features and limited samples. Operating seamlessly in both supervised and unsupervised settings, our method employs two key neural networks. The first leverages an autoencoder or supervised autoencoder for dimension reduction, extracting salient features from the ultra-high-dimensional genomic data. The second network, a regularized feed-forward model with a single hidden layer, is designed for precise feature selection. The introduction of the Frobenius norm penalty in the student network significantly boosts the method's resilience to the challenges posed by ultra-high-dimensional GWAS datasets. Experimental results showcase the efficacy of our approach in feature selection for GWAS data. The method not only handles the inherent complexities of ultra-high-dimensional settings but also demonstrates superior adaptability to the nuanced structures present in genomics data. The flexibility and versatility of our proposed methodology are underscored by its successful performance across a spectrum of experiments.
[ { "created": "Fri, 22 Dec 2023 20:35:47 GMT", "version": "v1" } ]
2023-12-27
[ [ "Li", "Kexuan", "" ] ]
Genome-Wide Association Studies (GWAS) face unique challenges in the era of big genomics data, particularly when dealing with ultra-high-dimensional datasets where the number of genetic features significantly exceeds the available samples. This paper introduces an extension to the feature selection methodology proposed by Mirzaei et al. (2020), specifically tailored to tackle the intricacies associated with ultra-high-dimensional GWAS data. Our extended approach enhances the original method by introducing a Frobenius norm penalty into the student network, augmenting its capacity to adapt to scenarios characterized by a multitude of features and limited samples. Operating seamlessly in both supervised and unsupervised settings, our method employs two key neural networks. The first leverages an autoencoder or supervised autoencoder for dimension reduction, extracting salient features from the ultra-high-dimensional genomic data. The second network, a regularized feed-forward model with a single hidden layer, is designed for precise feature selection. The introduction of the Frobenius norm penalty in the student network significantly boosts the method's resilience to the challenges posed by ultra-high-dimensional GWAS datasets. Experimental results showcase the efficacy of our approach in feature selection for GWAS data. The method not only handles the inherent complexities of ultra-high-dimensional settings but also demonstrates superior adaptability to the nuanced structures present in genomics data. The flexibility and versatility of our proposed methodology are underscored by its successful performance across a spectrum of experiments.
1612.02116
Tarunendu Mapder
Tarunendu Mapder
Signal Manifestation Trade-offs in Incoherent Feed-Forward Loops
10 pages, 4 figures
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Signal processing in biological systems is delicately executed by specialised networks, which are modular assemblies of network motifs. The motifs are independently functional circuits found in enormous numbers in any living cell. A very common network motif is the feed-forward loop (FFL), which regulates a downstream node by an upstream one in a direct and an indirect way within the network. If the direct and indirect regulations go antagonistic, the motif is known as an incoherent FFL (ICFFL). The current study is aimed at exploring the reason for the variation in the evolutionary selection of the four types of ICFFLs. As comparative measures, I compute sensitivity amplification, adaptation precision and efficiency from the temporal dynamics and mutual information between the input-output nodes of the motifs at steady state. The ICFFL II performs very efficiently in adaptation but poor in information processing. On the other hand, ICFFL I and III are better in information transmission compared to adaptation efficiency. Which is the fittest among them under the pressure of natural selection? To sort out this puzzle, I take help from the multi-objective Pareto efficiency. The results, found in the Pareto task space, are in good agreement with the reported abundance level of all the types in eukaryotes as well as prokaryotes.
[ { "created": "Wed, 7 Dec 2016 05:18:04 GMT", "version": "v1" } ]
2016-12-08
[ [ "Mapder", "Tarunendu", "" ] ]
Signal processing in biological systems is delicately executed by specialised networks, which are modular assemblies of network motifs. The motifs are independently functional circuits found in enormous numbers in any living cell. A very common network motif is the feed-forward loop (FFL), which regulates a downstream node by an upstream one in a direct and an indirect way within the network. If the direct and indirect regulations go antagonistic, the motif is known as an incoherent FFL (ICFFL). The current study is aimed at exploring the reason for the variation in the evolutionary selection of the four types of ICFFLs. As comparative measures, I compute sensitivity amplification, adaptation precision and efficiency from the temporal dynamics and mutual information between the input-output nodes of the motifs at steady state. The ICFFL II performs very efficiently in adaptation but poor in information processing. On the other hand, ICFFL I and III are better in information transmission compared to adaptation efficiency. Which is the fittest among them under the pressure of natural selection? To sort out this puzzle, I take help from the multi-objective Pareto efficiency. The results, found in the Pareto task space, are in good agreement with the reported abundance level of all the types in eukaryotes as well as prokaryotes.
1011.2699
Sang Hoon Lee
Sang Hoon Lee, Pan-Jun Kim, Hawoong Jeong
Global organization of protein complexome in the yeast Saccharomyces cerevisiae
48 pages, 6 figures, 3 tables, 8 additional files (3 supporting tables and 5 supporting figures) on the Web
BMC Syst. Biol. 5, 126 (2011)
10.1186/1752-0509-5-126
null
q-bio.QM physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Proteins in organisms, rather than act alone, usually form protein complexes to perform cellular functions. We analyze the topological network structure of protein complexes and their component proteins in the budding yeast in terms of the bipartite network and its projections, where the complexes and proteins are its two distinct components. Compared to conventional protein-protein interaction networks, the networks from the protein complexes show more homogeneous structures than those of the binary protein interactions, implying the formation of complexes that cause a relatively more uniform number of interaction partners. In addition, we suggest a new optimization method to determine the abundance and function of protein complexes, based on the information of their global organization. Estimating abundance and biological functions is of great importance for many researches, by providing a quantitative description of cell behaviors, instead of just a "catalogues" of the lists of protein interactions. With our new optimization method, we present genome-wide assignments of abundance and biological functions for complexes, as well as previously unknown abundance and functions of proteins, which can provide significant information for further investigations in proteomics. It is strongly supported by a number of biologically relevant examples, such as the relationship between the cytoskeleton proteins and signal transduction and the metabolic enzyme Eno2's involvement in the cell division process. We believe that our methods and findings are applicable not only to the specific area of proteomics, but also to much broader areas of systems biology with the concept of optimization principle.
[ { "created": "Thu, 11 Nov 2010 16:18:03 GMT", "version": "v1" }, { "created": "Mon, 11 Apr 2011 18:32:49 GMT", "version": "v2" }, { "created": "Thu, 11 Aug 2011 17:14:49 GMT", "version": "v3" }, { "created": "Mon, 15 Aug 2011 10:35:04 GMT", "version": "v4" } ]
2011-08-16
[ [ "Lee", "Sang Hoon", "" ], [ "Kim", "Pan-Jun", "" ], [ "Jeong", "Hawoong", "" ] ]
Proteins in organisms, rather than act alone, usually form protein complexes to perform cellular functions. We analyze the topological network structure of protein complexes and their component proteins in the budding yeast in terms of the bipartite network and its projections, where the complexes and proteins are its two distinct components. Compared to conventional protein-protein interaction networks, the networks from the protein complexes show more homogeneous structures than those of the binary protein interactions, implying the formation of complexes that cause a relatively more uniform number of interaction partners. In addition, we suggest a new optimization method to determine the abundance and function of protein complexes, based on the information of their global organization. Estimating abundance and biological functions is of great importance for many researches, by providing a quantitative description of cell behaviors, instead of just a "catalogues" of the lists of protein interactions. With our new optimization method, we present genome-wide assignments of abundance and biological functions for complexes, as well as previously unknown abundance and functions of proteins, which can provide significant information for further investigations in proteomics. It is strongly supported by a number of biologically relevant examples, such as the relationship between the cytoskeleton proteins and signal transduction and the metabolic enzyme Eno2's involvement in the cell division process. We believe that our methods and findings are applicable not only to the specific area of proteomics, but also to much broader areas of systems biology with the concept of optimization principle.
1010.2829
Andrew Noble
Andrew E. Noble, Nico M. Temme, William F. Fagan, Timothy H. Keitt
A sampling theory for asymmetric communities
46 pages, 3 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We introduce the first analytical model of asymmetric community dynamics to yield Hubbell's neutral theory in the limit of functional equivalence among all species. Our focus centers on an asymmetric extension of Hubbell's local community dynamics, while an analogous extension of Hubbell's metacommunity dynamics is deferred to an appendix. We find that mass-effects may facilitate coexistence in asymmetric local communities and generate unimodal species abundance distributions indistinguishable from those of symmetric communities. Multiple modes, however, only arise from asymmetric processes and provide a strong indication of non-neutral dynamics. Although the exact stationary distributions of fully asymmetric communities must be calculated numerically, we derive approximate sampling distributions for the general case and for nearly neutral communities where symmetry is broken by a single species distinct from all others in ecological fitness and dispersal ability. In the latter case, our approximate distributions are fully normalized, and novel asymptotic expansions of the required hypergeometric functions are provided to make evaluations tractable for large communities. Employing these results in a Bayesian analysis may provide a novel statistical test to assess the consistency of species abundance data with the neutral hypothesis.
[ { "created": "Thu, 14 Oct 2010 05:17:57 GMT", "version": "v1" }, { "created": "Fri, 3 Dec 2010 02:31:07 GMT", "version": "v2" } ]
2010-12-06
[ [ "Noble", "Andrew E.", "" ], [ "Temme", "Nico M.", "" ], [ "Fagan", "William F.", "" ], [ "Keitt", "Timothy H.", "" ] ]
We introduce the first analytical model of asymmetric community dynamics to yield Hubbell's neutral theory in the limit of functional equivalence among all species. Our focus centers on an asymmetric extension of Hubbell's local community dynamics, while an analogous extension of Hubbell's metacommunity dynamics is deferred to an appendix. We find that mass-effects may facilitate coexistence in asymmetric local communities and generate unimodal species abundance distributions indistinguishable from those of symmetric communities. Multiple modes, however, only arise from asymmetric processes and provide a strong indication of non-neutral dynamics. Although the exact stationary distributions of fully asymmetric communities must be calculated numerically, we derive approximate sampling distributions for the general case and for nearly neutral communities where symmetry is broken by a single species distinct from all others in ecological fitness and dispersal ability. In the latter case, our approximate distributions are fully normalized, and novel asymptotic expansions of the required hypergeometric functions are provided to make evaluations tractable for large communities. Employing these results in a Bayesian analysis may provide a novel statistical test to assess the consistency of species abundance data with the neutral hypothesis.
q-bio/0402018
Peng-Ye Wang
Ping Xie, Shuo-Xing Dou, Peng-Ye Wang
Dynamics of heterodimeric kinesins and cooperation of kinesins
18 pages, 5 figures
null
null
null
q-bio.BM
null
Using the model for the processive movement of a dimeric kinesin we proposed before, we study the dynamics of a number of mutant homodimeric and heterodimeric kinesins that were constructed by Kaseda et al. (Kaseda, K., Higuchi, H. and Hirose, K. PNAS 99, 16058 (2002)). The theoretical results of ATPase rate per head, moving velocity, and stall force of the motors show good agreement with the experimental results by Kaseda et al.: The puzzling dynamic behaviors of heterodimeric kinesin that consists of two distinct heads compared with its parent homodimers can be easily explained by using independent ATPase rates of the two heads in our model. We also study the collective kinetic behaviors of kinesins in MT-gliding motility. The results explains well that the average MT-gliding velocity is independent of the number of bound motors and is equal to the moving velocity of a single kinesin relative to MT.
[ { "created": "Mon, 9 Feb 2004 05:32:00 GMT", "version": "v1" } ]
2007-05-23
[ [ "Xie", "Ping", "" ], [ "Dou", "Shuo-Xing", "" ], [ "Wang", "Peng-Ye", "" ] ]
Using the model for the processive movement of a dimeric kinesin we proposed before, we study the dynamics of a number of mutant homodimeric and heterodimeric kinesins that were constructed by Kaseda et al. (Kaseda, K., Higuchi, H. and Hirose, K. PNAS 99, 16058 (2002)). The theoretical results of ATPase rate per head, moving velocity, and stall force of the motors show good agreement with the experimental results by Kaseda et al.: The puzzling dynamic behaviors of heterodimeric kinesin that consists of two distinct heads compared with its parent homodimers can be easily explained by using independent ATPase rates of the two heads in our model. We also study the collective kinetic behaviors of kinesins in MT-gliding motility. The results explains well that the average MT-gliding velocity is independent of the number of bound motors and is equal to the moving velocity of a single kinesin relative to MT.
1404.4005
Premal Shah
Premal Shah, David M. McCandlish and Joshua B. Plotkin
Historical contingency and entrenchment in protein evolution under purifying selection
42 pages, 13 figures
null
10.1073/pnas.1412933112
null
q-bio.PE q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The fitness contribution of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations under selection, and can shape the course of protein evolution across divergent species. Whereas epistasis between adaptive substitutions has been the subject of extensive study, relatively little is known about epistasis under purifying selection. Here we use mechanistic models of thermodynamic stability in a ligand-binding protein to explore the structure of epistatic interactions between substitutions that fix in protein sequences under purifying selection. We find that the selection coefficients of mutations that are nearly-neutral when they fix are highly contingent on the presence of preceding mutations. Conversely, mutations that are nearly-neutral when they fix are subsequently entrenched due to epistasis with later substitutions. Our evolutionary model includes insertions and deletions, as well as point mutations, and so it allows us to quantify epistasis within each of these classes of mutations, and also to study the evolution of protein length. We find that protein length remains largely constant over time, because indels are more deleterious than point mutations. Our results imply that, even under purifying selection, protein sequence evolution is highly contingent on history and so it cannot be predicted by the phenotypic effects of mutations assayed in the wild-type sequence.
[ { "created": "Tue, 15 Apr 2014 18:18:39 GMT", "version": "v1" }, { "created": "Tue, 29 Apr 2014 17:03:56 GMT", "version": "v2" }, { "created": "Tue, 15 Jul 2014 19:36:56 GMT", "version": "v3" } ]
2015-06-11
[ [ "Shah", "Premal", "" ], [ "McCandlish", "David M.", "" ], [ "Plotkin", "Joshua B.", "" ] ]
The fitness contribution of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations under selection, and can shape the course of protein evolution across divergent species. Whereas epistasis between adaptive substitutions has been the subject of extensive study, relatively little is known about epistasis under purifying selection. Here we use mechanistic models of thermodynamic stability in a ligand-binding protein to explore the structure of epistatic interactions between substitutions that fix in protein sequences under purifying selection. We find that the selection coefficients of mutations that are nearly-neutral when they fix are highly contingent on the presence of preceding mutations. Conversely, mutations that are nearly-neutral when they fix are subsequently entrenched due to epistasis with later substitutions. Our evolutionary model includes insertions and deletions, as well as point mutations, and so it allows us to quantify epistasis within each of these classes of mutations, and also to study the evolution of protein length. We find that protein length remains largely constant over time, because indels are more deleterious than point mutations. Our results imply that, even under purifying selection, protein sequence evolution is highly contingent on history and so it cannot be predicted by the phenotypic effects of mutations assayed in the wild-type sequence.
q-bio/0701028
Francesco Pederiva
M. Sega, P. Faccioli, F. Pederiva, G. Garberoglio, H. Orland
Quantitative Protein Dynamics from Dominant Folding Pathways
4 pages, 1 figure
null
10.1103/PhysRevLett.99.118102
null
q-bio.QM cond-mat.soft q-bio.BM
null
We develop a theoretical approach to the protein folding problem based on out-of-equilibrium stochastic dynamics. Within this framework, the computational difficulties related to the existence of large time scale gaps in the protein folding problem are removed and simulating the entire reaction in atomistic details using existing computers becomes feasible. In addition, this formalism provides a natural framework to investigate the relationships between thermodynamical and kinetic aspects of the folding. For example, it is possible to show that, in order to have a large probability to remain unchanged under Langevin diffusion, the native state has to be characterized by a small conformational entropy. We discuss how to determine the most probable folding pathway, to identify configurations representative of the transition state and to compute the most probable transition time. We perform an illustrative application of these ideas, studying the conformational evolution of alanine di-peptide, within an all-atom model based on the empiric GROMOS96 force field.
[ { "created": "Thu, 18 Jan 2007 10:18:25 GMT", "version": "v1" } ]
2009-11-13
[ [ "Sega", "M.", "" ], [ "Faccioli", "P.", "" ], [ "Pederiva", "F.", "" ], [ "Garberoglio", "G.", "" ], [ "Orland", "H.", "" ] ]
We develop a theoretical approach to the protein folding problem based on out-of-equilibrium stochastic dynamics. Within this framework, the computational difficulties related to the existence of large time scale gaps in the protein folding problem are removed and simulating the entire reaction in atomistic details using existing computers becomes feasible. In addition, this formalism provides a natural framework to investigate the relationships between thermodynamical and kinetic aspects of the folding. For example, it is possible to show that, in order to have a large probability to remain unchanged under Langevin diffusion, the native state has to be characterized by a small conformational entropy. We discuss how to determine the most probable folding pathway, to identify configurations representative of the transition state and to compute the most probable transition time. We perform an illustrative application of these ideas, studying the conformational evolution of alanine di-peptide, within an all-atom model based on the empiric GROMOS96 force field.
0807.1059
Michel Aoun
Michel Aoun, Jean-Yves Cabon, Annick Hourmant
Potential Phytoextraction with in-vitro regenerated plantlets of Brassica juncea (L.) Czern. in presence of CdCl$_2$: Cadmium accumulation and physiological parameter measurement
12 pages, 2 figures and 2 tables
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Heavy metal contamination of agricultural land is partly responsible for limiting crop productivity. Cd$^{2+}$ is known as a non-essentiel HM that can be harmful to plants even at low concentrations. Brassica juncea (L.) is able to accumulate more than 400 $\mu$g.g$^{-1}$ D.W. in the shoot, a physiological trait which may be exploited for the phytoremediation of contaminated soils and waters. . The application of 75 $\mu$M CdCl$_2$ for three days does not show any effect in the B. juncea growth parameters (F.W. and D.W.) whatever the type of plantlets. This application decreases also the contents of chlorophyll a, carotenoids and Chl a/b ratio (2.26) for plantlets regenerated in the absence of CdCl$_2$ but not those of plantlets regenerated in its presence. Roots have the highest contents (3071; 1544 $\mu$g.g$^{-1}$ D.W.) followed by stems (850; 687$\mu$g.g$^{-1}$ D.W.) and leaves (463; 264$\mu$g.g$^{-1}$ D.W.) respectively. In our conditions, we suggest that the low accumulation in the plantlets regenerated in the presence of CdCl$_2$ by the means of in-vitro regeneration technology is still benefical, to some extent, for the phytoextraction process and seems to be an interesting technology that allows the cultivation of these plantlets in contaminated soils with low accumulation of metal in their shoots and probably in their seeds used in many food technologies.
[ { "created": "Mon, 7 Jul 2008 16:13:56 GMT", "version": "v1" } ]
2008-07-08
[ [ "Aoun", "Michel", "" ], [ "Cabon", "Jean-Yves", "" ], [ "Hourmant", "Annick", "" ] ]
Heavy metal contamination of agricultural land is partly responsible for limiting crop productivity. Cd$^{2+}$ is known as a non-essentiel HM that can be harmful to plants even at low concentrations. Brassica juncea (L.) is able to accumulate more than 400 $\mu$g.g$^{-1}$ D.W. in the shoot, a physiological trait which may be exploited for the phytoremediation of contaminated soils and waters. . The application of 75 $\mu$M CdCl$_2$ for three days does not show any effect in the B. juncea growth parameters (F.W. and D.W.) whatever the type of plantlets. This application decreases also the contents of chlorophyll a, carotenoids and Chl a/b ratio (2.26) for plantlets regenerated in the absence of CdCl$_2$ but not those of plantlets regenerated in its presence. Roots have the highest contents (3071; 1544 $\mu$g.g$^{-1}$ D.W.) followed by stems (850; 687$\mu$g.g$^{-1}$ D.W.) and leaves (463; 264$\mu$g.g$^{-1}$ D.W.) respectively. In our conditions, we suggest that the low accumulation in the plantlets regenerated in the presence of CdCl$_2$ by the means of in-vitro regeneration technology is still benefical, to some extent, for the phytoextraction process and seems to be an interesting technology that allows the cultivation of these plantlets in contaminated soils with low accumulation of metal in their shoots and probably in their seeds used in many food technologies.
1903.10131
Zachary Kilpatrick PhD
Nicholas W. Barendregt, Kre\v{s}imir Josi\'c, and Zachary P. Kilpatrick
Analyzing dynamic decision-making models using Chapman-Kolmogorov equations
24 pages, 9 figures
null
null
null
q-bio.NC math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Decision-making in dynamic environments typically requires adaptive evidence accumulation that weights new evidence more heavily than old observations. Recent experimental studies of dynamic decision tasks require subjects to make decisions for which the correct choice switches stochastically throughout a single trial. In such cases, an ideal observer's belief is described by an evolution equation that is doubly stochastic, reflecting stochasticity in the both observations and environmental changes. In these contexts, we show that the probability density of the belief can be represented using differential Chapman-Kolmogorov equations, allowing efficient computation of ensemble statistics. This allows us to reliably compare normative models to near-normative approximations using, as model performance metrics, decision response accuracy and Kullback-Leibler divergence of the belief distributions. Such belief distributions could be obtained empirically from subjects by asking them to report their decision confidence. We also study how response accuracy is affected by additional internal noise, showing optimality requires longer integration timescales as more noise is added. Lastly, we demonstrate that our method can be applied to tasks in which evidence arrives in a discrete, pulsatile fashion, rather than continuously.
