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2208.09889
Enrui Zhang
Enrui Zhang, Bart Spronck, Jay D. Humphrey, George Em Karniadakis
G2{\Phi}net: Relating Genotype and Biomechanical Phenotype of Tissues with Deep Learning
41 pages, 9 figures
null
10.1371/journal.pcbi.1010660
null
q-bio.TO cs.LG
http://creativecommons.org/licenses/by/4.0/
Many genetic mutations adversely affect the structure and function of load-bearing soft tissues, with clinical sequelae often responsible for disability or death. Parallel advances in genetics and histomechanical characterization provide significant insight into these conditions, but there remains a pressing need to integrate such information. We present a novel genotype-to-biomechanical-phenotype neural network (G2{\Phi}net) for characterizing and classifying biomechanical properties of soft tissues, which serve as important functional readouts of tissue health or disease. We illustrate the utility of our approach by inferring the nonlinear, genotype-dependent constitutive behavior of the aorta for four mouse models involving defects or deficiencies in extracellular constituents. We show that G2{\Phi}net can infer the biomechanical response while simultaneously ascribing the associated genotype correctly by utilizing limited, noisy, and unstructured experimental data. More broadly, G2{\Phi}net provides a powerful method and a paradigm shift for correlating genotype and biomechanical phenotype quantitatively, promising a better understanding of their interplay in biological tissues.
[ { "created": "Sun, 21 Aug 2022 14:22:37 GMT", "version": "v1" } ]
2023-01-11
[ [ "Zhang", "Enrui", "" ], [ "Spronck", "Bart", "" ], [ "Humphrey", "Jay D.", "" ], [ "Karniadakis", "George Em", "" ] ]
Many genetic mutations adversely affect the structure and function of load-bearing soft tissues, with clinical sequelae often responsible for disability or death. Parallel advances in genetics and histomechanical characterization provide significant insight into these conditions, but there remains a pressing need to integrate such information. We present a novel genotype-to-biomechanical-phenotype neural network (G2{\Phi}net) for characterizing and classifying biomechanical properties of soft tissues, which serve as important functional readouts of tissue health or disease. We illustrate the utility of our approach by inferring the nonlinear, genotype-dependent constitutive behavior of the aorta for four mouse models involving defects or deficiencies in extracellular constituents. We show that G2{\Phi}net can infer the biomechanical response while simultaneously ascribing the associated genotype correctly by utilizing limited, noisy, and unstructured experimental data. More broadly, G2{\Phi}net provides a powerful method and a paradigm shift for correlating genotype and biomechanical phenotype quantitatively, promising a better understanding of their interplay in biological tissues.
q-bio/0501007
Anna Ochab-Marcinek
Anna Ochab-Marcinek
Pattern formation in a stochastic model of cancer growth
17 pages, 15 figures
Acta Physica Polonica B 36(6) (2005) 1963
null
null
q-bio.CB
null
We investigate noise-induced pattern formation in a model of cancer growth based on Michaelis-Menten kinetics, subject to additive and multiplicative noises. We analyse stability properties of the system and discuss the role of diffusion and noises in the system's dynamics. We find that random dichotomous fluctuations in the immune response intensity along with Gaussian environmental noise lead to emergence of a spatial pattern of two phases, in which cancer cells, or, respectively, immune cells predominate.
[ { "created": "Wed, 5 Jan 2005 21:50:06 GMT", "version": "v1" }, { "created": "Fri, 2 Dec 2005 14:59:55 GMT", "version": "v2" } ]
2007-05-23
[ [ "Ochab-Marcinek", "Anna", "" ] ]
We investigate noise-induced pattern formation in a model of cancer growth based on Michaelis-Menten kinetics, subject to additive and multiplicative noises. We analyse stability properties of the system and discuss the role of diffusion and noises in the system's dynamics. We find that random dichotomous fluctuations in the immune response intensity along with Gaussian environmental noise lead to emergence of a spatial pattern of two phases, in which cancer cells, or, respectively, immune cells predominate.
1607.04734
Guy Bunin
Guy Bunin
Interaction patterns and diversity in assembled ecological communities
null
null
null
null
q-bio.PE cond-mat.stat-mech physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The assembly of ecological communities from a pool of species is central to ecology, but the effect of this process on properties of community interaction networks is still largely unknown. Here, we use a systematic analytical framework to describe how assembly from a species pool gives rise to community network properties that differ from those of the pool: Compared to the pool, the community shows a bias towards higher carrying capacities, weaker competitive interactions and stronger beneficial interactions. Moreover, even if interactions between all pool species are completely random, community networks are more structured, with correlations between interspecies interactions, and between interactions and carrying capacities. Nonetheless, we show that these properties are not sufficient to explain the coexistence of all community species, and that it is a simple relation between interactions and species abundances that is responsible for the diversity within a community.
[ { "created": "Sat, 16 Jul 2016 12:28:38 GMT", "version": "v1" } ]
2016-07-19
[ [ "Bunin", "Guy", "" ] ]
The assembly of ecological communities from a pool of species is central to ecology, but the effect of this process on properties of community interaction networks is still largely unknown. Here, we use a systematic analytical framework to describe how assembly from a species pool gives rise to community network properties that differ from those of the pool: Compared to the pool, the community shows a bias towards higher carrying capacities, weaker competitive interactions and stronger beneficial interactions. Moreover, even if interactions between all pool species are completely random, community networks are more structured, with correlations between interspecies interactions, and between interactions and carrying capacities. Nonetheless, we show that these properties are not sufficient to explain the coexistence of all community species, and that it is a simple relation between interactions and species abundances that is responsible for the diversity within a community.
1707.02110
Irina Mizeva
Irina Mizeva, Elena Zharkikh, Victor Dremin, Evgeny Zherebtsov, Irina Makovik, Elena Potapova, Andrey Dunaev
Spectral analysis of the blood flow in the foot microvascular bed during thermal testing in patients with diabetes mellitus
7 pages, 8 figures
null
null
null
q-bio.TO
http://creativecommons.org/licenses/by-nc-sa/4.0/
Timely diagnostics of microcirculatory system abnormalities which are the most severe diabetic complications, is a significant problem of modern health care. Functional abnormalities manifest themselves earlier than the structural one and their assessment is the focus of present-day studies. In this study, the Laser Doppler flowmetry, a noninvasive technique for the cutaneous blood flow monitoring, was used together with local temperature tests and wavelet analysis. The study of the blood flow in the microvascular bed of toes was carried out in control group of 40 subjects, and two diabetic groups differing in the type of diabetes mellitus (17 of DM1 and 23 of DM2). The temperature tests demonstrated that diabetic patients have impaired vasodilation in response to local heating. The study of oscillating components shows a significant difference of the spectral properties even in the basal conditions. Low frequency pulsations of the blood flow associated with endothelial and activities are lower in both diabetes groups as well as the ones connected with cardiac activity. Local thermal tests induce variations both in the perfusion and its spectral characteristics, which are different in the groups under consideration. We assume that the results obtained provide a deeper understanding of pathological processes involved in the progress of microvascular abnormalities due to diabetes mellitus.
[ { "created": "Fri, 7 Jul 2017 10:26:49 GMT", "version": "v1" } ]
2017-07-10
[ [ "Mizeva", "Irina", "" ], [ "Zharkikh", "Elena", "" ], [ "Dremin", "Victor", "" ], [ "Zherebtsov", "Evgeny", "" ], [ "Makovik", "Irina", "" ], [ "Potapova", "Elena", "" ], [ "Dunaev", "Andrey", "" ] ]
Timely diagnostics of microcirculatory system abnormalities which are the most severe diabetic complications, is a significant problem of modern health care. Functional abnormalities manifest themselves earlier than the structural one and their assessment is the focus of present-day studies. In this study, the Laser Doppler flowmetry, a noninvasive technique for the cutaneous blood flow monitoring, was used together with local temperature tests and wavelet analysis. The study of the blood flow in the microvascular bed of toes was carried out in control group of 40 subjects, and two diabetic groups differing in the type of diabetes mellitus (17 of DM1 and 23 of DM2). The temperature tests demonstrated that diabetic patients have impaired vasodilation in response to local heating. The study of oscillating components shows a significant difference of the spectral properties even in the basal conditions. Low frequency pulsations of the blood flow associated with endothelial and activities are lower in both diabetes groups as well as the ones connected with cardiac activity. Local thermal tests induce variations both in the perfusion and its spectral characteristics, which are different in the groups under consideration. We assume that the results obtained provide a deeper understanding of pathological processes involved in the progress of microvascular abnormalities due to diabetes mellitus.
2007.02569
Joao Teixeira
Jo\~ao C Teixeira and Christian D Huber
Dismantling a dogma: the inflated significance of neutral genetic diversity in conservation genetics
31 pages, 4 figures, 1 Table, 1 Box
null
10.1073/pnas.2015096118
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The current rate of species extinction is rapidly approaching unprecedented highs and life on Earth presently faces a sixth mass extinction event driven by anthropogenic activity, climate change and ecological collapse. The field of conservation genetics aims at preserving species by using their levels of genetic diversity, usually measured as neutral genome-wide diversity, as a barometer for evaluating population health and extinction risk. A fundamental assumption is that higher levels of genetic diversity lead to an increase in fitness and long-term survival of a species. Here, we argue against the perceived importance of neutral genetic diversity for the conservation of wild populations and species. We demonstrate that no simple general relationship exists between neutral genetic diversity and the risk of species extinction. Instead, a better understanding of the properties of functional genetic diversity, demographic history, and ecological relationships, is necessary for developing and implementing effective conservation genetic strategies.
[ { "created": "Mon, 6 Jul 2020 07:35:29 GMT", "version": "v1" } ]
2022-10-12
[ [ "Teixeira", "João C", "" ], [ "Huber", "Christian D", "" ] ]
The current rate of species extinction is rapidly approaching unprecedented highs and life on Earth presently faces a sixth mass extinction event driven by anthropogenic activity, climate change and ecological collapse. The field of conservation genetics aims at preserving species by using their levels of genetic diversity, usually measured as neutral genome-wide diversity, as a barometer for evaluating population health and extinction risk. A fundamental assumption is that higher levels of genetic diversity lead to an increase in fitness and long-term survival of a species. Here, we argue against the perceived importance of neutral genetic diversity for the conservation of wild populations and species. We demonstrate that no simple general relationship exists between neutral genetic diversity and the risk of species extinction. Instead, a better understanding of the properties of functional genetic diversity, demographic history, and ecological relationships, is necessary for developing and implementing effective conservation genetic strategies.
1203.1287
Piyush Srivastava
Narendra M. Dixit and Piyush Srivastava and Nisheeth K. Vishnoi
A Finite Population Model of Molecular Evolution: Theory and Computation
null
null
null
null
q-bio.PE cs.DM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This paper is concerned with the evolution of haploid organisms that reproduce asexually. In a seminal piece of work, Eigen and coauthors proposed the quasispecies model in an attempt to understand such an evolutionary process. Their work has impacted antiviral treatment and vaccine design strategies. Yet, predictions of the quasispecies model are at best viewed as a guideline, primarily because it assumes an infinite population size, whereas realistic population sizes can be quite small. In this paper we consider a population genetics-based model aimed at understanding the evolution of such organisms with finite population sizes and present a rigorous study of the convergence and computational issues that arise therein. Our first result is structural and shows that, at any time during the evolution, as the population size tends to infinity, the distribution of genomes predicted by our model converges to that predicted by the quasispecies model. This justifies the continued use of the quasispecies model to derive guidelines for intervention. While the stationary state in the quasispecies model is readily obtained, due to the explosion of the state space in our model, exact computations are prohibitive. Our second set of results are computational in nature and address this issue. We derive conditions on the parameters of evolution under which our stochastic model mixes rapidly. Further, for a class of widely used fitness landscapes we give a fast deterministic algorithm which computes the stationary distribution of our model. These computational tools are expected to serve as a framework for the modeling of strategies for the deployment of mutagenic drugs.
[ { "created": "Tue, 6 Mar 2012 19:12:24 GMT", "version": "v1" } ]
2012-03-07
[ [ "Dixit", "Narendra M.", "" ], [ "Srivastava", "Piyush", "" ], [ "Vishnoi", "Nisheeth K.", "" ] ]
This paper is concerned with the evolution of haploid organisms that reproduce asexually. In a seminal piece of work, Eigen and coauthors proposed the quasispecies model in an attempt to understand such an evolutionary process. Their work has impacted antiviral treatment and vaccine design strategies. Yet, predictions of the quasispecies model are at best viewed as a guideline, primarily because it assumes an infinite population size, whereas realistic population sizes can be quite small. In this paper we consider a population genetics-based model aimed at understanding the evolution of such organisms with finite population sizes and present a rigorous study of the convergence and computational issues that arise therein. Our first result is structural and shows that, at any time during the evolution, as the population size tends to infinity, the distribution of genomes predicted by our model converges to that predicted by the quasispecies model. This justifies the continued use of the quasispecies model to derive guidelines for intervention. While the stationary state in the quasispecies model is readily obtained, due to the explosion of the state space in our model, exact computations are prohibitive. Our second set of results are computational in nature and address this issue. We derive conditions on the parameters of evolution under which our stochastic model mixes rapidly. Further, for a class of widely used fitness landscapes we give a fast deterministic algorithm which computes the stationary distribution of our model. These computational tools are expected to serve as a framework for the modeling of strategies for the deployment of mutagenic drugs.
2005.14258
Yujiang Wang
Christoforos A Papasavvas, Gabrielle M Schroeder, Beate Diehl, Gerold Baier, Peter N Taylor, Yujiang Wang
Band power modulation through intracranial EEG stimulation and its cross-session consistency
null
Journal of Neural Engineering, 17-054001 (2020)
10.1088/1741-2552/abbecf
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Background: Direct electrical stimulation of the brain through intracranial electrodes is currently used to probe the epileptic brain as part of pre-surgical evaluation, and it is also being considered for therapeutic treatments through neuromodulation. It is still unknown, however, how consistent intracranial direct electrical stimulation responses are across sessions, to allow effective neuromodulation design. Objective: To investigate the cross-session consistency of the electrophysiological effect of electrical stimulation delivered through intracranial EEG. Methods: We analysed data from 79 epilepsy patients implanted with intracranial EEG who underwent brain stimulation as part of a memory experiment. We quantified the effect of stimulation in terms of band power modulation and compared this effect from session to session. As a reference, we applied the same measures during baseline periods. Results: In most sessions, the effect of stimulation on band power could not be distinguished from baseline fluctuations of band power. Stimulation effect was also not consistent across sessions; only a third of the session pairs had a higher consistency than the baseline standards. Cross-session consistency is mainly associated with the strength of positive stimulation effects, and it also tends to be higher when the baseline conditions are more similar between sessions. Conclusion: These findings can inform our practices for designing neuromodulation with greater efficacy when using direct electrical brain stimulation as a therapeutic treatment.
[ { "created": "Thu, 28 May 2020 19:51:04 GMT", "version": "v1" } ]
2020-11-18
[ [ "Papasavvas", "Christoforos A", "" ], [ "Schroeder", "Gabrielle M", "" ], [ "Diehl", "Beate", "" ], [ "Baier", "Gerold", "" ], [ "Taylor", "Peter N", "" ], [ "Wang", "Yujiang", "" ] ]
Background: Direct electrical stimulation of the brain through intracranial electrodes is currently used to probe the epileptic brain as part of pre-surgical evaluation, and it is also being considered for therapeutic treatments through neuromodulation. It is still unknown, however, how consistent intracranial direct electrical stimulation responses are across sessions, to allow effective neuromodulation design. Objective: To investigate the cross-session consistency of the electrophysiological effect of electrical stimulation delivered through intracranial EEG. Methods: We analysed data from 79 epilepsy patients implanted with intracranial EEG who underwent brain stimulation as part of a memory experiment. We quantified the effect of stimulation in terms of band power modulation and compared this effect from session to session. As a reference, we applied the same measures during baseline periods. Results: In most sessions, the effect of stimulation on band power could not be distinguished from baseline fluctuations of band power. Stimulation effect was also not consistent across sessions; only a third of the session pairs had a higher consistency than the baseline standards. Cross-session consistency is mainly associated with the strength of positive stimulation effects, and it also tends to be higher when the baseline conditions are more similar between sessions. Conclusion: These findings can inform our practices for designing neuromodulation with greater efficacy when using direct electrical brain stimulation as a therapeutic treatment.
1309.5614
Boleslaw Szymanski
Konrad R. Fialkowski
Has our brain grown too big to think effectively?
null
null
null
Report 01-13
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A variant of microcephalin, MCPH1 gene, was introgressed about 37,000 years ago into Homo sapiens genetic pool from an archaic (Homo erectus) lineage and rose to exceptionally high frequency of around 70 percent worldwide today. It is involved in regulating neuroblast proliferation and its changes alter the rate of division and/or differentiation of neuroblasts during the neurogenic phase of embriogenesis, which could alter the size and structure of the resulting brain. At the time of introgression, images had already been painted on the walls of caves and speech has been in use for over 100,000 years, as had been abstract thinking. Like today, reasoning and thinking were the primary faculties of individuals. Homo erectus either did not possess those faculties or was markedly inferior to Homo sapiens in them. Its brain was smaller and the cortex was apparently less convoluted. Thus, introgressed microcephalin allele directed neurogenesis evolutionary back to less complicated brain structure typical for our evolutionary forefathers, slightly decreasing the level of complexity already achieved by Homo sapiens 37,000 years ago. Despite that, it proliferated at a rapid pace. It yields a supposition: 37,000 years ago the brains of Homo sapiens were too big and too complicated for the kind of thinking needed for the highest fitness of individuals. Since adaptation cannot by definition surpass selection requirements, the volume and complication of the human brain did not originate under selective pressure to improve effective thinking and they cannot be explained in terms of such selection. A proposal to solve this quandary is presented, claiming that Homo sapiens originated just by chance. Endurance running led to the emergence of Homo sapiens. The human mind and larynx used for speech are side-effects of more than a million years of endurance running by pre-human hunters.
[ { "created": "Sun, 22 Sep 2013 16:15:43 GMT", "version": "v1" } ]
2013-09-24
[ [ "Fialkowski", "Konrad R.", "" ] ]
A variant of microcephalin, MCPH1 gene, was introgressed about 37,000 years ago into Homo sapiens genetic pool from an archaic (Homo erectus) lineage and rose to exceptionally high frequency of around 70 percent worldwide today. It is involved in regulating neuroblast proliferation and its changes alter the rate of division and/or differentiation of neuroblasts during the neurogenic phase of embriogenesis, which could alter the size and structure of the resulting brain. At the time of introgression, images had already been painted on the walls of caves and speech has been in use for over 100,000 years, as had been abstract thinking. Like today, reasoning and thinking were the primary faculties of individuals. Homo erectus either did not possess those faculties or was markedly inferior to Homo sapiens in them. Its brain was smaller and the cortex was apparently less convoluted. Thus, introgressed microcephalin allele directed neurogenesis evolutionary back to less complicated brain structure typical for our evolutionary forefathers, slightly decreasing the level of complexity already achieved by Homo sapiens 37,000 years ago. Despite that, it proliferated at a rapid pace. It yields a supposition: 37,000 years ago the brains of Homo sapiens were too big and too complicated for the kind of thinking needed for the highest fitness of individuals. Since adaptation cannot by definition surpass selection requirements, the volume and complication of the human brain did not originate under selective pressure to improve effective thinking and they cannot be explained in terms of such selection. A proposal to solve this quandary is presented, claiming that Homo sapiens originated just by chance. Endurance running led to the emergence of Homo sapiens. The human mind and larynx used for speech are side-effects of more than a million years of endurance running by pre-human hunters.
2303.09649
Thomas Athey
Thomas L. Athey, Daniel J. Tward, Ulrich Mueller, Laurent Younes, Joshua T. Vogelstein, Michael I. Miller
Preserving Derivative Information while Transforming Neuronal Curves
null
null
null
null
q-bio.NC cs.NA math.NA
http://creativecommons.org/licenses/by/4.0/
The international neuroscience community is building the first comprehensive atlases of brain cell types to understand how the brain functions from a higher resolution, and more integrated perspective than ever before. In order to build these atlases, subsets of neurons (e.g. serotonergic neurons, prefrontal cortical neurons etc.) are traced in individual brain samples by placing points along dendrites and axons. Then, the traces are mapped to common coordinate systems by transforming the positions of their points, which neglects how the transformation bends the line segments in between. In this work, we apply the theory of jets to describe how to preserve derivatives of neuron traces up to any order. We provide a framework to compute possible error introduced by standard mapping methods, which involves the Jacobian of the mapping transformation. We show how our first order method improves mapping accuracy in both simulated and real neuron traces under random diffeomorphisms. Our method is freely available in our open-source Python package brainlit.
[ { "created": "Thu, 16 Mar 2023 21:01:18 GMT", "version": "v1" }, { "created": "Tue, 1 Aug 2023 19:32:24 GMT", "version": "v2" } ]
2023-08-03
[ [ "Athey", "Thomas L.", "" ], [ "Tward", "Daniel J.", "" ], [ "Mueller", "Ulrich", "" ], [ "Younes", "Laurent", "" ], [ "Vogelstein", "Joshua T.", "" ], [ "Miller", "Michael I.", "" ] ]
The international neuroscience community is building the first comprehensive atlases of brain cell types to understand how the brain functions from a higher resolution, and more integrated perspective than ever before. In order to build these atlases, subsets of neurons (e.g. serotonergic neurons, prefrontal cortical neurons etc.) are traced in individual brain samples by placing points along dendrites and axons. Then, the traces are mapped to common coordinate systems by transforming the positions of their points, which neglects how the transformation bends the line segments in between. In this work, we apply the theory of jets to describe how to preserve derivatives of neuron traces up to any order. We provide a framework to compute possible error introduced by standard mapping methods, which involves the Jacobian of the mapping transformation. We show how our first order method improves mapping accuracy in both simulated and real neuron traces under random diffeomorphisms. Our method is freely available in our open-source Python package brainlit.
q-bio/0401038
Jesse Bloom
Jesse D Bloom, Claus O Wilke, Frances H Arnold, Christoph Adami
Stability and the Evolvability of Function in a Model Protein
Biophysical Journal in press
Biophysical Journal, 86:2758-2764 (2004)
10.1016/S0006-3495(04)74329-5
null
q-bio.BM
null
Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability requirement and the capacity of a protein to evolve the function of binding to a ligand. Although our model contains no built-in tradeoff between stability and function, proteins evolved function more efficiently when the stability requirement was relaxed. Proteins with both high stability and high function evolved more efficiently when the stability requirement was gradually increased than when there was constant selection for high stability. These results show that in our model, the evolution of function is enhanced by allowing proteins to explore sequences corresponding to marginally stable structures, and that it is easier to improve stability while maintaining high function than to improve function while maintaining high stability. Our model also demonstrates that even in the absence of a fundamental biophysical tradeoff between stability and function, the speed with which function can evolve is limited by the stability requirement imposed on the protein.
[ { "created": "Wed, 28 Jan 2004 02:28:45 GMT", "version": "v1" } ]
2009-11-10
[ [ "Bloom", "Jesse D", "" ], [ "Wilke", "Claus O", "" ], [ "Arnold", "Frances H", "" ], [ "Adami", "Christoph", "" ] ]
Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability requirement and the capacity of a protein to evolve the function of binding to a ligand. Although our model contains no built-in tradeoff between stability and function, proteins evolved function more efficiently when the stability requirement was relaxed. Proteins with both high stability and high function evolved more efficiently when the stability requirement was gradually increased than when there was constant selection for high stability. These results show that in our model, the evolution of function is enhanced by allowing proteins to explore sequences corresponding to marginally stable structures, and that it is easier to improve stability while maintaining high function than to improve function while maintaining high stability. Our model also demonstrates that even in the absence of a fundamental biophysical tradeoff between stability and function, the speed with which function can evolve is limited by the stability requirement imposed on the protein.
2108.11640
Paul Kirk
Thomas Thorne and Paul D. W. Kirk and Heather A. Harrington
Topological Approximate Bayesian Computation for Parameter Inference of an Angiogenesis Model
7 pages, 2 figures. For associated code see: https://github.com/tt104/tabc_angio
null
null
null
q-bio.QM stat.ME
http://creativecommons.org/licenses/by/4.0/
Inferring the parameters of models describing biological systems is an important problem in the reverse engineering of the mechanisms underlying these systems. Much work has focused on parameter inference of stochastic and ordinary differential equation models using Approximate Bayesian Computation (ABC). While there is some recent work on inference in spatial models, this remains an open problem. Simultaneously, advances in topological data analysis (TDA), a field of computational mathematics, have enabled spatial patterns in data to be characterised. Here we focus on recent work using topological data analysis to study different regimes of parameter space for a well-studied model of angiogenesis. We propose a method for combining TDA with ABC to infer parameters in the Anderson-Chaplain model of angiogenesis. We demonstrate that this topological approach outperforms ABC approaches that use simpler statistics based on spatial features of the data. This is a first step towards a general framework of spatial parameter inference for biological systems, for which there may be a variety of filtrations, vectorisations, and summary statistics to be considered. All code used to produce our results is available as a Snakemake workflow.
[ { "created": "Thu, 26 Aug 2021 08:12:31 GMT", "version": "v1" }, { "created": "Mon, 8 Nov 2021 11:27:22 GMT", "version": "v2" } ]
2021-11-09
[ [ "Thorne", "Thomas", "" ], [ "Kirk", "Paul D. W.", "" ], [ "Harrington", "Heather A.", "" ] ]
Inferring the parameters of models describing biological systems is an important problem in the reverse engineering of the mechanisms underlying these systems. Much work has focused on parameter inference of stochastic and ordinary differential equation models using Approximate Bayesian Computation (ABC). While there is some recent work on inference in spatial models, this remains an open problem. Simultaneously, advances in topological data analysis (TDA), a field of computational mathematics, have enabled spatial patterns in data to be characterised. Here we focus on recent work using topological data analysis to study different regimes of parameter space for a well-studied model of angiogenesis. We propose a method for combining TDA with ABC to infer parameters in the Anderson-Chaplain model of angiogenesis. We demonstrate that this topological approach outperforms ABC approaches that use simpler statistics based on spatial features of the data. This is a first step towards a general framework of spatial parameter inference for biological systems, for which there may be a variety of filtrations, vectorisations, and summary statistics to be considered. All code used to produce our results is available as a Snakemake workflow.
2309.10884
Casey Barkan
Casey O. Barkan and Shenshen Wang
Migration feedback induces emergent ecotypes and abrupt transitions in evolving populations
10 pages, 3 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We explore the connection between migration patterns and emergent behaviors of evolving populations in spatially heterogeneous environments. Despite extensive studies in ecologically and medically important systems, a unifying framework that clarifies this connection and makes concrete predictions remains much needed. Using a simple evolutionary model on a network of interconnected habitats with distinct fitness landscapes, we demonstrate a fundamental connection between migration feedback, emergent ecotypes, and an unusual form of discontinuous critical transition. We show how migration feedback generates spatially non-local niches in which emergent ecotypes can specialize. Rugged fitness landscapes lead to a complex, yet understandable, phase diagram in which different ecotypes coexist under different migration patterns. The discontinuous transitions are distinct from the standard first-order phase transitions in statistical physics. They arise due to simultaneous transcritical bifurcations and exhibit a "fine structure" due to symmetry breaking between intra- and inter-ecotype interactions. We suggest feasible experiments to test our predictions.
[ { "created": "Tue, 19 Sep 2023 19:18:40 GMT", "version": "v1" }, { "created": "Tue, 9 Jan 2024 00:43:49 GMT", "version": "v2" } ]
2024-01-10
[ [ "Barkan", "Casey O.", "" ], [ "Wang", "Shenshen", "" ] ]
We explore the connection between migration patterns and emergent behaviors of evolving populations in spatially heterogeneous environments. Despite extensive studies in ecologically and medically important systems, a unifying framework that clarifies this connection and makes concrete predictions remains much needed. Using a simple evolutionary model on a network of interconnected habitats with distinct fitness landscapes, we demonstrate a fundamental connection between migration feedback, emergent ecotypes, and an unusual form of discontinuous critical transition. We show how migration feedback generates spatially non-local niches in which emergent ecotypes can specialize. Rugged fitness landscapes lead to a complex, yet understandable, phase diagram in which different ecotypes coexist under different migration patterns. The discontinuous transitions are distinct from the standard first-order phase transitions in statistical physics. They arise due to simultaneous transcritical bifurcations and exhibit a "fine structure" due to symmetry breaking between intra- and inter-ecotype interactions. We suggest feasible experiments to test our predictions.
2307.15857
Maria-Veronica Ciocanel
Maria-Veronica Ciocanel, Lee Ding, Lucas Mastromatteo, Sarah Reichheld, Sarah Cabral, Kimberly Mowry, Bjorn Sandstede
Parameter identifiability in PDE models of fluorescence recovery after photobleaching
19 pages, 10 figures
null
10.1007/s11538-024-01266-4
null
q-bio.QM math.DS
http://creativecommons.org/licenses/by/4.0/
Identifying unique parameters for mathematical models describing biological data can be challenging and often impossible. Parameter identifiability for partial differential equations models in cell biology is especially difficult given that many established \textit{in vivo} measurements of protein dynamics average out the spatial dimensions. Here, we are motivated by recent experiments on the binding dynamics of the RNA-binding protein PTBP3 in RNP granules of frog oocytes based on fluorescence recovery after photobleaching (FRAP) measurements. FRAP is a widely-used experimental technique for probing protein dynamics in living cells, and is often modeled using simple reaction-diffusion models of the protein dynamics. We show that current methods of structural and practical parameter identifiability provide limited insights into identifiability of kinetic parameters for these PDE models and spatially-averaged FRAP data. We thus propose a pipeline for assessing parameter identifiability and for learning parameter combinations based on re-parametrization and profile likelihoods analysis. We show that this method is able to recover parameter combinations for synthetic FRAP datasets and investigate its application to real experimental data.
