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2203.03840
Nida Obatake
Nida Obatake, Elise Walker
Newton-Okounkov bodies of chemical reaction systems
20 pages, 3 figures, 2 tables, 1 appendix
null
null
null
q-bio.MN math.AG
http://creativecommons.org/licenses/by/4.0/
Despite their noted potential in polynomial-system solving, there are few concrete examples of Newton-Okounkov bodies arising from applications. Accordingly, in this paper, we introduce a new application of Newton-Okounkov body theory to the study of chemical reaction networks, and compute several examples. An important invariant of a chemical reaction network is its maximum number of positive steady states, which is realized as the maximum number of positive real roots of a parametrized polynomial system. Here, we introduce a new upper bound on this number, namely the `Newton-Okounkov body bound' of a chemical reaction network. Through explicit examples, we show that the Newton-Okounkov body bound of a network gives a good upper bound on its maximum number of positive steady states. We also compare this Newton-Okounkov body bound to a related upper bound, namely the mixed volume of a chemical reaction network, and find that it often achieves better bounds.
[ { "created": "Tue, 8 Mar 2022 04:20:03 GMT", "version": "v1" } ]
2022-03-09
[ [ "Obatake", "Nida", "" ], [ "Walker", "Elise", "" ] ]
Despite their noted potential in polynomial-system solving, there are few concrete examples of Newton-Okounkov bodies arising from applications. Accordingly, in this paper, we introduce a new application of Newton-Okounkov body theory to the study of chemical reaction networks, and compute several examples. An important invariant of a chemical reaction network is its maximum number of positive steady states, which is realized as the maximum number of positive real roots of a parametrized polynomial system. Here, we introduce a new upper bound on this number, namely the `Newton-Okounkov body bound' of a chemical reaction network. Through explicit examples, we show that the Newton-Okounkov body bound of a network gives a good upper bound on its maximum number of positive steady states. We also compare this Newton-Okounkov body bound to a related upper bound, namely the mixed volume of a chemical reaction network, and find that it often achieves better bounds.
1706.04640
Fernando Antoneli Jr
Luiza Guimar\~aes, Diogo Castro, Bruno Gorzoni, Luiz Mario Ramos Janini, Fernando Antoneli
Stochastic Modeling and Simulation of Viral Evolution
34 pages, 10 figures, 4 tables, 1 appendix
Bulletin of Mathematical Biology, Volume 81, April 2019, 1031-1069
10.1007/s11538-018-00550-4
null
q-bio.PE math.PR physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
RNA viruses comprise vast populations of closely related, but highly genetically diverse, entities known as quasispecies. Understanding the mechanisms by which this extreme diversity is generated and maintained is fundamental when approaching viral persistence and pathobiology in infected hosts. In this paper, we access quasispecies theory through a mathematical model based on the theory of multitype branching processes, to better understand the roles of mechanisms resulting in viral diversity, persistence and extinction. We accomplish this understanding by a combination of computational simulations and the theoretical analysis of the model. In order to perform the simulations, we have implemented the mathematical model into a computational platform capable of running simulations and presenting the results in a graphical format in real time. Among other things, we show that the establishment of virus populations may display four distinct regimes from its introduction into new hosts until achieving equilibrium or undergoing extinction. Also, we were able to simulate different fitness distributions representing distinct environments within a host which could either be favorable or hostile to the viral success. We addressed the most used mechanisms for explaining the extinction of RNA virus populations called lethal mutagenesis and mutational meltdown. We were able to demonstrate a correspondence between these two mechanisms implying the existence of a unifying principle leading to the extinction of RNA viruses.
[ { "created": "Wed, 14 Jun 2017 19:12:15 GMT", "version": "v1" }, { "created": "Fri, 10 Nov 2017 16:22:18 GMT", "version": "v2" }, { "created": "Sun, 21 Jun 2020 14:49:27 GMT", "version": "v3" } ]
2021-05-27
[ [ "Guimarães", "Luiza", "" ], [ "Castro", "Diogo", "" ], [ "Gorzoni", "Bruno", "" ], [ "Janini", "Luiz Mario Ramos", "" ], [ "Antoneli", "Fernando", "" ] ]
RNA viruses comprise vast populations of closely related, but highly genetically diverse, entities known as quasispecies. Understanding the mechanisms by which this extreme diversity is generated and maintained is fundamental when approaching viral persistence and pathobiology in infected hosts. In this paper, we access quasispecies theory through a mathematical model based on the theory of multitype branching processes, to better understand the roles of mechanisms resulting in viral diversity, persistence and extinction. We accomplish this understanding by a combination of computational simulations and the theoretical analysis of the model. In order to perform the simulations, we have implemented the mathematical model into a computational platform capable of running simulations and presenting the results in a graphical format in real time. Among other things, we show that the establishment of virus populations may display four distinct regimes from its introduction into new hosts until achieving equilibrium or undergoing extinction. Also, we were able to simulate different fitness distributions representing distinct environments within a host which could either be favorable or hostile to the viral success. We addressed the most used mechanisms for explaining the extinction of RNA virus populations called lethal mutagenesis and mutational meltdown. We were able to demonstrate a correspondence between these two mechanisms implying the existence of a unifying principle leading to the extinction of RNA viruses.