[ { "created": "Mon, 25 Mar 2019 04:29:34 GMT", "version": "v1" } ]
2019-03-26
[ [ "Barendregt", "Nicholas W.", "" ], [ "Josić", "Krešimir", "" ], [ "Kilpatrick", "Zachary P.", "" ] ]
Decision-making in dynamic environments typically requires adaptive evidence accumulation that weights new evidence more heavily than old observations. Recent experimental studies of dynamic decision tasks require subjects to make decisions for which the correct choice switches stochastically throughout a single trial. In such cases, an ideal observer's belief is described by an evolution equation that is doubly stochastic, reflecting stochasticity in the both observations and environmental changes. In these contexts, we show that the probability density of the belief can be represented using differential Chapman-Kolmogorov equations, allowing efficient computation of ensemble statistics. This allows us to reliably compare normative models to near-normative approximations using, as model performance metrics, decision response accuracy and Kullback-Leibler divergence of the belief distributions. Such belief distributions could be obtained empirically from subjects by asking them to report their decision confidence. We also study how response accuracy is affected by additional internal noise, showing optimality requires longer integration timescales as more noise is added. Lastly, we demonstrate that our method can be applied to tasks in which evidence arrives in a discrete, pulsatile fashion, rather than continuously.
2212.12542
Antoine Villie
Antoine Villi\'e, Philippe Veber, Yohann de Castro, Laurent Jacob
Neural Networks beyond explainability: Selective inference for sequence motifs
null
null
null
null
q-bio.GN cs.LG stat.ML
http://creativecommons.org/licenses/by-nc-nd/4.0/
Over the past decade, neural networks have been successful at making predictions from biological sequences, especially in the context of regulatory genomics. As in other fields of deep learning, tools have been devised to extract features such as sequence motifs that can explain the predictions made by a trained network. Here we intend to go beyond explainable machine learning and introduce SEISM, a selective inference procedure to test the association between these extracted features and the predicted phenotype. In particular, we discuss how training a one-layer convolutional network is formally equivalent to selecting motifs maximizing some association score. We adapt existing sampling-based selective inference procedures by quantizing this selection over an infinite set to a large but finite grid. Finally, we show that sampling under a specific choice of parameters is sufficient to characterize the composite null hypothesis typically used for selective inference-a result that goes well beyond our particular framework. We illustrate the behavior of our method in terms of calibration, power and speed and discuss its power/speed trade-off with a simpler data-split strategy. SEISM paves the way to an easier analysis of neural networks used in regulatory genomics, and to more powerful methods for genome wide association studies (GWAS).
[ { "created": "Fri, 23 Dec 2022 10:49:07 GMT", "version": "v1" } ]
2022-12-27
[ [ "Villié", "Antoine", "" ], [ "Veber", "Philippe", "" ], [ "de Castro", "Yohann", "" ], [ "Jacob", "Laurent", "" ] ]
Over the past decade, neural networks have been successful at making predictions from biological sequences, especially in the context of regulatory genomics. As in other fields of deep learning, tools have been devised to extract features such as sequence motifs that can explain the predictions made by a trained network. Here we intend to go beyond explainable machine learning and introduce SEISM, a selective inference procedure to test the association between these extracted features and the predicted phenotype. In particular, we discuss how training a one-layer convolutional network is formally equivalent to selecting motifs maximizing some association score. We adapt existing sampling-based selective inference procedures by quantizing this selection over an infinite set to a large but finite grid. Finally, we show that sampling under a specific choice of parameters is sufficient to characterize the composite null hypothesis typically used for selective inference-a result that goes well beyond our particular framework. We illustrate the behavior of our method in terms of calibration, power and speed and discuss its power/speed trade-off with a simpler data-split strategy. SEISM paves the way to an easier analysis of neural networks used in regulatory genomics, and to more powerful methods for genome wide association studies (GWAS).
2303.04902
Yamin Li
Yamin Li, Saishuang Wu, Jiayang Xu, Haiwa Wang, Qi Zhu, Wen Shi, Yue Fang, Fan Jiang, Shanbao Tong, Yunting Zhang, Xiaoli Guo
Inter-brain substrates of role switching during mother-child interaction
null
null
10.1002/hbm.26672
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Mother-child interaction is highly dynamic and reciprocal. Switching roles in these back-and-forth interactions serves as a crucial feature of reciprocal behaviors while the underlying neural entrainment is still not well-studied. Here, we designed a role-controlled cooperative task with dual EEG recording to study how differently two brains interact when mothers and children hold different roles. When children were actors and mothers were observers, mother-child inter-brain synchrony emerged within the theta oscillations and the frontal lobe, which highly correlated with children's attachment to their mothers. When their roles were reversed, this synchrony was shifted to the alpha oscillations and the central area and associated with mothers' perception of their relationship with their children. The results suggested an observer-actor neural alignment within the actor's oscillations, which was modulated by the actor-toward-observer emotional bonding. Our findings contribute to the understanding of how inter-brain synchrony is established and dynamically changed during mother-child reciprocal interaction.
[ { "created": "Wed, 8 Mar 2023 21:43:26 GMT", "version": "v1" } ]
2024-04-04
[ [ "Li", "Yamin", "" ], [ "Wu", "Saishuang", "" ], [ "Xu", "Jiayang", "" ], [ "Wang", "Haiwa", "" ], [ "Zhu", "Qi", "" ], [ "Shi", "Wen", "" ], [ "Fang", "Yue", "" ], [ "Jiang", "Fan", "" ], [ "Tong", "Shanbao", "" ], [ "Zhang", "Yunting", "" ], [ "Guo", "Xiaoli", "" ] ]
Mother-child interaction is highly dynamic and reciprocal. Switching roles in these back-and-forth interactions serves as a crucial feature of reciprocal behaviors while the underlying neural entrainment is still not well-studied. Here, we designed a role-controlled cooperative task with dual EEG recording to study how differently two brains interact when mothers and children hold different roles. When children were actors and mothers were observers, mother-child inter-brain synchrony emerged within the theta oscillations and the frontal lobe, which highly correlated with children's attachment to their mothers. When their roles were reversed, this synchrony was shifted to the alpha oscillations and the central area and associated with mothers' perception of their relationship with their children. The results suggested an observer-actor neural alignment within the actor's oscillations, which was modulated by the actor-toward-observer emotional bonding. Our findings contribute to the understanding of how inter-brain synchrony is established and dynamically changed during mother-child reciprocal interaction.
1402.4824
Sergio G\'omez
Sara Teller, Clara Granell, Manlio De Domenico, Jordi Soriano, Sergio Gomez, Alex Arenas
Emergence of assortative mixing between clusters of cultured neurons
33 pages, 10 figures
PLOS Comput. Biol. 10(9) (2014) e1003796
10.1371/journal.pcbi.1003796
null
q-bio.NC cond-mat.dis-nn physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The analysis of the activity of neuronal cultures is considered to be a good proxy of the functional connectivity of in vivo neuronal tissues. Thus, the functional complex network inferred from activity patterns is a promising way to unravel the interplay between structure and functionality of neuronal systems. Here, we monitor the spontaneous self-sustained dynamics in neuronal cultures formed by interconnected aggregates of neurons (clusters). Dynamics is characterized by the fast activation of groups of clusters in sequences termed bursts. The analysis of the time delays between clusters' activations within the bursts allows the reconstruction of the directed functional connectivity of the network. We propose a method to statistically infer this connectivity and analyze the resulting properties of the associated complex networks. Surprisingly enough, in contrast to what has been reported for many biological networks, the clustered neuronal cultures present assortative mixing connectivity values, as well as a rich--club core, meaning that there is a preference for clusters to link to other clusters that share similar functional connectivity, which shapes a `connectivity backbone' in the network. These results point out that the grouping of neurons and the assortative connectivity between clusters are intrinsic survival mechanisms of the culture.
[ { "created": "Wed, 19 Feb 2014 21:05:25 GMT", "version": "v1" }, { "created": "Mon, 7 Jul 2014 19:13:46 GMT", "version": "v2" } ]
2014-09-09
[ [ "Teller", "Sara", "" ], [ "Granell", "Clara", "" ], [ "De Domenico", "Manlio", "" ], [ "Soriano", "Jordi", "" ], [ "Gomez", "Sergio", "" ], [ "Arenas", "Alex", "" ] ]
The analysis of the activity of neuronal cultures is considered to be a good proxy of the functional connectivity of in vivo neuronal tissues. Thus, the functional complex network inferred from activity patterns is a promising way to unravel the interplay between structure and functionality of neuronal systems. Here, we monitor the spontaneous self-sustained dynamics in neuronal cultures formed by interconnected aggregates of neurons (clusters). Dynamics is characterized by the fast activation of groups of clusters in sequences termed bursts. The analysis of the time delays between clusters' activations within the bursts allows the reconstruction of the directed functional connectivity of the network. We propose a method to statistically infer this connectivity and analyze the resulting properties of the associated complex networks. Surprisingly enough, in contrast to what has been reported for many biological networks, the clustered neuronal cultures present assortative mixing connectivity values, as well as a rich--club core, meaning that there is a preference for clusters to link to other clusters that share similar functional connectivity, which shapes a `connectivity backbone' in the network. These results point out that the grouping of neurons and the assortative connectivity between clusters are intrinsic survival mechanisms of the culture.
0910.2660
John Hopfield
J. J. Hopfield and Carlos D. Brody
Sequence reproduction, single trial learning, and mimicry based on a mammalian-like distributed code for time
18 pages
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Animals learn tasks requiring a sequence of actions over time. Waiting a given time before taking an action is a simple example. Mimicry is a complex example, e.g. in humans, humming a brief tune you have just heard. Re-experiencing a sensory pattern mentally must involve reproducing a sequence of neural activities over time. In mammals, neurons in prefrontal cortex have time-dependent firing rates that vary smoothly and slowly in a stereotyped fashion. We show through modeling that a Many are Equal computation can use such slowly-varying activities to identify each timepoint in a sequence by the population pattern of activity at the timepoint. The MAE operation implemented here is facilitated by a common inhibitory conductivity due to a theta rhythm. Sequences of analog values of discrete events, exemplified by a brief tune having notes of different durations and intensities, can be learned in a single trial through STDP. An action sequence can be played back sped up, slowed down, or reversed by modulating the system that generates the slowly changing stereotyped activities. Synaptic adaptation and cellular post-hyperpolarization rebound contribute to robustness. An ability to mimic a sequence only seconds after observing it requires the STDP to be effective within seconds.
[ { "created": "Wed, 14 Oct 2009 16:12:16 GMT", "version": "v1" } ]
2009-10-15
[ [ "Hopfield", "J. J.", "" ], [ "Brody", "Carlos D.", "" ] ]
Animals learn tasks requiring a sequence of actions over time. Waiting a given time before taking an action is a simple example. Mimicry is a complex example, e.g. in humans, humming a brief tune you have just heard. Re-experiencing a sensory pattern mentally must involve reproducing a sequence of neural activities over time. In mammals, neurons in prefrontal cortex have time-dependent firing rates that vary smoothly and slowly in a stereotyped fashion. We show through modeling that a Many are Equal computation can use such slowly-varying activities to identify each timepoint in a sequence by the population pattern of activity at the timepoint. The MAE operation implemented here is facilitated by a common inhibitory conductivity due to a theta rhythm. Sequences of analog values of discrete events, exemplified by a brief tune having notes of different durations and intensities, can be learned in a single trial through STDP. An action sequence can be played back sped up, slowed down, or reversed by modulating the system that generates the slowly changing stereotyped activities. Synaptic adaptation and cellular post-hyperpolarization rebound contribute to robustness. An ability to mimic a sequence only seconds after observing it requires the STDP to be effective within seconds.
2104.08334
Cem \"Ozel
Cem \"Ozel, Muharrem Erdem Bo\u{g}o\c{c}lu, Ceren Ke\c{c}eciler, Ecem Kaplan and Sevil Y\"ucel
Utilization of the simulated flue gas on the cultivation of Chlorella protothecoides
6 pages, 6 figures
Journal of the Indian Chemical Society (2019), 96, 1137-1142
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In recent years, fossil-based fuels have been used to supply the energy needs of the world. Fossil-based fuels induce accumulation of the atmospheric CO2 which causes global warming. One of CO2 source is flue gas emission from the power plant. The microalgae have been considered excellent biological materials for reduction CO2 with ability to photosynthesis. In this study, air, 10% CO2, 15% CO2 and simulated flue gas (containing 15% CO2) feed were used to observe effect CO2 concentration and flue gas on cell growth and lipid content of Chlorella protothecoides. The highest dry cell weight (1,5 g/L) and lipid content (45%) values were obtained with 15% CO2 feed while the highest growth rate (1,10), biomass productivity (0,125 g/L/day), and lipid weight (0,63 g/g) were observed in 10% CO2 feed. Cultures fed with flue gas did not inhibited C. protothecoides growth and showed similar results with those fed with 15% CO2 gas in terms of growth rate, dry cell weight, biomass productivity and lipid content. These results showed that C. protothecoides has great potential for reducing CO2 emission from flue gas.
[ { "created": "Fri, 16 Apr 2021 19:31:43 GMT", "version": "v1" } ]
2021-04-20
[ [ "Özel", "Cem", "" ], [ "Boğoçlu", "Muharrem Erdem", "" ], [ "Keçeciler", "Ceren", "" ], [ "Kaplan", "Ecem", "" ], [ "Yücel", "Sevil", "" ] ]
In recent years, fossil-based fuels have been used to supply the energy needs of the world. Fossil-based fuels induce accumulation of the atmospheric CO2 which causes global warming. One of CO2 source is flue gas emission from the power plant. The microalgae have been considered excellent biological materials for reduction CO2 with ability to photosynthesis. In this study, air, 10% CO2, 15% CO2 and simulated flue gas (containing 15% CO2) feed were used to observe effect CO2 concentration and flue gas on cell growth and lipid content of Chlorella protothecoides. The highest dry cell weight (1,5 g/L) and lipid content (45%) values were obtained with 15% CO2 feed while the highest growth rate (1,10), biomass productivity (0,125 g/L/day), and lipid weight (0,63 g/g) were observed in 10% CO2 feed. Cultures fed with flue gas did not inhibited C. protothecoides growth and showed similar results with those fed with 15% CO2 gas in terms of growth rate, dry cell weight, biomass productivity and lipid content. These results showed that C. protothecoides has great potential for reducing CO2 emission from flue gas.
0905.1458
Michael Krumin
Michael Krumin, Avner Shimron and Shy Shoham
Correlation-distortion based identification of Linear-Nonlinear-Poisson models
null
null
10.1007/s10827-009-0184-0
null
q-bio.NC q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Linear-Nonlinear-Poisson (LNP) models are a popular and powerful tool for describing encoding (stimulus-response) transformations by single sensory as well as motor neurons. Recently, there has been rising interest in the second- and higher-order correlation structure of neural spike trains, and how it may be related to specific encoding relationships. The distortion of signal correlations as they are transformed through particular LNP models is predictable and in some cases analytically tractable and invertible. Here, we propose that LNP encoding models can potentially be identified strictly from the correlation transformations they induce, and develop a computational method for identifying minimum-phase single-neuron temporal kernels under white and colored- random Gaussian excitation. Unlike reverse-correlation or maximum-likelihood, correlation-distortion based identification does not require the simultaneous observation of stimulus-response pairs - only their respective second order statistics. Although in principle filter kernels are not necessarily minimum-phase, and only their spectral amplitude can be uniquely determined from output correlations, we show that in practice this method provides excellent estimates of kernels from a range of parametric models of neural systems. We conclude by discussing how this approach could potentially enable neural models to be estimated from a much wider variety of experimental conditions and systems, and its limitations.
[ { "created": "Sun, 10 May 2009 09:01:18 GMT", "version": "v1" }, { "created": "Mon, 19 Oct 2009 01:00:23 GMT", "version": "v2" } ]
2016-09-08
[ [ "Krumin", "Michael", "" ], [ "Shimron", "Avner", "" ], [ "Shoham", "Shy", "" ] ]
Linear-Nonlinear-Poisson (LNP) models are a popular and powerful tool for describing encoding (stimulus-response) transformations by single sensory as well as motor neurons. Recently, there has been rising interest in the second- and higher-order correlation structure of neural spike trains, and how it may be related to specific encoding relationships. The distortion of signal correlations as they are transformed through particular LNP models is predictable and in some cases analytically tractable and invertible. Here, we propose that LNP encoding models can potentially be identified strictly from the correlation transformations they induce, and develop a computational method for identifying minimum-phase single-neuron temporal kernels under white and colored- random Gaussian excitation. Unlike reverse-correlation or maximum-likelihood, correlation-distortion based identification does not require the simultaneous observation of stimulus-response pairs - only their respective second order statistics. Although in principle filter kernels are not necessarily minimum-phase, and only their spectral amplitude can be uniquely determined from output correlations, we show that in practice this method provides excellent estimates of kernels from a range of parametric models of neural systems. We conclude by discussing how this approach could potentially enable neural models to be estimated from a much wider variety of experimental conditions and systems, and its limitations.
2112.03151
Refath Bari
Refath Bari
A Neuronal Noise Critique of Integrated Information Theory
Submitted to PLoS ONE
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
Integrated Information Theory (IIT) is an audacious attempt to pin down the abstract, phenomenological experiences of consciousness into a rigorous, mathematical framework. We show that IIT's stance in regards to neuronal noise is inconsistent with experimental data demonstrating that neuronal noise in the brain plays a critical role in learning, visual recognition, and even categorical representation. IIT predicts that entropy due to noise will reduce the information integration of a physical system, which is inconsistent with experimental data demonstrating that decision-related noise is a necessary condition for learning and visual recognition tasks. IIT must therefore be reformulated to accommodate experimental evidence showing both the successes and failures of noise.
[ { "created": "Mon, 6 Dec 2021 16:37:39 GMT", "version": "v1" }, { "created": "Thu, 9 Dec 2021 15:38:19 GMT", "version": "v2" } ]
2021-12-10
[ [ "Bari", "Refath", "" ] ]
Integrated Information Theory (IIT) is an audacious attempt to pin down the abstract, phenomenological experiences of consciousness into a rigorous, mathematical framework. We show that IIT's stance in regards to neuronal noise is inconsistent with experimental data demonstrating that neuronal noise in the brain plays a critical role in learning, visual recognition, and even categorical representation. IIT predicts that entropy due to noise will reduce the information integration of a physical system, which is inconsistent with experimental data demonstrating that decision-related noise is a necessary condition for learning and visual recognition tasks. IIT must therefore be reformulated to accommodate experimental evidence showing both the successes and failures of noise.
2007.03678
Ada Sedova
Scott LeGrand, Aaron Scheinberg, Andreas F. Tillack, Mathialakan Thavappiragasam, Josh V. Vermaas, Rupesh Agarwal, Jeff Larkin, Duncan Poole, Diogo Santos-Martins, Leonardo Solis-Vasquez, Andreas Koch, Stefano Forli, Oscar Hernandez, Jeremy C. Smith and Ada Sedova
GPU-Accelerated Drug Discovery with Docking on the Summit Supercomputer: Porting, Optimization, and Application to COVID-19 Research
null
null
10.1145/3388440.3412472
null
q-bio.BM q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Protein-ligand docking is an in silico tool used to screen potential drug compounds for their ability to bind to a given protein receptor within a drug-discovery campaign. Experimental drug screening is expensive and time consuming, and it is desirable to carry out large scale docking calculations in a high-throughput manner to narrow the experimental search space. Few of the existing computational docking tools were designed with high performance computing in mind. Therefore, optimizations to maximize use of high-performance computational resources available at leadership-class computing facilities enables these facilities to be leveraged for drug discovery. Here we present the porting, optimization, and validation of the AutoDock-GPU program for the Summit supercomputer, and its application to initial compound screening efforts to target proteins of the SARS-CoV-2 virus responsible for the current COVID-19 pandemic.
[ { "created": "Mon, 6 Jul 2020 20:31:12 GMT", "version": "v1" } ]
2020-11-16
[ [ "LeGrand", "Scott", "" ], [ "Scheinberg", "Aaron", "" ], [ "Tillack", "Andreas F.", "" ], [ "Thavappiragasam", "Mathialakan", "" ], [ "Vermaas", "Josh V.", "" ], [ "Agarwal", "Rupesh", "" ], [ "Larkin", "Jeff", "" ], [ "Poole", "Duncan", "" ], [ "Santos-Martins", "Diogo", "" ], [ "Solis-Vasquez", "Leonardo", "" ], [ "Koch", "Andreas", "" ], [ "Forli", "Stefano", "" ], [ "Hernandez", "Oscar", "" ], [ "Smith", "Jeremy C.", "" ], [ "Sedova", "Ada", "" ] ]
Protein-ligand docking is an in silico tool used to screen potential drug compounds for their ability to bind to a given protein receptor within a drug-discovery campaign. Experimental drug screening is expensive and time consuming, and it is desirable to carry out large scale docking calculations in a high-throughput manner to narrow the experimental search space. Few of the existing computational docking tools were designed with high performance computing in mind. Therefore, optimizations to maximize use of high-performance computational resources available at leadership-class computing facilities enables these facilities to be leveraged for drug discovery. Here we present the porting, optimization, and validation of the AutoDock-GPU program for the Summit supercomputer, and its application to initial compound screening efforts to target proteins of the SARS-CoV-2 virus responsible for the current COVID-19 pandemic.