[ { "created": "Sat, 29 Jul 2023 01:21:02 GMT", "version": "v1" }, { "created": "Sat, 2 Mar 2024 19:50:19 GMT", "version": "v2" } ]
2024-03-05
[ [ "Ciocanel", "Maria-Veronica", "" ], [ "Ding", "Lee", "" ], [ "Mastromatteo", "Lucas", "" ], [ "Reichheld", "Sarah", "" ], [ "Cabral", "Sarah", "" ], [ "Mowry", "Kimberly", "" ], [ "Sandstede", "Bjorn", "" ] ]
Identifying unique parameters for mathematical models describing biological data can be challenging and often impossible. Parameter identifiability for partial differential equations models in cell biology is especially difficult given that many established \textit{in vivo} measurements of protein dynamics average out the spatial dimensions. Here, we are motivated by recent experiments on the binding dynamics of the RNA-binding protein PTBP3 in RNP granules of frog oocytes based on fluorescence recovery after photobleaching (FRAP) measurements. FRAP is a widely-used experimental technique for probing protein dynamics in living cells, and is often modeled using simple reaction-diffusion models of the protein dynamics. We show that current methods of structural and practical parameter identifiability provide limited insights into identifiability of kinetic parameters for these PDE models and spatially-averaged FRAP data. We thus propose a pipeline for assessing parameter identifiability and for learning parameter combinations based on re-parametrization and profile likelihoods analysis. We show that this method is able to recover parameter combinations for synthetic FRAP datasets and investigate its application to real experimental data.
q-bio/0608016
Romulus Breban
Romulus Breban, Raffaele Vardavas and Sally Blower
Inductive Reasoning Games as Influenza Vaccination Models: Mean Field Analysis
20 pages, 7 figures
null
10.1103/PhysRevE.76.031127
null
q-bio.PE
null
We define and analyze an inductive reasoning game of voluntary yearly vaccination in order to establish whether or not a population of individuals acting in their own self-interest would be able to prevent influenza epidemics. We find that epidemics are rarely prevented. We also find that severe epidemics may occur without the introduction of pandemic strains. We further address the situation where market incentives are introduced to help ameliorating epidemics. Surprisingly, we find that vaccinating families exacerbates epidemics. However, a public health program requesting prepayment of vaccinations may significantly ameliorate influenza epidemics.
[ { "created": "Tue, 8 Aug 2006 01:23:56 GMT", "version": "v1" } ]
2013-05-29
[ [ "Breban", "Romulus", "" ], [ "Vardavas", "Raffaele", "" ], [ "Blower", "Sally", "" ] ]
We define and analyze an inductive reasoning game of voluntary yearly vaccination in order to establish whether or not a population of individuals acting in their own self-interest would be able to prevent influenza epidemics. We find that epidemics are rarely prevented. We also find that severe epidemics may occur without the introduction of pandemic strains. We further address the situation where market incentives are introduced to help ameliorating epidemics. Surprisingly, we find that vaccinating families exacerbates epidemics. However, a public health program requesting prepayment of vaccinations may significantly ameliorate influenza epidemics.
2408.02650
Rosalind J Allen
Andrea Iglesias-Ramas, Samuele Pio Lipani and Rosalind J. Allen
Population genetics: an introduction for physicists
null
null
null
null
q-bio.PE physics.bio-ph
http://creativecommons.org/licenses/by/4.0/
Population genetics lies at the heart of evolutionary theory. This topic forms part of many biological science curricula but is rarely taught to physics students. Since physicists are becoming increasingly interested in biological evolution, we aim to provide a brief introduction to population genetics, written for physicists. We start with two background chapters: chapter 1 provides a brief historical introduction to the topic, while chapter 2 provides some essential biological background. We begin our main content with chapter 3 which discusses the key concepts behind Darwinian natural selection and Mendelian inheritance. Chapter 4 covers the basics of how variation is maintained in populations, while chapter 5 discusses mutation and selection. In chapter 6 we discuss stochastic effects in population genetics using the Wright-Fisher model as our example, and finally we offer concluding thoughts and references to excellent textbooks in chapter 7.
[ { "created": "Mon, 5 Aug 2024 17:25:57 GMT", "version": "v1" }, { "created": "Wed, 7 Aug 2024 11:22:32 GMT", "version": "v2" }, { "created": "Thu, 8 Aug 2024 12:09:39 GMT", "version": "v3" } ]
2024-08-09
[ [ "Iglesias-Ramas", "Andrea", "" ], [ "Lipani", "Samuele Pio", "" ], [ "Allen", "Rosalind J.", "" ] ]
Population genetics lies at the heart of evolutionary theory. This topic forms part of many biological science curricula but is rarely taught to physics students. Since physicists are becoming increasingly interested in biological evolution, we aim to provide a brief introduction to population genetics, written for physicists. We start with two background chapters: chapter 1 provides a brief historical introduction to the topic, while chapter 2 provides some essential biological background. We begin our main content with chapter 3 which discusses the key concepts behind Darwinian natural selection and Mendelian inheritance. Chapter 4 covers the basics of how variation is maintained in populations, while chapter 5 discusses mutation and selection. In chapter 6 we discuss stochastic effects in population genetics using the Wright-Fisher model as our example, and finally we offer concluding thoughts and references to excellent textbooks in chapter 7.
1904.11219
Dongjie Xie
Dongjie Xie, Meng Pei and Yanjie Su
"Favoring my playmate seems fair": Inhibitory control and theory of mind in preschoolers' self-disadvantaging behaviors
24 pages, 3 figures
Journal of Experimental Child Psychology, 2019
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The purpose of this study was to investigate the relationship between preschoolers' cognitive abilities and their fairness-related allocation behaviors in a dilemma of equity-efficiency conflict. Four- to 6-year-olds in Experiment 1 (N = 99) decided how to allocate 5 reward bells. In the first-party condition, preschoolers were asked to choose among giving more to self (self-advantageous inequity), wasting one bell (equity) or giving more to other (self-disadvantageous inequity); while in the third-party condition, they chose to allocate the extra bell to one of two equally deserving recipients or to waste it. Results showed that compared to the pattern of decision in the third-party condition, preschoolers in the first-party condition were more likely to give the extra bell to other (self-disadvantaging behaviors), and age, inhibitory control (IC) and theory of mind (ToM) were positively correlated with their self-disadvantaging choices, but only IC mediated the relationship between age and self-disadvantaging behaviors. Experiment 2 (N = 41) showed that IC still predicted preschoolers' self-disadvantaging behaviors when they could choose only between equity and disadvantageous inequity. These results suggested that IC played a critical role in the implementation of self-disadvantaging behaviors when this required the control over selfishness and envy.
[ { "created": "Thu, 25 Apr 2019 08:56:49 GMT", "version": "v1" } ]
2019-04-26
[ [ "Xie", "Dongjie", "" ], [ "Pei", "Meng", "" ], [ "Su", "Yanjie", "" ] ]
The purpose of this study was to investigate the relationship between preschoolers' cognitive abilities and their fairness-related allocation behaviors in a dilemma of equity-efficiency conflict. Four- to 6-year-olds in Experiment 1 (N = 99) decided how to allocate 5 reward bells. In the first-party condition, preschoolers were asked to choose among giving more to self (self-advantageous inequity), wasting one bell (equity) or giving more to other (self-disadvantageous inequity); while in the third-party condition, they chose to allocate the extra bell to one of two equally deserving recipients or to waste it. Results showed that compared to the pattern of decision in the third-party condition, preschoolers in the first-party condition were more likely to give the extra bell to other (self-disadvantaging behaviors), and age, inhibitory control (IC) and theory of mind (ToM) were positively correlated with their self-disadvantaging choices, but only IC mediated the relationship between age and self-disadvantaging behaviors. Experiment 2 (N = 41) showed that IC still predicted preschoolers' self-disadvantaging behaviors when they could choose only between equity and disadvantageous inequity. These results suggested that IC played a critical role in the implementation of self-disadvantaging behaviors when this required the control over selfishness and envy.
1308.6158
Harold Fellermann
Shinpei Tanaka, Harold Fellermann and Steen Rasmussen
Sequence selection in an autocatalytic binary polymer model
null
null
10.1209/0295-5075/107/28004
null
q-bio.MN nlin.AO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
An autocatalytic pattern matching polymer system is studied as an abstract model for chemical ecosystem evolution. Highly ordered populations with particular sequence patterns appear spontaneously out of a vast number of possible states. The interplay between the selected microscopic sequence patterns and the macroscopic cooperative structures is examined. Stability, fluctuations, and evolutionary selection mechanisms are investigated for the involved self-organizing processes.
[ { "created": "Wed, 28 Aug 2013 14:15:18 GMT", "version": "v1" } ]
2015-06-17
[ [ "Tanaka", "Shinpei", "" ], [ "Fellermann", "Harold", "" ], [ "Rasmussen", "Steen", "" ] ]
An autocatalytic pattern matching polymer system is studied as an abstract model for chemical ecosystem evolution. Highly ordered populations with particular sequence patterns appear spontaneously out of a vast number of possible states. The interplay between the selected microscopic sequence patterns and the macroscopic cooperative structures is examined. Stability, fluctuations, and evolutionary selection mechanisms are investigated for the involved self-organizing processes.
2303.06041
Jamie Mullineaux
Jamie Mullineaux, Takoua Jendoubi, Baptiste Leurent
A Bayesian spatio-temporal study of meteorological factors affecting the spread of COVID-19
23 pages, 13 figures (inclusive of references and appendix)
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
The spread of COVID-19 has brought challenges to health, social and economic systems around the world. With little to no prior immunity in the global population transmission has been driven primarily by human interaction. However, as with common respiratory illnesses such as the flu it's suggested that COVID-19 may become seasonal as immunity grows. Yet the effects of meteorological conditions on the spread of COVID-19 are poorly understood with previous studies producing contrasting results, due at least in part to limited and inconsistent study designs. This study investigates the effect of meteorological conditions on COVID-19 infections in England using a spatio-temporal model applied to case counts during the initial England lockdown. By modelling spatial and temporal effects to account for the nature of a human transmissible virus the model isolates meteorological effects. Inference based on 95% highest posterior density intervals shows humidity is negatively associated with COVID-19 spread. The lack of evidence for other weather factors affecting COVID-19 transmission shows care should be taken with respect to seasonality when designing COVID-19 policies and public communications.
[ { "created": "Fri, 10 Mar 2023 16:30:59 GMT", "version": "v1" }, { "created": "Fri, 24 Mar 2023 00:08:24 GMT", "version": "v2" }, { "created": "Wed, 29 Mar 2023 22:42:50 GMT", "version": "v3" }, { "created": "Mon, 7 Aug 2023 21:12:09 GMT", "version": "v4" } ]
2023-08-09
[ [ "Mullineaux", "Jamie", "" ], [ "Jendoubi", "Takoua", "" ], [ "Leurent", "Baptiste", "" ] ]
The spread of COVID-19 has brought challenges to health, social and economic systems around the world. With little to no prior immunity in the global population transmission has been driven primarily by human interaction. However, as with common respiratory illnesses such as the flu it's suggested that COVID-19 may become seasonal as immunity grows. Yet the effects of meteorological conditions on the spread of COVID-19 are poorly understood with previous studies producing contrasting results, due at least in part to limited and inconsistent study designs. This study investigates the effect of meteorological conditions on COVID-19 infections in England using a spatio-temporal model applied to case counts during the initial England lockdown. By modelling spatial and temporal effects to account for the nature of a human transmissible virus the model isolates meteorological effects. Inference based on 95% highest posterior density intervals shows humidity is negatively associated with COVID-19 spread. The lack of evidence for other weather factors affecting COVID-19 transmission shows care should be taken with respect to seasonality when designing COVID-19 policies and public communications.
2407.13551
Eduardo Henrique Colombo
E.H. Colombo, L. Defaveri, C. Anteneodo
Decoding the interaction mediators from landscape-induced spatial patterns
null
null
null
null
q-bio.PE cond-mat.stat-mech
http://creativecommons.org/licenses/by/4.0/
Interactions between organisms are mediated by an intricate network of physico-chemical substances and other organisms. Understanding the dynamics of mediators and how they shape the population spatial distribution is key to predict ecological outcomes and how they would be transformed by changes in environmental constraints. However, due to the inherent complexity involved, this task is often unfeasible, from the empirical and theoretical perspectives. In this paper, we make progress in addressing this central issue, creating a bridge that provides a two-way connection between the features of the ensemble of underlying mediators and the wrinkles in the population density induced by a landscape defect (or spatial perturbation). The bridge is constructed by applying the Feynman-Vernon decomposition, which disentangles the influences among the focal population and the mediators in a compact way. This is achieved though an interaction kernel, which effectively incorporates the mediators' degrees of freedom, explaining the emergence of nonlocal influence between individuals, an ad hoc assumption in modeling population dynamics. Concrete examples are worked out and reveal the complexity behind a possible top-down inference procedure.
[ { "created": "Thu, 18 Jul 2024 14:25:18 GMT", "version": "v1" } ]
2024-07-19
[ [ "Colombo", "E. H.", "" ], [ "Defaveri", "L.", "" ], [ "Anteneodo", "C.", "" ] ]
Interactions between organisms are mediated by an intricate network of physico-chemical substances and other organisms. Understanding the dynamics of mediators and how they shape the population spatial distribution is key to predict ecological outcomes and how they would be transformed by changes in environmental constraints. However, due to the inherent complexity involved, this task is often unfeasible, from the empirical and theoretical perspectives. In this paper, we make progress in addressing this central issue, creating a bridge that provides a two-way connection between the features of the ensemble of underlying mediators and the wrinkles in the population density induced by a landscape defect (or spatial perturbation). The bridge is constructed by applying the Feynman-Vernon decomposition, which disentangles the influences among the focal population and the mediators in a compact way. This is achieved though an interaction kernel, which effectively incorporates the mediators' degrees of freedom, explaining the emergence of nonlocal influence between individuals, an ad hoc assumption in modeling population dynamics. Concrete examples are worked out and reveal the complexity behind a possible top-down inference procedure.
1005.1159
Igor Kulic
Herve Mohrbach, Albert Johner and Igor M. Kulic
Polymorphic Dynamics of Microtubules
null
null
null
null
q-bio.BM cond-mat.mes-hall cond-mat.soft physics.bio-ph q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Starting from the hypothesis that the tubulin dimer is a conformationally bistable molecule - fluctuating between a curved and a straight configuration at room temperature - we develop a model for polymorphic dynamics of the microtubule lattice. We show that tubulin bistability consistently explains unusual dynamic fluctuations, the apparent length-stiffness relation of grafted microtubules and the curved-helical appearance of microtubules in general. Analyzing experimental data we conclude that taxol stabilized microtubules exist in highly cooperative yet strongly fluctuating helical states. When clamped by the end the microtubule undergoes an unusual zero energy motion - in its effect reminiscent of a limited rotational hinge.
[ { "created": "Fri, 7 May 2010 09:03:06 GMT", "version": "v1" } ]
2010-05-10
[ [ "Mohrbach", "Herve", "" ], [ "Johner", "Albert", "" ], [ "Kulic", "Igor M.", "" ] ]
Starting from the hypothesis that the tubulin dimer is a conformationally bistable molecule - fluctuating between a curved and a straight configuration at room temperature - we develop a model for polymorphic dynamics of the microtubule lattice. We show that tubulin bistability consistently explains unusual dynamic fluctuations, the apparent length-stiffness relation of grafted microtubules and the curved-helical appearance of microtubules in general. Analyzing experimental data we conclude that taxol stabilized microtubules exist in highly cooperative yet strongly fluctuating helical states. When clamped by the end the microtubule undergoes an unusual zero energy motion - in its effect reminiscent of a limited rotational hinge.
2309.01670
Nathan Ng
Nathan Ng, Ji Won Park, Jae Hyeon Lee, Ryan Lewis Kelly, Stephen Ra, Kyunghyun Cho
Blind Biological Sequence Denoising with Self-Supervised Set Learning
null
null
null
null
q-bio.GN cs.LG
http://creativecommons.org/licenses/by/4.0/
Biological sequence analysis relies on the ability to denoise the imprecise output of sequencing platforms. We consider a common setting where a short sequence is read out repeatedly using a high-throughput long-read platform to generate multiple subreads, or noisy observations of the same sequence. Denoising these subreads with alignment-based approaches often fails when too few subreads are available or error rates are too high. In this paper, we propose a novel method for blindly denoising sets of sequences without directly observing clean source sequence labels. Our method, Self-Supervised Set Learning (SSSL), gathers subreads together in an embedding space and estimates a single set embedding as the midpoint of the subreads in both the latent and sequence spaces. This set embedding represents the "average" of the subreads and can be decoded into a prediction of the clean sequence. In experiments on simulated long-read DNA data, SSSL methods denoise small reads of $\leq 6$ subreads with 17% fewer errors and large reads of $>6$ subreads with 8% fewer errors compared to the best baseline. On a real dataset of antibody sequences, SSSL improves over baselines on two self-supervised metrics, with a significant improvement on difficult small reads that comprise over 60% of the test set. By accurately denoising these reads, SSSL promises to better realize the potential of high-throughput DNA sequencing data for downstream scientific applications.
[ { "created": "Mon, 4 Sep 2023 15:35:04 GMT", "version": "v1" } ]
2023-09-06
[ [ "Ng", "Nathan", "" ], [ "Park", "Ji Won", "" ], [ "Lee", "Jae Hyeon", "" ], [ "Kelly", "Ryan Lewis", "" ], [ "Ra", "Stephen", "" ], [ "Cho", "Kyunghyun", "" ] ]
Biological sequence analysis relies on the ability to denoise the imprecise output of sequencing platforms. We consider a common setting where a short sequence is read out repeatedly using a high-throughput long-read platform to generate multiple subreads, or noisy observations of the same sequence. Denoising these subreads with alignment-based approaches often fails when too few subreads are available or error rates are too high. In this paper, we propose a novel method for blindly denoising sets of sequences without directly observing clean source sequence labels. Our method, Self-Supervised Set Learning (SSSL), gathers subreads together in an embedding space and estimates a single set embedding as the midpoint of the subreads in both the latent and sequence spaces. This set embedding represents the "average" of the subreads and can be decoded into a prediction of the clean sequence. In experiments on simulated long-read DNA data, SSSL methods denoise small reads of $\leq 6$ subreads with 17% fewer errors and large reads of $>6$ subreads with 8% fewer errors compared to the best baseline. On a real dataset of antibody sequences, SSSL improves over baselines on two self-supervised metrics, with a significant improvement on difficult small reads that comprise over 60% of the test set. By accurately denoising these reads, SSSL promises to better realize the potential of high-throughput DNA sequencing data for downstream scientific applications.
1902.10234
Arvind Balijepalli
Son T. Le, Nicholas B. Guros, Robert C. Bruce, Antonio Cardone, Niranjana D. Amin, Siyuan Zhang, Jeffery B. Klauda, Harish C. Pant, Curt A. Richter and Arvind Balijepalli
Quantum Capacitance-Limited MoS2 Biosensors Enable Remote Label-Free Enzyme Measurements
null
null
10.1039/C9NR03171E
null
q-bio.QM physics.app-ph
http://creativecommons.org/licenses/by-nc-sa/4.0/
We have demonstrated atomically thin, quantum capacitance-limited, field-effect transistors (FETs) that enable the detection of pH changes with ~75-fold higher sensitivity (4.4 V/pH) over the Nernst value of 59 mV/pH at room temperature when used as a biosensor. The transistors, which are fabricated from a monolayer of MoS2 with a room temperature ionic liquid (RTIL) in place of a conventional oxide gate dielectric, exhibit very low intrinsic noise resulting in a pH limit of detection (LOD) of 92x10^-6 at 10 Hz. This high device performance, which is a function of the structure of our device, is achieved by remotely connecting the gate to a pH sensing element allowing the FETs to be reused. Because pH measurements are fundamentally important in biotechnology, the low limit of detection demonstrated here will benefit numerous applications ranging from pharmaceutical manufacturing to clinical diagnostics. As an example, we experimentally quantified the function of the kinase Cdk5, an enzyme implicated in Alzheimer's disease, at concentrations that are 5-fold lower than physiological values, and with sufficient time-resolution to allow the estimation of both steady-state and kinetic parameters in a single experiment. The high sensitivity, low LOD and fast turnaround time of the measurements will allow the development of early diagnostic tools and novel therapeutics to detect and treat neurological conditions years before currently possible.
[ { "created": "Fri, 21 Dec 2018 16:34:53 GMT", "version": "v1" } ]
2019-08-08
[ [ "Le", "Son T.", "" ], [ "Guros", "Nicholas B.", "" ], [ "Bruce", "Robert C.", "" ], [ "Cardone", "Antonio", "" ], [ "Amin", "Niranjana D.", "" ], [ "Zhang", "Siyuan", "" ], [ "Klauda", "Jeffery B.", "" ], [ "Pant", "Harish C.", "" ], [ "Richter", "Curt A.", "" ], [ "Balijepalli", "Arvind", "" ] ]
We have demonstrated atomically thin, quantum capacitance-limited, field-effect transistors (FETs) that enable the detection of pH changes with ~75-fold higher sensitivity (4.4 V/pH) over the Nernst value of 59 mV/pH at room temperature when used as a biosensor. The transistors, which are fabricated from a monolayer of MoS2 with a room temperature ionic liquid (RTIL) in place of a conventional oxide gate dielectric, exhibit very low intrinsic noise resulting in a pH limit of detection (LOD) of 92x10^-6 at 10 Hz. This high device performance, which is a function of the structure of our device, is achieved by remotely connecting the gate to a pH sensing element allowing the FETs to be reused. Because pH measurements are fundamentally important in biotechnology, the low limit of detection demonstrated here will benefit numerous applications ranging from pharmaceutical manufacturing to clinical diagnostics. As an example, we experimentally quantified the function of the kinase Cdk5, an enzyme implicated in Alzheimer's disease, at concentrations that are 5-fold lower than physiological values, and with sufficient time-resolution to allow the estimation of both steady-state and kinetic parameters in a single experiment. The high sensitivity, low LOD and fast turnaround time of the measurements will allow the development of early diagnostic tools and novel therapeutics to detect and treat neurological conditions years before currently possible.
1704.05628
Jae Kyoung Kim
Jae Kyoung Kim, Grzegorz A. Rempala, Hye-Won Kang
Reduction for stochastic biochemical reaction networks with multiscale conservations
27 pages, 5 figures, This pre-print has been accepted for publication in SIAM Multiscale Modeling & Simulation. The final copyedited version of this paper will be available at https://www.siam.org/journals/mms.php
null
null
null
q-bio.MN math.PR physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Biochemical reaction networks frequently consist of species evolving on multiple timescales. Stochastic simulations of such networks are often computationally challenging and therefore various methods have been developed to obtain sensible stochastic approximations on the timescale of interest. One of the rigorous and popular approaches is the multiscale approximation method for continuous time Markov processes. In this approach, by scaling species abundances and reaction rates, a family of processes parameterized by a scaling parameter is defined. The limiting process of this family is then used to approximate the original process. However, we find that such approximations become inaccurate when combinations of species with disparate abundances either constitute conservation laws or form virtual slow auxiliary species. To obtain more accurate approximation in such cases, we propose here an appropriate modification of the original method.
[ { "created": "Wed, 19 Apr 2017 06:49:59 GMT", "version": "v1" } ]
2017-04-20
[ [ "Kim", "Jae Kyoung", "" ], [ "Rempala", "Grzegorz A.", "" ], [ "Kang", "Hye-Won", "" ] ]
Biochemical reaction networks frequently consist of species evolving on multiple timescales. Stochastic simulations of such networks are often computationally challenging and therefore various methods have been developed to obtain sensible stochastic approximations on the timescale of interest. One of the rigorous and popular approaches is the multiscale approximation method for continuous time Markov processes. In this approach, by scaling species abundances and reaction rates, a family of processes parameterized by a scaling parameter is defined. The limiting process of this family is then used to approximate the original process. However, we find that such approximations become inaccurate when combinations of species with disparate abundances either constitute conservation laws or form virtual slow auxiliary species. To obtain more accurate approximation in such cases, we propose here an appropriate modification of the original method.
2307.15073
Tim G. J. Rudner
Leo Klarner, Tim G. J. Rudner, Michael Reutlinger, Torsten Schindler, Garrett M. Morris, Charlotte Deane, Yee Whye Teh
Drug Discovery under Covariate Shift with Domain-Informed Prior Distributions over Functions
Published in the Proceedings of the 40th International Conference on Machine Learning (ICML 2023)
null
null
null
q-bio.BM cs.LG stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Accelerating the discovery of novel and more effective therapeutics is an important pharmaceutical problem in which deep learning is playing an increasingly significant role. However, real-world drug discovery tasks are often characterized by a scarcity of labeled data and significant covariate shift$\unicode{x2013}\unicode{x2013}$a setting that poses a challenge to standard deep learning methods. In this paper, we present Q-SAVI, a probabilistic model able to address these challenges by encoding explicit prior knowledge of the data-generating process into a prior distribution over functions, presenting researchers with a transparent and probabilistically principled way to encode data-driven modeling preferences. Building on a novel, gold-standard bioactivity dataset that facilitates a meaningful comparison of models in an extrapolative regime, we explore different approaches to induce data shift and construct a challenging evaluation setup. We then demonstrate that using Q-SAVI to integrate contextualized prior knowledge of drug-like chemical space into the modeling process affords substantial gains in predictive accuracy and calibration, outperforming a broad range of state-of-the-art self-supervised pre-training and domain adaptation techniques.
[ { "created": "Fri, 14 Jul 2023 05:01:10 GMT", "version": "v1" } ]
2023-07-31
[ [ "Klarner", "Leo", "" ], [ "Rudner", "Tim G. J.", "" ], [ "Reutlinger", "Michael", "" ], [ "Schindler", "Torsten", "" ], [ "Morris", "Garrett M.", "" ], [ "Deane", "Charlotte", "" ], [ "Teh", "Yee Whye", "" ] ]
Accelerating the discovery of novel and more effective therapeutics is an important pharmaceutical problem in which deep learning is playing an increasingly significant role. However, real-world drug discovery tasks are often characterized by a scarcity of labeled data and significant covariate shift$\unicode{x2013}\unicode{x2013}$a setting that poses a challenge to standard deep learning methods. In this paper, we present Q-SAVI, a probabilistic model able to address these challenges by encoding explicit prior knowledge of the data-generating process into a prior distribution over functions, presenting researchers with a transparent and probabilistically principled way to encode data-driven modeling preferences. Building on a novel, gold-standard bioactivity dataset that facilitates a meaningful comparison of models in an extrapolative regime, we explore different approaches to induce data shift and construct a challenging evaluation setup. We then demonstrate that using Q-SAVI to integrate contextualized prior knowledge of drug-like chemical space into the modeling process affords substantial gains in predictive accuracy and calibration, outperforming a broad range of state-of-the-art self-supervised pre-training and domain adaptation techniques.
1405.7926
Grzegorz Nawrocki
Grzegorz Nawrocki and Marek Cieplak
Aqueous Amino Acids and Proteins Near the Surface of Gold in Hydrophilic and Hydrophobic Force Fields
null
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We calculate potentials of the mean force for twenty amino acids in the vicinity of the (111) surface of gold, for several dipeptides, and for some analogs of the side chains, using molecular dynamics simulations and the umbrella sampling method. We compare results obtained within three different force fields: one hydrophobic (for a contaminated surface) and two hydrophilic. All of these fields lead to good binding with very different specificities and different patterns in the density and polarization of water. The covalent bond with the sulfur atom on cysteine is modeled by the Morse potential. We demonstrate that binding energies of dipeptides are different than the combined binding energies of their amino-acidic components. For the hydrophobic gold, adsorption events of a small protein are driven by attraction to the strongest binding amino acids. This is not so in the hydrophilic cases - a result of smaller specificities combined with the difficulty for proteins, but not for single amino acids, to penetrate the first layer of water. The properties of water near the surface sensitively depend on the force field.
[ { "created": "Fri, 30 May 2014 17:43:00 GMT", "version": "v1" } ]
2014-06-02
[ [ "Nawrocki", "Grzegorz", "" ], [ "Cieplak", "Marek", "" ] ]
We calculate potentials of the mean force for twenty amino acids in the vicinity of the (111) surface of gold, for several dipeptides, and for some analogs of the side chains, using molecular dynamics simulations and the umbrella sampling method. We compare results obtained within three different force fields: one hydrophobic (for a contaminated surface) and two hydrophilic. All of these fields lead to good binding with very different specificities and different patterns in the density and polarization of water. The covalent bond with the sulfur atom on cysteine is modeled by the Morse potential. We demonstrate that binding energies of dipeptides are different than the combined binding energies of their amino-acidic components. For the hydrophobic gold, adsorption events of a small protein are driven by attraction to the strongest binding amino acids. This is not so in the hydrophilic cases - a result of smaller specificities combined with the difficulty for proteins, but not for single amino acids, to penetrate the first layer of water. The properties of water near the surface sensitively depend on the force field.