1511.04470
Richard Barnes
Richard Barnes, Clarence Lehman
Modeling of Bovine Spongiform Encephalopathy in a Two-Species Feedback Loop
12 pages, 4 figures
Epidemics. Vol. 5, Issue 2, June 2013, pp 85--91
10.1016/j.epidem.2013.04.001
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Bovine spongiform encephalopathy, otherwise known as mad cow disease, can spread when an individual cow consumes feed containing the infected tissues of another individual, forming a one-species feedback loop. Such feedback is the primary means of transmission for BSE during epidemic conditions. Following outbreaks in the European Union and elsewhere, many governments enacted legislation designed to limit the spread of such diseases via elimination or reduction of one-species feedback loops in agricultural systems. However, two-species feedback loops---those in which infectious material from one-species is consumed by a secondary species whose tissue is then consumed by the first species---were not universally prohibited and have not been studied before. Here we present a basic ecological disease model which examines the role feedback loops may play in the spread of BSE and related diseases. Our model shows that there are critical thresholds between the infection's expansion and decrease related to the lifespan of the hosts, the growth rate of the prions, and the amount of prions circulating between hosts. The ecological disease dynamics can be intrinsically oscillatory, having outbreaks as well as refractory periods which can make it appear that the disease is under control while it is still increasing. We show that non-susceptible species that have been intentionally inserted into a feedback loop to stop the spread of disease do not, strictly by themselves, guarantee its control, though they may give that appearance by increasing the refractory period of an epidemic's oscillations. We suggest ways in which age-related dynamics and cross-species coupling should be considered in continuing evaluations aimed at maintaining a safe food supply.
[ { "created": "Fri, 13 Nov 2015 22:01:12 GMT", "version": "v1" } ]
2015-11-17
[ [ "Barnes", "Richard", "" ], [ "Lehman", "Clarence", "" ] ]
Bovine spongiform encephalopathy, otherwise known as mad cow disease, can spread when an individual cow consumes feed containing the infected tissues of another individual, forming a one-species feedback loop. Such feedback is the primary means of transmission for BSE during epidemic conditions. Following outbreaks in the European Union and elsewhere, many governments enacted legislation designed to limit the spread of such diseases via elimination or reduction of one-species feedback loops in agricultural systems. However, two-species feedback loops---those in which infectious material from one-species is consumed by a secondary species whose tissue is then consumed by the first species---were not universally prohibited and have not been studied before. Here we present a basic ecological disease model which examines the role feedback loops may play in the spread of BSE and related diseases. Our model shows that there are critical thresholds between the infection's expansion and decrease related to the lifespan of the hosts, the growth rate of the prions, and the amount of prions circulating between hosts. The ecological disease dynamics can be intrinsically oscillatory, having outbreaks as well as refractory periods which can make it appear that the disease is under control while it is still increasing. We show that non-susceptible species that have been intentionally inserted into a feedback loop to stop the spread of disease do not, strictly by themselves, guarantee its control, though they may give that appearance by increasing the refractory period of an epidemic's oscillations. We suggest ways in which age-related dynamics and cross-species coupling should be considered in continuing evaluations aimed at maintaining a safe food supply.
2001.06773
Wei Zhao
Qing Nie, Lingxia Qiao, Yuchi Qiu, Lei Zhang and Wei Zhao
Noise control and utility: from regulatory network to spatial patterning
null
null
null
null
q-bio.MN q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Stochasticity (or noise) at cellular and molecular levels has been observed extensively as a universal feature for living systems. However, how living systems deal with noise while performing desirable biological functions remains a major mystery. Regulatory network configurations, such as their topology and timescale, are shown to be critical in attenuating noise, and noise is also found to facilitate cell fate decision. Here we review major recent findings on noise attenuation through regulatory control, the benefit of noise via noise-induced cellular plasticity during developmental patterning, and summarize key principles underlying noise control.
[ { "created": "Sun, 19 Jan 2020 04:39:38 GMT", "version": "v1" } ]
2020-01-22
[ [ "Nie", "Qing", "" ], [ "Qiao", "Lingxia", "" ], [ "Qiu", "Yuchi", "" ], [ "Zhang", "Lei", "" ], [ "Zhao", "Wei", "" ] ]
Stochasticity (or noise) at cellular and molecular levels has been observed extensively as a universal feature for living systems. However, how living systems deal with noise while performing desirable biological functions remains a major mystery. Regulatory network configurations, such as their topology and timescale, are shown to be critical in attenuating noise, and noise is also found to facilitate cell fate decision. Here we review major recent findings on noise attenuation through regulatory control, the benefit of noise via noise-induced cellular plasticity during developmental patterning, and summarize key principles underlying noise control.
1710.08149
Mo Zhang
Mo Zhang, Xiang Li, Mengjia Xu, Quanzheng Li
Image Segmentation and Classification for Sickle Cell Disease using Deformable U-Net
null
null
null
null
q-bio.CB cs.CV
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Reliable cell segmentation and classification from biomedical images is a crucial step for both scientific research and clinical practice. A major challenge for more robust segmentation and classification methods is the large variations in the size, shape and viewpoint of the cells, combining with the low image quality caused by noise and artifacts. To address this issue, in this work we propose a learning-based, simultaneous cell segmentation and classification method based on the deep U-Net structure with deformable convolution layers. The U-Net architecture for deep learning has been shown to offer a precise localization for image semantic segmentation. Moreover, deformable convolution layer enables the free form deformation of the feature learning process, thus makes the whole network more robust to various cell morphologies and image settings. The proposed method is tested on microscopic red blood cell images from patients with sickle cell disease. The results show that U-Net with deformable convolution achieves the highest accuracy for segmentation and classification, comparing with original U-Net structure.
[ { "created": "Mon, 23 Oct 2017 08:53:07 GMT", "version": "v1" }, { "created": "Tue, 24 Oct 2017 02:26:00 GMT", "version": "v2" }, { "created": "Sun, 29 Oct 2017 04:02:32 GMT", "version": "v3" } ]
2017-10-31
[ [ "Zhang", "Mo", "" ], [ "Li", "Xiang", "" ], [ "Xu", "Mengjia", "" ], [ "Li", "Quanzheng", "" ] ]
Reliable cell segmentation and classification from biomedical images is a crucial step for both scientific research and clinical practice. A major challenge for more robust segmentation and classification methods is the large variations in the size, shape and viewpoint of the cells, combining with the low image quality caused by noise and artifacts. To address this issue, in this work we propose a learning-based, simultaneous cell segmentation and classification method based on the deep U-Net structure with deformable convolution layers. The U-Net architecture for deep learning has been shown to offer a precise localization for image semantic segmentation. Moreover, deformable convolution layer enables the free form deformation of the feature learning process, thus makes the whole network more robust to various cell morphologies and image settings. The proposed method is tested on microscopic red blood cell images from patients with sickle cell disease. The results show that U-Net with deformable convolution achieves the highest accuracy for segmentation and classification, comparing with original U-Net structure.
2208.10545
Miguel Ib\'a\~nez Berganza
Miguel Ib\'a\~nez-Berganza, Carlo Lucibello, Luca Mariani, Giovanni Pezzulo
Information-theoretical analysis of the neural code for decoupled face representation
26 pages, 8 figures (+11 pages, 7 figures in the supporting information section). In v3: new figure 8 in section 3.2.3; further details added to the supporting information; title changed
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
Processing faces accurately and efficiently is a key capability of humans and other animals that engage in sophisticated social tasks. Recent studies reported a decoupled coding for faces in the primate inferotemporal cortex, with two separate neural populations coding for the geometric position of (texture-free) facial landmarks and for the image texture at fixed landmark positions, respectively. Here, we formally assess the efficiency of this decoupled coding by appealing to the information-theoretic notion of description length, which quantifies the amount of information that is saved when encoding novel facial images, with a given precision. We show that despite decoupled coding describes the facial images in terms of two sets of principal components (of landmark shape and image texture), it is more efficient (i.e., yields more information compression) than the encoding in terms of the image principal components only, which corresponds to the widely used eigenface method. The advantage of decoupled coding over eigenface coding increases with image resolution and is especially prominent when coding variants of training set images that only differ in facial expressions. Moreover, we demonstrate that decoupled coding entails better performance in three different tasks: the representation of facial images, the (daydream) sampling of novel facial images, and the recognition of facial identities and gender. In summary, our study provides a first principle perspective on the efficiency and accuracy of the decoupled coding of facial stimuli reported in the primate inferotemporal cortex.
[ { "created": "Mon, 22 Aug 2022 18:50:34 GMT", "version": "v1" }, { "created": "Fri, 26 Aug 2022 06:25:07 GMT", "version": "v2" }, { "created": "Wed, 18 Jan 2023 14:33:21 GMT", "version": "v3" } ]
2023-01-19
[ [ "Ibáñez-Berganza", "Miguel", "" ], [ "Lucibello", "Carlo", "" ], [ "Mariani", "Luca", "" ], [ "Pezzulo", "Giovanni", "" ] ]
Processing faces accurately and efficiently is a key capability of humans and other animals that engage in sophisticated social tasks. Recent studies reported a decoupled coding for faces in the primate inferotemporal cortex, with two separate neural populations coding for the geometric position of (texture-free) facial landmarks and for the image texture at fixed landmark positions, respectively. Here, we formally assess the efficiency of this decoupled coding by appealing to the information-theoretic notion of description length, which quantifies the amount of information that is saved when encoding novel facial images, with a given precision. We show that despite decoupled coding describes the facial images in terms of two sets of principal components (of landmark shape and image texture), it is more efficient (i.e., yields more information compression) than the encoding in terms of the image principal components only, which corresponds to the widely used eigenface method. The advantage of decoupled coding over eigenface coding increases with image resolution and is especially prominent when coding variants of training set images that only differ in facial expressions. Moreover, we demonstrate that decoupled coding entails better performance in three different tasks: the representation of facial images, the (daydream) sampling of novel facial images, and the recognition of facial identities and gender. In summary, our study provides a first principle perspective on the efficiency and accuracy of the decoupled coding of facial stimuli reported in the primate inferotemporal cortex.
1212.3807
Irina Kareva
Irina Kareva, Benjamin Morin, Georgy Karev
Preventing the tragedy of the commons through punishment of over-consumers and encouragement of under-consumers
null
null
null
null
q-bio.PE math.CA
http://creativecommons.org/licenses/publicdomain/
The conditions that can lead to the exploitative depletion of a shared resource, i.e, the tragedy of the commons, can be reformulated as a game of prisoner's dilemma: while preserving the common resource is in the best interest of the group, over-consumption is in the interest of each particular individual at any given point in time. One way to try and prevent the tragedy of the commons is through infliction of punishment for over-consumption and/or encouraging under-consumption, thus selecting against over-consumers. Here, the effectiveness of various punishment functions in an evolving consumer-resource system is evaluated within a framework of a parametrically heterogeneous system of ordinary differential equations (ODEs). Conditions leading to the possibility of sustainable coexistence with the common resource for a subset of cases are identified analytically using adaptive dynamics; the effects of punishment on heterogeneous populations with different initial composition are evaluated using the Reduction theorem for replicator equations. Obtained results suggest that one cannot prevent the tragedy of the commons through rewarding of under-consumers alone - there must also be an implementation of some degree of punishment that increases in a non-linear fashion with respect to over-consumption and which may vary depending on the initial distribution of clones in the population.
[ { "created": "Sun, 16 Dec 2012 17:28:41 GMT", "version": "v1" } ]
2012-12-18
[ [ "Kareva", "Irina", "" ], [ "Morin", "Benjamin", "" ], [ "Karev", "Georgy", "" ] ]
The conditions that can lead to the exploitative depletion of a shared resource, i.e, the tragedy of the commons, can be reformulated as a game of prisoner's dilemma: while preserving the common resource is in the best interest of the group, over-consumption is in the interest of each particular individual at any given point in time. One way to try and prevent the tragedy of the commons is through infliction of punishment for over-consumption and/or encouraging under-consumption, thus selecting against over-consumers. Here, the effectiveness of various punishment functions in an evolving consumer-resource system is evaluated within a framework of a parametrically heterogeneous system of ordinary differential equations (ODEs). Conditions leading to the possibility of sustainable coexistence with the common resource for a subset of cases are identified analytically using adaptive dynamics; the effects of punishment on heterogeneous populations with different initial composition are evaluated using the Reduction theorem for replicator equations. Obtained results suggest that one cannot prevent the tragedy of the commons through rewarding of under-consumers alone - there must also be an implementation of some degree of punishment that increases in a non-linear fashion with respect to over-consumption and which may vary depending on the initial distribution of clones in the population.
2305.02082
Jacob Thorstensen
Jacob Thorstensen, Tyler Henderson and Justin Kavanagh
Serotonergic and noradrenergic contributions to human motor cortical and spinal motoneuronal excitability
38 pages, 3 tables, no figures
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by-nc-nd/4.0/
Animal models indicate that motor behaviour is shaped by monoamine neurotransmitters released diffusely throughout the brain and spinal cord. We present strong evidence that human motor pathways are equally affected by neuromodulation through noradrenergic and serotonergic projections arising from the brainstem. To do so, we have identified and collated human experiments examining the off-label effects of well-characterised serotonergic and noradrenergic drugs on lab-based electrophysiology measures of corticospinal-motoneuronal excitability. Specifically, we focus on the effects that serotonin and noradrenaline associated drugs have on muscle responses to magnetic or electrical stimulation of the motor cortex and peripheral nerves, and other closely related tests of motoneuron excitability, to best segment drug effects to a supraspinal or spinal locus. We find that serotonin enhancing drugs tend to reduce the excitability of the human motor cortex, but that augmented noradrenergic transmission increases motor cortical excitability by enhancing measures of intracortical facilitation and reducing inhibition. Both monoamines tend to enhance the excitability of human motoneurons. Overall, this work details the importance of neuromodulators for the output of human motor pathways and suggests that commonly prescribed monoaminergic drugs have off-label motor control uses outside of their typical psychiatric/neurological indications.
[ { "created": "Thu, 27 Apr 2023 23:10:10 GMT", "version": "v1" } ]
2023-05-04
[ [ "Thorstensen", "Jacob", "" ], [ "Henderson", "Tyler", "" ], [ "Kavanagh", "Justin", "" ] ]
Animal models indicate that motor behaviour is shaped by monoamine neurotransmitters released diffusely throughout the brain and spinal cord. We present strong evidence that human motor pathways are equally affected by neuromodulation through noradrenergic and serotonergic projections arising from the brainstem. To do so, we have identified and collated human experiments examining the off-label effects of well-characterised serotonergic and noradrenergic drugs on lab-based electrophysiology measures of corticospinal-motoneuronal excitability. Specifically, we focus on the effects that serotonin and noradrenaline associated drugs have on muscle responses to magnetic or electrical stimulation of the motor cortex and peripheral nerves, and other closely related tests of motoneuron excitability, to best segment drug effects to a supraspinal or spinal locus. We find that serotonin enhancing drugs tend to reduce the excitability of the human motor cortex, but that augmented noradrenergic transmission increases motor cortical excitability by enhancing measures of intracortical facilitation and reducing inhibition. Both monoamines tend to enhance the excitability of human motoneurons. Overall, this work details the importance of neuromodulators for the output of human motor pathways and suggests that commonly prescribed monoaminergic drugs have off-label motor control uses outside of their typical psychiatric/neurological indications.
2309.15950
Susan Martonosi
Abraham Holleran and Susan E. Martonosi and Michael Veatch
To Give or Not To Give: Pandemic Vaccine Donation Policy
21 pages, 4 figures. arXiv admin note: substantial text overlap with arXiv:2303.05917
null
null
null
q-bio.PE math.OC physics.soc-ph
http://creativecommons.org/licenses/by/4.0/
The global SARS-CoV-2 (COVID-19) pandemic highlighted the challenge of equitable vaccine distribution between high- and low-income countries. Many high-income countries were reluctant or slow to distribute extra doses of the vaccine to lower-income countries via the COVID-19 Vaccines Global Access (COVAX) collaboration. In addition to moral objections to such vaccine nationalism, vaccine inequity during a pandemic could contribute to the evolution of new variants of the virus and possibly increase total deaths, including in the high-income countries. Using the COVID-19 pandemic as a case study, we use the epidemiological model of Holleran et al. that incorporates virus mutation. We identify realistic scenarios under which a donor country prefers to donate vaccines before distributing them locally in order to minimize local deaths during a pandemic. We demonstrate that a nondonor-first vaccination policy can delay, sometimes dramatically, the emergence of more-contagious variants. Even more surprising, donating all vaccines is sometimes better for the donor country than a sharing policy in which half of the vaccines are donated and half are retained because of the impact donation can have on delaying the emergence of a more contagious virus. Nondonor-first vaccine allocation is optimal in scenarios in which the local health impact of the vaccine is limited or when delaying emergence of a variant is especially valuable. In all cases, we find that vaccine distribution is not a zero-sum game between donor and nondonor countries. Thus, in addition to moral reasons to avoid vaccine nationalism, donor nations can also realize local health benefits from donating vaccines. The insights yielded by this framework can be used to guide equitable vaccine distribution in future pandemics.
[ { "created": "Wed, 27 Sep 2023 19:08:35 GMT", "version": "v1" } ]
2023-09-29
[ [ "Holleran", "Abraham", "" ], [ "Martonosi", "Susan E.", "" ], [ "Veatch", "Michael", "" ] ]
The global SARS-CoV-2 (COVID-19) pandemic highlighted the challenge of equitable vaccine distribution between high- and low-income countries. Many high-income countries were reluctant or slow to distribute extra doses of the vaccine to lower-income countries via the COVID-19 Vaccines Global Access (COVAX) collaboration. In addition to moral objections to such vaccine nationalism, vaccine inequity during a pandemic could contribute to the evolution of new variants of the virus and possibly increase total deaths, including in the high-income countries. Using the COVID-19 pandemic as a case study, we use the epidemiological model of Holleran et al. that incorporates virus mutation. We identify realistic scenarios under which a donor country prefers to donate vaccines before distributing them locally in order to minimize local deaths during a pandemic. We demonstrate that a nondonor-first vaccination policy can delay, sometimes dramatically, the emergence of more-contagious variants. Even more surprising, donating all vaccines is sometimes better for the donor country than a sharing policy in which half of the vaccines are donated and half are retained because of the impact donation can have on delaying the emergence of a more contagious virus. Nondonor-first vaccine allocation is optimal in scenarios in which the local health impact of the vaccine is limited or when delaying emergence of a variant is especially valuable. In all cases, we find that vaccine distribution is not a zero-sum game between donor and nondonor countries. Thus, in addition to moral reasons to avoid vaccine nationalism, donor nations can also realize local health benefits from donating vaccines. The insights yielded by this framework can be used to guide equitable vaccine distribution in future pandemics.
2407.08751
Auguste Schulz
Jaivardhan Kapoor, Auguste Schulz, Julius Vetter, Felix Pei, Richard Gao, Jakob H. Macke
Latent Diffusion for Neural Spiking Data
null
null
null
null
q-bio.NC cs.LG
http://creativecommons.org/licenses/by-nc-sa/4.0/
Modern datasets in neuroscience enable unprecedented inquiries into the relationship between complex behaviors and the activity of many simultaneously recorded neurons. While latent variable models can successfully extract low-dimensional embeddings from such recordings, using them to generate realistic spiking data, especially in a behavior-dependent manner, still poses a challenge. Here, we present Latent Diffusion for Neural Spiking data (LDNS), a diffusion-based generative model with a low-dimensional latent space: LDNS employs an autoencoder with structured state-space (S4) layers to project discrete high-dimensional spiking data into continuous time-aligned latents. On these inferred latents, we train expressive (conditional) diffusion models, enabling us to sample neural activity with realistic single-neuron and population spiking statistics. We validate LDNS on synthetic data, accurately recovering latent structure, firing rates, and spiking statistics. Next, we demonstrate its flexibility by generating variable-length data that mimics human cortical activity during attempted speech. We show how to equip LDNS with an expressive observation model that accounts for single-neuron dynamics not mediated by the latent state, further increasing the realism of generated samples. Finally, conditional LDNS trained on motor cortical activity during diverse reaching behaviors can generate realistic spiking data given reach direction or unseen reach trajectories. In summary, LDNS simultaneously enables inference of low-dimensional latents and realistic conditional generation of neural spiking datasets, opening up further possibilities for simulating experimentally testable hypotheses.
[ { "created": "Thu, 27 Jun 2024 13:47:06 GMT", "version": "v1" } ]
2024-07-15
[ [ "Kapoor", "Jaivardhan", "" ], [ "Schulz", "Auguste", "" ], [ "Vetter", "Julius", "" ], [ "Pei", "Felix", "" ], [ "Gao", "Richard", "" ], [ "Macke", "Jakob H.", "" ] ]
Modern datasets in neuroscience enable unprecedented inquiries into the relationship between complex behaviors and the activity of many simultaneously recorded neurons. While latent variable models can successfully extract low-dimensional embeddings from such recordings, using them to generate realistic spiking data, especially in a behavior-dependent manner, still poses a challenge. Here, we present Latent Diffusion for Neural Spiking data (LDNS), a diffusion-based generative model with a low-dimensional latent space: LDNS employs an autoencoder with structured state-space (S4) layers to project discrete high-dimensional spiking data into continuous time-aligned latents. On these inferred latents, we train expressive (conditional) diffusion models, enabling us to sample neural activity with realistic single-neuron and population spiking statistics. We validate LDNS on synthetic data, accurately recovering latent structure, firing rates, and spiking statistics. Next, we demonstrate its flexibility by generating variable-length data that mimics human cortical activity during attempted speech. We show how to equip LDNS with an expressive observation model that accounts for single-neuron dynamics not mediated by the latent state, further increasing the realism of generated samples. Finally, conditional LDNS trained on motor cortical activity during diverse reaching behaviors can generate realistic spiking data given reach direction or unseen reach trajectories. In summary, LDNS simultaneously enables inference of low-dimensional latents and realistic conditional generation of neural spiking datasets, opening up further possibilities for simulating experimentally testable hypotheses.
q-bio/0506012
Yongyun Ji
Yong-Yun Ji, You-Quan Li, Jun-Wen Mao and Xiao-Wei Tang
The prion-like folding behavior in aggregated proteins
7 pages, 6 figures
Physical Review E 72, 041912 (2005), Virtual Journal of Biological Physics Research(October 15, 2005)
10.1103/PhysRevE.72.041912
null
q-bio.BM
null
We investigate the folding behavior of protein sequences by numerically studying all sequences with maximally compact lattice model through exhaustive enumeration. We get the prion-like behavior of protein folding. Individual proteins remaining stable in the isolated native state may change their conformations when they aggregate. We observe the folding properties as the interfacial interaction strength changes, and find that the strength must be strong enough before the propagation of the most stable structures happens.
[ { "created": "Thu, 9 Jun 2005 05:11:24 GMT", "version": "v1" } ]
2014-11-18
[ [ "Ji", "Yong-Yun", "" ], [ "Li", "You-Quan", "" ], [ "Mao", "Jun-Wen", "" ], [ "Tang", "Xiao-Wei", "" ] ]
We investigate the folding behavior of protein sequences by numerically studying all sequences with maximally compact lattice model through exhaustive enumeration. We get the prion-like behavior of protein folding. Individual proteins remaining stable in the isolated native state may change their conformations when they aggregate. We observe the folding properties as the interfacial interaction strength changes, and find that the strength must be strong enough before the propagation of the most stable structures happens.
2109.06011
Jan Sosulski
Jan Sosulski, David H\"ubner, Aaron Klein, Michael Tangermann
Online Optimization of Stimulation Speed in an Auditory Brain-Computer Interface under Time Constraints
null
null
null
null
q-bio.NC cs.LG stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The decoding of brain signals recorded via, e.g., an electroencephalogram, using machine learning is key to brain-computer interfaces (BCIs). Stimulation parameters or other experimental settings of the BCI protocol typically are chosen according to the literature. The decoding performance directly depends on the choice of parameters, as they influence the elicited brain signals and optimal parameters are subject-dependent. Thus a fast and automated selection procedure for experimental parameters could greatly improve the usability of BCIs. We evaluate a standalone random search and a combined Bayesian optimization with random search in a closed-loop auditory event-related potential protocol. We aimed at finding the individually best stimulation speed -- also known as stimulus onset asynchrony (SOA) -- that maximizes the classification performance of a regularized linear discriminant analysis. To make the Bayesian optimization feasible under noise and the time pressure posed by an online BCI experiment, we first used offline simulations to initialize and constrain the internal optimization model. Then we evaluated our approach online with 13 healthy subjects. We could show that for 8 out of 13 subjects, the proposed approach using Bayesian optimization succeeded to select the individually optimal SOA out of multiple evaluated SOA values. Our data suggests, however, that subjects were influenced to very different degrees by the SOA parameter. This makes the automatic parameter selection infeasible for subjects where the influence is limited. Our work proposes an approach to exploit the benefits of individualized experimental protocols and evaluated it in an auditory BCI. When applied to other experimental parameters our approach could enhance the usability of BCI for different target groups -- specifically if an individual disease progress may prevent the use of standard parameters.
[ { "created": "Thu, 26 Aug 2021 08:18:03 GMT", "version": "v1" } ]
2021-09-14
[ [ "Sosulski", "Jan", "" ], [ "Hübner", "David", "" ], [ "Klein", "Aaron", "" ], [ "Tangermann", "Michael", "" ] ]
The decoding of brain signals recorded via, e.g., an electroencephalogram, using machine learning is key to brain-computer interfaces (BCIs). Stimulation parameters or other experimental settings of the BCI protocol typically are chosen according to the literature. The decoding performance directly depends on the choice of parameters, as they influence the elicited brain signals and optimal parameters are subject-dependent. Thus a fast and automated selection procedure for experimental parameters could greatly improve the usability of BCIs. We evaluate a standalone random search and a combined Bayesian optimization with random search in a closed-loop auditory event-related potential protocol. We aimed at finding the individually best stimulation speed -- also known as stimulus onset asynchrony (SOA) -- that maximizes the classification performance of a regularized linear discriminant analysis. To make the Bayesian optimization feasible under noise and the time pressure posed by an online BCI experiment, we first used offline simulations to initialize and constrain the internal optimization model. Then we evaluated our approach online with 13 healthy subjects. We could show that for 8 out of 13 subjects, the proposed approach using Bayesian optimization succeeded to select the individually optimal SOA out of multiple evaluated SOA values. Our data suggests, however, that subjects were influenced to very different degrees by the SOA parameter. This makes the automatic parameter selection infeasible for subjects where the influence is limited. Our work proposes an approach to exploit the benefits of individualized experimental protocols and evaluated it in an auditory BCI. When applied to other experimental parameters our approach could enhance the usability of BCI for different target groups -- specifically if an individual disease progress may prevent the use of standard parameters.
2209.08402
Heyrim Cho
Heyrim Cho, Allison L. Lewis, Kathleen M. Storey, Helen M. Byrne
Designing experimental conditions to use the Lotka-Volterra model to infer tumor cell line interaction types
25 pages, 18 figures
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
The Lotka-Volterra model is widely used to model interactions between two species. Here, we generate synthetic data mimicking competitive, mutualistic and antagonistic interactions between two tumor cell lines, and then use the Lotka-Volterra model to infer the interaction type. Structural identifiability of the Lotka-Volterra model is confirmed, and practical identifiability is assessed for three experimental designs: (a) use of a single data set, with a mixture of both cell lines observed over time, (b) a sequential design where growth rates and carrying capacities are estimated using data from experiments in which each cell line is grown in isolation, and then interaction parameters are estimated from an experiment involving a mixture of both cell lines, and (c) a parallel experimental design where all model parameters are fitted to data from two mixtures simultaneously. In addition to assessing each design for practical identifiability, we investigate how the predictive power of the model-i.e., its ability to fit data for initial ratios other than those to which it was calibrated-is affected by the choice of experimental design. The parallel calibration procedure is found to be optimal and is further tested on in silico data generated from a spatially-resolved cellular automaton model, which accounts for oxygen consumption and allows for variation in the intensity level of the interaction between the two cell lines. We use this study to highlight the care that must be taken when interpreting parameter estimates for the spatially-averaged Lotka-Volterra model when it is calibrated against data produced by the spatially-resolved cellular automaton model, since baseline competition for space and resources in the CA model may contribute to a discrepancy between the type of interaction used to generate the CA data and the type of interaction inferred by the LV model.
[ { "created": "Sat, 17 Sep 2022 20:59:42 GMT", "version": "v1" } ]
2022-09-20
[ [ "Cho", "Heyrim", "" ], [ "Lewis", "Allison L.", "" ], [ "Storey", "Kathleen M.", "" ], [ "Byrne", "Helen M.", "" ] ]
The Lotka-Volterra model is widely used to model interactions between two species. Here, we generate synthetic data mimicking competitive, mutualistic and antagonistic interactions between two tumor cell lines, and then use the Lotka-Volterra model to infer the interaction type. Structural identifiability of the Lotka-Volterra model is confirmed, and practical identifiability is assessed for three experimental designs: (a) use of a single data set, with a mixture of both cell lines observed over time, (b) a sequential design where growth rates and carrying capacities are estimated using data from experiments in which each cell line is grown in isolation, and then interaction parameters are estimated from an experiment involving a mixture of both cell lines, and (c) a parallel experimental design where all model parameters are fitted to data from two mixtures simultaneously. In addition to assessing each design for practical identifiability, we investigate how the predictive power of the model-i.e., its ability to fit data for initial ratios other than those to which it was calibrated-is affected by the choice of experimental design. The parallel calibration procedure is found to be optimal and is further tested on in silico data generated from a spatially-resolved cellular automaton model, which accounts for oxygen consumption and allows for variation in the intensity level of the interaction between the two cell lines. We use this study to highlight the care that must be taken when interpreting parameter estimates for the spatially-averaged Lotka-Volterra model when it is calibrated against data produced by the spatially-resolved cellular automaton model, since baseline competition for space and resources in the CA model may contribute to a discrepancy between the type of interaction used to generate the CA data and the type of interaction inferred by the LV model.
0910.1953
Yunfeng Shan Dr.
Yunfeng Shan, and Xiu-Qing Li
GeneSupport Maximum Gene-Support Tree Approach to Species Phylogeny Inference
Application note
null
null
null
q-bio.GN q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Summary: GeneSupport implements a genome-scale algorithm: Maximum Gene-Support Tree to estimate species tree from gene trees based on multilocus sequences. It provides a new option for multiple genes to infer species tree. It is incorporated into popular phylogentic program: PHYLIP package with the same usage and user interface. It is suitable for phylogenetic methods such as maximum parsimony, maximum likelihood, Baysian and neighbour-joining, which is used to reconstruct single gene trees firstly with a variety of phylogenetic inference programs.
[ { "created": "Sat, 10 Oct 2009 22:31:55 GMT", "version": "v1" } ]
2009-10-13
[ [ "Shan", "Yunfeng", "" ], [ "Li", "Xiu-Qing", "" ] ]
Summary: GeneSupport implements a genome-scale algorithm: Maximum Gene-Support Tree to estimate species tree from gene trees based on multilocus sequences. It provides a new option for multiple genes to infer species tree. It is incorporated into popular phylogentic program: PHYLIP package with the same usage and user interface. It is suitable for phylogenetic methods such as maximum parsimony, maximum likelihood, Baysian and neighbour-joining, which is used to reconstruct single gene trees firstly with a variety of phylogenetic inference programs.
2012.05538
Qiyao Peng
Qiyao Peng, Fred Vermolen, Daphne Weihs
A Formalism for Modelling Traction forces and Cell Shape Evolution during Cell Migration in Various Biomedical Processes
null
null
10.1007/s10237-021-01456-2
null
q-bio.CB cs.NA math.NA
http://creativecommons.org/licenses/by/4.0/
The phenomenological model for cell shape deformation and cell migration (Chen et.al. 2018; Vermolen and Gefen 2012) is extended with the incorporation of cell traction forces and the evolution of cell equilibrium shapes as a result of cell differentiation. Plastic deformations of the extracellular matrix are modelled using morphoelasticity theory. The resulting partial differential differential equations are solved by the use of the finite element method. The paper treats various biological scenarios that entail cell migration and cell shape evolution. The experimental observations in Mak et.al. (2013), where transmigration of cancer cells through narrow apertures is studied, are reproduced using a Monte Carlo framework.
[ { "created": "Thu, 10 Dec 2020 09:29:44 GMT", "version": "v1" }, { "created": "Mon, 26 Apr 2021 14:08:25 GMT", "version": "v2" } ]
2021-04-27
[ [ "Peng", "Qiyao", "" ], [ "Vermolen", "Fred", "" ], [ "Weihs", "Daphne", "" ] ]
The phenomenological model for cell shape deformation and cell migration (Chen et.al. 2018; Vermolen and Gefen 2012) is extended with the incorporation of cell traction forces and the evolution of cell equilibrium shapes as a result of cell differentiation. Plastic deformations of the extracellular matrix are modelled using morphoelasticity theory. The resulting partial differential differential equations are solved by the use of the finite element method. The paper treats various biological scenarios that entail cell migration and cell shape evolution. The experimental observations in Mak et.al. (2013), where transmigration of cancer cells through narrow apertures is studied, are reproduced using a Monte Carlo framework.
2009.00359
Eva Smij\'akov\'a
Lubos Brim, Samuel Pastva, David Safranek, Eva Smijakova
Parallel One-Step Control of Parametrised Boolean Networks
null
null
null
null
q-bio.MN cs.SY eess.SY
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Boolean network (BN) is a simple model widely used to study complex dynamic behaviour of biological systems. Nonetheless, it might be difficult to gather enough data to precisely capture the behavior of a biological system into a set of Boolean functions. These issues can be dealt with to some extent using parametrised Boolean networks (ParBNs), as it allows to leave some update functions unspecified. In this paper, we attack the control problem for ParBNs with asynchronous semantics. While there is an extensive work on controlling BNs without parameters, the problem of control for ParBNs has not been in fact addressed yet. The goal of control is to ensure the stabilisation of a system in a given state using as few interventions as possible. There are many ways to control BN dynamics. Here, we consider the one-step approach in which the system is instantaneously perturbed out of its actual state. A naive approach to handle control of ParBNs is using parameter scan and solve the control problem for each parameter valuation separately using known techniques for non-parametrised BNs. This approach is however highly inefficient as the parameter space of ParBNs grows doubly-exponentially in the worst case. In this paper, we propose a novel semi-symbolic algorithm for the one-step control problem of ParBNs, that builds on a symbolic data structures to avoid scanning individual parameters. We evaluate the performance of our approach on real biological models.
[ { "created": "Tue, 1 Sep 2020 11:29:43 GMT", "version": "v1" } ]
2020-09-02
[ [ "Brim", "Lubos", "" ], [ "Pastva", "Samuel", "" ], [ "Safranek", "David", "" ], [ "Smijakova", "Eva", "" ] ]
Boolean network (BN) is a simple model widely used to study complex dynamic behaviour of biological systems. Nonetheless, it might be difficult to gather enough data to precisely capture the behavior of a biological system into a set of Boolean functions. These issues can be dealt with to some extent using parametrised Boolean networks (ParBNs), as it allows to leave some update functions unspecified. In this paper, we attack the control problem for ParBNs with asynchronous semantics. While there is an extensive work on controlling BNs without parameters, the problem of control for ParBNs has not been in fact addressed yet. The goal of control is to ensure the stabilisation of a system in a given state using as few interventions as possible. There are many ways to control BN dynamics. Here, we consider the one-step approach in which the system is instantaneously perturbed out of its actual state. A naive approach to handle control of ParBNs is using parameter scan and solve the control problem for each parameter valuation separately using known techniques for non-parametrised BNs. This approach is however highly inefficient as the parameter space of ParBNs grows doubly-exponentially in the worst case. In this paper, we propose a novel semi-symbolic algorithm for the one-step control problem of ParBNs, that builds on a symbolic data structures to avoid scanning individual parameters. We evaluate the performance of our approach on real biological models.
1611.04872
Emanuela Merelli
Marco Piangerelli, Matteo Rucco and Emanuela Merelli
Topological classifier for detecting the emergence of epileptic seizures
Open data: Physionet data-set
BMC Res Notes 11, 392, 2018
10.1186/s13104-018-3482-7
null
q-bio.NC cs.IT math.IT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this work we study how to apply topological data analysis to create a method suitable to classify EEGs of patients affected by epilepsy. The topological space constructed from the collection of EEGs signals is analyzed by Persistent Entropy acting as a global topological feature for discriminating between healthy and epileptic signals. The Physionet data-set has been used for testing the classifier.
[ { "created": "Sat, 12 Nov 2016 10:11:30 GMT", "version": "v1" } ]
2020-09-14
[ [ "Piangerelli", "Marco", "" ], [ "Rucco", "Matteo", "" ], [ "Merelli", "Emanuela", "" ] ]
In this work we study how to apply topological data analysis to create a method suitable to classify EEGs of patients affected by epilepsy. The topological space constructed from the collection of EEGs signals is analyzed by Persistent Entropy acting as a global topological feature for discriminating between healthy and epileptic signals. The Physionet data-set has been used for testing the classifier.
2211.16599
Dale Zhou
Dale Zhou, Jason Z. Kim, Adam R. Pines, Valerie J. Sydnor, David R. Roalf, John A. Detre, Ruben C. Gur, Raquel E. Gur, Theodore D. Satterthwaite, Dani S. Bassett
Compression supports low-dimensional representations of behavior across neural circuits
arXiv admin note: text overlap with arXiv:2001.05078
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by-nc-sa/4.0/
Dimensionality reduction, a form of compression, can simplify representations of information to increase efficiency and reveal general patterns. Yet, this simplification also forfeits information, thereby reducing representational capacity. Hence, the brain may benefit from generating both compressed and uncompressed activity, and may do so in a heterogeneous manner across diverse neural circuits that represent low-level (sensory) or high-level (cognitive) stimuli. However, precisely how compression and representational capacity differ across the cortex remains unknown. Here we predict different levels of compression across regional circuits by using random walks on networks to model activity flow and to formulate rate-distortion functions, which are the basis of lossy compression. Using a large sample of youth ($n=1,040$), we test predictions in two ways: by measuring the dimensionality of spontaneous activity from sensorimotor to association cortex, and by assessing the representational capacity for 24 behaviors in neural circuits and 20 cognitive variables in recurrent neural networks. Our network theory of compression predicts the dimensionality of activity ($t=12.13, p<0.001$) and the representational capacity of biological ($r=0.53, p=0.016$) and artificial ($r=0.61, p<0.001$) networks. The model suggests how a basic form of compression is an emergent property of activity flow between distributed circuits that communicate with the rest of the network.
[ { "created": "Tue, 29 Nov 2022 21:26:10 GMT", "version": "v1" } ]
2022-12-01
[ [ "Zhou", "Dale", "" ], [ "Kim", "Jason Z.", "" ], [ "Pines", "Adam R.", "" ], [ "Sydnor", "Valerie J.", "" ], [ "Roalf", "David R.", "" ], [ "Detre", "John A.", "" ], [ "Gur", "Ruben C.", "" ], [ "Gur", "Raquel E.", "" ], [ "Satterthwaite", "Theodore D.", "" ], [ "Bassett", "Dani S.", "" ] ]
Dimensionality reduction, a form of compression, can simplify representations of information to increase efficiency and reveal general patterns. Yet, this simplification also forfeits information, thereby reducing representational capacity. Hence, the brain may benefit from generating both compressed and uncompressed activity, and may do so in a heterogeneous manner across diverse neural circuits that represent low-level (sensory) or high-level (cognitive) stimuli. However, precisely how compression and representational capacity differ across the cortex remains unknown. Here we predict different levels of compression across regional circuits by using random walks on networks to model activity flow and to formulate rate-distortion functions, which are the basis of lossy compression. Using a large sample of youth ($n=1,040$), we test predictions in two ways: by measuring the dimensionality of spontaneous activity from sensorimotor to association cortex, and by assessing the representational capacity for 24 behaviors in neural circuits and 20 cognitive variables in recurrent neural networks. Our network theory of compression predicts the dimensionality of activity ($t=12.13, p<0.001$) and the representational capacity of biological ($r=0.53, p=0.016$) and artificial ($r=0.61, p<0.001$) networks. The model suggests how a basic form of compression is an emergent property of activity flow between distributed circuits that communicate with the rest of the network.
1511.01956
Elizabeth Allman
Elizabeth S. Allman, John A. Rhodes, Seth Sullivant
Statistically-Consistent k-mer Methods for Phylogenetic Tree Reconstruction
25 pages, 9 figures figure added, to appear, JCB
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Frequencies of $k$-mers in sequences are sometimes used as a basis for inferring phylogenetic trees without first obtaining a multiple sequence alignment. We show that a standard approach of using the squared-Euclidean distance between $k$-mer vectors to approximate a tree metric can be statistically inconsistent. To remedy this, we derive model-based distance corrections for orthologous sequences without gaps, which lead to consistent tree inference. The identifiability of model parameters from $k$-mer frequencies is also studied. Finally, we report simulations showing the corrected distance out-performs many other $k$-mer methods, even when sequences are generated with an insertion and deletion process. These results have implications for multiple sequence alignment as well, since $k$-mer methods are usually the first step in constructing a guide tree for such algorithms.
[ { "created": "Thu, 5 Nov 2015 23:46:49 GMT", "version": "v1" }, { "created": "Thu, 14 Jan 2016 18:48:11 GMT", "version": "v2" } ]
2016-01-15
[ [ "Allman", "Elizabeth S.", "" ], [ "Rhodes", "John A.", "" ], [ "Sullivant", "Seth", "" ] ]
Frequencies of $k$-mers in sequences are sometimes used as a basis for inferring phylogenetic trees without first obtaining a multiple sequence alignment. We show that a standard approach of using the squared-Euclidean distance between $k$-mer vectors to approximate a tree metric can be statistically inconsistent. To remedy this, we derive model-based distance corrections for orthologous sequences without gaps, which lead to consistent tree inference. The identifiability of model parameters from $k$-mer frequencies is also studied. Finally, we report simulations showing the corrected distance out-performs many other $k$-mer methods, even when sequences are generated with an insertion and deletion process. These results have implications for multiple sequence alignment as well, since $k$-mer methods are usually the first step in constructing a guide tree for such algorithms.