2303.06975
Tim Downing Dr
Tim Downing, Nicos Angelopoulos
A primer on correlation-based dimension reduction methods for multi-omics analysis
30+ pages, 3 figures, 7 tables
null
null
null
q-bio.GN
http://creativecommons.org/licenses/by-nc-nd/4.0/
The continuing advances of omic technologies mean that it is now more tangible to measure the numerous features collectively reflecting the molecular properties of a sample. When multiple omic methods are used, statistical and computational approaches can exploit these large, connected profiles. Multi-omics is the integration of different omic data sources from the same biological sample. In this review, we focus on correlation-based dimension reduction approaches for single omic datasets, followed by methods for pairs of omics datasets, before detailing further techniques for three or more omic datasets. We also briefly detail network methods when three or more omic datasets are available and which complement correlation-oriented tools. To aid readers new to this area, these are all linked to relevant R packages that can implement these procedures. Finally, we discuss scenarios of experimental design and present road maps that simplify the selection of appropriate analysis methods. This review will guide researchers navigate the emerging methods for multi-omics and help them integrate diverse omic datasets appropriately and embrace the opportunity of population multi-omics.
[ { "created": "Mon, 13 Mar 2023 10:21:27 GMT", "version": "v1" }, { "created": "Wed, 15 Mar 2023 11:01:51 GMT", "version": "v2" }, { "created": "Sat, 27 May 2023 11:44:54 GMT", "version": "v3" }, { "created": "Mon, 5 Jun 2023 19:24:54 GMT", "version": "v4" }, { "created": "Wed, 7 Jun 2023 19:34:11 GMT", "version": "v5" }, { "created": "Thu, 15 Jun 2023 16:52:32 GMT", "version": "v6" }, { "created": "Fri, 11 Aug 2023 16:53:27 GMT", "version": "v7" } ]
2023-08-14
[ [ "Downing", "Tim", "" ], [ "Angelopoulos", "Nicos", "" ] ]
The continuing advances of omic technologies mean that it is now more tangible to measure the numerous features collectively reflecting the molecular properties of a sample. When multiple omic methods are used, statistical and computational approaches can exploit these large, connected profiles. Multi-omics is the integration of different omic data sources from the same biological sample. In this review, we focus on correlation-based dimension reduction approaches for single omic datasets, followed by methods for pairs of omics datasets, before detailing further techniques for three or more omic datasets. We also briefly detail network methods when three or more omic datasets are available and which complement correlation-oriented tools. To aid readers new to this area, these are all linked to relevant R packages that can implement these procedures. Finally, we discuss scenarios of experimental design and present road maps that simplify the selection of appropriate analysis methods. This review will guide researchers navigate the emerging methods for multi-omics and help them integrate diverse omic datasets appropriately and embrace the opportunity of population multi-omics.
q-bio/0501032
Gernot Klein A.
Gernot A. Klein, Karsten Kruse, Gianaurelio Cuniberti, Frank Juelicher
Filament depolymerization by motor molecules
null
null
10.1103/PhysRevLett.94.108102
null
q-bio.SC
null
Motor proteins that specifically interact with the ends of cytoskeletal filaments can induce filament depolymerization. A phenomenological description of this process is presented. We show that under certain conditions motors dynamically accumulate at the filament ends. We compare simulations of two microscopic models to the phenomenological description. The depolymerization rate can exhibit maxima and dynamic instabilities as a function of the bulk motor density for processive depolymerization. We discuss our results in relation to experimental studies of Kin-13 family motor proteins.
[ { "created": "Mon, 24 Jan 2005 16:13:27 GMT", "version": "v1" } ]
2009-11-11
[ [ "Klein", "Gernot A.", "" ], [ "Kruse", "Karsten", "" ], [ "Cuniberti", "Gianaurelio", "" ], [ "Juelicher", "Frank", "" ] ]
Motor proteins that specifically interact with the ends of cytoskeletal filaments can induce filament depolymerization. A phenomenological description of this process is presented. We show that under certain conditions motors dynamically accumulate at the filament ends. We compare simulations of two microscopic models to the phenomenological description. The depolymerization rate can exhibit maxima and dynamic instabilities as a function of the bulk motor density for processive depolymerization. We discuss our results in relation to experimental studies of Kin-13 family motor proteins.
2311.13466
Ian Dunn
Ian Dunn, David Ryan Koes
Accelerating Inference in Molecular Diffusion Models with Latent Representations of Protein Structure
This paper appeared as a spotlight paper at the NeurIPS 2023 Generative AI and Biology Workshop
null
null
null
q-bio.BM cs.LG
http://creativecommons.org/licenses/by-sa/4.0/
Diffusion generative models have emerged as a powerful framework for addressing problems in structural biology and structure-based drug design. These models operate directly on 3D molecular structures. Due to the unfavorable scaling of graph neural networks (GNNs) with graph size as well as the relatively slow inference speeds inherent to diffusion models, many existing molecular diffusion models rely on coarse-grained representations of protein structure to make training and inference feasible. However, such coarse-grained representations discard essential information for modeling molecular interactions and impair the quality of generated structures. In this work, we present a novel GNN-based architecture for learning latent representations of molecular structure. When trained end-to-end with a diffusion model for de novo ligand design, our model achieves comparable performance to one with an all-atom protein representation while exhibiting a 3-fold reduction in inference time.
[ { "created": "Wed, 22 Nov 2023 15:32:31 GMT", "version": "v1" }, { "created": "Wed, 8 May 2024 21:04:32 GMT", "version": "v2" } ]
2024-05-10
[ [ "Dunn", "Ian", "" ], [ "Koes", "David Ryan", "" ] ]
Diffusion generative models have emerged as a powerful framework for addressing problems in structural biology and structure-based drug design. These models operate directly on 3D molecular structures. Due to the unfavorable scaling of graph neural networks (GNNs) with graph size as well as the relatively slow inference speeds inherent to diffusion models, many existing molecular diffusion models rely on coarse-grained representations of protein structure to make training and inference feasible. However, such coarse-grained representations discard essential information for modeling molecular interactions and impair the quality of generated structures. In this work, we present a novel GNN-based architecture for learning latent representations of molecular structure. When trained end-to-end with a diffusion model for de novo ligand design, our model achieves comparable performance to one with an all-atom protein representation while exhibiting a 3-fold reduction in inference time.
1305.4963
Liao Chen
Liao Y Chen
Does Plasmodium falciparum have an Achilles' heel?
10 pages, 1 figure
Malaria Chemotherapy, Control, and Elimination 3, 114 (2014). DOI: 10.4172/2090-2778.1000114
null
null
q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Plasmodium falciparum is the parasite that causes the most severe form of malaria. Currently, science has been established about its cellular structures, its metabolic processes, and even the molecular structures of its intrinsic membrane proteins responsible for transporting water, nutrient, and waste molecules across the parasite plasma membrane (PPM). I hypothesize that Plasmodium falciparum has an Achilles' heel that can be attacked with erythritol, the well-known sweetener that is classified as generally safe. Most organisms have in their cell membrane two types of water-channel proteins: aquaporins to maintain hydro-homeostasis across the membrane and aquaglyceroporins to uptake glycerols etc. In contrast, P. falciparum has only one type of such proteins---the multi-functional aquaglyceroporin (PfAQP) expressed in the PPM---to do both jobs. Moreover, the parasite also uses PfAQP to excrete its metabolic wastes (ammonia included) produced at a very high rate in the blood stage. This extremely high efficiency of the bug using one protein for multiple essential tasks makes the parasite fatally vulnerable. Erythritol in the blood stream can kill the parasite by clogging up its PfAQP channel that needs to be open for maintaining hydro-homeostasis and for excreting toxic wastes across the bug's PPM. In vitro tests are to measure the growth/death rate of P. falciparum in blood with various erythritol concentrations. In vivo experiments are to administer groups of infected mice with various doses of erythritol and monitor the parasite growth levels from blood samples drawn from each group. Clinic trials can be performed to observe the added effects of administering to patients erythritol along with the known drugs because erythritol was classified as a safe food ingredient.
[ { "created": "Tue, 21 May 2013 21:01:28 GMT", "version": "v1" } ]
2014-07-15
[ [ "Chen", "Liao Y", "" ] ]
Plasmodium falciparum is the parasite that causes the most severe form of malaria. Currently, science has been established about its cellular structures, its metabolic processes, and even the molecular structures of its intrinsic membrane proteins responsible for transporting water, nutrient, and waste molecules across the parasite plasma membrane (PPM). I hypothesize that Plasmodium falciparum has an Achilles' heel that can be attacked with erythritol, the well-known sweetener that is classified as generally safe. Most organisms have in their cell membrane two types of water-channel proteins: aquaporins to maintain hydro-homeostasis across the membrane and aquaglyceroporins to uptake glycerols etc. In contrast, P. falciparum has only one type of such proteins---the multi-functional aquaglyceroporin (PfAQP) expressed in the PPM---to do both jobs. Moreover, the parasite also uses PfAQP to excrete its metabolic wastes (ammonia included) produced at a very high rate in the blood stage. This extremely high efficiency of the bug using one protein for multiple essential tasks makes the parasite fatally vulnerable. Erythritol in the blood stream can kill the parasite by clogging up its PfAQP channel that needs to be open for maintaining hydro-homeostasis and for excreting toxic wastes across the bug's PPM. In vitro tests are to measure the growth/death rate of P. falciparum in blood with various erythritol concentrations. In vivo experiments are to administer groups of infected mice with various doses of erythritol and monitor the parasite growth levels from blood samples drawn from each group. Clinic trials can be performed to observe the added effects of administering to patients erythritol along with the known drugs because erythritol was classified as a safe food ingredient.
q-bio/0412023
Wannapong Triampo
Paisan Kanthang, Waipot Ngamsaad, Charin Modchang, Wannapong Triampo, Narin Nuttawut, I-Ming Tang, Yongwimol Lenbury
The dynamics of the min proteins of Escherichia coli under the constant external fields
25 pages, 11 figures
null
null
null
q-bio.SC
null
In E. coli the determination of the middle of the cell and the proper placement of the septum is essential to the division of the cell. This step depends on the proteins MinC, MinD, and MinE. Exposure to a constant external field e.g., an electric field or magnetic field may cause the bacteria cell division mechanism to change resulting in an abnormal cytokinesis. To have insight into the effects of an external field on this process, we model the process using a set of the deterministic reaction diffusion equations, which incorporate the influence of an external field, min protein reactions, and diffusion of all species. Using the numerical method, we have found some changes in the dynamics of the oscillations of the min proteins from pole to pole when compared that of without the external field. The results show some interesting effects, which are qualitatively in good agreement with some experimental results.
[ { "created": "Mon, 13 Dec 2004 01:57:19 GMT", "version": "v1" } ]
2007-05-23
[ [ "Kanthang", "Paisan", "" ], [ "Ngamsaad", "Waipot", "" ], [ "Modchang", "Charin", "" ], [ "Triampo", "Wannapong", "" ], [ "Nuttawut", "Narin", "" ], [ "Tang", "I-Ming", "" ], [ "Lenbury", "Yongwimol", "" ] ]
In E. coli the determination of the middle of the cell and the proper placement of the septum is essential to the division of the cell. This step depends on the proteins MinC, MinD, and MinE. Exposure to a constant external field e.g., an electric field or magnetic field may cause the bacteria cell division mechanism to change resulting in an abnormal cytokinesis. To have insight into the effects of an external field on this process, we model the process using a set of the deterministic reaction diffusion equations, which incorporate the influence of an external field, min protein reactions, and diffusion of all species. Using the numerical method, we have found some changes in the dynamics of the oscillations of the min proteins from pole to pole when compared that of without the external field. The results show some interesting effects, which are qualitatively in good agreement with some experimental results.
2304.14932
Daniel Schindler
Michel Brueck, Bork A. Berghoff and Daniel Schindler
In silico design, in vitro construction and in vivo application of synthetic small regulatory RNAs in bacteria
24 pages, 7 figures
null
10.1007/978-1-0716-3658-9_27
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Small regulatory RNAs (sRNAs) are short non-coding RNAs in bacteria capable of post-transcriptional regulation. sRNAs have recently gained attention as tools in basic and applied sciences for example to fine-tune genetic circuits or biotechnological processes. Even though sRNAs often have a rather simple and modular structure, the design of functional synthetic sRNAs is not necessarily trivial. This protocol outlines how to use computational predictions and synthetic biology approaches to design, construct and validate synthetic sRNA functionality for their application in bacteria. The computational tool, SEEDling, matches the optimal seed region with the user-selected sRNA scaffold for repression of target mRNAs. The synthetic sRNAs are assembled using Golden Gate cloning and their functionality is subsequently validated. The protocol uses the acrA mRNA as an exemplary proof-of-concept target in Escherichia coli. Since AcrA is part of a multidrug efflux pump, acrA repression can be revealed by assessing oxacillin susceptibility in a phenotypic screen. However, in case target repression does not result in a screenable phenotype, an alternative validation of synthetic sRNA functionality based on a fluorescence reporter is described.
[ { "created": "Fri, 28 Apr 2023 15:43:07 GMT", "version": "v1" } ]
2024-04-18
[ [ "Brueck", "Michel", "" ], [ "Berghoff", "Bork A.", "" ], [ "Schindler", "Daniel", "" ] ]
Small regulatory RNAs (sRNAs) are short non-coding RNAs in bacteria capable of post-transcriptional regulation. sRNAs have recently gained attention as tools in basic and applied sciences for example to fine-tune genetic circuits or biotechnological processes. Even though sRNAs often have a rather simple and modular structure, the design of functional synthetic sRNAs is not necessarily trivial. This protocol outlines how to use computational predictions and synthetic biology approaches to design, construct and validate synthetic sRNA functionality for their application in bacteria. The computational tool, SEEDling, matches the optimal seed region with the user-selected sRNA scaffold for repression of target mRNAs. The synthetic sRNAs are assembled using Golden Gate cloning and their functionality is subsequently validated. The protocol uses the acrA mRNA as an exemplary proof-of-concept target in Escherichia coli. Since AcrA is part of a multidrug efflux pump, acrA repression can be revealed by assessing oxacillin susceptibility in a phenotypic screen. However, in case target repression does not result in a screenable phenotype, an alternative validation of synthetic sRNA functionality based on a fluorescence reporter is described.
1007.4490
Tsvi Tlusty
Shalev Itzkovitz, Tsvi Tlusty, Uri Alon
Coding limits on the number of transcription factors
http://www.weizmann.ac.il/complex/tlusty/papers/BMCGenomics2006.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1590034/ http://www.biomedcentral.com/1471-2164/7/239
BMC Genomics 2006, 7:239
10.1186/1471-2164-7-239
null
q-bio.BM physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Transcription factor proteins bind specific DNA sequences to control the expression of genes. They contain DNA binding domains which belong to several super-families, each with a specific mechanism of DNA binding. The total number of transcription factors encoded in a genome increases with the number of genes in the genome. Here, we examined the number of transcription factors from each super-family in diverse organisms. We find that the number of transcription factors from most super-families appears to be bounded. For example, the number of winged helix factors does not generally exceed 300, even in very large genomes. The magnitude of the maximal number of transcription factors from each super-family seems to correlate with the number of DNA bases effectively recognized by the binding mechanism of that super-family. Coding theory predicts that such upper bounds on the number of transcription factors should exist, in order to minimize cross-binding errors between transcription factors. This theory further predicts that factors with similar binding sequences should tend to have similar biological effect, so that errors based on mis-recognition are minimal. We present evidence that transcription factors with similar binding sequences tend to regulate genes with similar biological functions, supporting this prediction. The present study suggests limits on the transcription factor repertoire of cells, and suggests coding constraints that might apply more generally to the mapping between binding sites and biological function.
[ { "created": "Mon, 26 Jul 2010 15:59:24 GMT", "version": "v1" } ]
2010-07-27
[ [ "Itzkovitz", "Shalev", "" ], [ "Tlusty", "Tsvi", "" ], [ "Alon", "Uri", "" ] ]
Transcription factor proteins bind specific DNA sequences to control the expression of genes. They contain DNA binding domains which belong to several super-families, each with a specific mechanism of DNA binding. The total number of transcription factors encoded in a genome increases with the number of genes in the genome. Here, we examined the number of transcription factors from each super-family in diverse organisms. We find that the number of transcription factors from most super-families appears to be bounded. For example, the number of winged helix factors does not generally exceed 300, even in very large genomes. The magnitude of the maximal number of transcription factors from each super-family seems to correlate with the number of DNA bases effectively recognized by the binding mechanism of that super-family. Coding theory predicts that such upper bounds on the number of transcription factors should exist, in order to minimize cross-binding errors between transcription factors. This theory further predicts that factors with similar binding sequences should tend to have similar biological effect, so that errors based on mis-recognition are minimal. We present evidence that transcription factors with similar binding sequences tend to regulate genes with similar biological functions, supporting this prediction. The present study suggests limits on the transcription factor repertoire of cells, and suggests coding constraints that might apply more generally to the mapping between binding sites and biological function.
1308.5365
Shweta Bansal
Eric Mooring and Shweta Bansal
Increasing Herd Immunity with Influenza Revaccination
null
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by-nc-sa/3.0/
Seasonal influenza is a significant public health concern in the United States and globally. While influenza vaccines are the single most effective intervention to reduce influenza morbidity and mortality, there is considerable debate surrounding the merits and consequences of repeated seasonal vaccination. Here, we describe a two-season influenza epidemic contact network model and use it to demonstrate that increasing the level of continuity in vaccination across seasons reduces the burden on public health. We show that revaccination reduces the influenza attack rate not only because it reduces the overall number of susceptible individuals, but also because it better protects highly-connected individuals, who would otherwise make a disproportionately large contribution to influenza transmission. Our work thus contributes a population-level perspective to debates about the merits of repeated influenza vaccination and advocates for public health policy to incorporate individual vaccine histories.
[ { "created": "Sat, 24 Aug 2013 22:40:07 GMT", "version": "v1" }, { "created": "Tue, 6 Jan 2015 02:13:01 GMT", "version": "v2" } ]
2015-01-07
[ [ "Mooring", "Eric", "" ], [ "Bansal", "Shweta", "" ] ]
Seasonal influenza is a significant public health concern in the United States and globally. While influenza vaccines are the single most effective intervention to reduce influenza morbidity and mortality, there is considerable debate surrounding the merits and consequences of repeated seasonal vaccination. Here, we describe a two-season influenza epidemic contact network model and use it to demonstrate that increasing the level of continuity in vaccination across seasons reduces the burden on public health. We show that revaccination reduces the influenza attack rate not only because it reduces the overall number of susceptible individuals, but also because it better protects highly-connected individuals, who would otherwise make a disproportionately large contribution to influenza transmission. Our work thus contributes a population-level perspective to debates about the merits of repeated influenza vaccination and advocates for public health policy to incorporate individual vaccine histories.
2002.03268
Yen Ting Lin
Steven Sanche, Yen Ting Lin, Chonggang Xu, Ethan Romero-Severson, Nicolas W. Hengartner, Ruian Ke
The Novel Coronavirus, 2019-nCoV, is Highly Contagious and More Infectious Than Initially Estimated
8 pages, 3 figures, 1 Supplementary Text, 6 Supplementary figures, 2 Supplementary tables
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The novel coronavirus (2019-nCoV) is a recently emerged human pathogen that has spread widely since January 2020. Initially, the basic reproductive number, R0, was estimated to be 2.2 to 2.7. Here we provide a new estimate of this quantity. We collected extensive individual case reports and estimated key epidemiology parameters, including the incubation period. Integrating these estimates and high-resolution real-time human travel and infection data with mathematical models, we estimated that the number of infected individuals during early epidemic double every 2.4 days, and the R0 value is likely to be between 4.7 and 6.6. We further show that quarantine and contact tracing of symptomatic individuals alone may not be effective and early, strong control measures are needed to stop transmission of the virus.
[ { "created": "Sun, 9 Feb 2020 02:42:18 GMT", "version": "v1" } ]
2020-02-11
[ [ "Sanche", "Steven", "" ], [ "Lin", "Yen Ting", "" ], [ "Xu", "Chonggang", "" ], [ "Romero-Severson", "Ethan", "" ], [ "Hengartner", "Nicolas W.", "" ], [ "Ke", "Ruian", "" ] ]
The novel coronavirus (2019-nCoV) is a recently emerged human pathogen that has spread widely since January 2020. Initially, the basic reproductive number, R0, was estimated to be 2.2 to 2.7. Here we provide a new estimate of this quantity. We collected extensive individual case reports and estimated key epidemiology parameters, including the incubation period. Integrating these estimates and high-resolution real-time human travel and infection data with mathematical models, we estimated that the number of infected individuals during early epidemic double every 2.4 days, and the R0 value is likely to be between 4.7 and 6.6. We further show that quarantine and contact tracing of symptomatic individuals alone may not be effective and early, strong control measures are needed to stop transmission of the virus.
2105.08512
Laura Tupper
Laura L. Tupper and Charles R. Keese and David S. Matteson
Classifying Contaminated Cell Cultures using Time Series Features
30 pages, 7 figures
null
null
null
q-bio.QM stat.AP
http://creativecommons.org/licenses/by-nc-nd/4.0/
We examine the use of time series data, derived from Electric Cell-substrate Impedance Sensing (ECIS), to differentiate between standard mammalian cell cultures and those infected with a mycoplasma organism. With the goal of interpretable results, we perform low-dimensional feature-based classification, extracting application-relevant features from the ECIS time courses. We can achieve very high classification accuracy using only two features, which depend on the cell line under examination. Initial results also show the existence of experimental variation between plates and suggest types of features that may prove more robust to such variation. Our paper is the first to perform a broad examination of ECIS time course features in the context of detecting contamination; to combine different types of features to achieve classification accuracy while preserving interpretability; and to describe and suggest possibilities for ameliorating plate-to-plate variation.
[ { "created": "Sat, 15 May 2021 01:51:29 GMT", "version": "v1" }, { "created": "Tue, 22 Feb 2022 14:24:25 GMT", "version": "v2" } ]
2022-02-23
[ [ "Tupper", "Laura L.", "" ], [ "Keese", "Charles R.", "" ], [ "Matteson", "David S.", "" ] ]
We examine the use of time series data, derived from Electric Cell-substrate Impedance Sensing (ECIS), to differentiate between standard mammalian cell cultures and those infected with a mycoplasma organism. With the goal of interpretable results, we perform low-dimensional feature-based classification, extracting application-relevant features from the ECIS time courses. We can achieve very high classification accuracy using only two features, which depend on the cell line under examination. Initial results also show the existence of experimental variation between plates and suggest types of features that may prove more robust to such variation. Our paper is the first to perform a broad examination of ECIS time course features in the context of detecting contamination; to combine different types of features to achieve classification accuracy while preserving interpretability; and to describe and suggest possibilities for ameliorating plate-to-plate variation.
1504.05261
Takahiro Wada
Takahiro Wada, Norimasa Kamij and Shunichi Doi
A Mathematical Model of Motion Sickness in 6DOF Motion and Its Application to Vehicle Passengers
in International Digital Human Modeling Symposium, 2013
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A mathematical model of motion sickness incidence (MSI) is derived by integrating neurophysiological knowledge of the vestibular system to predict the severity of motion sickness of humans. Bos et al. proposed the successful mathematical model of motion sickness based on the neurophysiological mechanism based on the subject vertical conflict (SVC) theory. We expand this model to 6-DOF motion, including head rotation, by introducing the otolith-canal interaction. Then the model is applied to an analysis of passengers' comfort. It is known that the driver is less susceptible to motion sickness than are the passengers. In addition, it is known that the driver tilts his/her head toward the curve direction when curve driving, whereas the passengers' head movement is likely to occur in the opposite direction. Thus, the effect of the head tilt strategy on motion sickness was investigated by the proposed mathematical model. The head movements of drivers and passengers were measured in slalom driving. Then, the MSI of the drivers and that of the passengers predicted by the proposed model were compared. The results revealed that the head movement toward the centripetal direction has a significant effect in reducing the MSI in the sense of SVC theory.
[ { "created": "Mon, 20 Apr 2015 23:42:20 GMT", "version": "v1" } ]
2015-04-22
[ [ "Wada", "Takahiro", "" ], [ "Kamij", "Norimasa", "" ], [ "Doi", "Shunichi", "" ] ]
A mathematical model of motion sickness incidence (MSI) is derived by integrating neurophysiological knowledge of the vestibular system to predict the severity of motion sickness of humans. Bos et al. proposed the successful mathematical model of motion sickness based on the neurophysiological mechanism based on the subject vertical conflict (SVC) theory. We expand this model to 6-DOF motion, including head rotation, by introducing the otolith-canal interaction. Then the model is applied to an analysis of passengers' comfort. It is known that the driver is less susceptible to motion sickness than are the passengers. In addition, it is known that the driver tilts his/her head toward the curve direction when curve driving, whereas the passengers' head movement is likely to occur in the opposite direction. Thus, the effect of the head tilt strategy on motion sickness was investigated by the proposed mathematical model. The head movements of drivers and passengers were measured in slalom driving. Then, the MSI of the drivers and that of the passengers predicted by the proposed model were compared. The results revealed that the head movement toward the centripetal direction has a significant effect in reducing the MSI in the sense of SVC theory.
1308.1865
Wei Zhang
Eric R. Gamazon, Hae-Kyung Im, Shiwei Duan, Yves A. Lussier, Nancy J. Cox, M. Eileen Dolan, Wei Zhang
ExprTarget: An Integrative Approach to Predicting Human MicroRNA Targets
null
Gamazon ER, Im H-K, Duan S, Lussier YA, Cox NJ, Dolan ME, Zhang W. ExprTarget: An integrative approach to predicting human microRNA targets. PLoS ONE. 2010; 5(10): e13534
null
null
q-bio.QM q-bio.GN
http://creativecommons.org/licenses/by/3.0/
We developed an online database, ExprTargetDB, of human miRNA targets predicted by an approach that integrates gene expression profiling into a broader framework involving important features of miRNA target site predictions.
[ { "created": "Thu, 8 Aug 2013 14:53:30 GMT", "version": "v1" } ]
2013-08-09
[ [ "Gamazon", "Eric R.", "" ], [ "Im", "Hae-Kyung", "" ], [ "Duan", "Shiwei", "" ], [ "Lussier", "Yves A.", "" ], [ "Cox", "Nancy J.", "" ], [ "Dolan", "M. Eileen", "" ], [ "Zhang", "Wei", "" ] ]
We developed an online database, ExprTargetDB, of human miRNA targets predicted by an approach that integrates gene expression profiling into a broader framework involving important features of miRNA target site predictions.
2301.09566
Klaus Lehnertz
Klaus Lehnertz
Ordinal methods for a characterization of evolving functional brain networks
8 pages, 2 figures
null
10.1063/5.0136181
null
q-bio.NC nlin.CD
http://creativecommons.org/licenses/by/4.0/
Ordinal time series analysis is based on the idea to map time series to ordinal patterns, i.e., order relations between the values of a time series and not the values themselves, as introduced in 2002 by C. Bandt and B. Pompe. Despite a resulting loss of information, this approach captures meaningful information about the temporal structure of the underlying system dynamics as well as about properties of interactions between coupled systems. This - together with its conceptual simplicity and robustness against measurement noise - makes ordinal time series analysis well suited to improve characterization of the still poorly understood spatial-temporal dynamics of the human brain. This minireview briefly summarizes the state-of-the-art of uni- and bivariate ordinal time-series-analysis techniques together with applications in the neurosciences. It will highlight current limitations to stimulate further developments which would be necessary to advance characterization of evolving functional brain networks.
[ { "created": "Fri, 13 Jan 2023 15:26:13 GMT", "version": "v1" } ]
2023-02-03
[ [ "Lehnertz", "Klaus", "" ] ]
Ordinal time series analysis is based on the idea to map time series to ordinal patterns, i.e., order relations between the values of a time series and not the values themselves, as introduced in 2002 by C. Bandt and B. Pompe. Despite a resulting loss of information, this approach captures meaningful information about the temporal structure of the underlying system dynamics as well as about properties of interactions between coupled systems. This - together with its conceptual simplicity and robustness against measurement noise - makes ordinal time series analysis well suited to improve characterization of the still poorly understood spatial-temporal dynamics of the human brain. This minireview briefly summarizes the state-of-the-art of uni- and bivariate ordinal time-series-analysis techniques together with applications in the neurosciences. It will highlight current limitations to stimulate further developments which would be necessary to advance characterization of evolving functional brain networks.
1708.00353
Xiaobin Guan
Xiaobin Guan, Huanfeng Shen, Wenxia Gan, Gang Yang, Lunche Wang, Xinghua Li and Liangpei Zhang
A 33-year NPP monitoring study in southwest China by the fusion of multi-source remote sensing and station data
20 pages, 11 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Knowledge of regional net primary productivity (NPP) is important for the systematic understanding of the global carbon cycle. In this study, multi-source data were employed to conduct a 33-year regional NPP study in southwest China, at a 1-km scale. A multi-sensor fusion framework was applied to obtain a new normalized difference vegetation index (NDVI) time series from 1982 to 2014, combining the respective advantages of the different remote sensing datasets. As another key parameter for NPP modeling, the total solar radiation was calculated by the improved Yang hybrid model (YHM), using meteorological station data. The verification described in this paper proved the feasibility of all the applied data processes, and a greatly improved accuracy was obtained for the NPP calculated with the final processed NDVI. The spatio-temporal analysis results indicated that 68.07% of the study area showed an increasing NPP trend over the past three decades. Significant heterogeneity was found in the correlation between NPP and precipitation at a monthly scale, specifically, the negative correlation in the growing season and the positive correlation in the dry season. The lagged positive correlation in the growing season and no lag in the dry season indicated the important impact of precipitation on NPP.