2305.08316
Ziyuan Zhao
Ziyuan Zhao, Peisheng Qian, Xulei Yang, Zeng Zeng, Cuntai Guan, Wai Leong Tam, Xiaoli Li
SemiGNN-PPI: Self-Ensembling Multi-Graph Neural Network for Efficient and Generalizable Protein-Protein Interaction Prediction
Accepted by IJCAI 2023
null
null
null
q-bio.MN cs.AI cs.CE cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Protein-protein interactions (PPIs) are crucial in various biological processes and their study has significant implications for drug development and disease diagnosis. Existing deep learning methods suffer from significant performance degradation under complex real-world scenarios due to various factors, e.g., label scarcity and domain shift. In this paper, we propose a self-ensembling multigraph neural network (SemiGNN-PPI) that can effectively predict PPIs while being both efficient and generalizable. In SemiGNN-PPI, we not only model the protein correlations but explore the label dependencies by constructing and processing multiple graphs from the perspectives of both features and labels in the graph learning process. We further marry GNN with Mean Teacher to effectively leverage unlabeled graph-structured PPI data for self-ensemble graph learning. We also design multiple graph consistency constraints to align the student and teacher graphs in the feature embedding space, enabling the student model to better learn from the teacher model by incorporating more relationships. Extensive experiments on PPI datasets of different scales with different evaluation settings demonstrate that SemiGNN-PPI outperforms state-of-the-art PPI prediction methods, particularly in challenging scenarios such as training with limited annotations and testing on unseen data.
[ { "created": "Mon, 15 May 2023 03:06:44 GMT", "version": "v1" } ]
2023-05-16
[ [ "Zhao", "Ziyuan", "" ], [ "Qian", "Peisheng", "" ], [ "Yang", "Xulei", "" ], [ "Zeng", "Zeng", "" ], [ "Guan", "Cuntai", "" ], [ "Tam", "Wai Leong", "" ], [ "Li", "Xiaoli", "" ] ]
Protein-protein interactions (PPIs) are crucial in various biological processes and their study has significant implications for drug development and disease diagnosis. Existing deep learning methods suffer from significant performance degradation under complex real-world scenarios due to various factors, e.g., label scarcity and domain shift. In this paper, we propose a self-ensembling multigraph neural network (SemiGNN-PPI) that can effectively predict PPIs while being both efficient and generalizable. In SemiGNN-PPI, we not only model the protein correlations but explore the label dependencies by constructing and processing multiple graphs from the perspectives of both features and labels in the graph learning process. We further marry GNN with Mean Teacher to effectively leverage unlabeled graph-structured PPI data for self-ensemble graph learning. We also design multiple graph consistency constraints to align the student and teacher graphs in the feature embedding space, enabling the student model to better learn from the teacher model by incorporating more relationships. Extensive experiments on PPI datasets of different scales with different evaluation settings demonstrate that SemiGNN-PPI outperforms state-of-the-art PPI prediction methods, particularly in challenging scenarios such as training with limited annotations and testing on unseen data.
2405.09327
C\'ecile An\'e
Benjamin Teo, Paul Bastide, C\'ecile An\'e
Leveraging graphical model techniques to study evolution on phylogenetic networks
null
null
null
null
q-bio.PE stat.CO
http://creativecommons.org/licenses/by/4.0/
The evolution of molecular and phenotypic traits is commonly modelled using Markov processes along a rooted phylogeny. This phylogeny can be a tree, or a network if it includes reticulations, representing events such as hybridization or admixture. Computing the likelihood of data observed at the leaves is costly as the size and complexity of the phylogeny grows. Efficient algorithms exist for trees, but cannot be applied to networks. We show that a vast array of models for trait evolution along phylogenetic networks can be reformulated as graphical models, for which efficient belief propagation algorithms exist. We provide a brief review of belief propagation on general graphical models, then focus on linear Gaussian models for continuous traits. We show how belief propagation techniques can be applied for exact or approximate (but more scalable) likelihood and gradient calculations, and prove novel results for efficient parameter inference of some models. We highlight the possible fruitful interactions between graphical models and phylogenetic methods. For example, approximate likelihood approaches have the potential to greatly reduce computational costs for phylogenies with reticulations.
[ { "created": "Wed, 15 May 2024 13:27:03 GMT", "version": "v1" } ]
2024-05-16
[ [ "Teo", "Benjamin", "" ], [ "Bastide", "Paul", "" ], [ "Ané", "Cécile", "" ] ]
The evolution of molecular and phenotypic traits is commonly modelled using Markov processes along a rooted phylogeny. This phylogeny can be a tree, or a network if it includes reticulations, representing events such as hybridization or admixture. Computing the likelihood of data observed at the leaves is costly as the size and complexity of the phylogeny grows. Efficient algorithms exist for trees, but cannot be applied to networks. We show that a vast array of models for trait evolution along phylogenetic networks can be reformulated as graphical models, for which efficient belief propagation algorithms exist. We provide a brief review of belief propagation on general graphical models, then focus on linear Gaussian models for continuous traits. We show how belief propagation techniques can be applied for exact or approximate (but more scalable) likelihood and gradient calculations, and prove novel results for efficient parameter inference of some models. We highlight the possible fruitful interactions between graphical models and phylogenetic methods. For example, approximate likelihood approaches have the potential to greatly reduce computational costs for phylogenies with reticulations.
2104.01468
Nathan Ranno
Nathan Ranno, Dong Si
Neural Representations of Cryo-EM Maps and a Graph-Based Interpretation
15 pages, 8 figures
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Advances in imagery at atomic and near-atomic resolution, such as cryogenic electron microscopy (cryo-EM), have led to an influx of high resolution images of proteins and other macromolecular structures to data banks worldwide. Producing a protein structure from the discrete voxel grid data of cryo-EM maps involves interpolation into the continuous spatial domain. We present a novel data format called the neural cryo-EM map, which is formed from a set of neural networks that accurately parameterize cryo-EM maps and provide native, spatially continuous data for density and gradient. As a case study of this data format, we create graph-based interpretations of high resolution experimental cryo-EM maps. Normalized cryo-EM map values interpolated using the non-linear neural cryo-EM format are more accurate, consistently scoring less than 0.01 mean absolute error, than a conventional tri-linear interpolation, which scores up to 0.12 mean absolute error. Our graph-based interpretations of 115 experimental cryo-EM maps from 1.15 to 4.0 Angstrom resolution provide high coverage of the underlying amino acid residue locations, while accuracy of nodes is correlated with resolution. The nodes of graphs created from atomic resolution maps (higher than 1.6 Angstroms) provide greater than 99% residue coverage as well as 85% full atomic coverage with a mean of than 0.19 Angstrom root mean squared deviation (RMSD). Other graphs have a mean 84% residue coverage with less specificity of the nodes due to experimental noise and differences of density context at lower resolutions. This work may be generalized for transforming any 3D grid-based data format into non-linear, continuous, and differentiable format for the downstream geometric deep learning applications.
[ { "created": "Sat, 3 Apr 2021 19:49:16 GMT", "version": "v1" } ]
2021-04-06
[ [ "Ranno", "Nathan", "" ], [ "Si", "Dong", "" ] ]
Advances in imagery at atomic and near-atomic resolution, such as cryogenic electron microscopy (cryo-EM), have led to an influx of high resolution images of proteins and other macromolecular structures to data banks worldwide. Producing a protein structure from the discrete voxel grid data of cryo-EM maps involves interpolation into the continuous spatial domain. We present a novel data format called the neural cryo-EM map, which is formed from a set of neural networks that accurately parameterize cryo-EM maps and provide native, spatially continuous data for density and gradient. As a case study of this data format, we create graph-based interpretations of high resolution experimental cryo-EM maps. Normalized cryo-EM map values interpolated using the non-linear neural cryo-EM format are more accurate, consistently scoring less than 0.01 mean absolute error, than a conventional tri-linear interpolation, which scores up to 0.12 mean absolute error. Our graph-based interpretations of 115 experimental cryo-EM maps from 1.15 to 4.0 Angstrom resolution provide high coverage of the underlying amino acid residue locations, while accuracy of nodes is correlated with resolution. The nodes of graphs created from atomic resolution maps (higher than 1.6 Angstroms) provide greater than 99% residue coverage as well as 85% full atomic coverage with a mean of than 0.19 Angstrom root mean squared deviation (RMSD). Other graphs have a mean 84% residue coverage with less specificity of the nodes due to experimental noise and differences of density context at lower resolutions. This work may be generalized for transforming any 3D grid-based data format into non-linear, continuous, and differentiable format for the downstream geometric deep learning applications.
2303.14248
Mattia Sensi
Rossella Della Marca, Alberto d'Onofrio, Mattia Sensi, Sara Sottile
A geometric analysis of the impact of large but finite switching rates on vaccination evolutionary games
26 pages, 6 figures
Nonlinear Analysis: Real World Applications, Volume 75, February 2024, 103986
10.1016/j.nonrwa.2023.103986
null
q-bio.PE math.DS
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In contemporary society, social networks accelerate decision dynamics causing a rapid switch of opinions in a number of fields, including the prevention of infectious diseases by means of vaccines. This means that opinion dynamics can nowadays be much faster than the spread of epidemics. Hence, we propose a Susceptible-Infectious-Removed epidemic model coupled with an evolutionary vaccination game embedding the public health system efforts to increase vaccine uptake. This results in a global system ``epidemic model + evolutionary game''. The epidemiological novelty of this work is that we assume that the switching to the strategy ``pro vaccine'' depends on the incidence of the disease. As a consequence of the above-mentioned accelerated decisions, the dynamics of the system acts on two different scales: a fast scale for the vaccine decisions and a slower scale for the spread of the disease. Another, and more methodological, element of novelty is that we apply Geometrical Singular Perturbation Theory (GSPT) to such a two-scale model and we then compare the geometric analysis with the Quasi-Steady-State Approximation (QSSA) approach, showing a criticality in the latter. Later, we apply the GSPT approach to the disease prevalence-based model already studied in (Della Marca and d'Onofrio, Comm Nonl Sci Num Sim, 2021) via the QSSA approach by considering medium-large values of the strategy switching parameter.
[ { "created": "Fri, 24 Mar 2023 19:26:51 GMT", "version": "v1" } ]
2023-11-06
[ [ "Della Marca", "Rossella", "" ], [ "d'Onofrio", "Alberto", "" ], [ "Sensi", "Mattia", "" ], [ "Sottile", "Sara", "" ] ]
In contemporary society, social networks accelerate decision dynamics causing a rapid switch of opinions in a number of fields, including the prevention of infectious diseases by means of vaccines. This means that opinion dynamics can nowadays be much faster than the spread of epidemics. Hence, we propose a Susceptible-Infectious-Removed epidemic model coupled with an evolutionary vaccination game embedding the public health system efforts to increase vaccine uptake. This results in a global system ``epidemic model + evolutionary game''. The epidemiological novelty of this work is that we assume that the switching to the strategy ``pro vaccine'' depends on the incidence of the disease. As a consequence of the above-mentioned accelerated decisions, the dynamics of the system acts on two different scales: a fast scale for the vaccine decisions and a slower scale for the spread of the disease. Another, and more methodological, element of novelty is that we apply Geometrical Singular Perturbation Theory (GSPT) to such a two-scale model and we then compare the geometric analysis with the Quasi-Steady-State Approximation (QSSA) approach, showing a criticality in the latter. Later, we apply the GSPT approach to the disease prevalence-based model already studied in (Della Marca and d'Onofrio, Comm Nonl Sci Num Sim, 2021) via the QSSA approach by considering medium-large values of the strategy switching parameter.
2310.20601
Jacob Tanner
Jacob Tanner, Sina Mansour L., Ludovico Coletta, Alessandro Gozzi, Richard F. Betzel
Functional connectivity modules in recurrent neural networks: function, origin and dynamics
null
null
null
null
q-bio.NC cs.AI cs.LG
http://creativecommons.org/licenses/by-nc-nd/4.0/
Understanding the ubiquitous phenomenon of neural synchronization across species and organizational levels is crucial for decoding brain function. Despite its prevalence, the specific functional role, origin, and dynamical implication of modular structures in correlation-based networks remains ambiguous. Using recurrent neural networks trained on systems neuroscience tasks, this study investigates these important characteristics of modularity in correlation networks. We demonstrate that modules are functionally coherent units that contribute to specialized information processing. We show that modules form spontaneously from asymmetries in the sign and weight of projections from the input layer to the recurrent layer. Moreover, we show that modules define connections with similar roles in governing system behavior and dynamics. Collectively, our findings clarify the function, formation, and operational significance of functional connectivity modules, offering insights into cortical function and laying the groundwork for further studies on brain function, development, and dynamics.
[ { "created": "Tue, 31 Oct 2023 16:37:01 GMT", "version": "v1" } ]
2023-11-01
[ [ "Tanner", "Jacob", "" ], [ "L.", "Sina Mansour", "" ], [ "Coletta", "Ludovico", "" ], [ "Gozzi", "Alessandro", "" ], [ "Betzel", "Richard F.", "" ] ]
Understanding the ubiquitous phenomenon of neural synchronization across species and organizational levels is crucial for decoding brain function. Despite its prevalence, the specific functional role, origin, and dynamical implication of modular structures in correlation-based networks remains ambiguous. Using recurrent neural networks trained on systems neuroscience tasks, this study investigates these important characteristics of modularity in correlation networks. We demonstrate that modules are functionally coherent units that contribute to specialized information processing. We show that modules form spontaneously from asymmetries in the sign and weight of projections from the input layer to the recurrent layer. Moreover, we show that modules define connections with similar roles in governing system behavior and dynamics. Collectively, our findings clarify the function, formation, and operational significance of functional connectivity modules, offering insights into cortical function and laying the groundwork for further studies on brain function, development, and dynamics.
2311.13801
Sikta Das Adhikari
Sikta Das Adhikari, Jiaxin Yang, Jianrong Wang, Yuehua Cui
A selective review of recent developments in spatially variable gene detection for spatial transcriptomics
null
null
10.1016/j.csbj.2024.01.016
null
q-bio.GN
http://creativecommons.org/licenses/by/4.0/
With the emergence of advanced spatial transcriptomic technologies, there has been a surge in research papers dedicated to analyzing spatial transcriptomics data, resulting in significant contributions to our understanding of biology. The initial stage of downstream analysis of spatial transcriptomic data has centered on identifying spatially variable genes (SVGs) or genes expressed with specific spatial patterns across the tissue. SVG detection is an important task since many downstream analyses depend on these selected SVGs. Over the past few years, a plethora of new methods have been proposed for the detection of SVGs, accompanied by numerous innovative concepts and discussions. This article provides a selective review of methods and their practical implementations, offering valuable insights into the current literature in this field.
[ { "created": "Thu, 23 Nov 2023 04:20:14 GMT", "version": "v1" } ]
2024-04-11
[ [ "Adhikari", "Sikta Das", "" ], [ "Yang", "Jiaxin", "" ], [ "Wang", "Jianrong", "" ], [ "Cui", "Yuehua", "" ] ]
With the emergence of advanced spatial transcriptomic technologies, there has been a surge in research papers dedicated to analyzing spatial transcriptomics data, resulting in significant contributions to our understanding of biology. The initial stage of downstream analysis of spatial transcriptomic data has centered on identifying spatially variable genes (SVGs) or genes expressed with specific spatial patterns across the tissue. SVG detection is an important task since many downstream analyses depend on these selected SVGs. Over the past few years, a plethora of new methods have been proposed for the detection of SVGs, accompanied by numerous innovative concepts and discussions. This article provides a selective review of methods and their practical implementations, offering valuable insights into the current literature in this field.
1812.05668
Jiansheng Wu
Hang Yu, Ziyi Liu, Jiansheng Wu
Forgetting in order to Remember Better
4 pages, 2 figures
null
null
null
q-bio.NC physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In human memory, forgetting occur rapidly after the remembering and the rate of forgetting slowed down as time went. This is so-called the Ebbinghaus forgetting curve. There are many explanations of how this curve occur based on the properties of the brains. In this article, we use a simple mathematical model to explain the mechanism of forgetting based on rearrangement inequality and get a general formalism for short-term and long-term memory and use it to fit the Ebbinghaus forgetting curve. We also find out that forgetting is not a flaw, instead it is help to improve the efficiency of remembering when human confront different situations by reducing the interference of information and reducing the number of retrievals. Furthurmove, we find that the interference of informations limits the capacity of human memory, which is the "magic number seven".
[ { "created": "Wed, 12 Dec 2018 18:54:27 GMT", "version": "v1" } ]
2018-12-17
[ [ "Yu", "Hang", "" ], [ "Liu", "Ziyi", "" ], [ "Wu", "Jiansheng", "" ] ]
In human memory, forgetting occur rapidly after the remembering and the rate of forgetting slowed down as time went. This is so-called the Ebbinghaus forgetting curve. There are many explanations of how this curve occur based on the properties of the brains. In this article, we use a simple mathematical model to explain the mechanism of forgetting based on rearrangement inequality and get a general formalism for short-term and long-term memory and use it to fit the Ebbinghaus forgetting curve. We also find out that forgetting is not a flaw, instead it is help to improve the efficiency of remembering when human confront different situations by reducing the interference of information and reducing the number of retrievals. Furthurmove, we find that the interference of informations limits the capacity of human memory, which is the "magic number seven".
2201.08980
Thomas Sturm
Christoph L\"uders, Thomas Sturm, Ovidiu Radulescu
ODEbase: A Repository of ODE Systems for Systems Biology
null
null
null
null
q-bio.MN cs.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Recently, symbolic computation and computer algebra systems have been successfully applied in systems biology, especially in chemical reaction network theory. One advantage of symbolic computation is its potential for qualitative answers to biological questions. Qualitative methods analyze dynamical input systems as formal objects, in contrast to investigating only part of the state space, as is the case with numerical simulation. However, symbolic computation tools and libraries have a different set of requirements for their input data than their numerical counterparts. A common format used in mathematical modeling of biological processes is SBML. We illustrate that the use of SBML data in symbolic computation requires significant pre-processing, incorporating external biological and mathematical expertise. ODEbase provides high quality symbolic computation input data derived from established existing biomodels, covering in particular the BioModels database.
[ { "created": "Sat, 22 Jan 2022 07:22:01 GMT", "version": "v1" } ]
2022-01-25
[ [ "Lüders", "Christoph", "" ], [ "Sturm", "Thomas", "" ], [ "Radulescu", "Ovidiu", "" ] ]
Recently, symbolic computation and computer algebra systems have been successfully applied in systems biology, especially in chemical reaction network theory. One advantage of symbolic computation is its potential for qualitative answers to biological questions. Qualitative methods analyze dynamical input systems as formal objects, in contrast to investigating only part of the state space, as is the case with numerical simulation. However, symbolic computation tools and libraries have a different set of requirements for their input data than their numerical counterparts. A common format used in mathematical modeling of biological processes is SBML. We illustrate that the use of SBML data in symbolic computation requires significant pre-processing, incorporating external biological and mathematical expertise. ODEbase provides high quality symbolic computation input data derived from established existing biomodels, covering in particular the BioModels database.
0710.1333
Jesus M. Cortes
J.M. Cortes, A. Greve, A.B. Barrett and M.C.W. van Rossum
Dynamics and robustness of familiarity memory
22 pages, 3 figures
null
null
null
q-bio.NC
null
When one is presented with an item or a face, one can sometimes have a sense of recognition without being able to recall where or when one has encountered it before. This sense of recognition is known as familiarity. Following previous computational models of familiarity memory we investigate the dynamical properties of familiarity discrimination, and contrast two different familiarity discriminators: one based on the energy of the neural network, and the other based on the time derivative of the energy. We show how the familiarity signal decays after a stimulus is presented, and examine the robustness of the familiarity discriminator in the presence of random fluctuations in neural activity. For both discriminators we establish, via a combined method of signal-to-noise ratio and mean field analysis, how the maximum number of successfully discriminated stimuli depends on the noise level.
[ { "created": "Sun, 7 Oct 2007 00:14:07 GMT", "version": "v1" } ]
2007-10-09
[ [ "Cortes", "J. M.", "" ], [ "Greve", "A.", "" ], [ "Barrett", "A. B.", "" ], [ "van Rossum", "M. C. W.", "" ] ]
When one is presented with an item or a face, one can sometimes have a sense of recognition without being able to recall where or when one has encountered it before. This sense of recognition is known as familiarity. Following previous computational models of familiarity memory we investigate the dynamical properties of familiarity discrimination, and contrast two different familiarity discriminators: one based on the energy of the neural network, and the other based on the time derivative of the energy. We show how the familiarity signal decays after a stimulus is presented, and examine the robustness of the familiarity discriminator in the presence of random fluctuations in neural activity. For both discriminators we establish, via a combined method of signal-to-noise ratio and mean field analysis, how the maximum number of successfully discriminated stimuli depends on the noise level.
q-bio/0406004
Manoj Gopalakrishnan
Manoj Gopalakrishnan, Kimberly Forsten-Williams, Theressa R. Cassino, Luz Padro, Thomas E. Ryan and Uwe C. Tauber
Ligand Rebinding: Self-consistent Mean-field Theory and Numerical Simulations Applied to SPR Studies
minor errors in notation corrected, added figure, appendix and glossary, 37 pages, to appear in Eur. Biophys. J
Eur. Biophys. J. 34 (2005) 943
null
null
q-bio.QM cond-mat.stat-mech q-bio.SC
null
Rebinding of dissociated ligands from cell surface proteins can confound quantitative measurements of dissociation rates important for characterizing the affinity of binding interactions. This can be true also for in vitro techniques such as surface plasmon resonance (SPR). We present experimental results using SPR for the interaction of insulin-like growth factor-I (IGF-I) with one of its binding proteins, IGF binding protein-3 (IGFBP-3), and show that rebinding, even with the addition of soluble heparin in the dissociation phase, does not exhibit the expected exponential decay characteristic of a 1:1 binding reaction. We thus consider the effect of (multiple) rebinding events and, within a self-consistent mean-field approximation, we derive the complete mathematical form for the fraction of bound ligand as a function of time. We show that, except for very low surface coverage/association rate, this function is non-exponential at all times, indicating that multiple rebinding events strongly influence dissociation even at early times. We compare the mean-field results with numerical simulations and find good agreement, although deviations are measurable in certain cases. Our analysis of the IGF-I-IGFBP-3 data indicates that rebinding is prominent for this system and that the theoretical predictions fit the experimental data well. Our results provide a means for analyzing SPR biosensor data where rebinding is problematic and a methodology to do so is presented.