[ { "created": "Tue, 1 Aug 2017 14:23:34 GMT", "version": "v1" } ]
2017-08-02
[ [ "Guan", "Xiaobin", "" ], [ "Shen", "Huanfeng", "" ], [ "Gan", "Wenxia", "" ], [ "Yang", "Gang", "" ], [ "Wang", "Lunche", "" ], [ "Li", "Xinghua", "" ], [ "Zhang", "Liangpei", "" ] ]
Knowledge of regional net primary productivity (NPP) is important for the systematic understanding of the global carbon cycle. In this study, multi-source data were employed to conduct a 33-year regional NPP study in southwest China, at a 1-km scale. A multi-sensor fusion framework was applied to obtain a new normalized difference vegetation index (NDVI) time series from 1982 to 2014, combining the respective advantages of the different remote sensing datasets. As another key parameter for NPP modeling, the total solar radiation was calculated by the improved Yang hybrid model (YHM), using meteorological station data. The verification described in this paper proved the feasibility of all the applied data processes, and a greatly improved accuracy was obtained for the NPP calculated with the final processed NDVI. The spatio-temporal analysis results indicated that 68.07% of the study area showed an increasing NPP trend over the past three decades. Significant heterogeneity was found in the correlation between NPP and precipitation at a monthly scale, specifically, the negative correlation in the growing season and the positive correlation in the dry season. The lagged positive correlation in the growing season and no lag in the dry season indicated the important impact of precipitation on NPP.
0906.0114
Deepak Chandran
Deepak Chandran and Herbert M. Sauro
An Optimization Algorithm for Finding Parameters for Bistability
5 pages, 4 figures
null
null
null
q-bio.MN q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Motivation: Many biochemical pathways are known, but the numerous parameters required to correctly explore the dynamics of the pathways are not known. For this reason, algorithms that can make inferences by looking at the topology of a network are desirable. In this work, we are particular interested in the question of whether a given pathway can potentially harbor multiple stable steady states. In other words, the challenge is to find the set of parameters such that the dynamical system defined by a set of ordinary differential equations will contain multiple stable steady states. Being able to find parameters that cause a network to be bistable may also be benefitial for engineering synthetic bistable systems where the engineer needs to know a working set of parameters. Result: We have developed an algorithm that optimizes the parameters of a dynamical system so that the system will contain at least one saddle or unstable point. The algorithm then looks at trajectories around this saddle or unstable point to see whether the different trajectories converge to different stable points. The algorithm returns the parameters that causes the system to exhibit multiple stable points. Since this is an optimization algorithm, it is not quaranteed to find a solution. Repeated runs are often required to find a solution for systems where only a narrow set of parameters exhibit bistability. Availability: The C code for the algorithm is available at http://tinkercell.googlecode.com
[ { "created": "Sat, 30 May 2009 21:33:08 GMT", "version": "v1" }, { "created": "Thu, 23 Jul 2009 15:59:43 GMT", "version": "v2" } ]
2009-07-23
[ [ "Chandran", "Deepak", "" ], [ "Sauro", "Herbert M.", "" ] ]
Motivation: Many biochemical pathways are known, but the numerous parameters required to correctly explore the dynamics of the pathways are not known. For this reason, algorithms that can make inferences by looking at the topology of a network are desirable. In this work, we are particular interested in the question of whether a given pathway can potentially harbor multiple stable steady states. In other words, the challenge is to find the set of parameters such that the dynamical system defined by a set of ordinary differential equations will contain multiple stable steady states. Being able to find parameters that cause a network to be bistable may also be benefitial for engineering synthetic bistable systems where the engineer needs to know a working set of parameters. Result: We have developed an algorithm that optimizes the parameters of a dynamical system so that the system will contain at least one saddle or unstable point. The algorithm then looks at trajectories around this saddle or unstable point to see whether the different trajectories converge to different stable points. The algorithm returns the parameters that causes the system to exhibit multiple stable points. Since this is an optimization algorithm, it is not quaranteed to find a solution. Repeated runs are often required to find a solution for systems where only a narrow set of parameters exhibit bistability. Availability: The C code for the algorithm is available at http://tinkercell.googlecode.com
1208.0986
Stephen Eglen
Stephen J. Eglen and James C. T. Wong
Spatial constraints underlying the retinal mosaics of two types of horizontal cells in cat and macaque
null
Visual Neuroscience (2008) 25:209--214
10.1017/S0952523808080176
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Most types of retinal neurons are spatially positioned in non-random patterns, termed retinal mosaics. Several developmental mechanisms are thought to be important in the formation of these mosaics. Most evidence to date suggests that homotypic constraints within a type of neuron are dominant, and that heterotypic interactions between different types of neuron are rare. In an analysis of macaque H1 and H2 horizontal cell mosaics, W\"assle et al. (2000) suggested that the high regularity index of the combined H1 and H2 mosaic might be caused by heterotypic interactions during development. Here we use computer modelling to suggest that the high regularity index of the combined H1 and H2 mosaic is a by-product of the basic constraint that two neurons cannot occupy the same space. The spatial arrangement of type A and type B horizontal cells in cat retina also follow this same principle.
[ { "created": "Sun, 5 Aug 2012 07:17:40 GMT", "version": "v1" } ]
2012-08-07
[ [ "Eglen", "Stephen J.", "" ], [ "Wong", "James C. T.", "" ] ]
Most types of retinal neurons are spatially positioned in non-random patterns, termed retinal mosaics. Several developmental mechanisms are thought to be important in the formation of these mosaics. Most evidence to date suggests that homotypic constraints within a type of neuron are dominant, and that heterotypic interactions between different types of neuron are rare. In an analysis of macaque H1 and H2 horizontal cell mosaics, W\"assle et al. (2000) suggested that the high regularity index of the combined H1 and H2 mosaic might be caused by heterotypic interactions during development. Here we use computer modelling to suggest that the high regularity index of the combined H1 and H2 mosaic is a by-product of the basic constraint that two neurons cannot occupy the same space. The spatial arrangement of type A and type B horizontal cells in cat retina also follow this same principle.
1408.4815
Chitra Nayak R
Chitra R. Nayak, Aidan I. Brown, and Andrew D. Rutenberg
Protein translocation without specific quality control in a computational model of the Tat system
20 pages, Accepted for publication in Physical Biology - This is not a copy edited version of the manuscript
null
10.1088/1478-3975/11/5/056005
null
q-bio.SC physics.bio-ph q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The twin-arginine translocation (Tat) system transports folded proteins of various sizes across both bacterial and plant thylakoid membranes. The membrane-associated TatA protein is an essential component of the Tat translocon, and a broad distribution of different sized TatA-clusters is observed in bacterial membranes. We assume that the size dynamics of TatA clusters are affected by substrate binding, unbinding, and translocation to associated TatBC clusters, where clusters with bound translocation substrates favour growth and those without associated substrates favour shrinkage. With a stochastic model of substrate binding and cluster dynamics, we numerically determine the TatA cluster size distribution. We include a proportion of targeted but non-translocatable (NT) substrates, with the simplifying hypothesis that the substrate translocatability does not directly affect cluster dynamical rate constants or substrate binding or unbinding rates. This amounts to a translocation model without specific quality control. Nevertheless, NT substrates will remain associated with TatA clusters until unbound and so will affect cluster sizes and translocation rates. We find that the number of larger TatA clusters depends on the NT fraction $f$. The translocation rate can be optimized by tuning the rate of spontaneous substrate unbinding, $\Gamma_U$. We present an analytically solvable three-state model of substrate translocation without cluster size dynamics that follows our computed translocation rates, and that is consistent with {\em in vitro} Tat-translocation data in the presence of NT substrates.
[ { "created": "Wed, 20 Aug 2014 20:33:56 GMT", "version": "v1" } ]
2015-06-22
[ [ "Nayak", "Chitra R.", "" ], [ "Brown", "Aidan I.", "" ], [ "Rutenberg", "Andrew D.", "" ] ]
The twin-arginine translocation (Tat) system transports folded proteins of various sizes across both bacterial and plant thylakoid membranes. The membrane-associated TatA protein is an essential component of the Tat translocon, and a broad distribution of different sized TatA-clusters is observed in bacterial membranes. We assume that the size dynamics of TatA clusters are affected by substrate binding, unbinding, and translocation to associated TatBC clusters, where clusters with bound translocation substrates favour growth and those without associated substrates favour shrinkage. With a stochastic model of substrate binding and cluster dynamics, we numerically determine the TatA cluster size distribution. We include a proportion of targeted but non-translocatable (NT) substrates, with the simplifying hypothesis that the substrate translocatability does not directly affect cluster dynamical rate constants or substrate binding or unbinding rates. This amounts to a translocation model without specific quality control. Nevertheless, NT substrates will remain associated with TatA clusters until unbound and so will affect cluster sizes and translocation rates. We find that the number of larger TatA clusters depends on the NT fraction $f$. The translocation rate can be optimized by tuning the rate of spontaneous substrate unbinding, $\Gamma_U$. We present an analytically solvable three-state model of substrate translocation without cluster size dynamics that follows our computed translocation rates, and that is consistent with {\em in vitro} Tat-translocation data in the presence of NT substrates.
1711.08145
Mike Steel Prof.
Anica Hoppe, Sonja T\"urpitz, Mike Steel
Species notions that combine phylogenetic trees and phenotypic partitions
19 pages, 5 figures
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A recent paper (Manceau and Lambert, 2016) developed a novel approach for describing two well-defined notions of 'species' based on a phylogenetic tree and a phenotypic partition. In this paper, we explore some further combinatorial properties of this approach and describe an extension that allows an arbitrary number of phenotypic partitions to be combined with a phylogenetic tree for these two species notions.
[ { "created": "Wed, 22 Nov 2017 06:17:21 GMT", "version": "v1" } ]
2017-11-23
[ [ "Hoppe", "Anica", "" ], [ "Türpitz", "Sonja", "" ], [ "Steel", "Mike", "" ] ]
A recent paper (Manceau and Lambert, 2016) developed a novel approach for describing two well-defined notions of 'species' based on a phylogenetic tree and a phenotypic partition. In this paper, we explore some further combinatorial properties of this approach and describe an extension that allows an arbitrary number of phenotypic partitions to be combined with a phylogenetic tree for these two species notions.
2008.08875
Paul Cabacungan
Vanessa Marie V. Calabia, Ma. Lucila M. Perez, Gregory L. Tangonan Paul M. Cabacungan, Ivan B. Culaba, Jeremy E. De Guzman
Bilirubin lowering effect and safety of a prototype low cost blue light emitting diode (LED) phototherapy device in the treatment of indirect hyperbilirubinemia among healthy term infants in a tertiary government hospital: a pilot study
38 pages, 6 figures, submitted to Philippines Pediatric Society
null
null
null
q-bio.TO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Objective: This pilot study was done to evaluate the capability of a prototype low cost blue light emitting diode (LED) phototherapy device in lowering bilirubin levels among healthy term infants diagnosed with indirect hyperbilirubinemia. Methods: Experimental study on term infants diagnosed with indirect hyperbilirubinemia in Ospital ng Makati from May 2016 to November 2016 who underwent phototherapy using the low cost blue LED phototherapy prototype. Results: After 24 hours of phototherapy under the prototype LED phototherapy unit, 16% of the total patients completed treatment as they were already classified in the low risk zone, and another 36% of patients completed treatment after 48 hours. The total bilirubin significantly decreased from baseline bilirubin levels after 24 hours by 16.5% (p = 0.0001). The mean percentage of change of bilirubin reduced after 48 hours of 29.9% was also significant. The proportion of subjects in the high risk zone during baseline to 24th hour went down significantly from 80% to 28% (p = 0.0003), while comparing baseline to 48th hour, the percentage of high risk zone went down from 80% to 9.5% (p = 0.0001). No subjects were reported to have rebound hyperbilirubinemia after discontinuation of phototherapy treatment under the LED prototype. No patient experienced any complication while on phototherapy treatment. Conclusion: The prototype low cost blue light emitting diode (LED) phototherapy was able to lower total serum bilirubin among healthy term infants with indirect hyperbilirubinemia and was safe to use.
[ { "created": "Thu, 20 Aug 2020 10:30:49 GMT", "version": "v1" } ]
2020-08-21
[ [ "Calabia", "Vanessa Marie V.", "" ], [ "Perez", "Ma. Lucila M.", "" ], [ "Cabacungan", "Gregory L. Tangonan Paul M.", "" ], [ "Culaba", "Ivan B.", "" ], [ "De Guzman", "Jeremy E.", "" ] ]
Objective: This pilot study was done to evaluate the capability of a prototype low cost blue light emitting diode (LED) phototherapy device in lowering bilirubin levels among healthy term infants diagnosed with indirect hyperbilirubinemia. Methods: Experimental study on term infants diagnosed with indirect hyperbilirubinemia in Ospital ng Makati from May 2016 to November 2016 who underwent phototherapy using the low cost blue LED phototherapy prototype. Results: After 24 hours of phototherapy under the prototype LED phototherapy unit, 16% of the total patients completed treatment as they were already classified in the low risk zone, and another 36% of patients completed treatment after 48 hours. The total bilirubin significantly decreased from baseline bilirubin levels after 24 hours by 16.5% (p = 0.0001). The mean percentage of change of bilirubin reduced after 48 hours of 29.9% was also significant. The proportion of subjects in the high risk zone during baseline to 24th hour went down significantly from 80% to 28% (p = 0.0003), while comparing baseline to 48th hour, the percentage of high risk zone went down from 80% to 9.5% (p = 0.0001). No subjects were reported to have rebound hyperbilirubinemia after discontinuation of phototherapy treatment under the LED prototype. No patient experienced any complication while on phototherapy treatment. Conclusion: The prototype low cost blue light emitting diode (LED) phototherapy was able to lower total serum bilirubin among healthy term infants with indirect hyperbilirubinemia and was safe to use.
2011.05860
Alejandro Ramos Lora
Mar\'ia J. C\'aceres and Alejandro Ramos-Lora
An understanding of the physical solutions and the blow-up phenomenon for Nonlinear Noisy Leaky Integrate and Fire neuronal models
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The Nonlinear Noisy Leaky Integrate and Fire neuronal models are mathematical models that describe the activity of neural networks. These models have been studied at a microscopic level, using Stochastic Differential Equations, and at a mesoscopic/macroscopic level, through the mean field limits using Fokker-Planck type equations. The aim of this paper is to improve their understanding, using a numerical study of their particle systems. We analyse in depth the behaviour of the classical and physical solutions of the Stochastic Differential Equations and, we compare it with what is already known about the Fokker-Planck equation. This allows us to better understand what happens in the neural network when an explosion occurs in finite time. After firing all neurons at the same time, if the system is weakly connected, the neural network converges towards its unique steady state. Otherwise, its behaviour is more complex, because it can tend towards a stationary state or a "plateau" distribution.
[ { "created": "Tue, 27 Oct 2020 20:00:38 GMT", "version": "v1" } ]
2020-11-12
[ [ "Cáceres", "María J.", "" ], [ "Ramos-Lora", "Alejandro", "" ] ]
The Nonlinear Noisy Leaky Integrate and Fire neuronal models are mathematical models that describe the activity of neural networks. These models have been studied at a microscopic level, using Stochastic Differential Equations, and at a mesoscopic/macroscopic level, through the mean field limits using Fokker-Planck type equations. The aim of this paper is to improve their understanding, using a numerical study of their particle systems. We analyse in depth the behaviour of the classical and physical solutions of the Stochastic Differential Equations and, we compare it with what is already known about the Fokker-Planck equation. This allows us to better understand what happens in the neural network when an explosion occurs in finite time. After firing all neurons at the same time, if the system is weakly connected, the neural network converges towards its unique steady state. Otherwise, its behaviour is more complex, because it can tend towards a stationary state or a "plateau" distribution.
1407.5847
Nicolae Radu Zabet
Armin P. Schoech and Nicolae Radu Zabet
Facilitated diffusion buffers noise in gene expression
12 pages, 5 figures, 1 table
Phys. Rev. E 90:3 (2014) 032701
10.1103/PhysRevE.90.032701
null
q-bio.MN q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Transcription factors perform facilitated diffusion (3D diffusion in the cytosol and 1D diffusion on the DNA) when binding to their target sites to regulate gene expression. Here, we investigated the influence of this binding mechanism on the noise in gene expression. Our results showed that, for biologically relevant parameters, the binding process can be represented by a two-state Markov model and that the accelerated target finding due to facilitated diffusion leads to a reduction in both the mRNA and the protein noise.
[ { "created": "Tue, 22 Jul 2014 13:06:36 GMT", "version": "v1" }, { "created": "Wed, 3 Sep 2014 09:06:07 GMT", "version": "v2" } ]
2014-09-04
[ [ "Schoech", "Armin P.", "" ], [ "Zabet", "Nicolae Radu", "" ] ]
Transcription factors perform facilitated diffusion (3D diffusion in the cytosol and 1D diffusion on the DNA) when binding to their target sites to regulate gene expression. Here, we investigated the influence of this binding mechanism on the noise in gene expression. Our results showed that, for biologically relevant parameters, the binding process can be represented by a two-state Markov model and that the accelerated target finding due to facilitated diffusion leads to a reduction in both the mRNA and the protein noise.
2010.16193
J\"urgen Jost
J\"urgen Jost
Biological Information
to appear in Theory in Biosciences
null
10.1007/s12064-020-00327-1
null
q-bio.PE nlin.AO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In computer science, we can theoretically neatly separate transmission and processing of information, hardware and software, and programs and their inputs. This is much more intricate in biology, Nevertheless, I argue that Shannon's concept of information is useful in biology, although its application is not as straightforward as many people think. In fact, the recently developed theory of information decomposition can shed much light on the complementarity between coding and regulatory, or internal and environmental information. The key challenge that we formulate in this contribution is to understand how genetic information and external factors combine to create an organism, and conversely, how the genome has learned in the course of evolution how to harness the environment, and analogously, how coding, regulation and spatial organization interact in cellular processes.
[ { "created": "Fri, 30 Oct 2020 11:06:39 GMT", "version": "v1" } ]
2020-11-02
[ [ "Jost", "Jürgen", "" ] ]
In computer science, we can theoretically neatly separate transmission and processing of information, hardware and software, and programs and their inputs. This is much more intricate in biology, Nevertheless, I argue that Shannon's concept of information is useful in biology, although its application is not as straightforward as many people think. In fact, the recently developed theory of information decomposition can shed much light on the complementarity between coding and regulatory, or internal and environmental information. The key challenge that we formulate in this contribution is to understand how genetic information and external factors combine to create an organism, and conversely, how the genome has learned in the course of evolution how to harness the environment, and analogously, how coding, regulation and spatial organization interact in cellular processes.
1311.4851
Vasily Mironov
Vasily Mironov, Alexander Romanov, Alexander Simonov, Maria Vedunova and Victor Kazantsev
Oscillations in a neurite growth model with extracellular feedback
null
null
null
null
q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We take into account the influence of extracellular signalling on neurite elongation in a model of neurite growth mediated by building proteins (e.g. tubulin). Tubulin production dynamics was supplied by a function describing the influence of the extracellular signalling that can promote or depress the elongation. We found that such extracellular feedback can generate neurite length oscillations with periodic sequence of elongations and retractions. The oscillations prevent further outgrowth of the neurite which becomes trapped in the non-uniform extracellular field. We analyzed the characteristics of the elongation process for different distributions of attracting and repelling sources of the extracellular signal molecules. The model predicts three different scenarios of the neurite development in the extracellular field including monotonic and oscillatory outgrowth, localized limit cycle oscillations and complete depression of the growth.
[ { "created": "Tue, 19 Nov 2013 19:43:24 GMT", "version": "v1" } ]
2013-11-20
[ [ "Mironov", "Vasily", "" ], [ "Romanov", "Alexander", "" ], [ "Simonov", "Alexander", "" ], [ "Vedunova", "Maria", "" ], [ "Kazantsev", "Victor", "" ] ]
We take into account the influence of extracellular signalling on neurite elongation in a model of neurite growth mediated by building proteins (e.g. tubulin). Tubulin production dynamics was supplied by a function describing the influence of the extracellular signalling that can promote or depress the elongation. We found that such extracellular feedback can generate neurite length oscillations with periodic sequence of elongations and retractions. The oscillations prevent further outgrowth of the neurite which becomes trapped in the non-uniform extracellular field. We analyzed the characteristics of the elongation process for different distributions of attracting and repelling sources of the extracellular signal molecules. The model predicts three different scenarios of the neurite development in the extracellular field including monotonic and oscillatory outgrowth, localized limit cycle oscillations and complete depression of the growth.
2004.00991
Weixing Ji
Jie Liu, Xiaotian Wu, Kai Zhang, Bing Liu, Renyi Bao, Xiao Chen, Yiran Cai, Yiming Shen, Xinjun He, Jun Yan, Weixing Ji
Computational Performance of a Germline Variant Calling Pipeline for Next Generation Sequencing
6 pages, 6 figures, 3 tables
null
null
null
q-bio.GN cs.PF
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
With the booming of next generation sequencing technology and its implementation in clinical practice and life science research, the need for faster and more efficient data analysis methods becomes pressing in the field of sequencing. Here we report on the evaluation of an optimized germline mutation calling pipeline, HummingBird, by assessing its performance against the widely accepted BWA-GATK pipeline. We found that the HummingBird pipeline can significantly reduce the running time of the primary data analysis for whole genome sequencing and whole exome sequencing while without significantly sacrificing the variant calling accuracy. Thus, we conclude that expansion of such software usage will help to improve the primary data analysis efficiency for next generation sequencing.
[ { "created": "Wed, 1 Apr 2020 12:55:11 GMT", "version": "v1" } ]
2020-04-03
[ [ "Liu", "Jie", "" ], [ "Wu", "Xiaotian", "" ], [ "Zhang", "Kai", "" ], [ "Liu", "Bing", "" ], [ "Bao", "Renyi", "" ], [ "Chen", "Xiao", "" ], [ "Cai", "Yiran", "" ], [ "Shen", "Yiming", "" ], [ "He", "Xinjun", "" ], [ "Yan", "Jun", "" ], [ "Ji", "Weixing", "" ] ]
With the booming of next generation sequencing technology and its implementation in clinical practice and life science research, the need for faster and more efficient data analysis methods becomes pressing in the field of sequencing. Here we report on the evaluation of an optimized germline mutation calling pipeline, HummingBird, by assessing its performance against the widely accepted BWA-GATK pipeline. We found that the HummingBird pipeline can significantly reduce the running time of the primary data analysis for whole genome sequencing and whole exome sequencing while without significantly sacrificing the variant calling accuracy. Thus, we conclude that expansion of such software usage will help to improve the primary data analysis efficiency for next generation sequencing.
1404.5210
Norshuhaila Mohamed Sunar N.M.Sunar
N. M. Sunar, E.I. Stentiford, D.I. Stewart and L.A. Fletcher
The Process and Pathogen Behavior in Composting: A Review
Proceeding UMT-MSD 2009 Post Graduate Seminar 2009. Universiti Malaysia Terengganu, Malaysian Student Department UK & Institute for Transport Studies University of Leeds. pp: 78-87; ISBN: 978-967-5366-04-8
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Composting is defined as the biological decomposition and stabilization of organic substrates under aerobic conditions to allow the development of thermophilic temperatures. This thermophilic temperature is a result of biologically produced heat. Composting produces the final product which is sufficiently stable for storage and application to land without adverse environmental effects. There are many factors which affect the decomposition of organic matter in the composting process. Since the composting process is very intricate, it is not easy to estimate the effect of a single factor on the rate of organic matter decomposition. This paper looked at the main factors affecting the composting process. Problems regarding the controlling, inactivation and regrowth of pathogen in compost material are also discussed.
[ { "created": "Mon, 21 Apr 2014 14:29:49 GMT", "version": "v1" } ]
2014-04-22
[ [ "Sunar", "N. M.", "" ], [ "Stentiford", "E. I.", "" ], [ "Stewart", "D. I.", "" ], [ "Fletcher", "L. A.", "" ] ]
Composting is defined as the biological decomposition and stabilization of organic substrates under aerobic conditions to allow the development of thermophilic temperatures. This thermophilic temperature is a result of biologically produced heat. Composting produces the final product which is sufficiently stable for storage and application to land without adverse environmental effects. There are many factors which affect the decomposition of organic matter in the composting process. Since the composting process is very intricate, it is not easy to estimate the effect of a single factor on the rate of organic matter decomposition. This paper looked at the main factors affecting the composting process. Problems regarding the controlling, inactivation and regrowth of pathogen in compost material are also discussed.
2102.01303
Tijl Grootswagers
Tijl Grootswagers, Amanda K. Robinson, Sophia M. Shatek, Thomas A. Carlson
The neural dynamics underlying prioritisation of task-relevant information
Published in Neurons, Behavior, Data analysis, and Theory (NBDT)
Neurons, Behavior, Data Analysis, and Theory (2021), 5(1)
10.51628/001c.21174
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
The human brain prioritises relevant sensory information to perform different tasks. Enhancement of task-relevant information requires flexible allocation of attentional resources, but it is still a mystery how this is operationalised in the brain. We investigated how attentional mechanisms operate in situations where multiple stimuli are presented in the same location and at the same time. In two experiments, participants performed a challenging two-back task on different types of visual stimuli that were presented simultaneously and superimposed over each other. Using electroencephalography and multivariate decoding, we analysed the effect of attention on the neural responses to each individual stimulus. Whole brain neural responses contained considerable information about both the attended and unattended stimuli, even though they were presented simultaneously and represented in overlapping receptive fields. As expected, attention increased the decodability of stimulus-related information contained in the neural responses, but this effect was evident earlier for stimuli that were presented at smaller sizes. Our results show that early neural responses to stimuli in fast-changing displays contain remarkable information about the sensory environment but are also modulated by attention in a manner dependent on perceptual characteristics of the relevant stimuli. Stimuli, code, and data for this study can be found at https://osf.io/7zhwp/.
[ { "created": "Tue, 2 Feb 2021 04:24:51 GMT", "version": "v1" }, { "created": "Fri, 19 Feb 2021 05:02:07 GMT", "version": "v2" } ]
2021-02-22
[ [ "Grootswagers", "Tijl", "" ], [ "Robinson", "Amanda K.", "" ], [ "Shatek", "Sophia M.", "" ], [ "Carlson", "Thomas A.", "" ] ]
The human brain prioritises relevant sensory information to perform different tasks. Enhancement of task-relevant information requires flexible allocation of attentional resources, but it is still a mystery how this is operationalised in the brain. We investigated how attentional mechanisms operate in situations where multiple stimuli are presented in the same location and at the same time. In two experiments, participants performed a challenging two-back task on different types of visual stimuli that were presented simultaneously and superimposed over each other. Using electroencephalography and multivariate decoding, we analysed the effect of attention on the neural responses to each individual stimulus. Whole brain neural responses contained considerable information about both the attended and unattended stimuli, even though they were presented simultaneously and represented in overlapping receptive fields. As expected, attention increased the decodability of stimulus-related information contained in the neural responses, but this effect was evident earlier for stimuli that were presented at smaller sizes. Our results show that early neural responses to stimuli in fast-changing displays contain remarkable information about the sensory environment but are also modulated by attention in a manner dependent on perceptual characteristics of the relevant stimuli. Stimuli, code, and data for this study can be found at https://osf.io/7zhwp/.
1708.06641
Adam Noel
Adam Noel, Dimitrios Makrakis, Andrew W. Eckford
Distortion Distribution of Neural Spike Train Sequence Matching with Optogenetics
13 pages, 10 figures. To appear in IEEE Transactions on Biomedical Engineering. A conference version, which was presented at 2017 IEEE Globecom, can be found at arXiv:1704.04795
null
10.1109/TBME.2018.2819200
null
q-bio.NC cs.IT math.IT physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This paper uses a simple optogenetic model to compare the timing distortion between a randomly-generated target spike sequence and an externally-stimulated neuron spike sequence. Optogenetics is an emerging field of neuroscience where neurons are genetically modified to express light-sensitive receptors that enable external control over when the neurons fire. Given the prominence of neuronal signaling within the brain and throughout the body, optogenetics has significant potential to improve the understanding of the nervous system and to develop treatments for neurological diseases. This paper primarily considers two different distortion measures. The first measure is the delay in externally-stimulated spikes. The second measure is the root mean square error between the filtered outputs of the target and stimulated spike sequences. The mean and the distribution of the distortion is derived in closed form when the target sequence generation rate is sufficiently low. All derived results are supported with simulations. This work is a step towards an analytical model to predict whether different spike trains were observed from the same stimulus, and the broader goal of understanding the quantity and reliability of information that can be carried by neurons.
[ { "created": "Tue, 22 Aug 2017 14:30:13 GMT", "version": "v1" }, { "created": "Thu, 22 Mar 2018 10:09:18 GMT", "version": "v2" } ]
2020-04-24
[ [ "Noel", "Adam", "" ], [ "Makrakis", "Dimitrios", "" ], [ "Eckford", "Andrew W.", "" ] ]
This paper uses a simple optogenetic model to compare the timing distortion between a randomly-generated target spike sequence and an externally-stimulated neuron spike sequence. Optogenetics is an emerging field of neuroscience where neurons are genetically modified to express light-sensitive receptors that enable external control over when the neurons fire. Given the prominence of neuronal signaling within the brain and throughout the body, optogenetics has significant potential to improve the understanding of the nervous system and to develop treatments for neurological diseases. This paper primarily considers two different distortion measures. The first measure is the delay in externally-stimulated spikes. The second measure is the root mean square error between the filtered outputs of the target and stimulated spike sequences. The mean and the distribution of the distortion is derived in closed form when the target sequence generation rate is sufficiently low. All derived results are supported with simulations. This work is a step towards an analytical model to predict whether different spike trains were observed from the same stimulus, and the broader goal of understanding the quantity and reliability of information that can be carried by neurons.