[ { "created": "Wed, 2 Jun 2004 07:05:42 GMT", "version": "v1" }, { "created": "Wed, 6 Oct 2004 08:23:48 GMT", "version": "v2" }, { "created": "Tue, 1 Feb 2005 12:16:39 GMT", "version": "v3" } ]
2007-05-23
[ [ "Gopalakrishnan", "Manoj", "" ], [ "Forsten-Williams", "Kimberly", "" ], [ "Cassino", "Theressa R.", "" ], [ "Padro", "Luz", "" ], [ "Ryan", "Thomas E.", "" ], [ "Tauber", "Uwe C.", "" ] ]
Rebinding of dissociated ligands from cell surface proteins can confound quantitative measurements of dissociation rates important for characterizing the affinity of binding interactions. This can be true also for in vitro techniques such as surface plasmon resonance (SPR). We present experimental results using SPR for the interaction of insulin-like growth factor-I (IGF-I) with one of its binding proteins, IGF binding protein-3 (IGFBP-3), and show that rebinding, even with the addition of soluble heparin in the dissociation phase, does not exhibit the expected exponential decay characteristic of a 1:1 binding reaction. We thus consider the effect of (multiple) rebinding events and, within a self-consistent mean-field approximation, we derive the complete mathematical form for the fraction of bound ligand as a function of time. We show that, except for very low surface coverage/association rate, this function is non-exponential at all times, indicating that multiple rebinding events strongly influence dissociation even at early times. We compare the mean-field results with numerical simulations and find good agreement, although deviations are measurable in certain cases. Our analysis of the IGF-I-IGFBP-3 data indicates that rebinding is prominent for this system and that the theoretical predictions fit the experimental data well. Our results provide a means for analyzing SPR biosensor data where rebinding is problematic and a methodology to do so is presented.
2105.02144
Sandeep Juneja
Sandeep Juneja and Daksh Mittal
Modelling the Second Covid-19 Wave in Mumbai
34 pages, 33 figures (including 3 tables)
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
India has been hit by a huge second wave of Covid-19 that started in mid-February 2021. Mumbai was amongst the first cities to see the increase. In this report, we use our agent based simulator to computationally study the second wave in Mumbai. We build upon our earlier analysis, where projections were made from November 2020 onwards. We use our simulator to conduct an extensive scenario analysis - we play out many plausible scenarios through varying economic activity, reinfection levels, population compliance, infectiveness, prevalence and lethality of the possible variant strains, and infection spread via local trains to arrive at those that may better explain the second wave fatality numbers. We observe and highlight that timings of peak and valley of the fatalities in the second wave are robust to many plausible scenarios, suggesting that they are likely to be accurate projections for Mumbai. During the second wave, the observed fatalities were low in February and mid-March and saw a phase change or a steep increase in the growth rate after around late March. We conduct extensive experiments to replicate this observed sharp convexity. This is not an easy phenomena to replicate, and we find that explanations such as increased laxity in the population, increased reinfections, increased intensity of infections in Mumbai transportation, increased lethality in the virus, or a combination amongst them, generally do a poor job of matching this pattern. We find that the most likely explanation is presence of small amount of extremely infective variant on February 1 that grows rapidly thereafter and becomes a dominant strain by Mid-March. From a prescriptive view, this points to an urgent need for extensive and continuous genome sequencing to establish existence and prevalence of different virus strains in Mumbai and in India, as they evolve over time.
[ { "created": "Wed, 5 May 2021 15:51:56 GMT", "version": "v1" } ]
2021-05-06
[ [ "Juneja", "Sandeep", "" ], [ "Mittal", "Daksh", "" ] ]
India has been hit by a huge second wave of Covid-19 that started in mid-February 2021. Mumbai was amongst the first cities to see the increase. In this report, we use our agent based simulator to computationally study the second wave in Mumbai. We build upon our earlier analysis, where projections were made from November 2020 onwards. We use our simulator to conduct an extensive scenario analysis - we play out many plausible scenarios through varying economic activity, reinfection levels, population compliance, infectiveness, prevalence and lethality of the possible variant strains, and infection spread via local trains to arrive at those that may better explain the second wave fatality numbers. We observe and highlight that timings of peak and valley of the fatalities in the second wave are robust to many plausible scenarios, suggesting that they are likely to be accurate projections for Mumbai. During the second wave, the observed fatalities were low in February and mid-March and saw a phase change or a steep increase in the growth rate after around late March. We conduct extensive experiments to replicate this observed sharp convexity. This is not an easy phenomena to replicate, and we find that explanations such as increased laxity in the population, increased reinfections, increased intensity of infections in Mumbai transportation, increased lethality in the virus, or a combination amongst them, generally do a poor job of matching this pattern. We find that the most likely explanation is presence of small amount of extremely infective variant on February 1 that grows rapidly thereafter and becomes a dominant strain by Mid-March. From a prescriptive view, this points to an urgent need for extensive and continuous genome sequencing to establish existence and prevalence of different virus strains in Mumbai and in India, as they evolve over time.
2304.12825
Fang Sun
Fang Sun, Zhihao Zhan, Hongyu Guo, Ming Zhang, Jian Tang
GraphVF: Controllable Protein-Specific 3D Molecule Generation with Variational Flow
15 pages, 8 figures
null
null
null
q-bio.BM cs.AI cs.LG
http://creativecommons.org/licenses/by-sa/4.0/
Designing molecules that bind to specific target proteins is a fundamental task in drug discovery. Recent models leverage geometric constraints to generate ligand molecules that bind cohesively with specific protein pockets. However, these models cannot effectively generate 3D molecules with 2D skeletal curtailments and property constraints, which are pivotal to drug potency and development. To tackle this challenge, we propose GraphVF, a variational flow-based framework that combines 2D topology and 3D geometry, for controllable generation of binding 3D molecules. Empirically, our method achieves state-of-the-art binding affinity and realistic sub-structural layouts for protein-specific generation. In particular, GraphVF represents the first controllable geometry-aware, protein-specific molecule generation method, which can generate binding 3D molecules with tailored sub-structures and physio-chemical properties. Our code is available at https://github.com/Franco-Solis/GraphVF-code.
[ { "created": "Thu, 23 Feb 2023 17:32:49 GMT", "version": "v1" } ]
2023-04-26
[ [ "Sun", "Fang", "" ], [ "Zhan", "Zhihao", "" ], [ "Guo", "Hongyu", "" ], [ "Zhang", "Ming", "" ], [ "Tang", "Jian", "" ] ]
Designing molecules that bind to specific target proteins is a fundamental task in drug discovery. Recent models leverage geometric constraints to generate ligand molecules that bind cohesively with specific protein pockets. However, these models cannot effectively generate 3D molecules with 2D skeletal curtailments and property constraints, which are pivotal to drug potency and development. To tackle this challenge, we propose GraphVF, a variational flow-based framework that combines 2D topology and 3D geometry, for controllable generation of binding 3D molecules. Empirically, our method achieves state-of-the-art binding affinity and realistic sub-structural layouts for protein-specific generation. In particular, GraphVF represents the first controllable geometry-aware, protein-specific molecule generation method, which can generate binding 3D molecules with tailored sub-structures and physio-chemical properties. Our code is available at https://github.com/Franco-Solis/GraphVF-code.
2209.00380
Nathalie Buonviso
Maxime Juventin, Mickael Zbili, Nicolas Fourcaud-Trocm\'e, Samuel Garcia, Nathalie Buonviso (CRNL), Corine Amat
Respiratory rhythm entrains membrane potential and spiking of non-olfactory neurons
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In recent years, several studies have tended to show a respiratory drive in numerous brain areas so that the respiratory rhythm could be considered as a master clock promoting communication between distant brain areas. However, outside of the olfactory system it is not known if respiration-related oscillation (RRo) could exist in the membrane potential (MP) of neurons neither if it can structure spiking discharge. To fill this gap, we co-recorded MP and LFP activities in different non-olfactory brain areas: median prefrontal cortex (mPFC), primary somatosensory cortex (S1), primary visual cortex (V1), and hippocampus (HPC), in urethane-anesthetized rats. Using respiratory cycle by respiratory cycle analysis, we observed that respiration could modulate both MP and spiking discharges in all recorded areas. Further quantifications revealed RRo episodes were transient in most neurons (5 consecutive cycles in average). RRo development in MP was largely influenced by the presence of respiratory modulation in the LFP. Finally, moderate hyperpolarization reduced RRo occurence within cells of mpFC and S1. By showing the respiratory rhythm influenced brain activity deep to the MP of non-olfactory neurons, our data support the idea respiratory rhythm could mediate long-range communication.
[ { "created": "Thu, 1 Sep 2022 11:49:58 GMT", "version": "v1" } ]
2022-09-02
[ [ "Juventin", "Maxime", "", "CRNL" ], [ "Zbili", "Mickael", "", "CRNL" ], [ "Fourcaud-Trocmé", "Nicolas", "", "CRNL" ], [ "Garcia", "Samuel", "", "CRNL" ], [ "Buonviso", "Nathalie", "", "CRNL" ], [ "Amat", "Corine", "" ] ]
In recent years, several studies have tended to show a respiratory drive in numerous brain areas so that the respiratory rhythm could be considered as a master clock promoting communication between distant brain areas. However, outside of the olfactory system it is not known if respiration-related oscillation (RRo) could exist in the membrane potential (MP) of neurons neither if it can structure spiking discharge. To fill this gap, we co-recorded MP and LFP activities in different non-olfactory brain areas: median prefrontal cortex (mPFC), primary somatosensory cortex (S1), primary visual cortex (V1), and hippocampus (HPC), in urethane-anesthetized rats. Using respiratory cycle by respiratory cycle analysis, we observed that respiration could modulate both MP and spiking discharges in all recorded areas. Further quantifications revealed RRo episodes were transient in most neurons (5 consecutive cycles in average). RRo development in MP was largely influenced by the presence of respiratory modulation in the LFP. Finally, moderate hyperpolarization reduced RRo occurence within cells of mpFC and S1. By showing the respiratory rhythm influenced brain activity deep to the MP of non-olfactory neurons, our data support the idea respiratory rhythm could mediate long-range communication.
1105.0515
Yunkyu Sohn
Yunkyu Sohn, Jung-Kyoo Choi and T.K. Ahn
Core-Periphery Segregation in Evolving Prisoner's Dilemma Networks
null
null
null
null
q-bio.PE cs.SI physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Dense cooperative networks are an essential element of social capital for a prosperous society. These networks enable individuals to overcome collective action dilemmas by enhancing trust. In many biological and social settings, network structures evolve endogenously as agents exit relationships and build new ones. However, the process by which evolutionary dynamics lead to self-organization of dense cooperative networks has not been explored. Our large group prisoner's dilemma experiments with exit and partner choice options show that core-periphery segregation of cooperators and defectors drives the emergence of cooperation. Cooperators' Quit-for-Tat and defectors' Roving strategy lead to a highly asymmetric core and periphery structure. Densely connected to each other, cooperators successfully isolate defectors and earn larger payoffs than defectors. Our analysis of the topological characteristics of evolving networks illuminates how social capital is generated.
[ { "created": "Tue, 3 May 2011 08:40:31 GMT", "version": "v1" }, { "created": "Sun, 9 Dec 2012 14:38:34 GMT", "version": "v2" } ]
2012-12-11
[ [ "Sohn", "Yunkyu", "" ], [ "Choi", "Jung-Kyoo", "" ], [ "Ahn", "T. K.", "" ] ]
Dense cooperative networks are an essential element of social capital for a prosperous society. These networks enable individuals to overcome collective action dilemmas by enhancing trust. In many biological and social settings, network structures evolve endogenously as agents exit relationships and build new ones. However, the process by which evolutionary dynamics lead to self-organization of dense cooperative networks has not been explored. Our large group prisoner's dilemma experiments with exit and partner choice options show that core-periphery segregation of cooperators and defectors drives the emergence of cooperation. Cooperators' Quit-for-Tat and defectors' Roving strategy lead to a highly asymmetric core and periphery structure. Densely connected to each other, cooperators successfully isolate defectors and earn larger payoffs than defectors. Our analysis of the topological characteristics of evolving networks illuminates how social capital is generated.
2004.01011
Ellen Baake
Ellen Baake and Anton Wakolbinger
Microbial populations under selection
to appear in: Probabilistic Structures in Evolution, E.~Baake and A.~Wakolbinger (eds.), EMS Publishing House, Zurich
in: Probabilistic Structures in Evolution (E. Baake, A. Wakolbinger, eds.), EMS Press, Berlin, 2021, pp. 43-68
null
null
q-bio.PE math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This chapter gives a synopsis of recent approaches to model and analyse the evolution of microbial populations under selection. The first part reviews two population genetic models of Lenski's long-term evolution experiment with Escherichia coli, where models aim at explaining the observed curve of the evolution of the mean fitness. The second part describes a model of a host-pathogen system where the population of pathogenes experiences balancing selection, migration, and mutation, as motivated by observations of the genetic diversity of HCMV (the human cytomegalovirus) across hosts.
[ { "created": "Thu, 2 Apr 2020 14:04:27 GMT", "version": "v1" } ]
2021-06-30
[ [ "Baake", "Ellen", "" ], [ "Wakolbinger", "Anton", "" ] ]
This chapter gives a synopsis of recent approaches to model and analyse the evolution of microbial populations under selection. The first part reviews two population genetic models of Lenski's long-term evolution experiment with Escherichia coli, where models aim at explaining the observed curve of the evolution of the mean fitness. The second part describes a model of a host-pathogen system where the population of pathogenes experiences balancing selection, migration, and mutation, as motivated by observations of the genetic diversity of HCMV (the human cytomegalovirus) across hosts.
1304.2960
Kieran Smallbone
Kieran Smallbone
Standardized network reconstruction of E. coli metabolism
null
null
null
null
q-bio.MN
http://creativecommons.org/licenses/publicdomain/
We have created a genome-scale network reconstruction of Escherichia coli metabolism. Existing reconstructions were improved in terms of annotation standards, to facilitate their subsequent use in dynamic modelling. The resultant network is available from EcoliNet (http://ecoli.sf.net/).
[ { "created": "Tue, 9 Apr 2013 09:07:13 GMT", "version": "v1" } ]
2013-04-11
[ [ "Smallbone", "Kieran", "" ] ]
We have created a genome-scale network reconstruction of Escherichia coli metabolism. Existing reconstructions were improved in terms of annotation standards, to facilitate their subsequent use in dynamic modelling. The resultant network is available from EcoliNet (http://ecoli.sf.net/).
2108.12386
Kapila Gunasekera PhD
Daniel Nilsson, Kapila Gunasekera, Jan Mani, Magne Osteras, Laurent Farinelli, Loic Baerlocher, Isabel Roditi, Torsten Ochsenreiter
Spliced Leader Trapping Reveals Widespread Alternative Splicing Patterns in the Highly Dynamic Transcriptome of Trypanosoma brucei
13 pages, 8 figures
null
10.1371/journal.ppat.1001037
null
q-bio.GN q-bio.QM
http://creativecommons.org/licenses/by-nc-nd/4.0/
Trans-splicing of leader sequences onto the 59ends of mRNAs is a widespread phenomenon in protozoa, nematodes and some chordates. Using parallel sequencing we have developed a method to simultaneously map 59splice sites and analyze the corresponding gene expression profile, that we term spliced leader trapping (SLT). The method can be applied to any organism with a sequenced genome and trans-splicing of a conserved leader sequence. We analyzed the expression profiles and splicing patterns of bloodstream and insect forms of the parasite Trypanosoma brucei. We detected the 59splice sites of 85% of the annotated protein-coding genes and, contrary to previous reports, found up to 40% of transcripts to be differentially expressed. Furthermore, we discovered more than 2500 alternative splicing events, many of which appear to be stage-regulated. Based on our findings we hypothesize that alternatively spliced transcripts present a new means of regulating gene expression and could potentially contribute to protein diversity in the parasite. The entire dataset can be accessed online at TriTrypDB or through: http://splicer.unibe.ch/.
[ { "created": "Fri, 27 Aug 2021 16:48:46 GMT", "version": "v1" } ]
2021-08-30
[ [ "Nilsson", "Daniel", "" ], [ "Gunasekera", "Kapila", "" ], [ "Mani", "Jan", "" ], [ "Osteras", "Magne", "" ], [ "Farinelli", "Laurent", "" ], [ "Baerlocher", "Loic", "" ], [ "Roditi", "Isabel", "" ], [ "Ochsenreiter", "Torsten", "" ] ]
Trans-splicing of leader sequences onto the 59ends of mRNAs is a widespread phenomenon in protozoa, nematodes and some chordates. Using parallel sequencing we have developed a method to simultaneously map 59splice sites and analyze the corresponding gene expression profile, that we term spliced leader trapping (SLT). The method can be applied to any organism with a sequenced genome and trans-splicing of a conserved leader sequence. We analyzed the expression profiles and splicing patterns of bloodstream and insect forms of the parasite Trypanosoma brucei. We detected the 59splice sites of 85% of the annotated protein-coding genes and, contrary to previous reports, found up to 40% of transcripts to be differentially expressed. Furthermore, we discovered more than 2500 alternative splicing events, many of which appear to be stage-regulated. Based on our findings we hypothesize that alternatively spliced transcripts present a new means of regulating gene expression and could potentially contribute to protein diversity in the parasite. The entire dataset can be accessed online at TriTrypDB or through: http://splicer.unibe.ch/.
1008.4938
Randen Patterson
Yoojin Hong, Kyung Dae Ko, Gaurav Bhardwaj, Zhenhai Zhang, Damian B. van Rossum, and Randen L. Patterson
Towards Solving the Inverse Protein Folding Problem
22 pages, 11 figures
null
null
null
q-bio.QM cs.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Accurately assigning folds for divergent protein sequences is a major obstacle to structural studies and underlies the inverse protein folding problem. Herein, we outline our theories for fold-recognition in the "twilight-zone" of sequence similarity (<25% identity). Our analyses demonstrate that structural sequence profiles built using Position-Specific Scoring Matrices (PSSMs) significantly outperform multiple popular homology-modeling algorithms for relating and predicting structures given only their amino acid sequences. Importantly, structural sequence profiles reconstitute SCOP fold classifications in control and test datasets. Results from our experiments suggest that structural sequence profiles can be used to rapidly annotate protein folds at proteomic scales. We propose that encoding the entire Protein DataBank (~1070 folds) into structural sequence profiles would extract interoperable information capable of improving most if not all methods of structural modeling.
[ { "created": "Sun, 29 Aug 2010 15:34:02 GMT", "version": "v1" } ]
2010-08-31
[ [ "Hong", "Yoojin", "" ], [ "Ko", "Kyung Dae", "" ], [ "Bhardwaj", "Gaurav", "" ], [ "Zhang", "Zhenhai", "" ], [ "van Rossum", "Damian B.", "" ], [ "Patterson", "Randen L.", "" ] ]
Accurately assigning folds for divergent protein sequences is a major obstacle to structural studies and underlies the inverse protein folding problem. Herein, we outline our theories for fold-recognition in the "twilight-zone" of sequence similarity (<25% identity). Our analyses demonstrate that structural sequence profiles built using Position-Specific Scoring Matrices (PSSMs) significantly outperform multiple popular homology-modeling algorithms for relating and predicting structures given only their amino acid sequences. Importantly, structural sequence profiles reconstitute SCOP fold classifications in control and test datasets. Results from our experiments suggest that structural sequence profiles can be used to rapidly annotate protein folds at proteomic scales. We propose that encoding the entire Protein DataBank (~1070 folds) into structural sequence profiles would extract interoperable information capable of improving most if not all methods of structural modeling.
1307.4789
Wes Maciejewski
Wes Maciejewski
Reproductive Value in Graph-structured Populations
null
Journal of Theoretical Biology, (2014), vol.340, pp.285-293
10.1016/j.jtbi.2013.09.032
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Evolutionary graph theory has grown to be an area of intense study. Despite the amount of interest in the field, it seems to have grown separate from other subfields of population genetics and evolution. In the current work I introduce the concept of Fisher's (1930) reproductive value into the study of evolution on graphs. Reproductive value is a measure of the expected genetic contribution of an individual to a distant future generation. In a heterogeneous graph-structured population, differences in the number of connections among individuals translates into differences in the expected number of offspring, even if all individuals have the same fecundity. These differences are accounted for by reproductive value. The introduction of reproductive value permits the calculation of the fixation probability of a mutant in a neutral evolutionary process in any graph-structured population for either the moran birth-death or death-birth process.