1602.02492
Dinesh Kumar Dr.
Dinesh Kumar, Atul Rawat, Durgesh Dubey, Umesh Kumar, Amit K Keshari, Sudipta Saha and Anupam Guleria
NMR based Pharmaco-metabolomics: An efficient and agile tool for therapeutic evaluation of Traditional Herbal Medicines
17 pages, 8 Figures and 62 references
null
null
null
q-bio.BM q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Traditional Indian (Ayurvedic) and Chinese herbal medicines have been used in the treatment of a variety of diseases for thousands of years because of their natural origin and lesser side effects. However, the safety and efficacy data (including dose and quality parameters) on most of these traditional medicines are far from sufficient to meet the criteria needed to support their world-wide therapeutic use. Also, the mechanistic understanding of most of these herbal medicines is still lacking due to their complex components which further limits their wider application and acceptance. Metabolomics -a novel approach to reveal altered metabolism (biochemical effects) produced in response to a disease or its therapeutic intervention- has huge potential to assess the pharmacology and toxicology of traditional herbal medicines (THMs). Therefore, it is gradually becoming a mutually complementary technique to genomics, transcriptomics and proteomics for therapeutic evaluation of pharmaceutical products (including THMs); the approach is so called pharmaco-metabolomics. The whole paradigm is based on its ability to provide metabolic signatures to confirm the diseased condition and then to use the concentration profiles of these biomarkers to assess the therapeutic response. Nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate data analysis is currently the method of choice for pharmaco-metabolomics studies owing to its unbiased, non-destructive nature and minimal sample preparation requirement. In recent past, dozens of NMR based pharmaco-metabolomic studies have been devoted to prove the therapeutic efficacy/safety and to explore the underlying mechanisms of THMs, with promising results. The current perspective article summarizes various such studies in addition to describing the technical and conceptual aspects involved in NMR based pharmaco-metabolomics.
[ { "created": "Mon, 8 Feb 2016 08:30:22 GMT", "version": "v1" } ]
2016-02-09
[ [ "Kumar", "Dinesh", "" ], [ "Rawat", "Atul", "" ], [ "Dubey", "Durgesh", "" ], [ "Kumar", "Umesh", "" ], [ "Keshari", "Amit K", "" ], [ "Saha", "Sudipta", "" ], [ "Guleria", "Anupam", "" ] ]
Traditional Indian (Ayurvedic) and Chinese herbal medicines have been used in the treatment of a variety of diseases for thousands of years because of their natural origin and lesser side effects. However, the safety and efficacy data (including dose and quality parameters) on most of these traditional medicines are far from sufficient to meet the criteria needed to support their world-wide therapeutic use. Also, the mechanistic understanding of most of these herbal medicines is still lacking due to their complex components which further limits their wider application and acceptance. Metabolomics -a novel approach to reveal altered metabolism (biochemical effects) produced in response to a disease or its therapeutic intervention- has huge potential to assess the pharmacology and toxicology of traditional herbal medicines (THMs). Therefore, it is gradually becoming a mutually complementary technique to genomics, transcriptomics and proteomics for therapeutic evaluation of pharmaceutical products (including THMs); the approach is so called pharmaco-metabolomics. The whole paradigm is based on its ability to provide metabolic signatures to confirm the diseased condition and then to use the concentration profiles of these biomarkers to assess the therapeutic response. Nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate data analysis is currently the method of choice for pharmaco-metabolomics studies owing to its unbiased, non-destructive nature and minimal sample preparation requirement. In recent past, dozens of NMR based pharmaco-metabolomic studies have been devoted to prove the therapeutic efficacy/safety and to explore the underlying mechanisms of THMs, with promising results. The current perspective article summarizes various such studies in addition to describing the technical and conceptual aspects involved in NMR based pharmaco-metabolomics.
1611.04747
Bashar Ibrahim
Bashar Ibrahim
Toward a systems-level view of mitotic checkpoints
null
Prog Biophys Mol Biol. 2015 Mar;117(2-3):217-24
10.1016/j.pbiomolbio.2015.02.005
null
q-bio.SC q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Reproduction and natural selection are the key elements of life. In order to reproduce, the genetic material must be doubled, separated and placed into two new daughter cells, each containing a complete set of chromosomes and organelles. In mitosis, transition from one process to the next is guided by intricate surveillance mechanisms, known as the mitotic checkpoints. Dis-regulation of cell division through checkpoint malfunction can lead to developmental defects and contribute to the development or progression of tumors. This review approaches two important mitotic checkpoints, the spindle assembly checkpoint (SAC) and the spindle position checkpoint (SPOC). The highly conserved spindle assembly checkpoint (SAC) controls the onset of anaphase by preventing premature segregation of the sister chromatids of the duplicated genome, to the spindle poles. In contrast, the spindle position checkpoint (SPOC), in the budding yeast S. cerevisiae, ensures that during asymmetric cell division mitotic exit does not occur until the spindle is properly aligned with the cell polarity axis. Although there are no known homologs, there is indication that functionally similar checkpoints exist also in animal cells.
[ { "created": "Tue, 15 Nov 2016 09:01:57 GMT", "version": "v1" } ]
2016-11-16
[ [ "Ibrahim", "Bashar", "" ] ]
Reproduction and natural selection are the key elements of life. In order to reproduce, the genetic material must be doubled, separated and placed into two new daughter cells, each containing a complete set of chromosomes and organelles. In mitosis, transition from one process to the next is guided by intricate surveillance mechanisms, known as the mitotic checkpoints. Dis-regulation of cell division through checkpoint malfunction can lead to developmental defects and contribute to the development or progression of tumors. This review approaches two important mitotic checkpoints, the spindle assembly checkpoint (SAC) and the spindle position checkpoint (SPOC). The highly conserved spindle assembly checkpoint (SAC) controls the onset of anaphase by preventing premature segregation of the sister chromatids of the duplicated genome, to the spindle poles. In contrast, the spindle position checkpoint (SPOC), in the budding yeast S. cerevisiae, ensures that during asymmetric cell division mitotic exit does not occur until the spindle is properly aligned with the cell polarity axis. Although there are no known homologs, there is indication that functionally similar checkpoints exist also in animal cells.
2304.10725
Charles Semple
Magnus Bordewich, Charles Semple
Quantifying the difference between phylogenetic diversity and diversity indices
26 pages, 5 figures
null
null
null
q-bio.PE math.CO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Phylogenetic diversity is a popular measure for quantifying the biodiversity of a collection $Y$ of species, while phylogenetic diversity indices provide a way to apportion phylogenetic diversity to individual species. Typically, for some specific diversity index, the phylogenetic diversity of $Y$ is not equal to the sum of the diversity indices of the species in $Y.$ In this paper, we investigate the extent of this difference for two commonly-used indices: Fair Proportion and Equal Splits. In particular, we determine the maximum value of this difference under various instances including when the associated rooted phylogenetic tree is allowed to vary across all root phylogenetic trees with the same leaf set and whose edge lengths are constrained by either their total sum or their maximum value.
[ { "created": "Fri, 21 Apr 2023 03:40:40 GMT", "version": "v1" } ]
2023-04-24
[ [ "Bordewich", "Magnus", "" ], [ "Semple", "Charles", "" ] ]
Phylogenetic diversity is a popular measure for quantifying the biodiversity of a collection $Y$ of species, while phylogenetic diversity indices provide a way to apportion phylogenetic diversity to individual species. Typically, for some specific diversity index, the phylogenetic diversity of $Y$ is not equal to the sum of the diversity indices of the species in $Y.$ In this paper, we investigate the extent of this difference for two commonly-used indices: Fair Proportion and Equal Splits. In particular, we determine the maximum value of this difference under various instances including when the associated rooted phylogenetic tree is allowed to vary across all root phylogenetic trees with the same leaf set and whose edge lengths are constrained by either their total sum or their maximum value.
2007.12692
Guo-Wei Wei
Rui Wang, Jiahui Chen, Kaifu Gao, Yuta Hozumi, Changchuan Yin, and Guo-Wei Wei
Characterizing SARS-CoV-2 mutations in the United States
31 pages, 20 figures, and 4 tables
null
null
null
q-bio.GN q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been mutating since it was first sequenced in early January 2020. The genetic variants have developed into a few distinct clusters with different properties. Since the United States (US) has the highest number of viral infected patients globally, it is essential to understand the US SARS-CoV-2. Using genotyping, sequence-alignment, time-evolution, $k$-means clustering, protein-folding stability, algebraic topology, and network theory, we reveal that the US SARS-CoV-2 has four substrains and five top US SARS-CoV-2 mutations were first detected in China (2 cases), Singapore (2 cases), and the United Kingdom (1 case). The next three top US SARS-CoV-2 mutations were first detected in the US. These eight top mutations belong to two disconnected groups. The first group consisting of 5 concurrent mutations is prevailing, while the other group with three concurrent mutations gradually fades out. Our analysis suggests that female immune systems are more active than those of males in responding to SARS-CoV-2 infections. We identify that one of the top mutations, 27964C$>$T-(S24L) on ORF8, has an unusually strong gender dependence. Based on the analysis of all mutations on the spike protein, we further uncover that three of four US SASR-CoV-2 substrains become more infectious. Our study calls for effective viral control and containing strategies in the US.
[ { "created": "Fri, 24 Jul 2020 14:25:24 GMT", "version": "v1" } ]
2020-07-28
[ [ "Wang", "Rui", "" ], [ "Chen", "Jiahui", "" ], [ "Gao", "Kaifu", "" ], [ "Hozumi", "Yuta", "" ], [ "Yin", "Changchuan", "" ], [ "Wei", "Guo-Wei", "" ] ]
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been mutating since it was first sequenced in early January 2020. The genetic variants have developed into a few distinct clusters with different properties. Since the United States (US) has the highest number of viral infected patients globally, it is essential to understand the US SARS-CoV-2. Using genotyping, sequence-alignment, time-evolution, $k$-means clustering, protein-folding stability, algebraic topology, and network theory, we reveal that the US SARS-CoV-2 has four substrains and five top US SARS-CoV-2 mutations were first detected in China (2 cases), Singapore (2 cases), and the United Kingdom (1 case). The next three top US SARS-CoV-2 mutations were first detected in the US. These eight top mutations belong to two disconnected groups. The first group consisting of 5 concurrent mutations is prevailing, while the other group with three concurrent mutations gradually fades out. Our analysis suggests that female immune systems are more active than those of males in responding to SARS-CoV-2 infections. We identify that one of the top mutations, 27964C$>$T-(S24L) on ORF8, has an unusually strong gender dependence. Based on the analysis of all mutations on the spike protein, we further uncover that three of four US SASR-CoV-2 substrains become more infectious. Our study calls for effective viral control and containing strategies in the US.
1102.5604
John Hawks
John Hawks
Selection for smaller brains in Holocene human evolution
17 text pages, 3 bibliography pages, 1 figure
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Background: Human populations during the last 10,000 years have undergone rapid decreases in average brain size as measured by endocranial volume or as estimated from linear measurements of the cranium. A null hypothesis to explain the evolution of brain size is that reductions result from genetic correlation of brain size with body mass or stature. Results: The absolute change of endocranial volume in the study samples was significantly greater than would be predicted from observed changes in body mass or stature. Conclusions: The evolution of smaller brains in many recent human populations must have resulted from selection upon brain size itself or on other features more highly correlated with brain size than are gross body dimensions. This selection may have resulted from energetic or nutritional demands in Holocene populations, or to life history constraints on brain development.
[ { "created": "Mon, 28 Feb 2011 06:22:01 GMT", "version": "v1" } ]
2011-03-01
[ [ "Hawks", "John", "" ] ]
Background: Human populations during the last 10,000 years have undergone rapid decreases in average brain size as measured by endocranial volume or as estimated from linear measurements of the cranium. A null hypothesis to explain the evolution of brain size is that reductions result from genetic correlation of brain size with body mass or stature. Results: The absolute change of endocranial volume in the study samples was significantly greater than would be predicted from observed changes in body mass or stature. Conclusions: The evolution of smaller brains in many recent human populations must have resulted from selection upon brain size itself or on other features more highly correlated with brain size than are gross body dimensions. This selection may have resulted from energetic or nutritional demands in Holocene populations, or to life history constraints on brain development.
2405.15928
Dea Gogishvili
Dea Gogishvili, Emmanuel Minois-Genin, Jan van Eck, Sanne Abeln
PatchProt: Hydrophobic patch prediction using protein foundation models
null
null
null
null
q-bio.QM cs.AI cs.LG
http://creativecommons.org/licenses/by/4.0/
Hydrophobic patches on protein surfaces play important functional roles in protein-protein and protein-ligand interactions. Large hydrophobic surfaces are also involved in the progression of aggregation diseases. Predicting exposed hydrophobic patches from a protein sequence has been shown to be a difficult task. Fine-tuning foundation models allows for adapting a model to the specific nuances of a new task using a much smaller dataset. Additionally, multi-task deep learning offers a promising solution for addressing data gaps, simultaneously outperforming single-task methods. In this study, we harnessed a recently released leading large language model ESM-2. Efficient fine-tuning of ESM-2 was achieved by leveraging a recently developed parameter-efficient fine-tuning method. This approach enabled comprehensive training of model layers without excessive parameters and without the need to include a computationally expensive multiple sequence analysis. We explored several related tasks, at local (residue) and global (protein) levels, to improve the representation of the model. As a result, our fine-tuned ESM-2 model, PatchProt, cannot only predict hydrophobic patch areas but also outperforms existing methods at predicting primary tasks, including secondary structure and surface accessibility predictions. Importantly, our analysis shows that including related local tasks can improve predictions on more difficult global tasks. This research sets a new standard for sequence-based protein property prediction and highlights the remarkable potential of fine-tuning foundation models enriching the model representation by training over related tasks.
[ { "created": "Fri, 24 May 2024 20:37:02 GMT", "version": "v1" } ]
2024-05-28
[ [ "Gogishvili", "Dea", "" ], [ "Minois-Genin", "Emmanuel", "" ], [ "van Eck", "Jan", "" ], [ "Abeln", "Sanne", "" ] ]
Hydrophobic patches on protein surfaces play important functional roles in protein-protein and protein-ligand interactions. Large hydrophobic surfaces are also involved in the progression of aggregation diseases. Predicting exposed hydrophobic patches from a protein sequence has been shown to be a difficult task. Fine-tuning foundation models allows for adapting a model to the specific nuances of a new task using a much smaller dataset. Additionally, multi-task deep learning offers a promising solution for addressing data gaps, simultaneously outperforming single-task methods. In this study, we harnessed a recently released leading large language model ESM-2. Efficient fine-tuning of ESM-2 was achieved by leveraging a recently developed parameter-efficient fine-tuning method. This approach enabled comprehensive training of model layers without excessive parameters and without the need to include a computationally expensive multiple sequence analysis. We explored several related tasks, at local (residue) and global (protein) levels, to improve the representation of the model. As a result, our fine-tuned ESM-2 model, PatchProt, cannot only predict hydrophobic patch areas but also outperforms existing methods at predicting primary tasks, including secondary structure and surface accessibility predictions. Importantly, our analysis shows that including related local tasks can improve predictions on more difficult global tasks. This research sets a new standard for sequence-based protein property prediction and highlights the remarkable potential of fine-tuning foundation models enriching the model representation by training over related tasks.
1406.3316
Fabricio Forgerini
Fabricio L. Forgerini and Nuno Crokidakis
Competition and evolution in restricted space
null
J. Stat. Mech. P07016 (2014)
10.1088/1742-5468/2014/07/P07016
null
q-bio.PE cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We study the competition and the evolution of nodes embedded in Euclidean restricted spaces. The population evolves by a branching process in which new nodes are generated when up to two new nodes are attached to the previous ones at each time unit. The competition in the population is introduced by considering the effect of overcrowding of nodes in the embedding space. The branching process is suppressed if the newborn node is closer than a distance $\xi$ of the previous nodes. This rule may be relevant to describe a competition for resources, limiting the density of individuals and therefore the total population. This results in an exponential growth in the initial period, and, after some crossover time, approaching some limiting value. Our results show that the competition among the nodes associated with geometric restrictions can even, for certain conditions, lead the entire population to extinction.
[ { "created": "Thu, 12 Jun 2014 18:52:57 GMT", "version": "v1" } ]
2014-07-21
[ [ "Forgerini", "Fabricio L.", "" ], [ "Crokidakis", "Nuno", "" ] ]
We study the competition and the evolution of nodes embedded in Euclidean restricted spaces. The population evolves by a branching process in which new nodes are generated when up to two new nodes are attached to the previous ones at each time unit. The competition in the population is introduced by considering the effect of overcrowding of nodes in the embedding space. The branching process is suppressed if the newborn node is closer than a distance $\xi$ of the previous nodes. This rule may be relevant to describe a competition for resources, limiting the density of individuals and therefore the total population. This results in an exponential growth in the initial period, and, after some crossover time, approaching some limiting value. Our results show that the competition among the nodes associated with geometric restrictions can even, for certain conditions, lead the entire population to extinction.
1705.09718
Christian Yates
Christian A Yates, Matthew J Ford and Richard L Mort
A multi-stage representation of cell proliferation as a Markov process
null
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The stochastic simulation algorithm commonly known as Gillespie's algorithm is now used ubiquitously in the modelling of biological processes in which stochastic effects play an important role. In well-mixed scenarios at the sub-cellular level it is often reasonable to assume that times between successive reaction/interaction events are exponentially distributed and can be appropriately modelled as a Markov process and hence simulated by the Gillespie algorithm. However, Gillespie's algorithm is routinely applied to model biological systems for which it was never intended. In particular, processes in which cell proliferation is important should not be simulated naively using the Gillespie algorithm since the history-dependent nature of the cell cycle breaks the Markov process. The variance in experimentally measured cell cycle times is far less than in an exponential cell cycle time distribution with the same mean. Here we suggest a method of modelling the cell cycle that restores the memoryless property to the system and is therefore consistent with simulation via the Gillespie algorithm. By breaking the cell cycle into a number of independent exponentially distributed stages we can restore the Markov property at the same time as more accurately approximating the appropriate cell cycle time distributions. The consequences of our revised mathematical model are explored analytically. We demonstrate the importance of employing the correct cell cycle time distribution by considering two models incorporating cellular proliferation (one spatial and one non-spatial) and demonstrating that changing the cell cycle time distribution makes quantitative and qualitative differences to their outcomes. Our adaptation will allow modellers and experimentalists alike to appropriately represent cellular proliferation, whilst still being able to take advantage of the Gillespie algorithm.
[ { "created": "Fri, 26 May 2017 20:57:10 GMT", "version": "v1" }, { "created": "Mon, 14 Aug 2017 21:24:29 GMT", "version": "v2" }, { "created": "Mon, 22 Jul 2019 16:19:50 GMT", "version": "v3" } ]
2019-07-23
[ [ "Yates", "Christian A", "" ], [ "Ford", "Matthew J", "" ], [ "Mort", "Richard L", "" ] ]
The stochastic simulation algorithm commonly known as Gillespie's algorithm is now used ubiquitously in the modelling of biological processes in which stochastic effects play an important role. In well-mixed scenarios at the sub-cellular level it is often reasonable to assume that times between successive reaction/interaction events are exponentially distributed and can be appropriately modelled as a Markov process and hence simulated by the Gillespie algorithm. However, Gillespie's algorithm is routinely applied to model biological systems for which it was never intended. In particular, processes in which cell proliferation is important should not be simulated naively using the Gillespie algorithm since the history-dependent nature of the cell cycle breaks the Markov process. The variance in experimentally measured cell cycle times is far less than in an exponential cell cycle time distribution with the same mean. Here we suggest a method of modelling the cell cycle that restores the memoryless property to the system and is therefore consistent with simulation via the Gillespie algorithm. By breaking the cell cycle into a number of independent exponentially distributed stages we can restore the Markov property at the same time as more accurately approximating the appropriate cell cycle time distributions. The consequences of our revised mathematical model are explored analytically. We demonstrate the importance of employing the correct cell cycle time distribution by considering two models incorporating cellular proliferation (one spatial and one non-spatial) and demonstrating that changing the cell cycle time distribution makes quantitative and qualitative differences to their outcomes. Our adaptation will allow modellers and experimentalists alike to appropriately represent cellular proliferation, whilst still being able to take advantage of the Gillespie algorithm.
2004.12676
Alban Bornet
Adrien Doerig, Alban Bornet, Oh-Hyeon Choung, Micahel H. Herzog
Crowding Reveals Fundamental Differences in Local vs. Global Processing in Humans and Machines
null
Vision Research, 167, 39-45 (2020)
10.1016/j.visres.2019.12.006
null
q-bio.NC
http://creativecommons.org/licenses/by-nc-sa/4.0/
Feedforward Convolutional Neural Networks (ffCNNs) have become state-of-the-art models both in computer vision and neuroscience. However, human-like performance of ffCNNs does not necessarily imply human-like computations. Previous studies have suggested that current ffCNNs do not make use of global shape information. However, it is currently unclear whether this reflects fundamental differences between ffCNN and human processing or is merely an artefact of how ffCNNs are trained. Here, we use visual crowding as a well-controlled, specific probe to test global shape computations. Our results provide evidence that ffCNNs cannot produce human-like global shape computations for principled architectural reasons. We lay out approaches that may address shortcomings of ffCNNs to provide better models of the human visual system.
[ { "created": "Mon, 27 Apr 2020 09:43:27 GMT", "version": "v1" } ]
2020-04-29
[ [ "Doerig", "Adrien", "" ], [ "Bornet", "Alban", "" ], [ "Choung", "Oh-Hyeon", "" ], [ "Herzog", "Micahel H.", "" ] ]
Feedforward Convolutional Neural Networks (ffCNNs) have become state-of-the-art models both in computer vision and neuroscience. However, human-like performance of ffCNNs does not necessarily imply human-like computations. Previous studies have suggested that current ffCNNs do not make use of global shape information. However, it is currently unclear whether this reflects fundamental differences between ffCNN and human processing or is merely an artefact of how ffCNNs are trained. Here, we use visual crowding as a well-controlled, specific probe to test global shape computations. Our results provide evidence that ffCNNs cannot produce human-like global shape computations for principled architectural reasons. We lay out approaches that may address shortcomings of ffCNNs to provide better models of the human visual system.
1912.00791
Anindita Bhadra
Arunita Banerjee and Anindita Bhadra
Time-activity budget of urban-adapted free-ranging dogs
5 figures
Acta Ethologica 25, 2022
10.1007/s10211-021-00379-6
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The domestic dog is known to have evolved from gray wolves, about 15,000 years ago. They majorly exist as free-ranging populations across the world. They are typically scavengers and well adapted to living among humans. Most canids living in and around urban habitats tend to avoid humans and show crepuscular activity peaks. In this study, we carried out a detailed population-level survey on free-ranging dogs in West Bengal, India, to understand the activity patterns of free-ranging dogs in relation to human activity. Using 5669 sightings of dogs, over a period of 1 year, covering the 24 hours of the day, we carried out an analysis of the time-activity budget of free-ranging dogs to conclude that they are generalists in their habit. They remain active when humans are active. Their activity levels are affected significantly by age class and time of the day. Multivariate analysis revealed the presence of certain behavioural clusters on the basis of time of the day and energy expenditure in the behaviours. In addition, we provide a detailed ethogram of free-ranging dogs. This, to our knowledge, is the first study of this kind, which might be used to further study the eco-ethology of these dogs.
[ { "created": "Fri, 29 Nov 2019 15:42:21 GMT", "version": "v1" } ]
2022-08-12
[ [ "Banerjee", "Arunita", "" ], [ "Bhadra", "Anindita", "" ] ]
The domestic dog is known to have evolved from gray wolves, about 15,000 years ago. They majorly exist as free-ranging populations across the world. They are typically scavengers and well adapted to living among humans. Most canids living in and around urban habitats tend to avoid humans and show crepuscular activity peaks. In this study, we carried out a detailed population-level survey on free-ranging dogs in West Bengal, India, to understand the activity patterns of free-ranging dogs in relation to human activity. Using 5669 sightings of dogs, over a period of 1 year, covering the 24 hours of the day, we carried out an analysis of the time-activity budget of free-ranging dogs to conclude that they are generalists in their habit. They remain active when humans are active. Their activity levels are affected significantly by age class and time of the day. Multivariate analysis revealed the presence of certain behavioural clusters on the basis of time of the day and energy expenditure in the behaviours. In addition, we provide a detailed ethogram of free-ranging dogs. This, to our knowledge, is the first study of this kind, which might be used to further study the eco-ethology of these dogs.
2008.06996
Dmitry Krotov
Dmitry Krotov, John Hopfield
Large Associative Memory Problem in Neurobiology and Machine Learning
Accepted for publication at ICLR 2021
null
null
null
q-bio.NC cond-mat.dis-nn cs.CL cs.LG stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Dense Associative Memories or modern Hopfield networks permit storage and reliable retrieval of an exponentially large (in the dimension of feature space) number of memories. At the same time, their naive implementation is non-biological, since it seemingly requires the existence of many-body synaptic junctions between the neurons. We show that these models are effective descriptions of a more microscopic (written in terms of biological degrees of freedom) theory that has additional (hidden) neurons and only requires two-body interactions between them. For this reason our proposed microscopic theory is a valid model of large associative memory with a degree of biological plausibility. The dynamics of our network and its reduced dimensional equivalent both minimize energy (Lyapunov) functions. When certain dynamical variables (hidden neurons) are integrated out from our microscopic theory, one can recover many of the models that were previously discussed in the literature, e.g. the model presented in "Hopfield Networks is All You Need" paper. We also provide an alternative derivation of the energy function and the update rule proposed in the aforementioned paper and clarify the relationships between various models of this class.
[ { "created": "Sun, 16 Aug 2020 21:03:52 GMT", "version": "v1" }, { "created": "Tue, 2 Mar 2021 20:06:50 GMT", "version": "v2" }, { "created": "Tue, 27 Apr 2021 22:20:05 GMT", "version": "v3" } ]
2021-04-29
[ [ "Krotov", "Dmitry", "" ], [ "Hopfield", "John", "" ] ]
Dense Associative Memories or modern Hopfield networks permit storage and reliable retrieval of an exponentially large (in the dimension of feature space) number of memories. At the same time, their naive implementation is non-biological, since it seemingly requires the existence of many-body synaptic junctions between the neurons. We show that these models are effective descriptions of a more microscopic (written in terms of biological degrees of freedom) theory that has additional (hidden) neurons and only requires two-body interactions between them. For this reason our proposed microscopic theory is a valid model of large associative memory with a degree of biological plausibility. The dynamics of our network and its reduced dimensional equivalent both minimize energy (Lyapunov) functions. When certain dynamical variables (hidden neurons) are integrated out from our microscopic theory, one can recover many of the models that were previously discussed in the literature, e.g. the model presented in "Hopfield Networks is All You Need" paper. We also provide an alternative derivation of the energy function and the update rule proposed in the aforementioned paper and clarify the relationships between various models of this class.
2310.02553
Zaixi Zhang
Zaixi Zhang, Zepu Lu, Zhongkai Hao, Marinka Zitnik, Qi Liu
Full-Atom Protein Pocket Design via Iterative Refinement
NeurIPS 2023 Spotlight
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by/4.0/
The design of \emph{de novo} functional proteins that bind specific ligand molecules is paramount in therapeutics and bio-engineering. A critical yet formidable task in this endeavor is the design of the protein pocket, which is the cavity region of the protein where the ligand binds. Current methods are plagued by inefficient generation, inadequate context modeling of the ligand molecule, and the inability to generate side-chain atoms. Here, we present the Full-Atom Iterative Refinement (FAIR) method, designed to address these challenges by facilitating the co-design of protein pocket sequences, specifically residue types, and their corresponding 3D structures. FAIR operates in two steps, proceeding in a coarse-to-fine manner (transitioning from protein backbone to atoms, including side chains) for a full-atom generation. In each iteration, all residue types and structures are simultaneously updated, a process termed full-shot refinement. In the initial stage, the residue types and backbone coordinates are refined using a hierarchical context encoder, complemented by two structure refinement modules that capture both inter-residue and pocket-ligand interactions. The subsequent stage delves deeper, modeling the side-chain atoms of the pockets and updating residue types to ensure sequence-structure congruence. Concurrently, the structure of the binding ligand is refined across iterations to accommodate its inherent flexibility. Comprehensive experiments show that FAIR surpasses existing methods in designing superior pocket sequences and structures, producing average improvement exceeding 10\% in AAR and RMSD metrics. FAIR is available at \url{https://github.com/zaixizhang/FAIR}.
[ { "created": "Wed, 4 Oct 2023 03:23:00 GMT", "version": "v1" }, { "created": "Fri, 20 Oct 2023 03:42:03 GMT", "version": "v2" } ]
2023-10-23
[ [ "Zhang", "Zaixi", "" ], [ "Lu", "Zepu", "" ], [ "Hao", "Zhongkai", "" ], [ "Zitnik", "Marinka", "" ], [ "Liu", "Qi", "" ] ]
The design of \emph{de novo} functional proteins that bind specific ligand molecules is paramount in therapeutics and bio-engineering. A critical yet formidable task in this endeavor is the design of the protein pocket, which is the cavity region of the protein where the ligand binds. Current methods are plagued by inefficient generation, inadequate context modeling of the ligand molecule, and the inability to generate side-chain atoms. Here, we present the Full-Atom Iterative Refinement (FAIR) method, designed to address these challenges by facilitating the co-design of protein pocket sequences, specifically residue types, and their corresponding 3D structures. FAIR operates in two steps, proceeding in a coarse-to-fine manner (transitioning from protein backbone to atoms, including side chains) for a full-atom generation. In each iteration, all residue types and structures are simultaneously updated, a process termed full-shot refinement. In the initial stage, the residue types and backbone coordinates are refined using a hierarchical context encoder, complemented by two structure refinement modules that capture both inter-residue and pocket-ligand interactions. The subsequent stage delves deeper, modeling the side-chain atoms of the pockets and updating residue types to ensure sequence-structure congruence. Concurrently, the structure of the binding ligand is refined across iterations to accommodate its inherent flexibility. Comprehensive experiments show that FAIR surpasses existing methods in designing superior pocket sequences and structures, producing average improvement exceeding 10\% in AAR and RMSD metrics. FAIR is available at \url{https://github.com/zaixizhang/FAIR}.