[ { "created": "Wed, 17 Jul 2013 20:56:44 GMT", "version": "v1" } ]
2014-07-30
[ [ "Maciejewski", "Wes", "" ] ]
Evolutionary graph theory has grown to be an area of intense study. Despite the amount of interest in the field, it seems to have grown separate from other subfields of population genetics and evolution. In the current work I introduce the concept of Fisher's (1930) reproductive value into the study of evolution on graphs. Reproductive value is a measure of the expected genetic contribution of an individual to a distant future generation. In a heterogeneous graph-structured population, differences in the number of connections among individuals translates into differences in the expected number of offspring, even if all individuals have the same fecundity. These differences are accounted for by reproductive value. The introduction of reproductive value permits the calculation of the fixation probability of a mutant in a neutral evolutionary process in any graph-structured population for either the moran birth-death or death-birth process.
2107.12799
Mohammad Reza Dayer
Mohammad Reza Dayer
New Candidates for Furin Inhibition as Probable Treat for COVID-19: Docking Output
null
null
null
null
q-bio.BM q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Furin is a serine protease that takes part in the processing and activation of the host cell pre-proteins. The enzyme also plays an important role in the activation of several viruses like the newly emerging SARS-CoV-2 virus that causes COVID-19 disease with a high rate of virulence and mortality. Unlike viral enzymes, furin owns a constant sequence and active site characteristics and seems to be a better target for drug design for COVID-19 treatment. Considering furin active site as receptor and some approved drugs from different classes including antiviral, antibiotics, and anti protozoa/anti parasites with suspected beneficial effects on COVID-19, as ligands we have carried out docking experiments in HEX software to pickup those capable to bind furin active site with high affinity and suggest them as probable candidates for clinical trials assessments. Our docking experiments show that saquinavir, nelfinavir, and atazanavir with cumulative inhibitory effects of 2.52, 2.16, and 2.13 respectively seem to be the best candidates for furin inhibition even in severe cases of COVID-19 as adjuvant therapy, while clarithromycin, niclosamide, and erythromycin with cumulative inhibitory indices of 1.97, 1.90, and 1.84 respectively with lower side effects than antiviral drugs could be suggested as prophylaxes for the first stage of COVID-19 as a promising treat.
[ { "created": "Tue, 27 Jul 2021 13:12:57 GMT", "version": "v1" } ]
2021-07-28
[ [ "Dayer", "Mohammad Reza", "" ] ]
Furin is a serine protease that takes part in the processing and activation of the host cell pre-proteins. The enzyme also plays an important role in the activation of several viruses like the newly emerging SARS-CoV-2 virus that causes COVID-19 disease with a high rate of virulence and mortality. Unlike viral enzymes, furin owns a constant sequence and active site characteristics and seems to be a better target for drug design for COVID-19 treatment. Considering furin active site as receptor and some approved drugs from different classes including antiviral, antibiotics, and anti protozoa/anti parasites with suspected beneficial effects on COVID-19, as ligands we have carried out docking experiments in HEX software to pickup those capable to bind furin active site with high affinity and suggest them as probable candidates for clinical trials assessments. Our docking experiments show that saquinavir, nelfinavir, and atazanavir with cumulative inhibitory effects of 2.52, 2.16, and 2.13 respectively seem to be the best candidates for furin inhibition even in severe cases of COVID-19 as adjuvant therapy, while clarithromycin, niclosamide, and erythromycin with cumulative inhibitory indices of 1.97, 1.90, and 1.84 respectively with lower side effects than antiviral drugs could be suggested as prophylaxes for the first stage of COVID-19 as a promising treat.
2008.01810
Neta Maimon
Assaf Suberry, Neta B. Maimon and Zohar Eitan
Sad syntax? Tonal closure Affects Children's Perception of Emotional Valence
44 pages, 7 figures, 1 table, 1 appendix
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Western music is largely governed by tonality, a quasi syntactic system regulating musical continuity and closure. Converging measures have established the psychological reality of tonality as a cognitive schema raising distinct expectancy for both adults and children. However, while tonal expectations were associated with emotion in adults, little is known about the tonality emotional effects in children. Here we examine whether children associate levels of tonal closure with emotional valence, whether such associations are age dependent, and how they interact with other musical dimensions. 52 children, aged 7, 11, listened to chord progressions implying closure followed by a probe tone. Probes could realize closure (tonic note), violate it mildly (unstable diatonic note) or extremely (out of key note). Three timbres (piano, guitar, woodwinds) and three pitch heights were used for each closure level. Stimuli were described to participants as exchanges between two children (chords, probe). Participants chose one of two emojis, suggesting positive or negative emotions, as representing the 2nd child response. A significant effect of tonal closure was found, with no interactions with age, instrument, or pitch height. Results suggest that tonality, a non referential cognitive schema, affects children perception of emotion in music early, robustly and independently of basic musical dimensions.
[ { "created": "Tue, 4 Aug 2020 20:13:53 GMT", "version": "v1" } ]
2020-08-06
[ [ "Suberry", "Assaf", "" ], [ "Maimon", "Neta B.", "" ], [ "Eitan", "Zohar", "" ] ]
Western music is largely governed by tonality, a quasi syntactic system regulating musical continuity and closure. Converging measures have established the psychological reality of tonality as a cognitive schema raising distinct expectancy for both adults and children. However, while tonal expectations were associated with emotion in adults, little is known about the tonality emotional effects in children. Here we examine whether children associate levels of tonal closure with emotional valence, whether such associations are age dependent, and how they interact with other musical dimensions. 52 children, aged 7, 11, listened to chord progressions implying closure followed by a probe tone. Probes could realize closure (tonic note), violate it mildly (unstable diatonic note) or extremely (out of key note). Three timbres (piano, guitar, woodwinds) and three pitch heights were used for each closure level. Stimuli were described to participants as exchanges between two children (chords, probe). Participants chose one of two emojis, suggesting positive or negative emotions, as representing the 2nd child response. A significant effect of tonal closure was found, with no interactions with age, instrument, or pitch height. Results suggest that tonality, a non referential cognitive schema, affects children perception of emotion in music early, robustly and independently of basic musical dimensions.
2405.09953
Jessica Thompson
Jessica A.F. Thompson, Hannah Sheahan, Tsvetomira Dumbalska, Julian Sandbrink, Manuela Piazza, Christopher Summerfield
Zero-shot counting with a dual-stream neural network model
null
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
Deep neural networks have provided a computational framework for understanding object recognition, grounded in the neurophysiology of the primate ventral stream, but fail to account for how we process relational aspects of a scene. For example, deep neural networks fail at problems that involve enumerating the number of elements in an array, a problem that in humans relies on parietal cortex. Here, we build a 'dual-stream' neural network model which, equipped with both dorsal and ventral streams, can generalise its counting ability to wholly novel items ('zero-shot' counting). In doing so, it forms spatial response fields and lognormal number codes that resemble those observed in macaque posterior parietal cortex. We use the dual-stream network to make successful predictions about behavioural studies of the human gaze during similar counting tasks.
[ { "created": "Thu, 16 May 2024 09:56:37 GMT", "version": "v1" } ]
2024-05-17
[ [ "Thompson", "Jessica A. F.", "" ], [ "Sheahan", "Hannah", "" ], [ "Dumbalska", "Tsvetomira", "" ], [ "Sandbrink", "Julian", "" ], [ "Piazza", "Manuela", "" ], [ "Summerfield", "Christopher", "" ] ]
Deep neural networks have provided a computational framework for understanding object recognition, grounded in the neurophysiology of the primate ventral stream, but fail to account for how we process relational aspects of a scene. For example, deep neural networks fail at problems that involve enumerating the number of elements in an array, a problem that in humans relies on parietal cortex. Here, we build a 'dual-stream' neural network model which, equipped with both dorsal and ventral streams, can generalise its counting ability to wholly novel items ('zero-shot' counting). In doing so, it forms spatial response fields and lognormal number codes that resemble those observed in macaque posterior parietal cortex. We use the dual-stream network to make successful predictions about behavioural studies of the human gaze during similar counting tasks.
2003.05694
Maryam Al Shehhi Dr
Maryam R. Al Shehhi, David Nelson, Rashid R Alkhori, Rashid Alshihi, and Kourosh Salehi-Ashtiani
Characterizing Algal blooms in a shallow and a deep channel over a decade (2008-2018)
null
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The outbreaks of algal blooms occur in both shallow and deep-water bodies. To compare the characteristics of algal blooms in the shallow and deep water, we consider the Arabian Gulf and Sea of Oman as a case study. While the Arabian Gulf is a shallow region dominated by advective features, the Sea of Oman is a deep channel dominated by numerous eddies. Both these regions is have rarely been studied due to lack of available data thus preventing the characterization of phenomenon such as algal blooms in the regions. Nonetheless, a recent unique and comprehensive dataset of the frequent algal blooms collected over the last decade in the Arabian Gulf and Oman Sea is utilized in this study to analyze the spatio-temporal variability of the blooms thereof. These data are also used to characterize the algal bloom species and analyze the relationship between the water properties and the algal blooms in the shallow and deep waters. There is a general decreasing trend of the algal bloom events from 2010 to 2018 in the Arabian Gulf while in the Sea of Oman there is an increasing trend. We reveal a clear seasonality with the highest frequency of algal blooms during winter and spring. We have noticed that algal blooms have the feature of the annual cycle with initial blooms happening in November-December and December-January in the Arabian Gulf and Sea of Oman, respectively. The analysis further demonstrates that the algal blooms grow better at salinity levels of 39-40 psu/37-37.5 psu, temperature of 23-24 oC, and pH of 8 in the Arabian Gulf/Oman Sea. Findings of this study provide insight into the relationship between water properties and algal bloom frequency, and a basis for future research into the drivers behind these observed spatio-temporal trends.
[ { "created": "Thu, 12 Mar 2020 10:30:41 GMT", "version": "v1" }, { "created": "Mon, 16 Mar 2020 14:12:33 GMT", "version": "v2" } ]
2020-03-17
[ [ "Shehhi", "Maryam R. Al", "" ], [ "Nelson", "David", "" ], [ "Alkhori", "Rashid R", "" ], [ "Alshihi", "Rashid", "" ], [ "Salehi-Ashtiani", "Kourosh", "" ] ]
The outbreaks of algal blooms occur in both shallow and deep-water bodies. To compare the characteristics of algal blooms in the shallow and deep water, we consider the Arabian Gulf and Sea of Oman as a case study. While the Arabian Gulf is a shallow region dominated by advective features, the Sea of Oman is a deep channel dominated by numerous eddies. Both these regions is have rarely been studied due to lack of available data thus preventing the characterization of phenomenon such as algal blooms in the regions. Nonetheless, a recent unique and comprehensive dataset of the frequent algal blooms collected over the last decade in the Arabian Gulf and Oman Sea is utilized in this study to analyze the spatio-temporal variability of the blooms thereof. These data are also used to characterize the algal bloom species and analyze the relationship between the water properties and the algal blooms in the shallow and deep waters. There is a general decreasing trend of the algal bloom events from 2010 to 2018 in the Arabian Gulf while in the Sea of Oman there is an increasing trend. We reveal a clear seasonality with the highest frequency of algal blooms during winter and spring. We have noticed that algal blooms have the feature of the annual cycle with initial blooms happening in November-December and December-January in the Arabian Gulf and Sea of Oman, respectively. The analysis further demonstrates that the algal blooms grow better at salinity levels of 39-40 psu/37-37.5 psu, temperature of 23-24 oC, and pH of 8 in the Arabian Gulf/Oman Sea. Findings of this study provide insight into the relationship between water properties and algal bloom frequency, and a basis for future research into the drivers behind these observed spatio-temporal trends.
1402.0451
Adriano Barra Dr.
Elena Agliari and Elena Biselli and Adele De Ninno and Giovanna Schiavoni and Lucia Gabriele and Anna Gerardino and Fabrizio Mattei and Adriano Barra and Luca Businaro
Cancer-driven dynamics of immune cells in a microfluidic environment
null
Nature Scientific Reports 4, 6639 (2014)
10.1038/srep06639
Roma01.Math
q-bio.CB cond-mat.dis-nn physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Scope of the present work is to frame into a rigorous, quantitative scaffold - stemmed from stochastic process theory - two sets of experiments designed to infer the spontaneous organization of leukocytes against cancer cells, namely mice splenocytes vs. B16 mouse tumor cells, and embedded in an "ad hoc" microfluidic environment developed on a LabOnChip technology. In the former, splenocytes from knocked out (KO) mice engineered to silence the transcription factor IRF-8, crucial for the development and function of several immune populations, were used. In this case lymphocytes and cancer cells exhibited a poor reciprocal exchange, resulting in the inability of coordinating or mounting an effective immune response against melanoma. In the second class of tests, wild type (WT) splenocytes were able to interact with and to coordinate a response against the tumor cells through physical interaction. The environment where cells moved was built of by two different chambers, containing respectively melanoma cells and splenocytes, connected by capillary migration channels allowing leucocytes to migrate from their chamber toward the melanoma one. We collected and analyzed data on the motility of the cells and found that the first ensemble of IRF-8 KO cells performed pure uncorrelated random walks, while WT splenocytes were able to make singular drifted random walks, that, averaged over the ensemble of cells, collapsed on a straight ballistic motion for the system as a whole. At a finer level of investigation, we found that IRF-8 KO splenocytes moved rather uniformly since their step lengths were exponentially distributed, while WT counterpart displayed a qualitatively broader motion as their step lengths along the direction of the melanoma were log-normally distributed.
[ { "created": "Mon, 3 Feb 2014 18:11:20 GMT", "version": "v1" } ]
2016-02-02
[ [ "Agliari", "Elena", "" ], [ "Biselli", "Elena", "" ], [ "De Ninno", "Adele", "" ], [ "Schiavoni", "Giovanna", "" ], [ "Gabriele", "Lucia", "" ], [ "Gerardino", "Anna", "" ], [ "Mattei", "Fabrizio", "" ], [ "Barra", "Adriano", "" ], [ "Businaro", "Luca", "" ] ]
Scope of the present work is to frame into a rigorous, quantitative scaffold - stemmed from stochastic process theory - two sets of experiments designed to infer the spontaneous organization of leukocytes against cancer cells, namely mice splenocytes vs. B16 mouse tumor cells, and embedded in an "ad hoc" microfluidic environment developed on a LabOnChip technology. In the former, splenocytes from knocked out (KO) mice engineered to silence the transcription factor IRF-8, crucial for the development and function of several immune populations, were used. In this case lymphocytes and cancer cells exhibited a poor reciprocal exchange, resulting in the inability of coordinating or mounting an effective immune response against melanoma. In the second class of tests, wild type (WT) splenocytes were able to interact with and to coordinate a response against the tumor cells through physical interaction. The environment where cells moved was built of by two different chambers, containing respectively melanoma cells and splenocytes, connected by capillary migration channels allowing leucocytes to migrate from their chamber toward the melanoma one. We collected and analyzed data on the motility of the cells and found that the first ensemble of IRF-8 KO cells performed pure uncorrelated random walks, while WT splenocytes were able to make singular drifted random walks, that, averaged over the ensemble of cells, collapsed on a straight ballistic motion for the system as a whole. At a finer level of investigation, we found that IRF-8 KO splenocytes moved rather uniformly since their step lengths were exponentially distributed, while WT counterpart displayed a qualitatively broader motion as their step lengths along the direction of the melanoma were log-normally distributed.
0910.1830
Navodit Misra
Navodit Misra, Guy Blelloch, R. Ravi and Russell Schwartz
Generalized Buneman pruning for inferring the most parsimonious multi-state phylogeny
15 pages
null
10.1007/978-3-642-12683-3_24
null
q-bio.PE q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Accurate reconstruction of phylogenies remains a key challenge in evolutionary biology. Most biologically plausible formulations of the problem are formally NP-hard, with no known efficient solution. The standard in practice are fast heuristic methods that are empirically known to work very well in general, but can yield results arbitrarily far from optimal. Practical exact methods, which yield exponential worst-case running times but generally much better times in practice, provide an important alternative. We report progress in this direction by introducing a provably optimal method for the weighted multi-state maximum parsimony phylogeny problem. The method is based on generalizing the notion of the Buneman graph, a construction key to efficient exact methods for binary sequences, so as to apply to sequences with arbitrary finite numbers of states with arbitrary state transition weights. We implement an integer linear programming (ILP) method for the multi-state problem using this generalized Buneman graph and demonstrate that the resulting method is able to solve data sets that are intractable by prior exact methods in run times comparable with popular heuristics. Our work provides the first method for provably optimal maximum parsimony phylogeny inference that is practical for multi-state data sets of more than a few characters.
[ { "created": "Fri, 9 Oct 2009 19:59:00 GMT", "version": "v1" }, { "created": "Fri, 9 Oct 2009 20:11:16 GMT", "version": "v2" }, { "created": "Thu, 15 Apr 2010 01:46:04 GMT", "version": "v3" } ]
2015-05-14
[ [ "Misra", "Navodit", "" ], [ "Blelloch", "Guy", "" ], [ "Ravi", "R.", "" ], [ "Schwartz", "Russell", "" ] ]
Accurate reconstruction of phylogenies remains a key challenge in evolutionary biology. Most biologically plausible formulations of the problem are formally NP-hard, with no known efficient solution. The standard in practice are fast heuristic methods that are empirically known to work very well in general, but can yield results arbitrarily far from optimal. Practical exact methods, which yield exponential worst-case running times but generally much better times in practice, provide an important alternative. We report progress in this direction by introducing a provably optimal method for the weighted multi-state maximum parsimony phylogeny problem. The method is based on generalizing the notion of the Buneman graph, a construction key to efficient exact methods for binary sequences, so as to apply to sequences with arbitrary finite numbers of states with arbitrary state transition weights. We implement an integer linear programming (ILP) method for the multi-state problem using this generalized Buneman graph and demonstrate that the resulting method is able to solve data sets that are intractable by prior exact methods in run times comparable with popular heuristics. Our work provides the first method for provably optimal maximum parsimony phylogeny inference that is practical for multi-state data sets of more than a few characters.
q-bio/0601038
Michele Bezzi
Michele Bezzi
Quantifying the information transmitted in a single stimulus
13 pages, 4 figures
null
null
null
q-bio.NC q-bio.QM
null
Shannon mutual information provides a measure of how much information is, on average, contained in a set of neural activities about a set of stimuli. It has been extensively used to study neural coding in different brain areas. To apply a similar approach to investigate single stimulus encoding, we need to introduce a quantity specific for a single stimulus. This quantity has been defined in literature by four different measures, but none of them satisfies the same intuitive properties (non-negativity, additivity), that characterize mutual information. We present here a detailed analysis of the different meanings and properties of these four definitions. We show that all these measures satisfy, at least, a weaker additivity condition, i.e. limited to the response set. This allows us to use them for analysing correlated coding, as we illustrate in a toy-example from hippocampal place cells.
[ { "created": "Mon, 23 Jan 2006 13:51:28 GMT", "version": "v1" } ]
2007-05-23
[ [ "Bezzi", "Michele", "" ] ]
Shannon mutual information provides a measure of how much information is, on average, contained in a set of neural activities about a set of stimuli. It has been extensively used to study neural coding in different brain areas. To apply a similar approach to investigate single stimulus encoding, we need to introduce a quantity specific for a single stimulus. This quantity has been defined in literature by four different measures, but none of them satisfies the same intuitive properties (non-negativity, additivity), that characterize mutual information. We present here a detailed analysis of the different meanings and properties of these four definitions. We show that all these measures satisfy, at least, a weaker additivity condition, i.e. limited to the response set. This allows us to use them for analysing correlated coding, as we illustrate in a toy-example from hippocampal place cells.
2402.10387
Peter Eckmann
Peter Eckmann, Dongxia Wu, Germano Heinzelmann, Michael K Gilson, Rose Yu
MFBind: a Multi-Fidelity Approach for Evaluating Drug Compounds in Practical Generative Modeling
9 pages, 4 figures
null
null
null
q-bio.BM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Current generative models for drug discovery primarily use molecular docking to evaluate the quality of generated compounds. However, such models are often not useful in practice because even compounds with high docking scores do not consistently show experimental activity. More accurate methods for activity prediction exist, such as molecular dynamics based binding free energy calculations, but they are too computationally expensive to use in a generative model. We propose a multi-fidelity approach, Multi-Fidelity Bind (MFBind), to achieve the optimal trade-off between accuracy and computational cost. MFBind integrates docking and binding free energy simulators to train a multi-fidelity deep surrogate model with active learning. Our deep surrogate model utilizes a pretraining technique and linear prediction heads to efficiently fit small amounts of high-fidelity data. We perform extensive experiments and show that MFBind (1) outperforms other state-of-the-art single and multi-fidelity baselines in surrogate modeling, and (2) boosts the performance of generative models with markedly higher quality compounds.
[ { "created": "Fri, 16 Feb 2024 00:48:20 GMT", "version": "v1" } ]
2024-02-19
[ [ "Eckmann", "Peter", "" ], [ "Wu", "Dongxia", "" ], [ "Heinzelmann", "Germano", "" ], [ "Gilson", "Michael K", "" ], [ "Yu", "Rose", "" ] ]
Current generative models for drug discovery primarily use molecular docking to evaluate the quality of generated compounds. However, such models are often not useful in practice because even compounds with high docking scores do not consistently show experimental activity. More accurate methods for activity prediction exist, such as molecular dynamics based binding free energy calculations, but they are too computationally expensive to use in a generative model. We propose a multi-fidelity approach, Multi-Fidelity Bind (MFBind), to achieve the optimal trade-off between accuracy and computational cost. MFBind integrates docking and binding free energy simulators to train a multi-fidelity deep surrogate model with active learning. Our deep surrogate model utilizes a pretraining technique and linear prediction heads to efficiently fit small amounts of high-fidelity data. We perform extensive experiments and show that MFBind (1) outperforms other state-of-the-art single and multi-fidelity baselines in surrogate modeling, and (2) boosts the performance of generative models with markedly higher quality compounds.