1410.7959
Sebastiano Stramaglia
Ibai Diez, Paolo Bonifazi, I\~naki Escudero, Beatriz Mateos, Miguel A. Mu\~noz, Sebastiano Stramaglia and Jesus M. Cortes
A novel brain partition highlights the modular skeleton shared by structure and function
Accepted in Nature Scientific Reports. 56 pages, 15 figures
null
null
null
q-bio.NC q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent technical and methodological progress in neuroimaging has helped advance our understanding of this important issue, with diffusion weighted images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). However, comparing these two distinct datasets, each of which can be encoded into a different complex network, is by no means trivial as pairwise link-to-link comparisons represent a relatively restricted perspective and provide only limited information. Thus, we have adopted a more integrative systems approach, exploiting theoretical graph analyses to study both SC and rsFC datasets gathered independently from healthy human subjects. The aim is to find the main architectural traits shared by the structural and functional networks by paying special attention to their common hierarchical modular organization. This approach allows us to identify a common skeleton from which a new, optimal, brain partition can be extracted, with modules sharing both structure and function. We describe these emerging common structure-function modules (SFMs) in detail. In addition, we compare SFMs with the classical Resting State Networks derived from independent component analysis of rs-fMRI functional activity, as well as with anatomical parcellations in the Automated Anatomical Labeling atlas and with the Broadmann partition, highlighting their similitude and differences. The unveiling of SFMs brings to light the strong correspondence between brain structure and resting-state dynamics.
[ { "created": "Wed, 29 Oct 2014 12:53:35 GMT", "version": "v1" }, { "created": "Thu, 30 Apr 2015 17:10:37 GMT", "version": "v2" } ]
2015-05-01
[ [ "Diez", "Ibai", "" ], [ "Bonifazi", "Paolo", "" ], [ "Escudero", "Iñaki", "" ], [ "Mateos", "Beatriz", "" ], [ "Muñoz", "Miguel A.", "" ], [ "Stramaglia", "Sebastiano", "" ], [ "Cortes", "Jesus M.", "" ] ]
Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent technical and methodological progress in neuroimaging has helped advance our understanding of this important issue, with diffusion weighted images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). However, comparing these two distinct datasets, each of which can be encoded into a different complex network, is by no means trivial as pairwise link-to-link comparisons represent a relatively restricted perspective and provide only limited information. Thus, we have adopted a more integrative systems approach, exploiting theoretical graph analyses to study both SC and rsFC datasets gathered independently from healthy human subjects. The aim is to find the main architectural traits shared by the structural and functional networks by paying special attention to their common hierarchical modular organization. This approach allows us to identify a common skeleton from which a new, optimal, brain partition can be extracted, with modules sharing both structure and function. We describe these emerging common structure-function modules (SFMs) in detail. In addition, we compare SFMs with the classical Resting State Networks derived from independent component analysis of rs-fMRI functional activity, as well as with anatomical parcellations in the Automated Anatomical Labeling atlas and with the Broadmann partition, highlighting their similitude and differences. The unveiling of SFMs brings to light the strong correspondence between brain structure and resting-state dynamics.
2301.02918
Hyeongseon Jeon
Hyeongseon Jeon, Juan Xie, Yeseul Jeon, Kyeong Joo Jung, Arkobrato Gupta, Won Chang, Dongjun Chung
Statistical Power Analysis for Designing Bulk, Single-Cell, and Spatial Transcriptomics Experiments: Review, Tutorial, and Perspectives
null
null
null
null
q-bio.GN
http://creativecommons.org/licenses/by-nc-nd/4.0/
Gene expression profiling technologies have been used in various applications such as cancer biology. The development of gene expression profiling has expanded the scope of target discovery in transcriptomic studies, and each technology produces data with distinct characteristics. In order to guarantee biologically meaningful findings using transcriptomic experiments, it is important to consider various experimental factors in a systematic way through statistical power analysis. In this paper, we review and discuss the power analysis for three types of gene expression profiling technologies from a practical standpoint, including bulk RNA-seq, single-cell RNA-seq, and high-throughput spatial transcriptomics. Specifically, we describe the existing power analysis tools for each research objective for each of the bulk RNA-seq and scRNA-seq experiments, along with recommendations. On the other hand, since there are no power analysis tools for high-throughput spatial transcriptomics at this point, we instead investigate the factors that can influence power analysis.
[ { "created": "Sat, 7 Jan 2023 18:42:28 GMT", "version": "v1" } ]
2023-01-10
[ [ "Jeon", "Hyeongseon", "" ], [ "Xie", "Juan", "" ], [ "Jeon", "Yeseul", "" ], [ "Jung", "Kyeong Joo", "" ], [ "Gupta", "Arkobrato", "" ], [ "Chang", "Won", "" ], [ "Chung", "Dongjun", "" ] ]
Gene expression profiling technologies have been used in various applications such as cancer biology. The development of gene expression profiling has expanded the scope of target discovery in transcriptomic studies, and each technology produces data with distinct characteristics. In order to guarantee biologically meaningful findings using transcriptomic experiments, it is important to consider various experimental factors in a systematic way through statistical power analysis. In this paper, we review and discuss the power analysis for three types of gene expression profiling technologies from a practical standpoint, including bulk RNA-seq, single-cell RNA-seq, and high-throughput spatial transcriptomics. Specifically, we describe the existing power analysis tools for each research objective for each of the bulk RNA-seq and scRNA-seq experiments, along with recommendations. On the other hand, since there are no power analysis tools for high-throughput spatial transcriptomics at this point, we instead investigate the factors that can influence power analysis.
0704.3259
James P. Sethna
Christopher R. Myers, Ryan N. Gutenkunst, and James. P. Sethna
Python Unleashed on Systems Biology
Submitted to special issue of CiSE
null
null
null
q-bio.QM q-bio.MN
null
We have built an open-source software system for the modeling of biomolecular reaction networks, SloppyCell, which is written in Python and makes substantial use of third-party libraries for numerics, visualization, and parallel programming. We highlight here some of the powerful features that Python provides that enable SloppyCell to do dynamic code synthesis, symbolic manipulation, and parallel exploration of complex parameter spaces.
[ { "created": "Tue, 24 Apr 2007 18:48:18 GMT", "version": "v1" } ]
2007-05-23
[ [ "Myers", "Christopher R.", "" ], [ "Gutenkunst", "Ryan N.", "" ], [ "Sethna", "James. P.", "" ] ]
We have built an open-source software system for the modeling of biomolecular reaction networks, SloppyCell, which is written in Python and makes substantial use of third-party libraries for numerics, visualization, and parallel programming. We highlight here some of the powerful features that Python provides that enable SloppyCell to do dynamic code synthesis, symbolic manipulation, and parallel exploration of complex parameter spaces.
q-bio/0508001
Ruriko Yoshida
Dan Levy, Ruriko Yoshida, Lior Pachter
Neighbor joining with phylogenetic diversity estimates
null
null
null
null
q-bio.QM math.CO
null
The Neighbor-Joining algorithm is a recursive procedure for reconstructing trees that is based on a transformation of pairwise distances between leaves. We present a generalization of the neighbor-joining transformation, which uses estimates of phylogenetic diversity rather than pairwise distances in the tree. This leads to an improved neighbor-joining algorithm whose total running time is still polynomial in the number of taxa. On simulated data, the method outperforms other distance-based methods. We have implemented neighbor-joining for subtree weights in a program called MJOIN which is freely available under the Gnu Public License at http://bio.math.berkeley.edu/mjoin/ .
[ { "created": "Sat, 30 Jul 2005 18:28:10 GMT", "version": "v1" } ]
2007-05-23
[ [ "Levy", "Dan", "" ], [ "Yoshida", "Ruriko", "" ], [ "Pachter", "Lior", "" ] ]
The Neighbor-Joining algorithm is a recursive procedure for reconstructing trees that is based on a transformation of pairwise distances between leaves. We present a generalization of the neighbor-joining transformation, which uses estimates of phylogenetic diversity rather than pairwise distances in the tree. This leads to an improved neighbor-joining algorithm whose total running time is still polynomial in the number of taxa. On simulated data, the method outperforms other distance-based methods. We have implemented neighbor-joining for subtree weights in a program called MJOIN which is freely available under the Gnu Public License at http://bio.math.berkeley.edu/mjoin/ .
2211.01960
Vladislav Lomtev
Vladislav Lomtev, Alexander Kovalev, Alexey Timchenko
FingerFlex: Inferring Finger Trajectories from ECoG signals
6 pages, 3 figures, 4 tables. Preprint. Under review
null
null
null
q-bio.NC cs.HC cs.LG
http://creativecommons.org/licenses/by/4.0/
Motor brain-computer interface (BCI) development relies critically on neural time series decoding algorithms. Recent advances in deep learning architectures allow for automatic feature selection to approximate higher-order dependencies in data. This article presents the FingerFlex model - a convolutional encoder-decoder architecture adapted for finger movement regression on electrocorticographic (ECoG) brain data. State-of-the-art performance was achieved on a publicly available BCI competition IV dataset 4 with a correlation coefficient between true and predicted trajectories up to 0.74. The presented method provides the opportunity for developing fully-functional high-precision cortical motor brain-computer interfaces.
[ { "created": "Sun, 23 Oct 2022 16:26:01 GMT", "version": "v1" }, { "created": "Tue, 25 Apr 2023 19:14:18 GMT", "version": "v2" } ]
2023-04-27
[ [ "Lomtev", "Vladislav", "" ], [ "Kovalev", "Alexander", "" ], [ "Timchenko", "Alexey", "" ] ]
Motor brain-computer interface (BCI) development relies critically on neural time series decoding algorithms. Recent advances in deep learning architectures allow for automatic feature selection to approximate higher-order dependencies in data. This article presents the FingerFlex model - a convolutional encoder-decoder architecture adapted for finger movement regression on electrocorticographic (ECoG) brain data. State-of-the-art performance was achieved on a publicly available BCI competition IV dataset 4 with a correlation coefficient between true and predicted trajectories up to 0.74. The presented method provides the opportunity for developing fully-functional high-precision cortical motor brain-computer interfaces.
1604.04203
Christian Scheppach
Christian Scheppach
High- and low-conductance NMDA receptors are present in layer 4 spiny stellate and layer 2/3 pyramidal neurons of mouse barrel cortex
null
Physiological Reports, 30th Dec. 2016, Vol. 4 no. e13051
10.14814/phy2.13051
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
NMDA receptors are ion channels activated by the neurotransmitter glutamate in the mammalian brain and are important in synaptic function and plasticity, but are also found in extrasynaptic locations and influence neuronal excitability. There are different NMDA receptor subtypes which differ in their single-channel conductance. Recently, synaptic plasticity has been studied in mouse barrel cortex, the primary sensory cortex for input from the animal's whiskers. Pharmacological data imply the presence of low-conductance NMDA receptors in spiny stellate neurons of cortical layer 4, but of high-conductance NMDA receptors in pyramidal neurons of layer 2/3. Here, to obtain complementary electrophysiological information on the functional NMDA receptors expressed in layer 4 and layer 2/3 neurons, single NMDA receptor currents were recorded with the patch-clamp method. Both cell types were found to contain high-conductance as well as low-conductance NMDA receptors. The results are consistent with the reported pharmacological data on synaptic plasticity, and with previous claims of a prominent role of low-conductance NMDA receptors in layer 4 spiny stellate neurons, including broad integration, amplification and distribution of excitation within the barrel in response to whisker stimulation, as well as modulation of excitability by ambient glutamate. However, layer 4 cells also expressed high-conductance NMDA receptors. The presence of low-conductance NMDA receptors in layer 2/3 pyramidal neurons suggests that some of these functions may be shared with layer 4 spiny stellate neurons.
[ { "created": "Thu, 14 Apr 2016 16:07:58 GMT", "version": "v1" }, { "created": "Mon, 5 Sep 2016 17:05:44 GMT", "version": "v2" } ]
2017-12-13
[ [ "Scheppach", "Christian", "" ] ]
NMDA receptors are ion channels activated by the neurotransmitter glutamate in the mammalian brain and are important in synaptic function and plasticity, but are also found in extrasynaptic locations and influence neuronal excitability. There are different NMDA receptor subtypes which differ in their single-channel conductance. Recently, synaptic plasticity has been studied in mouse barrel cortex, the primary sensory cortex for input from the animal's whiskers. Pharmacological data imply the presence of low-conductance NMDA receptors in spiny stellate neurons of cortical layer 4, but of high-conductance NMDA receptors in pyramidal neurons of layer 2/3. Here, to obtain complementary electrophysiological information on the functional NMDA receptors expressed in layer 4 and layer 2/3 neurons, single NMDA receptor currents were recorded with the patch-clamp method. Both cell types were found to contain high-conductance as well as low-conductance NMDA receptors. The results are consistent with the reported pharmacological data on synaptic plasticity, and with previous claims of a prominent role of low-conductance NMDA receptors in layer 4 spiny stellate neurons, including broad integration, amplification and distribution of excitation within the barrel in response to whisker stimulation, as well as modulation of excitability by ambient glutamate. However, layer 4 cells also expressed high-conductance NMDA receptors. The presence of low-conductance NMDA receptors in layer 2/3 pyramidal neurons suggests that some of these functions may be shared with layer 4 spiny stellate neurons.
2403.13098
Patrick Lawton
Patrick Lawton, Ashkaan K. Fahimipour, Kurt E. Anderson
Interspecific dispersal constraints suppress pattern formation in metacommunities
null
null
null
null
q-bio.PE nlin.AO
http://creativecommons.org/licenses/by/4.0/
Decisions to disperse from a habitat stand out among organismal behaviors as pivotal drivers of ecosystem dynamics across scales. Encounters with other species are an important component of adaptive decision-making in dispersal, resulting in widespread behaviors like tracking resources or avoiding consumers in space. Despite this, metacommunity models often treat dispersal as a function of intraspecific density alone. We show, focusing initially on three-species network motifs, that interspecific dispersal rules generally drive a transition in metacommunities from homogeneous steady states to self-organized heterogeneous spatial patterns. However, when ecologically realistic constraints reflecting adaptive behaviors are imposed -- prey tracking and predator avoidance -- a pronounced homogenizing effect emerges where spatial pattern formation is suppressed. We demonstrate this effect for each motif by computing master stability functions that separate the contributions of local and spatial interactions to pattern formation. We extend this result to species rich food webs using a random matrix approach, where we find that eventually webs become large enough to override the homogenizing effect of adaptive dispersal behaviors, leading once again to predominately pattern forming dynamics. Our results emphasize the critical role of interspecific dispersal rules in shaping spatial patterns across landscapes, highlighting the need to incorporate adaptive behavioral constraints in efforts to link local species interactions and metacommunity structure.
[ { "created": "Tue, 19 Mar 2024 19:00:43 GMT", "version": "v1" } ]
2024-03-21
[ [ "Lawton", "Patrick", "" ], [ "Fahimipour", "Ashkaan K.", "" ], [ "Anderson", "Kurt E.", "" ] ]
Decisions to disperse from a habitat stand out among organismal behaviors as pivotal drivers of ecosystem dynamics across scales. Encounters with other species are an important component of adaptive decision-making in dispersal, resulting in widespread behaviors like tracking resources or avoiding consumers in space. Despite this, metacommunity models often treat dispersal as a function of intraspecific density alone. We show, focusing initially on three-species network motifs, that interspecific dispersal rules generally drive a transition in metacommunities from homogeneous steady states to self-organized heterogeneous spatial patterns. However, when ecologically realistic constraints reflecting adaptive behaviors are imposed -- prey tracking and predator avoidance -- a pronounced homogenizing effect emerges where spatial pattern formation is suppressed. We demonstrate this effect for each motif by computing master stability functions that separate the contributions of local and spatial interactions to pattern formation. We extend this result to species rich food webs using a random matrix approach, where we find that eventually webs become large enough to override the homogenizing effect of adaptive dispersal behaviors, leading once again to predominately pattern forming dynamics. Our results emphasize the critical role of interspecific dispersal rules in shaping spatial patterns across landscapes, highlighting the need to incorporate adaptive behavioral constraints in efforts to link local species interactions and metacommunity structure.
2107.01706
Hamid Rahkooy
Hamid Rahkooy, Thomas Sturm
Testing Binomiality of Chemical Reaction Networks Using Comprehensive Gr\"obner Systems
null
null
null
null
q-bio.MN cs.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We consider the problem of binomiality of the steady state ideals of biochemical reaction networks. We are interested in finding polynomial conditions on the parameters such that the steady state ideal of a chemical reaction network is binomial under every specialisation of the parameters if the conditions on the parameters hold. We approach the binomiality problem using Comprehensive Gr\"obner systems. Considering rate constants as parameters, we compute comprehensive Gr\"obner systems for various reactions. In particular, we make automatic computations on n-site phosphorylations and biomodels from the Biomodels repository using the grobcov library of the computer algebra system Singular.
[ { "created": "Sun, 4 Jul 2021 18:44:07 GMT", "version": "v1" }, { "created": "Wed, 7 Jul 2021 09:15:25 GMT", "version": "v2" } ]
2021-07-08
[ [ "Rahkooy", "Hamid", "" ], [ "Sturm", "Thomas", "" ] ]
We consider the problem of binomiality of the steady state ideals of biochemical reaction networks. We are interested in finding polynomial conditions on the parameters such that the steady state ideal of a chemical reaction network is binomial under every specialisation of the parameters if the conditions on the parameters hold. We approach the binomiality problem using Comprehensive Gr\"obner systems. Considering rate constants as parameters, we compute comprehensive Gr\"obner systems for various reactions. In particular, we make automatic computations on n-site phosphorylations and biomodels from the Biomodels repository using the grobcov library of the computer algebra system Singular.
2010.16265
Delfim F. M. Torres
Houssine Zine, Adnane Boukhouima, El Mehdi Lotfi, Marouane Mahrouf, Delfim F. M. Torres, Noura Yousfi
A stochastic time-delayed model for the effectiveness of Moroccan COVID-19 deconfinement strategy
This is a preprint of a paper whose final and definite form is published by 'Mathematical Modelling of Natural Phenomena' at [http://doi.org/10.1051/mmnp/2020040]. Paper Submitted 16-May-2020; Revised 20-Aug-2020; Accepted 28-Oct-2020
Math. Model. Nat. Phenom. 15 (2020), Art. 50, 14 pp
10.1051/mmnp/2020040
null
q-bio.PE math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Coronavirus disease 2019 (COVID-19) poses a great threat to public health and the economy worldwide. Currently, COVID-19 evolves in many countries to a second stage, characterized by the need for the liberation of the economy and relaxation of the human psychological effects. To this end, numerous countries decided to implement adequate deconfinement strategies. After the first prolongation of the established confinement, Morocco moves to the deconfinement stage on May 20, 2020. The relevant question concerns the impact on the COVID-19 propagation by considering an additional degree of realism related to stochastic noises due to the effectiveness level of the adapted measures. In this paper, we propose a delayed stochastic mathematical model to predict the epidemiological trend of COVID-19 in Morocco after the deconfinement. To ensure the well-posedness of the model, we prove the existence and uniqueness of a positive solution. Based on the large number theorem for martingales, we discuss the extinction of the disease under an appropriate threshold parameter. Moreover, numerical simulations are performed in order to test the efficiency of the deconfinement strategies chosen by the Moroccan authorities to help the policy makers and public health administration to make suitable decisions in the near future.
[ { "created": "Wed, 28 Oct 2020 18:45:02 GMT", "version": "v1" } ]
2020-11-12
[ [ "Zine", "Houssine", "" ], [ "Boukhouima", "Adnane", "" ], [ "Lotfi", "El Mehdi", "" ], [ "Mahrouf", "Marouane", "" ], [ "Torres", "Delfim F. M.", "" ], [ "Yousfi", "Noura", "" ] ]
Coronavirus disease 2019 (COVID-19) poses a great threat to public health and the economy worldwide. Currently, COVID-19 evolves in many countries to a second stage, characterized by the need for the liberation of the economy and relaxation of the human psychological effects. To this end, numerous countries decided to implement adequate deconfinement strategies. After the first prolongation of the established confinement, Morocco moves to the deconfinement stage on May 20, 2020. The relevant question concerns the impact on the COVID-19 propagation by considering an additional degree of realism related to stochastic noises due to the effectiveness level of the adapted measures. In this paper, we propose a delayed stochastic mathematical model to predict the epidemiological trend of COVID-19 in Morocco after the deconfinement. To ensure the well-posedness of the model, we prove the existence and uniqueness of a positive solution. Based on the large number theorem for martingales, we discuss the extinction of the disease under an appropriate threshold parameter. Moreover, numerical simulations are performed in order to test the efficiency of the deconfinement strategies chosen by the Moroccan authorities to help the policy makers and public health administration to make suitable decisions in the near future.
2006.11036
Friedrich Schuessler
Friedrich Schuessler, Francesca Mastrogiuseppe, Alexis Dubreuil, Srdjan Ostojic, Omri Barak
The interplay between randomness and structure during learning in RNNs
Presented at Neurips 2020
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Recurrent neural networks (RNNs) trained on low-dimensional tasks have been widely used to model functional biological networks. However, the solutions found by learning and the effect of initial connectivity are not well understood. Here, we examine RNNs trained using gradient descent on different tasks inspired by the neuroscience literature. We find that the changes in recurrent connectivity can be described by low-rank matrices, despite the unconstrained nature of the learning algorithm. To identify the origin of the low-rank structure, we turn to an analytically tractable setting: training a linear RNN on a simplified task. We show how the low-dimensional task structure leads to low-rank changes to connectivity. This low-rank structure allows us to explain and quantify the phenomenon of accelerated learning in the presence of random initial connectivity. Altogether, our study opens a new perspective to understanding trained RNNs in terms of both the learning process and the resulting network structure.
[ { "created": "Fri, 19 Jun 2020 09:40:19 GMT", "version": "v1" }, { "created": "Sun, 25 Oct 2020 17:57:31 GMT", "version": "v2" }, { "created": "Tue, 16 Mar 2021 13:18:02 GMT", "version": "v3" }, { "created": "Thu, 13 May 2021 19:14:49 GMT", "version": "v4" } ]
2021-05-17
[ [ "Schuessler", "Friedrich", "" ], [ "Mastrogiuseppe", "Francesca", "" ], [ "Dubreuil", "Alexis", "" ], [ "Ostojic", "Srdjan", "" ], [ "Barak", "Omri", "" ] ]
Recurrent neural networks (RNNs) trained on low-dimensional tasks have been widely used to model functional biological networks. However, the solutions found by learning and the effect of initial connectivity are not well understood. Here, we examine RNNs trained using gradient descent on different tasks inspired by the neuroscience literature. We find that the changes in recurrent connectivity can be described by low-rank matrices, despite the unconstrained nature of the learning algorithm. To identify the origin of the low-rank structure, we turn to an analytically tractable setting: training a linear RNN on a simplified task. We show how the low-dimensional task structure leads to low-rank changes to connectivity. This low-rank structure allows us to explain and quantify the phenomenon of accelerated learning in the presence of random initial connectivity. Altogether, our study opens a new perspective to understanding trained RNNs in terms of both the learning process and the resulting network structure.
1706.10145
Alexander L\"uck
Alexander L\"uck, Pascal Giehr, J\"orn Walter, Verena Wolf
A Stochastic Model for the Formation of Spatial Methylation Patterns
18 pages, 7 figures, content of former appendix now included in the main part; accepted by 15th International Conference on Computational Methods in Systems Biology (CMSB), 2017
null
null
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
DNA methylation is an epigenetic mechanism whose important role in development has been widely recognized. This epigenetic modification results in heritable changes in gene expression not encoded by the DNA sequence. The underlying mechanisms controlling DNA methylation are only partly understood and recently different mechanistic models of enzyme activities responsible for DNA methylation have been proposed. Here we extend existing Hidden Markov Models (HMMs) for DNA methylation by describing the occurrence of spatial methylation patterns over time and propose several models with different neighborhood dependencies. We perform numerical analysis of the HMMs applied to bisulfite sequencing measurements and accurately predict wild-type data. In addition, we find evidence that the enzymes' activities depend on the left 5' neighborhood but not on the right 3' neighborhood.
[ { "created": "Fri, 30 Jun 2017 11:44:06 GMT", "version": "v1" }, { "created": "Mon, 10 Jul 2017 07:37:49 GMT", "version": "v2" } ]
2017-07-11
[ [ "Lück", "Alexander", "" ], [ "Giehr", "Pascal", "" ], [ "Walter", "Jörn", "" ], [ "Wolf", "Verena", "" ] ]
DNA methylation is an epigenetic mechanism whose important role in development has been widely recognized. This epigenetic modification results in heritable changes in gene expression not encoded by the DNA sequence. The underlying mechanisms controlling DNA methylation are only partly understood and recently different mechanistic models of enzyme activities responsible for DNA methylation have been proposed. Here we extend existing Hidden Markov Models (HMMs) for DNA methylation by describing the occurrence of spatial methylation patterns over time and propose several models with different neighborhood dependencies. We perform numerical analysis of the HMMs applied to bisulfite sequencing measurements and accurately predict wild-type data. In addition, we find evidence that the enzymes' activities depend on the left 5' neighborhood but not on the right 3' neighborhood.
2004.12503
Arturo Sanchez-Lorenzo
Arturo Sanchez-Lorenzo, Javier Vaquero-Mart\'inez, Josep Calb\'o, Martin Wild, Ana Santurt\'un, Joan-A. Lopez-Bustins, Jose-M. Vaquero, Doris Folini, Manuel Ant\'on
Anomalous atmospheric circulation favored the spread of COVID-19 in Europe
22 pages, 4 figures, Supplementary Information with 8 figures
null
null
null
q-bio.PE physics.ao-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The current pandemic caused by the coronavirus SARS-CoV-2 is having negative health, social and economic consequences worldwide. In Europe, the pandemic started to develop strongly at the end of February and beginning of March 2020. It has subsequently spread over the continent, with special virulence in northern Italy and inland Spain. In this study we show that an unusual persistent anticyclonic situation prevailing in southwestern Europe during February 2020 (i.e. anomalously strong positive phase of the North Atlantic and Arctic Oscillations) could have resulted in favorable conditions, in terms of air temperature and humidity, in Italy and Spain for a quicker spread of the virus compared with the rest of the European countries. It seems plausible that the strong atmospheric stability and associated dry conditions that dominated in these regions may have favored the virus's propagation, by short-range droplet transmission as well as likely by long-range aerosol (airborne) transmission.
[ { "created": "Sun, 26 Apr 2020 23:23:36 GMT", "version": "v1" } ]
2020-04-28
[ [ "Sanchez-Lorenzo", "Arturo", "" ], [ "Vaquero-Martínez", "Javier", "" ], [ "Calbó", "Josep", "" ], [ "Wild", "Martin", "" ], [ "Santurtún", "Ana", "" ], [ "Lopez-Bustins", "Joan-A.", "" ], [ "Vaquero", "Jose-M.", "" ], [ "Folini", "Doris", "" ], [ "Antón", "Manuel", "" ] ]
The current pandemic caused by the coronavirus SARS-CoV-2 is having negative health, social and economic consequences worldwide. In Europe, the pandemic started to develop strongly at the end of February and beginning of March 2020. It has subsequently spread over the continent, with special virulence in northern Italy and inland Spain. In this study we show that an unusual persistent anticyclonic situation prevailing in southwestern Europe during February 2020 (i.e. anomalously strong positive phase of the North Atlantic and Arctic Oscillations) could have resulted in favorable conditions, in terms of air temperature and humidity, in Italy and Spain for a quicker spread of the virus compared with the rest of the European countries. It seems plausible that the strong atmospheric stability and associated dry conditions that dominated in these regions may have favored the virus's propagation, by short-range droplet transmission as well as likely by long-range aerosol (airborne) transmission.
1602.00776
Pan-Jun Kim
Mathias Foo, David E. Somers, Pan-Jun Kim
Kernel Architecture of the Genetic Circuitry of the Arabidopsis Circadian System
Supplementary material is available at the journal website
PLoS Comput. Biol. 12, e1004748 (2016)
10.1371/journal.pcbi.1004748
null
q-bio.MN physics.bio-ph q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A wide range of organisms features molecular machines, circadian clocks, which generate endogenous oscillations with ~24 h periodicity and thereby synchronize biological processes to diurnal environmental fluctuations. Recently, it has become clear that plants harbor more complex gene regulatory circuits within the core circadian clocks than other organisms, inspiring a fundamental question: are all these regulatory interactions between clock genes equally crucial for the establishment and maintenance of circadian rhythms? Our mechanistic simulation for Arabidopsis thaliana demonstrates that at least half of the total regulatory interactions must be present to express the circadian molecular profiles observed in wild-type plants. A set of those essential interactions is called herein a kernel of the circadian system. The kernel structure unbiasedly reveals four interlocked negative feedback loops contributing to circadian rhythms, and three feedback loops among them drive the autonomous oscillation itself. Strikingly, the kernel structure, as well as the whole clock circuitry, is overwhelmingly composed of inhibitory, rather than activating, interactions between genes. We found that this tendency underlies plant circadian molecular profiles which often exhibit sharply-shaped, cuspidate waveforms. Through the generation of these cuspidate profiles, inhibitory interactions may facilitate the global coordination of temporally-distant clock events that are markedly peaked at very specific times of day. Our systematic approach resulting in experimentally-testable predictions provides insights into a design principle of biological clockwork, with implications for synthetic biology.