1906.01224
Tomokazu Konishi
Tomokazu Konishi, Haruna Ohrui
A distribution-dependent analysis of open-field test movies
30 pages, 3 Figures, including supplementary data
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Although the open-field test has been widely used, its reliability and compatibility are frequently questioned. Although many indicating parameters were introduced for this test, they did not take data distributions into consideration. This oversight may have caused the problems mentioned above. Here, an exploratory approach for the analysis of video records of tests of elderly mice was taken that described the distributions using the least number of parameters. First, the locomotor activity of the animals was separated into two clusters: dash and search. The accelerations found in each of the clusters were distributed normally. The speed and the duration of the clusters exhibited an exponential distribution. Although the exponential model includes a single parameter, an additional parameter that indicated instability of the behaviour was required in many cases for fitting to the data. As this instability parameter exhibited an inverse correlation with speed, the function of the brain that maintained stability would be required for a better performance. According to the distributions, the travel distance, which has been regarded as an important indicator, was not a robust estimator of the animals' condition.
[ { "created": "Tue, 4 Jun 2019 06:49:49 GMT", "version": "v1" } ]
2019-06-05
[ [ "Konishi", "Tomokazu", "" ], [ "Ohrui", "Haruna", "" ] ]
Although the open-field test has been widely used, its reliability and compatibility are frequently questioned. Although many indicating parameters were introduced for this test, they did not take data distributions into consideration. This oversight may have caused the problems mentioned above. Here, an exploratory approach for the analysis of video records of tests of elderly mice was taken that described the distributions using the least number of parameters. First, the locomotor activity of the animals was separated into two clusters: dash and search. The accelerations found in each of the clusters were distributed normally. The speed and the duration of the clusters exhibited an exponential distribution. Although the exponential model includes a single parameter, an additional parameter that indicated instability of the behaviour was required in many cases for fitting to the data. As this instability parameter exhibited an inverse correlation with speed, the function of the brain that maintained stability would be required for a better performance. According to the distributions, the travel distance, which has been regarded as an important indicator, was not a robust estimator of the animals' condition.
0704.2454
Vahid Rezania
Vahid Rezania, Jack Tuszynski, Michael Hendzel
Modeling transcription factor binding events to DNA using a random walker/jumper representation on a 1D/2D lattice with different affinity sites
24 pages, 9 figures
Physical Biology, 4, 256-267 (2007)
10.1088/1478-3975/4/4/003
null
q-bio.QM q-bio.BM
null
Surviving in a diverse environment requires corresponding organism responses. At the cellular level, such adjustment relies on the transcription factors (TFs) which must rapidly find their target sequences amidst a vast amount of non-relevant sequences on DNA molecules. Whether these transcription factors locate their target sites through a 1D or 3D pathway is still a matter of speculation. It has been suggested that the optimum search time is when the protein equally shares its search time between 1D and 3D diffusions. In this paper, we study the above problem using a Monte Carlo simulation by considering a very simple physical model. A 1D strip, representing a DNA, with a number of low affinity sites, corresponding to non-target sites, and high affinity sites, corresponding to target sites, is considered and later extended to a 2D strip. We study the 1D and 3D exploration pathways, and combinations of the two modes by considering three different types of molecules: a walker that randomly walks along the strip with no dissociation; a jumper that represents dissociation and then re-association of a TF with the strip at later time at a distant site; and a hopper that is similar to the jumper but it dissociates and then re-associates at a faster rate than the jumper. We analyze the final probability distribution of molecules for each case and find that TFs can locate their targets fast enough even if they spend 15% of their search time diffusing freely in the solution. This indeed agrees with recent experimental results obtained by Elf et al. 2007 and is in contrast with theoretical expectation.
[ { "created": "Thu, 19 Apr 2007 03:20:02 GMT", "version": "v1" }, { "created": "Thu, 9 Aug 2007 17:44:57 GMT", "version": "v2" } ]
2009-11-13
[ [ "Rezania", "Vahid", "" ], [ "Tuszynski", "Jack", "" ], [ "Hendzel", "Michael", "" ] ]
Surviving in a diverse environment requires corresponding organism responses. At the cellular level, such adjustment relies on the transcription factors (TFs) which must rapidly find their target sequences amidst a vast amount of non-relevant sequences on DNA molecules. Whether these transcription factors locate their target sites through a 1D or 3D pathway is still a matter of speculation. It has been suggested that the optimum search time is when the protein equally shares its search time between 1D and 3D diffusions. In this paper, we study the above problem using a Monte Carlo simulation by considering a very simple physical model. A 1D strip, representing a DNA, with a number of low affinity sites, corresponding to non-target sites, and high affinity sites, corresponding to target sites, is considered and later extended to a 2D strip. We study the 1D and 3D exploration pathways, and combinations of the two modes by considering three different types of molecules: a walker that randomly walks along the strip with no dissociation; a jumper that represents dissociation and then re-association of a TF with the strip at later time at a distant site; and a hopper that is similar to the jumper but it dissociates and then re-associates at a faster rate than the jumper. We analyze the final probability distribution of molecules for each case and find that TFs can locate their targets fast enough even if they spend 15% of their search time diffusing freely in the solution. This indeed agrees with recent experimental results obtained by Elf et al. 2007 and is in contrast with theoretical expectation.
2406.09094
Luis Aniello La Rocca
Luis A. La Rocca, Konrad Gerischer, Anton Bovier and Peter M. Krawitz
Refining the drift barrier hypothesis: a role of recessive gene count and an inhomogeneous Muller`s ratchet
21 pages, 4 figures
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by-nc-sa/4.0/
The drift-barrier hypothesis states that random genetic drift constrains the refinement of a phenotype under natural selection. The influence of effective population size and the genome-wide deleterious mutation rate were studied theoretically, and an inverse relationship between mutation rate and genome size has been observed for many species. However, the effect of the recessive gene count, an important feature of the genomic architecture, is unknown. In a Wright-Fisher model, we studied the mutation burden for a growing number of N completely recessive and lethal disease genes. Diploid individuals are represented with a binary $2 \times N$ matrix denoting wild-type and mutated alleles. Analytic results for specific cases were complemented by simulations across a broad parameter regime for gene count, mutation and recombination rates. Simulations revealed transitions to higher mutation burden and prevalence within a few generations that were linked to the extinction of the wild-type haplotype (least-loaded class). This metastability, that is, phases of quasi-equilibrium with intermittent transitions, persists over $100\,000$ generations. The drift-barrier hypothesis is confirmed by a high mutation burden resulting in population collapse. Simulations showed the emergence of mutually exclusive haplotypes for a mutation rate above 0.02 lethal equivalents per generation for a genomic architecture and population size representing complex multicellular organisms such as humans. In such systems, recombination proves pivotal, preventing population collapse and maintaining a mutation burden below 10. This study advances our understanding of gene pool stability, and particularly the role of the number of recessive disorders. Insights into Muller`s ratchet dynamics are provided, and the essential role of recombination in curbing mutation burden and stabilizing the gene pool is demonstrated.
[ { "created": "Thu, 13 Jun 2024 13:22:41 GMT", "version": "v1" }, { "created": "Fri, 14 Jun 2024 08:58:03 GMT", "version": "v2" }, { "created": "Tue, 23 Jul 2024 09:37:34 GMT", "version": "v3" }, { "created": "Wed, 24 Jul 2024 10:23:03 GMT", "version": "v4" } ]
2024-07-25
[ [ "La Rocca", "Luis A.", "" ], [ "Gerischer", "Konrad", "" ], [ "Bovier", "Anton", "" ], [ "Krawitz", "Peter M.", "" ] ]
The drift-barrier hypothesis states that random genetic drift constrains the refinement of a phenotype under natural selection. The influence of effective population size and the genome-wide deleterious mutation rate were studied theoretically, and an inverse relationship between mutation rate and genome size has been observed for many species. However, the effect of the recessive gene count, an important feature of the genomic architecture, is unknown. In a Wright-Fisher model, we studied the mutation burden for a growing number of N completely recessive and lethal disease genes. Diploid individuals are represented with a binary $2 \times N$ matrix denoting wild-type and mutated alleles. Analytic results for specific cases were complemented by simulations across a broad parameter regime for gene count, mutation and recombination rates. Simulations revealed transitions to higher mutation burden and prevalence within a few generations that were linked to the extinction of the wild-type haplotype (least-loaded class). This metastability, that is, phases of quasi-equilibrium with intermittent transitions, persists over $100\,000$ generations. The drift-barrier hypothesis is confirmed by a high mutation burden resulting in population collapse. Simulations showed the emergence of mutually exclusive haplotypes for a mutation rate above 0.02 lethal equivalents per generation for a genomic architecture and population size representing complex multicellular organisms such as humans. In such systems, recombination proves pivotal, preventing population collapse and maintaining a mutation burden below 10. This study advances our understanding of gene pool stability, and particularly the role of the number of recessive disorders. Insights into Muller`s ratchet dynamics are provided, and the essential role of recombination in curbing mutation burden and stabilizing the gene pool is demonstrated.
2012.06848
Arnaud Liehrmann
Arnaud Liehrmann, Guillem Rigaill and Toby Dylan Hocking
Increased peak detection accuracy in over-dispersed ChIP-seq data with supervised segmentation models
20 pages, 8 figures; updated broken citations and references
null
null
null
q-bio.QM stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Motivation: Histone modification constitutes a basic mechanism for the genetic regulation of gene expression. In early 2000s, a powerful technique has emerged that couples chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq). This technique provides a direct survey of the DNA regions associated to these modifications. In order to realize the full potential of this technique, increasingly sophisticated statistical algorithms have been developed or adapted to analyze the massive amount of data it generates. Many of these algorithms were built around natural assumptions such as the Poisson one to model the noise in the count data. In this work we start from these natural assumptions and show that it is possible to improve upon them. Results: The results of our comparisons on seven reference datasets of histone modifications (H3K36me3 and H3K4me3) suggest that natural assumptions are not always realistic under application conditions. We show that the unconstrained multiple changepoint detection model, with alternative noise assumptions and a suitable setup, reduces the over-dispersion exhibited by count data and turns out to detect peaks more accurately than algorithms which rely on these natural assumptions.
[ { "created": "Sat, 12 Dec 2020 16:03:27 GMT", "version": "v1" }, { "created": "Tue, 15 Dec 2020 12:34:48 GMT", "version": "v2" } ]
2020-12-16
[ [ "Liehrmann", "Arnaud", "" ], [ "Rigaill", "Guillem", "" ], [ "Hocking", "Toby Dylan", "" ] ]
Motivation: Histone modification constitutes a basic mechanism for the genetic regulation of gene expression. In early 2000s, a powerful technique has emerged that couples chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq). This technique provides a direct survey of the DNA regions associated to these modifications. In order to realize the full potential of this technique, increasingly sophisticated statistical algorithms have been developed or adapted to analyze the massive amount of data it generates. Many of these algorithms were built around natural assumptions such as the Poisson one to model the noise in the count data. In this work we start from these natural assumptions and show that it is possible to improve upon them. Results: The results of our comparisons on seven reference datasets of histone modifications (H3K36me3 and H3K4me3) suggest that natural assumptions are not always realistic under application conditions. We show that the unconstrained multiple changepoint detection model, with alternative noise assumptions and a suitable setup, reduces the over-dispersion exhibited by count data and turns out to detect peaks more accurately than algorithms which rely on these natural assumptions.
2005.12446
Massimo Marchiori
Massimo Marchiori
COVID-19 and the Social Distancing Paradox: dangers and solutions
8 pages with 4 figures
null
null
null
q-bio.PE eess.SP physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Background: Without proven effect treatments and vaccines, Social Distancing is the key protection factor against COVID-19. Social distancing alone should have been enough to protect again the virus, yet things have gone very differently, with a big mismatch between theory and practice. What are the reasons? A big problem is that there is no actual social distancing data, and the corresponding people behavior in a pandemic is unknown. We collect the world-first dataset on social distancing during the COVID-19 outbreak, so to see for the first time how people really implement social distancing, identify dangers of the current situation, and find solutions against this and future pandemics. Methods: Using a sensor-based social distancing belt we collected social distance data from people in Italy for over two months during the most critical COVID-19 outbreak. Additionally, we investigated if and how wearing various Personal Protection Equipment, like masks, influences social distancing. Results: Without masks, people adopt a counter-intuitively dangerous strategy, a paradox that could explain the relative lack of effectiveness of social distancing. Using masks radically changes the situation, breaking the paradoxical behavior and leading to a safe social distance behavior. In shortage of masks, DIY (Do It Yourself) masks can also be used: even without filtering protection, they provide social distancing protection. Goggles should be recommended for general use, as they give an extra powerful safety boost. Generic Public Health policies and media campaigns do not work well on social distancing: explicit focus on the behavioral problems of necessary mobility are needed.
[ { "created": "Tue, 26 May 2020 00:01:53 GMT", "version": "v1" } ]
2020-05-27
[ [ "Marchiori", "Massimo", "" ] ]
Background: Without proven effect treatments and vaccines, Social Distancing is the key protection factor against COVID-19. Social distancing alone should have been enough to protect again the virus, yet things have gone very differently, with a big mismatch between theory and practice. What are the reasons? A big problem is that there is no actual social distancing data, and the corresponding people behavior in a pandemic is unknown. We collect the world-first dataset on social distancing during the COVID-19 outbreak, so to see for the first time how people really implement social distancing, identify dangers of the current situation, and find solutions against this and future pandemics. Methods: Using a sensor-based social distancing belt we collected social distance data from people in Italy for over two months during the most critical COVID-19 outbreak. Additionally, we investigated if and how wearing various Personal Protection Equipment, like masks, influences social distancing. Results: Without masks, people adopt a counter-intuitively dangerous strategy, a paradox that could explain the relative lack of effectiveness of social distancing. Using masks radically changes the situation, breaking the paradoxical behavior and leading to a safe social distance behavior. In shortage of masks, DIY (Do It Yourself) masks can also be used: even without filtering protection, they provide social distancing protection. Goggles should be recommended for general use, as they give an extra powerful safety boost. Generic Public Health policies and media campaigns do not work well on social distancing: explicit focus on the behavioral problems of necessary mobility are needed.
0811.2837
Tom Chou
Pak-Wing Fok, Chin-Lin Guo, Tom Chou
Charge transport-mediated recruitment of DNA repair enzymes
9 Figures, Accepted to J. Chem. Phys
Journal of Chemical Physics, 129, 235101, (2008)
10.1063/1.3026735
null
q-bio.BM q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Damaged or mismatched bases in DNA can be repaired by Base Excision Repair (BER) enzymes that replace the defective base. Although the detailed molecular structures of many BER enzymes are known, how they colocalize to lesions remains unclear. One hypothesis involves charge transport (CT) along DNA [Yavin, {\it et al.}, PNAS, {\bf 102}, 3546, (2005)]. In this CT mechanism, electrons are released by recently adsorbed BER enzymes and travel along the DNA. The electrons can scatter (by heterogeneities along the DNA) back to the enzyme, destabilizing and knocking it off the DNA, or, they can be absorbed by nearby lesions and guanine radicals. We develop a stochastic model to describe the electron dynamics, and compute probabilities of electron capture by guanine radicals and repair enzymes. We also calculate first passage times of electron return, and ensemble-average these results over guanine radical distributions. Our statistical results provide the rules that enable us to perform implicit-electron Monte-Carlo simulations of repair enzyme binding and redistribution near lesions. When lesions are electron absorbing, we show that the CT mechanism suppresses wasteful buildup of enzymes along intact portions of the DNA, maximizing enzyme concentration near lesions.
[ { "created": "Tue, 18 Nov 2008 04:38:18 GMT", "version": "v1" } ]
2009-11-13
[ [ "Fok", "Pak-Wing", "" ], [ "Guo", "Chin-Lin", "" ], [ "Chou", "Tom", "" ] ]
Damaged or mismatched bases in DNA can be repaired by Base Excision Repair (BER) enzymes that replace the defective base. Although the detailed molecular structures of many BER enzymes are known, how they colocalize to lesions remains unclear. One hypothesis involves charge transport (CT) along DNA [Yavin, {\it et al.}, PNAS, {\bf 102}, 3546, (2005)]. In this CT mechanism, electrons are released by recently adsorbed BER enzymes and travel along the DNA. The electrons can scatter (by heterogeneities along the DNA) back to the enzyme, destabilizing and knocking it off the DNA, or, they can be absorbed by nearby lesions and guanine radicals. We develop a stochastic model to describe the electron dynamics, and compute probabilities of electron capture by guanine radicals and repair enzymes. We also calculate first passage times of electron return, and ensemble-average these results over guanine radical distributions. Our statistical results provide the rules that enable us to perform implicit-electron Monte-Carlo simulations of repair enzyme binding and redistribution near lesions. When lesions are electron absorbing, we show that the CT mechanism suppresses wasteful buildup of enzymes along intact portions of the DNA, maximizing enzyme concentration near lesions.
1304.5836
Bin Ao
Bin Ao, Sheng Zhang, Caiyong Ye, Lei Chang, Guangming Zhou, Lei Yang
Oscillation in microRNA Feedback Loop
There were some mistakes in the analysis in this paper's first version submitted on 22 Apr 2013. We corrected them in the second version submitted on 23 Sep 2013. So please delete the "v1" version of this paper, Thank you!
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q-bio.MN nlin.PS
http://creativecommons.org/licenses/by-nc-sa/3.0/
The dynamic behaviors of microRNA and mRNA under external stress are studied with biological experiments and mathematics models. In this study, we developed a mathematic model to describe the biological phenomenon and for the first time reported that, as responses to external stress, the expression levels of microRNA and mRNA sustained oscillation. And the period of the oscillation is much shorter than several reported transcriptional regulation negative feedback loop.
[ { "created": "Mon, 22 Apr 2013 05:39:26 GMT", "version": "v1" }, { "created": "Mon, 23 Sep 2013 09:36:46 GMT", "version": "v2" }, { "created": "Mon, 16 Dec 2013 07:52:20 GMT", "version": "v3" } ]
2013-12-17
[ [ "Ao", "Bin", "" ], [ "Zhang", "Sheng", "" ], [ "Ye", "Caiyong", "" ], [ "Chang", "Lei", "" ], [ "Zhou", "Guangming", "" ], [ "Yang", "Lei", "" ] ]
The dynamic behaviors of microRNA and mRNA under external stress are studied with biological experiments and mathematics models. In this study, we developed a mathematic model to describe the biological phenomenon and for the first time reported that, as responses to external stress, the expression levels of microRNA and mRNA sustained oscillation. And the period of the oscillation is much shorter than several reported transcriptional regulation negative feedback loop.
2108.01982
Farzad Fatehi
Farzad Fatehi, Richard J. Bingham, Eric C. Dykeman, Peter G. Stockley, and Reidun Twarock
An age-structured model of hepatitis B viral infection highlights the potential of different therapeutic strategies
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q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Hepatitis B virus is a global health threat, and its elimination by 2030 has been prioritised by the World Health Organisation. Here we present an age-structured model for the immune response to an HBV infection, which takes into account contributions from both cell-mediated and humoral immunity. The model has been validated using published patient data recorded during acute infection. It has been adapted to the scenarios of chronic infection, clearance of infection, and flare-ups via variation of the immune response parameters. The impacts of immune response exhaustion and non-infectious subviral particles on the immune response dynamics are analysed. A comparison of different treatment options in the context of this model reveals that drugs targeting aspects of the viral life cycle are more effective than exhaustion therapy, a form of therapy mitigating immune response exhaustion. Our results suggest that antiviral treatment is best started when viral load is declining rather than in a flare-up. The model suggests that a fast antibody production rate always lead to viral clearance, highlighting the promise of antibody therapies currently in clinical trials.
[ { "created": "Wed, 4 Aug 2021 11:45:12 GMT", "version": "v1" } ]
2021-08-05
[ [ "Fatehi", "Farzad", "" ], [ "Bingham", "Richard J.", "" ], [ "Dykeman", "Eric C.", "" ], [ "Stockley", "Peter G.", "" ], [ "Twarock", "Reidun", "" ] ]
Hepatitis B virus is a global health threat, and its elimination by 2030 has been prioritised by the World Health Organisation. Here we present an age-structured model for the immune response to an HBV infection, which takes into account contributions from both cell-mediated and humoral immunity. The model has been validated using published patient data recorded during acute infection. It has been adapted to the scenarios of chronic infection, clearance of infection, and flare-ups via variation of the immune response parameters. The impacts of immune response exhaustion and non-infectious subviral particles on the immune response dynamics are analysed. A comparison of different treatment options in the context of this model reveals that drugs targeting aspects of the viral life cycle are more effective than exhaustion therapy, a form of therapy mitigating immune response exhaustion. Our results suggest that antiviral treatment is best started when viral load is declining rather than in a flare-up. The model suggests that a fast antibody production rate always lead to viral clearance, highlighting the promise of antibody therapies currently in clinical trials.