[ { "created": "Tue, 2 Feb 2016 03:24:24 GMT", "version": "v1" } ]
2016-02-03
[ [ "Foo", "Mathias", "" ], [ "Somers", "David E.", "" ], [ "Kim", "Pan-Jun", "" ] ]
A wide range of organisms features molecular machines, circadian clocks, which generate endogenous oscillations with ~24 h periodicity and thereby synchronize biological processes to diurnal environmental fluctuations. Recently, it has become clear that plants harbor more complex gene regulatory circuits within the core circadian clocks than other organisms, inspiring a fundamental question: are all these regulatory interactions between clock genes equally crucial for the establishment and maintenance of circadian rhythms? Our mechanistic simulation for Arabidopsis thaliana demonstrates that at least half of the total regulatory interactions must be present to express the circadian molecular profiles observed in wild-type plants. A set of those essential interactions is called herein a kernel of the circadian system. The kernel structure unbiasedly reveals four interlocked negative feedback loops contributing to circadian rhythms, and three feedback loops among them drive the autonomous oscillation itself. Strikingly, the kernel structure, as well as the whole clock circuitry, is overwhelmingly composed of inhibitory, rather than activating, interactions between genes. We found that this tendency underlies plant circadian molecular profiles which often exhibit sharply-shaped, cuspidate waveforms. Through the generation of these cuspidate profiles, inhibitory interactions may facilitate the global coordination of temporally-distant clock events that are markedly peaked at very specific times of day. Our systematic approach resulting in experimentally-testable predictions provides insights into a design principle of biological clockwork, with implications for synthetic biology.
2207.02314
Lucas Flores
Lucas S. Flores, Marco A. Amaral, Mendeli H. Vainstein, Heitor C. M. Fernandes
Cooperation in regular lattices
null
null
10.1016/j.chaos.2022.112744
null
q-bio.PE cond-mat.stat-mech physics.comp-ph physics.soc-ph
http://creativecommons.org/licenses/by/4.0/
In the context of Evolutionary Game Theory, one of the most noteworthy mechanisms to support cooperation is spatial reciprocity, usually accomplished by distributing players in a spatial structure allowing cooperators to cluster together and avoid exploitation. This raises an important question: how is the survival of cooperation affected by different topologies? Here, to address this question, we explore the Focal Public Goods (FPGG) and classic Public Goods Games (PGG), and the Prisoner's Dilemma (PD) on several regular lattices: honeycomb, square (with von Neumann and Moore neighborhoods), kagome, triangular, cubic, and 4D hypercubic lattices using both analytical methods and agent-based Monte Carlo simulations. We found that for both Public Goods Games, a consistent trend appears on all two-dimensional lattices: as the number of first neighbors increases, cooperation is enhanced. However, this is only visible by analysing the results in terms of the payoff's synergistic factor normalized by the number of connections. Besides this, clustered topologies, i.e., those that allow two connected players to share neighbors, are the most beneficial to cooperation for the FPGG. The same is not always true for the classic PGG, where having shared neighbors between connected players may or may not benefit cooperation. We also provide a reinterpretation of the classic PGG as a focal game by representing the lattice structure of this category of games as a single interaction game with longer-ranged, weighted neighborhoods, an approach valid for any regular lattice topology. Finally, we show that depending on the payoff parametrization of the PD, there can be an equivalency between the PD and the FPGG; when the mapping between the two games is imperfect, the definition of an effective synergy parameter can still be useful to show their similarities.
[ { "created": "Tue, 5 Jul 2022 21:05:25 GMT", "version": "v1" } ]
2022-10-12
[ [ "Flores", "Lucas S.", "" ], [ "Amaral", "Marco A.", "" ], [ "Vainstein", "Mendeli H.", "" ], [ "Fernandes", "Heitor C. M.", "" ] ]
In the context of Evolutionary Game Theory, one of the most noteworthy mechanisms to support cooperation is spatial reciprocity, usually accomplished by distributing players in a spatial structure allowing cooperators to cluster together and avoid exploitation. This raises an important question: how is the survival of cooperation affected by different topologies? Here, to address this question, we explore the Focal Public Goods (FPGG) and classic Public Goods Games (PGG), and the Prisoner's Dilemma (PD) on several regular lattices: honeycomb, square (with von Neumann and Moore neighborhoods), kagome, triangular, cubic, and 4D hypercubic lattices using both analytical methods and agent-based Monte Carlo simulations. We found that for both Public Goods Games, a consistent trend appears on all two-dimensional lattices: as the number of first neighbors increases, cooperation is enhanced. However, this is only visible by analysing the results in terms of the payoff's synergistic factor normalized by the number of connections. Besides this, clustered topologies, i.e., those that allow two connected players to share neighbors, are the most beneficial to cooperation for the FPGG. The same is not always true for the classic PGG, where having shared neighbors between connected players may or may not benefit cooperation. We also provide a reinterpretation of the classic PGG as a focal game by representing the lattice structure of this category of games as a single interaction game with longer-ranged, weighted neighborhoods, an approach valid for any regular lattice topology. Finally, we show that depending on the payoff parametrization of the PD, there can be an equivalency between the PD and the FPGG; when the mapping between the two games is imperfect, the definition of an effective synergy parameter can still be useful to show their similarities.
q-bio/0405025
Mark Ya. Azbel'
Mark Ya. Azbel'
Universal Mortality Law, Life Expectancy and Immortality
null
null
10.1016/j.physa.2004.06.065
null
q-bio.PE q-bio.QM
null
Well protected human and laboratory animal populations with abundant resources are evolutionary unprecedented, and their survival far beyond reproductive age may be a byproduct rather than tool of evolution. Physical approach, which takes advantage of their extensively quantified mortality, establishes that its dominant fraction yields the exact law, and suggests its unusual mechanism. The law is universal for all animals, from yeast to humans, despite their drastically different biology and evolution. It predicts that the universal mortality has short memory of the life history, at any age may be reset to its value at a significantly younger age, and mean life expectancy extended (by biologically unprecedented small changes) from its current maximal value to immortality. Mortality change is rapid and stepwise. Demographic data and recent experiments verify these predictions for humans, rats, flies, nematodes and yeast. In particular, mean life expectancy increased 6-fold (to "human" 430 years), with no apparent loss in health and vitality, in nematodes with a small number of perturbed genes and tissues. Universality allows one to study unusual mortality mechanism and the ways to immortality.
[ { "created": "Sat, 29 May 2004 08:22:02 GMT", "version": "v1" }, { "created": "Tue, 1 Jun 2004 20:51:11 GMT", "version": "v2" } ]
2015-06-26
[ [ "Azbel'", "Mark Ya.", "" ] ]
Well protected human and laboratory animal populations with abundant resources are evolutionary unprecedented, and their survival far beyond reproductive age may be a byproduct rather than tool of evolution. Physical approach, which takes advantage of their extensively quantified mortality, establishes that its dominant fraction yields the exact law, and suggests its unusual mechanism. The law is universal for all animals, from yeast to humans, despite their drastically different biology and evolution. It predicts that the universal mortality has short memory of the life history, at any age may be reset to its value at a significantly younger age, and mean life expectancy extended (by biologically unprecedented small changes) from its current maximal value to immortality. Mortality change is rapid and stepwise. Demographic data and recent experiments verify these predictions for humans, rats, flies, nematodes and yeast. In particular, mean life expectancy increased 6-fold (to "human" 430 years), with no apparent loss in health and vitality, in nematodes with a small number of perturbed genes and tissues. Universality allows one to study unusual mortality mechanism and the ways to immortality.
1907.00849
R\'obert Juh\'asz
R. Juh\'asz, I. A. Kov\'acs
Population boundary across an environmental gradient: Effects of quenched disorder
13 pages, 14 figures
Phys. Rev. Research 2, 013123 (2020)
10.1103/PhysRevResearch.2.013123
null
q-bio.PE cond-mat.dis-nn cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Population boundary is a classic indicator of climatic response in ecology. In addition to known challenges, the spatial and dynamical characteristics of the boundary are not only affected by the spatial gradient in the environmental factors, but also by local heterogeneities in the regional characteristics. Here, we capture the effects of quenched heterogeneities on the ecological boundary with the disordered contact process in one and two dimensions with a linear spatial trend in the local control parameter. We apply the strong-disorder renormalization group method to calculate the sites occupied with an $O(1)$ probability in the stationary state, readily yielding the population front's position as the outermost site locally as well as globally for the entire boundary. We show that under a quasistatic change of the global environment, mimicking climate change, the front advances intermittently: long quiescent periods are interrupted by rare but long jumps. The characteristics of this intermittent dynamics are found to obey universal scaling laws in terms of the gradient, conjectured to be related to the correlation-length exponent of the model. Our results suggest that current observations might misleadingly show little to no climate response for an extended period of time, concealing the long-term effects of climate change.
[ { "created": "Mon, 1 Jul 2019 15:16:34 GMT", "version": "v1" }, { "created": "Wed, 5 Feb 2020 17:02:47 GMT", "version": "v2" } ]
2020-02-06
[ [ "Juhász", "R.", "" ], [ "Kovács", "I. A.", "" ] ]
Population boundary is a classic indicator of climatic response in ecology. In addition to known challenges, the spatial and dynamical characteristics of the boundary are not only affected by the spatial gradient in the environmental factors, but also by local heterogeneities in the regional characteristics. Here, we capture the effects of quenched heterogeneities on the ecological boundary with the disordered contact process in one and two dimensions with a linear spatial trend in the local control parameter. We apply the strong-disorder renormalization group method to calculate the sites occupied with an $O(1)$ probability in the stationary state, readily yielding the population front's position as the outermost site locally as well as globally for the entire boundary. We show that under a quasistatic change of the global environment, mimicking climate change, the front advances intermittently: long quiescent periods are interrupted by rare but long jumps. The characteristics of this intermittent dynamics are found to obey universal scaling laws in terms of the gradient, conjectured to be related to the correlation-length exponent of the model. Our results suggest that current observations might misleadingly show little to no climate response for an extended period of time, concealing the long-term effects of climate change.
1010.4517
Jake Bouvrie
Jake Bouvrie, Jean-Jacques Slotine
Synchronization and Redundancy: Implications for Robustness of Neural Learning and Decision Making
Preprint, accepted for publication in Neural Computation
null
null
null
q-bio.NC cs.NE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Learning and decision making in the brain are key processes critical to survival, and yet are processes implemented by non-ideal biological building blocks which can impose significant error. We explore quantitatively how the brain might cope with this inherent source of error by taking advantage of two ubiquitous mechanisms, redundancy and synchronization. In particular we consider a neural process whose goal is to learn a decision function by implementing a nonlinear gradient dynamics. The dynamics, however, are assumed to be corrupted by perturbations modeling the error which might be incurred due to limitations of the biology, intrinsic neuronal noise, and imperfect measurements. We show that error, and the associated uncertainty surrounding a learned solution, can be controlled in large part by trading off synchronization strength among multiple redundant neural systems against the noise amplitude. The impact of the coupling between such redundant systems is quantified by the spectrum of the network Laplacian, and we discuss the role of network topology in synchronization and in reducing the effect of noise. A range of situations in which the mechanisms we model arise in brain science are discussed, and we draw attention to experimental evidence suggesting that cortical circuits capable of implementing the computations of interest here can be found on several scales. Finally, simulations comparing theoretical bounds to the relevant empirical quantities show that the theoretical estimates we derive can be tight.
[ { "created": "Thu, 21 Oct 2010 16:34:43 GMT", "version": "v1" }, { "created": "Sat, 16 Apr 2011 17:01:04 GMT", "version": "v2" } ]
2011-04-19
[ [ "Bouvrie", "Jake", "" ], [ "Slotine", "Jean-Jacques", "" ] ]
Learning and decision making in the brain are key processes critical to survival, and yet are processes implemented by non-ideal biological building blocks which can impose significant error. We explore quantitatively how the brain might cope with this inherent source of error by taking advantage of two ubiquitous mechanisms, redundancy and synchronization. In particular we consider a neural process whose goal is to learn a decision function by implementing a nonlinear gradient dynamics. The dynamics, however, are assumed to be corrupted by perturbations modeling the error which might be incurred due to limitations of the biology, intrinsic neuronal noise, and imperfect measurements. We show that error, and the associated uncertainty surrounding a learned solution, can be controlled in large part by trading off synchronization strength among multiple redundant neural systems against the noise amplitude. The impact of the coupling between such redundant systems is quantified by the spectrum of the network Laplacian, and we discuss the role of network topology in synchronization and in reducing the effect of noise. A range of situations in which the mechanisms we model arise in brain science are discussed, and we draw attention to experimental evidence suggesting that cortical circuits capable of implementing the computations of interest here can be found on several scales. Finally, simulations comparing theoretical bounds to the relevant empirical quantities show that the theoretical estimates we derive can be tight.
2106.00637
Emmanuelle Tognoli
Emmanuelle Tognoli, Daniela Benites, J. A. Scott Kelso
A Blueprint for the Study of the Brain's Spatiotemporal Patterns
null
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by-nc-nd/4.0/
The functioning of an organ such as the brain emerges from interactions between its constituent parts. Further, this interaction is not immutable in time but rather unfolds in a succession of patterns, thereby allowing the brain to adapt to constantly changing exterior and interior milieus. This calls for a framework able to study patterned spatiotemporal interactions between components of the brain. A theoretical and methodological framework is developed to study the brain's coordination dynamics. Here we present a toolset designed to decipher the continuous dynamics of electrophysiological data and its relation to (dys-) function. Understanding the spatiotemporal organization of brain patterns and their association with behavioral, cognitive and clinically-relevant variables is an important challenge for the fields of neuroscience and biologically-inspired engineering. It is hoped that such a comprehensive framework will shed light not only on human behavior and the human mind but also help in understanding the growing number of pathologies that are linked to disorders of brain connectivity.
[ { "created": "Tue, 1 Jun 2021 17:09:37 GMT", "version": "v1" } ]
2021-06-02
[ [ "Tognoli", "Emmanuelle", "" ], [ "Benites", "Daniela", "" ], [ "Kelso", "J. A. Scott", "" ] ]
The functioning of an organ such as the brain emerges from interactions between its constituent parts. Further, this interaction is not immutable in time but rather unfolds in a succession of patterns, thereby allowing the brain to adapt to constantly changing exterior and interior milieus. This calls for a framework able to study patterned spatiotemporal interactions between components of the brain. A theoretical and methodological framework is developed to study the brain's coordination dynamics. Here we present a toolset designed to decipher the continuous dynamics of electrophysiological data and its relation to (dys-) function. Understanding the spatiotemporal organization of brain patterns and their association with behavioral, cognitive and clinically-relevant variables is an important challenge for the fields of neuroscience and biologically-inspired engineering. It is hoped that such a comprehensive framework will shed light not only on human behavior and the human mind but also help in understanding the growing number of pathologies that are linked to disorders of brain connectivity.
1110.2189
Jaewook Joo
Jaewook Joo and Jinmyung Choi
Network architectural conditions for prominent and robust stochastic oscillations
5 figures
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Understanding relationship between noisy dynamics and biological network architecture is a fundamentally important question, particularly in order to elucidate how cells encode and process information. We analytically and numerically investigate general network architectural conditions that are necessary to generate stochastic amplified and coherent oscillations. We enumerate all possible topologies of coupled negative feedbacks in the underlying biochemical networks with three components, negative feedback loops, and mass action kinetics. Using the linear noise approximation to analytically obtain the time-dependent solution of the master equation and derive the algebraic expression of power spectra, we find that (a) all networks with coupled negative feedbacks are capable of generating stochastic amplified and coherent oscillations; (b) networks with a single negative feedback are better stochastic amplified and coherent oscillators than those with multiple coupled negative feedbacks; (c) multiple timescale difference among the kinetic rate constants is required for stochastic amplified and coherent oscillations.
[ { "created": "Mon, 10 Oct 2011 20:11:37 GMT", "version": "v1" } ]
2011-10-12
[ [ "Joo", "Jaewook", "" ], [ "Choi", "Jinmyung", "" ] ]
Understanding relationship between noisy dynamics and biological network architecture is a fundamentally important question, particularly in order to elucidate how cells encode and process information. We analytically and numerically investigate general network architectural conditions that are necessary to generate stochastic amplified and coherent oscillations. We enumerate all possible topologies of coupled negative feedbacks in the underlying biochemical networks with three components, negative feedback loops, and mass action kinetics. Using the linear noise approximation to analytically obtain the time-dependent solution of the master equation and derive the algebraic expression of power spectra, we find that (a) all networks with coupled negative feedbacks are capable of generating stochastic amplified and coherent oscillations; (b) networks with a single negative feedback are better stochastic amplified and coherent oscillators than those with multiple coupled negative feedbacks; (c) multiple timescale difference among the kinetic rate constants is required for stochastic amplified and coherent oscillations.
2212.07747
Paul Jenkins
Robert C. Griffiths and Paul A. Jenkins
An estimator for the recombination rate from a continuously observed diffusion of haplotype frequencies
28 pages, 3 figures
null
null
null
q-bio.PE math.PR math.ST stat.TH
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Recombination is a fundamental evolutionary force, but it is difficult to quantify because the effect of a recombination event on patterns of variation in a sample of genetic data can be hard to discern. Estimators for the recombination rate, which are usually based on the idea of integrating over the unobserved possible evolutionary histories of a sample, can therefore be noisy. Here we consider a related question: how would an estimator behave if the evolutionary history actually was observed? This would offer an upper bound on the performance of estimators used in practice. In this paper we derive an expression for the maximum likelihood estimator for the recombination rate based on a continuously observed, multi-locus, Wright--Fisher diffusion of haplotype frequencies, complementing existing work for an estimator of selection. We show that, contrary to selection, the estimator has unusual properties because the observed information matrix can explode in finite time whereupon the recombination parameter is learned without error. We also show that the recombination estimator is robust to the presence of selection in the sense that incorporating selection into the model leaves the estimator unchanged. We study the properties of the estimator by simulation and show that its distribution can be quite sensitive to the underlying mutation rates.
[ { "created": "Thu, 15 Dec 2022 11:59:30 GMT", "version": "v1" }, { "created": "Thu, 4 May 2023 07:53:47 GMT", "version": "v2" } ]
2023-05-05
[ [ "Griffiths", "Robert C.", "" ], [ "Jenkins", "Paul A.", "" ] ]
Recombination is a fundamental evolutionary force, but it is difficult to quantify because the effect of a recombination event on patterns of variation in a sample of genetic data can be hard to discern. Estimators for the recombination rate, which are usually based on the idea of integrating over the unobserved possible evolutionary histories of a sample, can therefore be noisy. Here we consider a related question: how would an estimator behave if the evolutionary history actually was observed? This would offer an upper bound on the performance of estimators used in practice. In this paper we derive an expression for the maximum likelihood estimator for the recombination rate based on a continuously observed, multi-locus, Wright--Fisher diffusion of haplotype frequencies, complementing existing work for an estimator of selection. We show that, contrary to selection, the estimator has unusual properties because the observed information matrix can explode in finite time whereupon the recombination parameter is learned without error. We also show that the recombination estimator is robust to the presence of selection in the sense that incorporating selection into the model leaves the estimator unchanged. We study the properties of the estimator by simulation and show that its distribution can be quite sensitive to the underlying mutation rates.
2110.03518
Johannes Kleiner
Johannes Kleiner, Stephan Hartmann
The Closure of the Physical, Consciousness and Scientific Practice
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We analyse the implications of the closure of the physical for experiments in the scientific study of consciousness when all the details are considered, especially how measurement results relate to physical events. It turns out that the closure of the physical has surprising implications that conflict with scientific practice. These implications point to a fundamental flaw in the paradigm underlying many experiments conducted to date and pose a challenge to any research programme that aims to ground a physical functionalist or identity-based understanding of consciousness on empirical observations.
[ { "created": "Fri, 24 Sep 2021 14:26:18 GMT", "version": "v1" }, { "created": "Sun, 5 Feb 2023 18:26:41 GMT", "version": "v2" } ]
2023-02-07
[ [ "Kleiner", "Johannes", "" ], [ "Hartmann", "Stephan", "" ] ]
We analyse the implications of the closure of the physical for experiments in the scientific study of consciousness when all the details are considered, especially how measurement results relate to physical events. It turns out that the closure of the physical has surprising implications that conflict with scientific practice. These implications point to a fundamental flaw in the paradigm underlying many experiments conducted to date and pose a challenge to any research programme that aims to ground a physical functionalist or identity-based understanding of consciousness on empirical observations.
1708.02967
Daniel Toker
Daniel Toker and Friedrich T. Sommer
Information Integration In Large Brain Networks
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
An outstanding problem in neuroscience is to understand how information is integrated across the many modules of the brain. While classic information-theoretic measures have transformed our understanding of feedforward information processing in the brain's sensory periphery, comparable measures for information flow in the massively recurrent networks of the rest of the brain have been lacking. To address this, recent work in information theory has produced a sound measure of network-wide "integrated information," which can be estimated from time-series data. But, a computational hurdle has stymied attempts to measure large-scale information integration in real brains. Specifically, the measurement of integrated information involves a combinatorial search for the informational "weakest link" of a network, a process whose computation time explodes super-exponentially with network size. Here, we show that spectral clustering, applied on the correlation matrix of time-series data, provides an approximate but robust solution to the search for the the informational weakest link of large networks. This reduces the computation time for integrated information in large systems from longer than the lifespan of the universe to just minutes. We evaluate this solution in brain-like systems of coupled oscillators as well as in high-density electrocortigraphy data from two macaque monkeys, and show that the informational "weakest link" of the monkey cortex splits posterior sensory areas from anterior association areas. Finally, we use our solution to provide evidence in support of the long-standing hypothesis that information integration is maximized by networks with a high global efficiency, and that modular network structures promote the segregation of information.
[ { "created": "Wed, 9 Aug 2017 18:37:54 GMT", "version": "v1" }, { "created": "Tue, 23 Jan 2018 21:26:58 GMT", "version": "v2" }, { "created": "Fri, 8 Feb 2019 21:16:03 GMT", "version": "v3" } ]
2019-02-12
[ [ "Toker", "Daniel", "" ], [ "Sommer", "Friedrich T.", "" ] ]
An outstanding problem in neuroscience is to understand how information is integrated across the many modules of the brain. While classic information-theoretic measures have transformed our understanding of feedforward information processing in the brain's sensory periphery, comparable measures for information flow in the massively recurrent networks of the rest of the brain have been lacking. To address this, recent work in information theory has produced a sound measure of network-wide "integrated information," which can be estimated from time-series data. But, a computational hurdle has stymied attempts to measure large-scale information integration in real brains. Specifically, the measurement of integrated information involves a combinatorial search for the informational "weakest link" of a network, a process whose computation time explodes super-exponentially with network size. Here, we show that spectral clustering, applied on the correlation matrix of time-series data, provides an approximate but robust solution to the search for the the informational weakest link of large networks. This reduces the computation time for integrated information in large systems from longer than the lifespan of the universe to just minutes. We evaluate this solution in brain-like systems of coupled oscillators as well as in high-density electrocortigraphy data from two macaque monkeys, and show that the informational "weakest link" of the monkey cortex splits posterior sensory areas from anterior association areas. Finally, we use our solution to provide evidence in support of the long-standing hypothesis that information integration is maximized by networks with a high global efficiency, and that modular network structures promote the segregation of information.
1405.2120
Christopher Whidden
Christopher Whidden and Frederick A. Matsen IV
Quantifying MCMC Exploration of Phylogenetic Tree Space
62 pages, 17 figures; revised in response to peer review
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In order to gain an understanding of the effectiveness of phylogenetic Markov chain Monte Carlo (MCMC), it is important to understand how quickly the empirical distribution of the MCMC converges to the posterior distribution. In this paper we investigate this problem on phylogenetic tree topologies with a metric that is especially well suited to the task: the subtree prune-and-regraft (SPR) metric. This metric directly corresponds to the minimum number of MCMC rearrangements required to move between trees in common phylogenetic MCMC implementations. We develop a novel graph-based approach to analyze tree posteriors and find that the SPR metric is much more informative than simpler metrics that are unrelated to MCMC moves. In doing so we show conclusively that topological peaks do occur in Bayesian phylogenetic posteriors from real data sets as sampled with standard MCMC approaches, investigate the efficiency of Metropolis-coupled MCMC (MCMCMC) in traversing the valleys between peaks, and show that conditional clade distribution (CCD) can have systematic problems when there are multiple peaks.
[ { "created": "Thu, 8 May 2014 23:03:35 GMT", "version": "v1" }, { "created": "Fri, 17 Oct 2014 17:56:04 GMT", "version": "v2" } ]
2014-10-20
[ [ "Whidden", "Christopher", "" ], [ "Matsen", "Frederick A.", "IV" ] ]
In order to gain an understanding of the effectiveness of phylogenetic Markov chain Monte Carlo (MCMC), it is important to understand how quickly the empirical distribution of the MCMC converges to the posterior distribution. In this paper we investigate this problem on phylogenetic tree topologies with a metric that is especially well suited to the task: the subtree prune-and-regraft (SPR) metric. This metric directly corresponds to the minimum number of MCMC rearrangements required to move between trees in common phylogenetic MCMC implementations. We develop a novel graph-based approach to analyze tree posteriors and find that the SPR metric is much more informative than simpler metrics that are unrelated to MCMC moves. In doing so we show conclusively that topological peaks do occur in Bayesian phylogenetic posteriors from real data sets as sampled with standard MCMC approaches, investigate the efficiency of Metropolis-coupled MCMC (MCMCMC) in traversing the valleys between peaks, and show that conditional clade distribution (CCD) can have systematic problems when there are multiple peaks.
2407.15322
Daniel Packwood Dr
Fatemeh Etezadi, Shunichi Ito, Kosuke Yasui, Rodi Kado Abdalkader, Itsunari Minami, Motonari Uesugi, Ganesh Pandian Namasivayam, Haruko Nakano, Atsushi Nakano, Daniel M. Packwood
Molecular design for cardiac cell differentiation using a small dataset and decorated shape features
26 pages (main paper), including 7 figures and 3 tables. 23 pages of supporting information. To be submitted to a journal
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by/4.0/
The discovery of small organic compounds for inducing stem cell differentiation is a time- and resource-intensive process. While data science could, in principle, facilitate the discovery of these compounds, novel approaches are required due to the difficulty of acquiring training data from large numbers of example compounds. In this paper, we demonstrate the design of a new compound for inducing cardiomyocyte differentiation using simple regression models trained with a data set containing only 80 examples. We introduce decorated shape descriptors, an information-rich molecular feature representation that integrates both molecular shape and hydrophilicity information. These models demonstrate improved performance compared to ones using standard molecular descriptors based on shape alone. Model overtraining is diagnosed using a new type of sensitivity analysis. Our new compound is designed using a conservative molecular design strategy, and its effectiveness is confirmed through expression profiles of cardiomyocyte-related marker genes using real-time polymerase chain reaction experiments on human iPS cell lines. This work demonstrates a viable data-driven strategy for designing new compounds for stem cell differentiation protocols and will be useful in situations where training data is limited.
[ { "created": "Mon, 22 Jul 2024 01:31:29 GMT", "version": "v1" } ]
2024-07-23
[ [ "Etezadi", "Fatemeh", "" ], [ "Ito", "Shunichi", "" ], [ "Yasui", "Kosuke", "" ], [ "Abdalkader", "Rodi Kado", "" ], [ "Minami", "Itsunari", "" ], [ "Uesugi", "Motonari", "" ], [ "Namasivayam", "Ganesh Pandian", "" ], [ "Nakano", "Haruko", "" ], [ "Nakano", "Atsushi", "" ], [ "Packwood", "Daniel M.", "" ] ]
The discovery of small organic compounds for inducing stem cell differentiation is a time- and resource-intensive process. While data science could, in principle, facilitate the discovery of these compounds, novel approaches are required due to the difficulty of acquiring training data from large numbers of example compounds. In this paper, we demonstrate the design of a new compound for inducing cardiomyocyte differentiation using simple regression models trained with a data set containing only 80 examples. We introduce decorated shape descriptors, an information-rich molecular feature representation that integrates both molecular shape and hydrophilicity information. These models demonstrate improved performance compared to ones using standard molecular descriptors based on shape alone. Model overtraining is diagnosed using a new type of sensitivity analysis. Our new compound is designed using a conservative molecular design strategy, and its effectiveness is confirmed through expression profiles of cardiomyocyte-related marker genes using real-time polymerase chain reaction experiments on human iPS cell lines. This work demonstrates a viable data-driven strategy for designing new compounds for stem cell differentiation protocols and will be useful in situations where training data is limited.
q-bio/0601047
Thomas R. Weikl
Purushottam D. Dixit and Thomas R. Weikl
A simple measure of native-state topology and chain connectivity predicts the folding rates of two-state proteins with and without crosslinks
13 pages, 2 tables, and 2 figures
null
null
null
q-bio.BM cond-mat.soft
null
The folding rates of two-state proteins have been found to correlate with simple measures of native-state topology. The most prominent among these measures is the relative contact order (CO), which is the average CO or 'localness' of all contacts in the native protein structure, divided by the chain length. Here, we test whether such measures can be generalized to capture the effect of chain crosslinks on the folding rate. Crosslinks change the chain connectivity and therefore also the localness of some of the the native contacts. These changes in localness can be taken into account by the graph-theoretical concept of effective contact order (ECO). The relative ECO, however, the natural extension of the relative CO for proteins with crosslinks, overestimates the changes in the folding rates caused by crosslinks. We suggest here a novel measure of native-state topology, the relative logCO, and its natural extension, the relative logECO. The relative logCO is the average value for the logarithm of the CO of all contacts, divided by the logarithm of the chain length. The relative log(E)CO reproduces the folding rates of a set of 26 two-state proteins without crosslinks with essentially the same high correlation coefficient as the relative CO. In addition, it also captures the folding rates of 8 two-state proteins with crosslinks.
[ { "created": "Sat, 28 Jan 2006 17:38:26 GMT", "version": "v1" } ]
2007-05-23
[ [ "Dixit", "Purushottam D.", "" ], [ "Weikl", "Thomas R.", "" ] ]
The folding rates of two-state proteins have been found to correlate with simple measures of native-state topology. The most prominent among these measures is the relative contact order (CO), which is the average CO or 'localness' of all contacts in the native protein structure, divided by the chain length. Here, we test whether such measures can be generalized to capture the effect of chain crosslinks on the folding rate. Crosslinks change the chain connectivity and therefore also the localness of some of the the native contacts. These changes in localness can be taken into account by the graph-theoretical concept of effective contact order (ECO). The relative ECO, however, the natural extension of the relative CO for proteins with crosslinks, overestimates the changes in the folding rates caused by crosslinks. We suggest here a novel measure of native-state topology, the relative logCO, and its natural extension, the relative logECO. The relative logCO is the average value for the logarithm of the CO of all contacts, divided by the logarithm of the chain length. The relative log(E)CO reproduces the folding rates of a set of 26 two-state proteins without crosslinks with essentially the same high correlation coefficient as the relative CO. In addition, it also captures the folding rates of 8 two-state proteins with crosslinks.
2203.13946
Alexandra Lee
Alexandra J. Lee, Taylor Reiter, Georgia Doing, Julia Oh, Deborah A. Hogan, Casey S. Greene
Using genome-wide expression compendia to study microorganisms
null
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
A gene expression compendium is a heterogeneous collection of gene expression experiments assembled from data collected for diverse purposes. The widely varied experimental conditions and genetic backgrounds across samples creates a tremendous opportunity for gaining a systems level understanding of the transcriptional responses that influence phenotypes. Variety in experimental design is particularly important for studying microbes, where the transcriptional responses integrate many signals and demonstrate plasticity across strains including response to what nutrients are available and what microbes are present. Advances in high-throughput measurement technology have made it feasible to construct compendia for many microbes. In this review we discuss how these compendia are constructed and analyzed to reveal transcriptional patterns.
[ { "created": "Sat, 26 Mar 2022 00:16:27 GMT", "version": "v1" } ]
2022-03-29
[ [ "Lee", "Alexandra J.", "" ], [ "Reiter", "Taylor", "" ], [ "Doing", "Georgia", "" ], [ "Oh", "Julia", "" ], [ "Hogan", "Deborah A.", "" ], [ "Greene", "Casey S.", "" ] ]
A gene expression compendium is a heterogeneous collection of gene expression experiments assembled from data collected for diverse purposes. The widely varied experimental conditions and genetic backgrounds across samples creates a tremendous opportunity for gaining a systems level understanding of the transcriptional responses that influence phenotypes. Variety in experimental design is particularly important for studying microbes, where the transcriptional responses integrate many signals and demonstrate plasticity across strains including response to what nutrients are available and what microbes are present. Advances in high-throughput measurement technology have made it feasible to construct compendia for many microbes. In this review we discuss how these compendia are constructed and analyzed to reveal transcriptional patterns.
1102.3342
Mateusz Sikora
Lukasz Peplowski, Mateusz Sikora, Wieslaw Nowak and Marek Cieplak
Molecular jamming - the cystine slipknot mechanical clamp in all-atom simulations
null
null
10.1063/1.3553801
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A recent survey of 17 134 proteins has identified a new class of proteins which are expected to yield stretching induced force-peaks in the range of 1 nN. Such high force peaks should be due to forcing of a slip-loop through a cystine ring, i.e. by generating a cystine slipknot. The survey has been performed in a simple coarse grained model. Here, we perform all-atom steered molecular dynamics simulations on 15 cystine knot proteins and determine their resistance to stretching. In agreement with previous studies within a coarse grained structure based model, the level of resistance is found to be substantially higher than in proteins in which the mechanical clamp operates through shear. The large stretching forces arise through formation of the cystine slipknot mechanical clamp and the resulting steric jamming. We elucidate the workings of such a clamp in an atomic detail. We also study the behavior of five top strength proteins with the shear-based mechanostability in which no jamming is involved. We show that in the atomic model, the jamming state is relieved by moving one amino acid at a time and there is a choice in the selection of the amino acid that advances the first. In contrast, the coarse grained model also allows for a simultaneous passage of two amino acids.
[ { "created": "Wed, 16 Feb 2011 14:13:28 GMT", "version": "v1" } ]
2015-05-27
[ [ "Peplowski", "Lukasz", "" ], [ "Sikora", "Mateusz", "" ], [ "Nowak", "Wieslaw", "" ], [ "Cieplak", "Marek", "" ] ]
A recent survey of 17 134 proteins has identified a new class of proteins which are expected to yield stretching induced force-peaks in the range of 1 nN. Such high force peaks should be due to forcing of a slip-loop through a cystine ring, i.e. by generating a cystine slipknot. The survey has been performed in a simple coarse grained model. Here, we perform all-atom steered molecular dynamics simulations on 15 cystine knot proteins and determine their resistance to stretching. In agreement with previous studies within a coarse grained structure based model, the level of resistance is found to be substantially higher than in proteins in which the mechanical clamp operates through shear. The large stretching forces arise through formation of the cystine slipknot mechanical clamp and the resulting steric jamming. We elucidate the workings of such a clamp in an atomic detail. We also study the behavior of five top strength proteins with the shear-based mechanostability in which no jamming is involved. We show that in the atomic model, the jamming state is relieved by moving one amino acid at a time and there is a choice in the selection of the amino acid that advances the first. In contrast, the coarse grained model also allows for a simultaneous passage of two amino acids.
1209.2911
Shi Huang
Dejian Yuan, Zuobin Zhu, Xiaohua Tan, Jie Liang, Ceng Zeng, Jiegen Zhang, Jun Chen, Long Ma, Ayca Dogan, Gudrun Brockmann, Oliver Goldmann, Eva Medina, Amanda D. Rice, Richard W. Moyer, Xian Man, Ke Yi, Yanke Li, Qing Lu, Yimin Huang, Dapeng Wang, Jun Yu, Hui Guo, Kun Xia, and Shi Huang
Methods for scoring the collective effect of SNPs: Minor alleles of common SNPs quantitatively affect traits/diseases and are under both positive and negative selection
null
Sci China Life Sci. 57:876-888. (2014)
10.1007/s11427-014-4704-4
null
q-bio.GN q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Most common SNPs are popularly assumed to be neutral. We here developed novel methods to examine in animal models and humans whether extreme amount of minor alleles (MAs) carried by an individual may represent extreme trait values and common diseases. We analyzed panels of genetic reference populations and identified the MAs in each panel and the MA content (MAC) that each strain carried. We also analyzed 21 published GWAS datasets of human diseases and identified the MAC of each case or control. MAC was nearly linearly linked to quantitative variations in numerous traits in model organisms, including life span, tumor susceptibility, learning and memory, sensitivity to alcohol and anti-psychotic drugs, and two correlated traits poor reproductive fitness and strong immunity. Similarly, in Europeans or European Americans, enrichment of MAs of fast but not slow evolutionary rate was linked to autoimmune and numerous other diseases, including type 2 diabetes, Parkinson's disease, psychiatric disorders, alcohol and cocaine addictions, cancer, and less life span. Therefore, both high and low MAC correlated with extreme values in many traits, indicating stabilizing selection on most MAs. The methods here are broadly applicable and may help solve the missing heritability problem in complex traits and diseases.
[ { "created": "Wed, 12 Sep 2012 06:30:22 GMT", "version": "v1" }, { "created": "Tue, 16 Jul 2013 02:17:45 GMT", "version": "v2" } ]
2019-04-04
[ [ "Yuan", "Dejian", "" ], [ "Zhu", "Zuobin", "" ], [ "Tan", "Xiaohua", "" ], [ "Liang", "Jie", "" ], [ "Zeng", "Ceng", "" ], [ "Zhang", "Jiegen", "" ], [ "Chen", "Jun", "" ], [ "Ma", "Long", "" ], [ "Dogan", "Ayca", "" ], [ "Brockmann", "Gudrun", "" ], [ "Goldmann", "Oliver", "" ], [ "Medina", "Eva", "" ], [ "Rice", "Amanda D.", "" ], [ "Moyer", "Richard W.", "" ], [ "Man", "Xian", "" ], [ "Yi", "Ke", "" ], [ "Li", "Yanke", "" ], [ "Lu", "Qing", "" ], [ "Huang", "Yimin", "" ], [ "Wang", "Dapeng", "" ], [ "Yu", "Jun", "" ], [ "Guo", "Hui", "" ], [ "Xia", "Kun", "" ], [ "Huang", "Shi", "" ] ]
Most common SNPs are popularly assumed to be neutral. We here developed novel methods to examine in animal models and humans whether extreme amount of minor alleles (MAs) carried by an individual may represent extreme trait values and common diseases. We analyzed panels of genetic reference populations and identified the MAs in each panel and the MA content (MAC) that each strain carried. We also analyzed 21 published GWAS datasets of human diseases and identified the MAC of each case or control. MAC was nearly linearly linked to quantitative variations in numerous traits in model organisms, including life span, tumor susceptibility, learning and memory, sensitivity to alcohol and anti-psychotic drugs, and two correlated traits poor reproductive fitness and strong immunity. Similarly, in Europeans or European Americans, enrichment of MAs of fast but not slow evolutionary rate was linked to autoimmune and numerous other diseases, including type 2 diabetes, Parkinson's disease, psychiatric disorders, alcohol and cocaine addictions, cancer, and less life span. Therefore, both high and low MAC correlated with extreme values in many traits, indicating stabilizing selection on most MAs. The methods here are broadly applicable and may help solve the missing heritability problem in complex traits and diseases.
0904.2254
Hao Ge
Hao Ge, Hong Qian, Min Qian
Synchronized Dynamics and Nonequilibrium Steady States in a Stochastic Yeast Cell-Cycle Network
23 pages,6 figures; in Mathematical Bioscience 2008
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Applying the mathematical circulation theory of Markov chains, we investigate the synchronized stochastic dynamics of a discrete network model of yeast cell-cycle regulation where stochasticity has been kept rather than being averaged out. By comparing the network dynamics of the stochastic model with its corresponding deterministic network counterpart, we show that the synchronized dynamics can be soundly characterized by a dominant circulation in the stochastic model, which is the natural generalization of the deterministic limit cycle in the deterministic system. Moreover, the period of the main peak in the power spectrum, which is in common use to characterize the synchronized dynamics, perfectly corresponds to the number of states in the main cycle with dominant circulation. Such a large separation in the magnitude of the circulations, between a dominant, main cycle and the rest, gives rise to the stochastic synchronization phenomenon.
[ { "created": "Wed, 15 Apr 2009 07:47:35 GMT", "version": "v1" } ]
2009-04-16
[ [ "Ge", "Hao", "" ], [ "Qian", "Hong", "" ], [ "Qian", "Min", "" ] ]
Applying the mathematical circulation theory of Markov chains, we investigate the synchronized stochastic dynamics of a discrete network model of yeast cell-cycle regulation where stochasticity has been kept rather than being averaged out. By comparing the network dynamics of the stochastic model with its corresponding deterministic network counterpart, we show that the synchronized dynamics can be soundly characterized by a dominant circulation in the stochastic model, which is the natural generalization of the deterministic limit cycle in the deterministic system. Moreover, the period of the main peak in the power spectrum, which is in common use to characterize the synchronized dynamics, perfectly corresponds to the number of states in the main cycle with dominant circulation. Such a large separation in the magnitude of the circulations, between a dominant, main cycle and the rest, gives rise to the stochastic synchronization phenomenon.
1312.4748
Gerardo Gonz\'alez-Aguilar
Y. Casta\~no Guerrero and G. Gonz\'alez-Aguilar
Shiga Toxin Detection Methods : A Short Review
16 pages, 2 figures
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The Shiga toxins comprise a family of related protein toxins secreted by certain types of bacteria. Shigella dysenteriae, some strain of Escherichia coli and other bacterias can express toxins which caused serious complication during the infection. Shiga toxin and the closely related Shiga-like toxins represent a group of very similar cytotoxins that may play an important role in diarrheal disease and hemolytic-uremic syndrome. The outbreaks caused by this toxin raised serious public health crisis and caused economic losses. These toxins have the same biologic activities and according to recent studies also share the same binding receptor, globotriosyl ceramide (Gb3). Rapid detection of food contamination is therefore relevant for the containment of food-borne pathogens. The conventional methods to detect pathogens, such as microbiological and biochemical identification are time-consuming and laborious. The immunological or nucleic acid-based techniques require extensive sample preparation and are not amenable to miniaturization for on-site detection. In the present are necessary of techniques of rapid identification, simple and sensitive which can be employed in the countryside with minimally-sophisticated instrumentation. Biosensors have shown tremendous promise to overcome these limitations and are being aggressively studied to provide rapid, reliable and sensitive detection platforms for such applications.
[ { "created": "Tue, 17 Dec 2013 12:38:27 GMT", "version": "v1" } ]
2013-12-18
[ [ "Guerrero", "Y. Castaño", "" ], [ "González-Aguilar", "G.", "" ] ]
The Shiga toxins comprise a family of related protein toxins secreted by certain types of bacteria. Shigella dysenteriae, some strain of Escherichia coli and other bacterias can express toxins which caused serious complication during the infection. Shiga toxin and the closely related Shiga-like toxins represent a group of very similar cytotoxins that may play an important role in diarrheal disease and hemolytic-uremic syndrome. The outbreaks caused by this toxin raised serious public health crisis and caused economic losses. These toxins have the same biologic activities and according to recent studies also share the same binding receptor, globotriosyl ceramide (Gb3). Rapid detection of food contamination is therefore relevant for the containment of food-borne pathogens. The conventional methods to detect pathogens, such as microbiological and biochemical identification are time-consuming and laborious. The immunological or nucleic acid-based techniques require extensive sample preparation and are not amenable to miniaturization for on-site detection. In the present are necessary of techniques of rapid identification, simple and sensitive which can be employed in the countryside with minimally-sophisticated instrumentation. Biosensors have shown tremendous promise to overcome these limitations and are being aggressively studied to provide rapid, reliable and sensitive detection platforms for such applications.
2205.13875
Samuel Johnston
David Cheek and Samuel G. G. Johnston
Ancestral reproductive bias in branching processes
18 pages, 4 figures
null
null
null
q-bio.PE math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Consider a branching process with a homogeneous reproduction law. Sampling a single cell uniformly from the population at a time $T > 0$ and looking along the sampled cell's ancestral lineage, we find that the reproduction law is heterogeneous - the expected reproductive output of ancestral cells on the lineage from time $0$ to time $T$ continuously increases. This `inspection paradox' is due to sampling bias, that cells with a larger number of offspring are more likely to have one of their descendants sampled by virtue of their prolificity, and the bias's strength grows with the random population size and/or the sampling time $T$. Our main result explicitly characterises the evolution of reproduction rates and sizes along the sampled ancestral lineage as a mixture of Poisson processes, which simplifies in special cases. The ancestral bias helps to explain recently observed variation in mutation rates along lineages of the developing human embryo.
[ { "created": "Fri, 27 May 2022 10:12:32 GMT", "version": "v1" } ]
2022-05-30
[ [ "Cheek", "David", "" ], [ "Johnston", "Samuel G. G.", "" ] ]
Consider a branching process with a homogeneous reproduction law. Sampling a single cell uniformly from the population at a time $T > 0$ and looking along the sampled cell's ancestral lineage, we find that the reproduction law is heterogeneous - the expected reproductive output of ancestral cells on the lineage from time $0$ to time $T$ continuously increases. This `inspection paradox' is due to sampling bias, that cells with a larger number of offspring are more likely to have one of their descendants sampled by virtue of their prolificity, and the bias's strength grows with the random population size and/or the sampling time $T$. Our main result explicitly characterises the evolution of reproduction rates and sizes along the sampled ancestral lineage as a mixture of Poisson processes, which simplifies in special cases. The ancestral bias helps to explain recently observed variation in mutation rates along lineages of the developing human embryo.
2105.01340
Anna Maltsev
Guillermo Veron, Victor A. Maltsev, Michael D. Stern, Anna V. Maltsev
Elementary Intracellular Ca Signals are Initiated by a Transition of Release Channel System from a Metastable State
12 pages main text, 4 figures, 13 pages Python code, 1 page table
null
null
null
q-bio.SC physics.bio-ph q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Cardiac muscle contraction is initiated by an elementary Ca signal (called Ca spark) which is achieved by collective action of Ca release channels in a cluster. The mechanism of this synchronization remains uncertain. This paper approaches Ca spark activation as an emergent phenomenon of an interactive system of release channels. We construct a Markov chain that applies an Ising model formalism to such release channel clusters and realistic open channel configurations to demonstrate that spark activation is described as a system transition from a metastable to an absorbing state, analogous to the pressure required to overcome surface tension in bubble formation. This yields quantitative estimates of the spark generation probability as a function of various system parameters. Our model of the release channel system yields similar results for the sarcoplasmic reticulum Ca concentration threshold for spark activation as previous experimental results, providing a mechanistic explanation of the spark initiation. Additionally, we perform numerical simulations to find spark probabilities as a function of sarcoplasmic reticulum Ca concentration obtaining similar values for spark activation threshold as our analytic model, as well as those reported in experimental studies.
[ { "created": "Tue, 4 May 2021 07:39:46 GMT", "version": "v1" }, { "created": "Fri, 6 Aug 2021 19:05:10 GMT", "version": "v2" } ]
2021-08-10
[ [ "Veron", "Guillermo", "" ], [ "Maltsev", "Victor A.", "" ], [ "Stern", "Michael D.", "" ], [ "Maltsev", "Anna V.", "" ] ]
Cardiac muscle contraction is initiated by an elementary Ca signal (called Ca spark) which is achieved by collective action of Ca release channels in a cluster. The mechanism of this synchronization remains uncertain. This paper approaches Ca spark activation as an emergent phenomenon of an interactive system of release channels. We construct a Markov chain that applies an Ising model formalism to such release channel clusters and realistic open channel configurations to demonstrate that spark activation is described as a system transition from a metastable to an absorbing state, analogous to the pressure required to overcome surface tension in bubble formation. This yields quantitative estimates of the spark generation probability as a function of various system parameters. Our model of the release channel system yields similar results for the sarcoplasmic reticulum Ca concentration threshold for spark activation as previous experimental results, providing a mechanistic explanation of the spark initiation. Additionally, we perform numerical simulations to find spark probabilities as a function of sarcoplasmic reticulum Ca concentration obtaining similar values for spark activation threshold as our analytic model, as well as those reported in experimental studies.
2110.05139
Arindam Mishra
Mousumi Roy, Abhishek Senapati, Swarup Poria, Arindam Mishra, and Chittaranjan Hens
Role of assortativity in predicting burst synchronization using echo state network
null
null
10.1103/PhysRevE.105.064205
null
q-bio.NC nlin.CD
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this study, we use a reservoir computing based echo state network (ESN) to predict the collective burst synchronization of neurons. Specifically, we investigate the ability of ESN in predicting the burst synchronization of an ensemble of Rulkov neurons placed on a scale-free network. We have shown that a limited number of nodal dynamics used as input in the machine can capture the real trend of burst synchronization in this network. Further, we investigate on the proper selection of nodal inputs of degree-degree (positive and negative) correlated networks. We show that for a disassortative network, selection of different input nodes based on degree has no significant role in machine's prediction. However, in the case of assortative network, training the machine with the information (i.e time series) of low-degree nodes gives better results in predicting the burst synchronization. Finally, we explain the underlying mechanism responsible for observing this differences in prediction in a degree correlated network.
[ { "created": "Mon, 11 Oct 2021 10:31:08 GMT", "version": "v1" }, { "created": "Wed, 13 Oct 2021 20:52:23 GMT", "version": "v2" } ]
2022-06-22
[ [ "Roy", "Mousumi", "" ], [ "Senapati", "Abhishek", "" ], [ "Poria", "Swarup", "" ], [ "Mishra", "Arindam", "" ], [ "Hens", "Chittaranjan", "" ] ]
In this study, we use a reservoir computing based echo state network (ESN) to predict the collective burst synchronization of neurons. Specifically, we investigate the ability of ESN in predicting the burst synchronization of an ensemble of Rulkov neurons placed on a scale-free network. We have shown that a limited number of nodal dynamics used as input in the machine can capture the real trend of burst synchronization in this network. Further, we investigate on the proper selection of nodal inputs of degree-degree (positive and negative) correlated networks. We show that for a disassortative network, selection of different input nodes based on degree has no significant role in machine's prediction. However, in the case of assortative network, training the machine with the information (i.e time series) of low-degree nodes gives better results in predicting the burst synchronization. Finally, we explain the underlying mechanism responsible for observing this differences in prediction in a degree correlated network.
1911.13220
Daniel Mas Montserrat
Daniel Mas Montserrat, Carlos Bustamante, Alexander Ioannidis
Class-Conditional VAE-GAN for Local-Ancestry Simulation
null
null
null
null
q-bio.GN cs.LG stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Local ancestry inference (LAI) allows identification of the ancestry of all chromosomal segments in admixed individuals, and it is a critical step in the analysis of human genomes with applications from pharmacogenomics and precision medicine to genome-wide association studies. In recent years, many LAI techniques have been developed in both industry and academic research. However, these methods require large training data sets of human genomic sequences from the ancestries of interest. Such reference data sets are usually limited, proprietary, protected by privacy restrictions, or otherwise not accessible to the public. Techniques to generate training samples that resemble real haploid sequences from ancestries of interest can be useful tools in such scenarios, since a generalized model can often be shared, but the unique human sample sequences cannot. In this work we present a class-conditional VAE-GAN to generate new human genomic sequences that can be used to train local ancestry inference (LAI) algorithms. We evaluate the quality of our generated data by comparing the performance of a state-of-the-art LAI method when trained with generated versus real data.
[ { "created": "Wed, 27 Nov 2019 18:06:39 GMT", "version": "v1" } ]
2019-12-02
[ [ "Montserrat", "Daniel Mas", "" ], [ "Bustamante", "Carlos", "" ], [ "Ioannidis", "Alexander", "" ] ]
Local ancestry inference (LAI) allows identification of the ancestry of all chromosomal segments in admixed individuals, and it is a critical step in the analysis of human genomes with applications from pharmacogenomics and precision medicine to genome-wide association studies. In recent years, many LAI techniques have been developed in both industry and academic research. However, these methods require large training data sets of human genomic sequences from the ancestries of interest. Such reference data sets are usually limited, proprietary, protected by privacy restrictions, or otherwise not accessible to the public. Techniques to generate training samples that resemble real haploid sequences from ancestries of interest can be useful tools in such scenarios, since a generalized model can often be shared, but the unique human sample sequences cannot. In this work we present a class-conditional VAE-GAN to generate new human genomic sequences that can be used to train local ancestry inference (LAI) algorithms. We evaluate the quality of our generated data by comparing the performance of a state-of-the-art LAI method when trained with generated versus real data.
1112.0045
Aleksandar Stojmirovi\'c
Aleksandar Stojmirovi\'c, Alexander Bliskovsky and Yi-Kuo Yu
CytoITMprobe: a network information flow plugin for Cytoscape
16 pages, 6 figures. Version 2
null
null
null
q-bio.QM cs.DB q-bio.MN
http://creativecommons.org/licenses/publicdomain/
To provide the Cytoscape users the possibility of integrating ITM Probe into their workflows, we developed CytoITMprobe, a new Cytoscape plugin. CytoITMprobe maintains all the desirable features of ITM Probe and adds additional flexibility not achievable through its web service version. It provides access to ITM Probe either through a web server or locally. The input, consisting of a Cytoscape network, together with the desired origins and/or destinations of information and a dissipation coefficient, is specified through a query form. The results are shown as a subnetwork of significant nodes and several summary tables. Users can control the composition and appearance of the subnetwork and interchange their ITM Probe results with other software tools through tab-delimited files. The main strength of CytoITMprobe is its flexibility. It allows the user to specify as input any Cytoscape network, rather than being restricted to the pre-compiled protein-protein interaction networks available through the ITM Probe web service. Users may supply their own edge weights and directionalities. Consequently, as opposed to ITM Probe web service, CytoITMprobe can be applied to many other domains of network-based research beyond protein-networks. It also enables seamless integration of ITM Probe results with other Cytoscape plugins having complementary functionality for data analysis.
[ { "created": "Wed, 30 Nov 2011 22:10:50 GMT", "version": "v1" }, { "created": "Mon, 19 Mar 2012 22:22:23 GMT", "version": "v2" } ]
2012-03-21
[ [ "Stojmirović", "Aleksandar", "" ], [ "Bliskovsky", "Alexander", "" ], [ "Yu", "Yi-Kuo", "" ] ]
To provide the Cytoscape users the possibility of integrating ITM Probe into their workflows, we developed CytoITMprobe, a new Cytoscape plugin. CytoITMprobe maintains all the desirable features of ITM Probe and adds additional flexibility not achievable through its web service version. It provides access to ITM Probe either through a web server or locally. The input, consisting of a Cytoscape network, together with the desired origins and/or destinations of information and a dissipation coefficient, is specified through a query form. The results are shown as a subnetwork of significant nodes and several summary tables. Users can control the composition and appearance of the subnetwork and interchange their ITM Probe results with other software tools through tab-delimited files. The main strength of CytoITMprobe is its flexibility. It allows the user to specify as input any Cytoscape network, rather than being restricted to the pre-compiled protein-protein interaction networks available through the ITM Probe web service. Users may supply their own edge weights and directionalities. Consequently, as opposed to ITM Probe web service, CytoITMprobe can be applied to many other domains of network-based research beyond protein-networks. It also enables seamless integration of ITM Probe results with other Cytoscape plugins having complementary functionality for data analysis.
0712.4224
Jens Christian Claussen
Jens Christian Claussen
Drift reversal in asymmetric coevolutionary conflicts: Influence of microscopic processes and population size
9 pages, color online figs on p.3+4
European Physical Journal B 60, 391-399 (2007)
10.1140/epjb/e2007-00357-2
null
q-bio.PE physics.soc-ph q-bio.QM
null
The coevolutionary dynamics in finite populations currently is investigated in a wide range of disciplines, as chemical catalysis, biological evolution, social and economic systems. The dynamics of those systems can be formulated within the unifying framework of evolutionary game theory. However it is not a priori clear which mathematical description is appropriate when populations are not infinitely large. Whereas the replicator equation approach describes the infinite population size limit by deterministic differential equations, in finite populations the dynamics is inherently stochastic which can lead to new effects. Recently, an explicit mean-field description in the form of a Fokker-Planck equation was derived for frequency-dependent selection in finite populations based on microscopic processes. In asymmetric conflicts between two populations with a cyclic dominance, a finite-size dependent drift reversal was demonstrated, depending on the underlying microscopic process of the evolutionary update. Cyclic dynamics appears widely in biological coevolution, be it within a homogeneous population, or be it between disjunct populations as female and male. Here explicit analytic address is given and the average drift is calculated for the frequency-dependent Moran process and for different pairwise comparison processes. It is explicitely shown that the drift reversal cannot occur if the process relies on payoff differences between pairs of individuals. Further, also a linear comparison with the average payoff does not lead to a drift towards the internal fixed point. Hence the nonlinear comparison function of the frequency-dependent Moran process, together with its usage of nonlocal information via the average payoff, is the essential part of the mechanism.
[ { "created": "Thu, 27 Dec 2007 12:08:59 GMT", "version": "v1" } ]
2012-06-12
[ [ "Claussen", "Jens Christian", "" ] ]
The coevolutionary dynamics in finite populations currently is investigated in a wide range of disciplines, as chemical catalysis, biological evolution, social and economic systems. The dynamics of those systems can be formulated within the unifying framework of evolutionary game theory. However it is not a priori clear which mathematical description is appropriate when populations are not infinitely large. Whereas the replicator equation approach describes the infinite population size limit by deterministic differential equations, in finite populations the dynamics is inherently stochastic which can lead to new effects. Recently, an explicit mean-field description in the form of a Fokker-Planck equation was derived for frequency-dependent selection in finite populations based on microscopic processes. In asymmetric conflicts between two populations with a cyclic dominance, a finite-size dependent drift reversal was demonstrated, depending on the underlying microscopic process of the evolutionary update. Cyclic dynamics appears widely in biological coevolution, be it within a homogeneous population, or be it between disjunct populations as female and male. Here explicit analytic address is given and the average drift is calculated for the frequency-dependent Moran process and for different pairwise comparison processes. It is explicitely shown that the drift reversal cannot occur if the process relies on payoff differences between pairs of individuals. Further, also a linear comparison with the average payoff does not lead to a drift towards the internal fixed point. Hence the nonlinear comparison function of the frequency-dependent Moran process, together with its usage of nonlocal information via the average payoff, is the essential part of the mechanism.