2210.16813
Yongtong Wu
Yongtong Wu, Kejia Hu, Shenquan Liu
Computational model advance deep brain stimulation for Parkinson's disease
27 pages, 8 figures
null
null
null
q-bio.NC
http://creativecommons.org/licenses/by/4.0/
Deep brain stimulation(DBS)has become an effective intervention for advanced Parkinson's disease, but the exact mechanism of DBS is still unclear. In this review, we discuss the history of DBS, the anatomy and internal architecture of the basal ganglia(BG), the abnormal pathological changes of the BG in Parkinson's disease, and how computational models can help understand and advance DBS. We also describe two types of models:mathematical theoretical models and clinical predictive models. Mathematical theoretical models simulate neurons or neural networks of BG to shed light on the mechanistic principle underlying DBS, while clinical predictive models focus more on patients' outcomes, helping to adapt treatment plans for each patient and advance novel electrode designs. Finally, we provide insights and an outlook on future technologies.
[ { "created": "Sun, 30 Oct 2022 11:21:38 GMT", "version": "v1" }, { "created": "Thu, 23 Mar 2023 12:06:41 GMT", "version": "v2" } ]
2023-03-24
[ [ "Wu", "Yongtong", "" ], [ "Hu", "Kejia", "" ], [ "Liu", "Shenquan", "" ] ]
Deep brain stimulation(DBS)has become an effective intervention for advanced Parkinson's disease, but the exact mechanism of DBS is still unclear. In this review, we discuss the history of DBS, the anatomy and internal architecture of the basal ganglia(BG), the abnormal pathological changes of the BG in Parkinson's disease, and how computational models can help understand and advance DBS. We also describe two types of models:mathematical theoretical models and clinical predictive models. Mathematical theoretical models simulate neurons or neural networks of BG to shed light on the mechanistic principle underlying DBS, while clinical predictive models focus more on patients' outcomes, helping to adapt treatment plans for each patient and advance novel electrode designs. Finally, we provide insights and an outlook on future technologies.
1506.00373
Mariusz Pietruszka PhD
Mariusz Pietruszka and Aleksandra Haduch-Sendecka
Frequency landscape of tip-growing plants
9 pages, 3 figures
null
null
null
q-bio.CB
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
It has been interesting that nearly all of the ion activities that have been analysed thus far have exhibited oscillations that are tightly coupled to growth. Here, we present discrete Fourier transform (DFT) spectra with a finite sampling of tip-growing cells and organs that were obtained from voltage measurements of the elongating coleoptiles of maize in situ. The electromotive force (EMF) oscillations (~ 0.1 {\mu}V) were measured in a simple but highly sensitive RL circuit, in which the solenoid was initially placed at the tip of the specimen and then was moved thus changing its position in relation to growth (EMF can be measured first at the tip, then at the sub-apical part and finally at the shank). The influx- and efflux-induced oscillations of Ca$^{2+}$, along with H$^{+}$, K$^{+}$ and Cl$^{-}$ were densely sampled (preserving the Nyquist theorem in order to 'grasp the structure' of the pulse), the logarithmic amplitude of pulse spectrum was calculated, and the detected frequencies, which displayed a periodic sequence of pulses, were compared with the literature data. A band of life vital individual pulses was obtained in a single run of the experiment, which not only allowed the fundamental frequencies (and intensities of the processes) to be determined but also permitted the phase relations of the various transport processes in the plasma membrane and tonoplast to be established. A discrete frequency spectrum (like the hydrogen spectrum in quantum physics) was achieved for a growing plant for the first time, while all of the metabolic and enzymatic functions of the life cell cycle were preserved using this totally non-invasive treatment.
[ { "created": "Mon, 1 Jun 2015 07:56:17 GMT", "version": "v1" }, { "created": "Tue, 28 Jul 2015 07:26:43 GMT", "version": "v2" } ]
2015-07-29
[ [ "Pietruszka", "Mariusz", "" ], [ "Haduch-Sendecka", "Aleksandra", "" ] ]
It has been interesting that nearly all of the ion activities that have been analysed thus far have exhibited oscillations that are tightly coupled to growth. Here, we present discrete Fourier transform (DFT) spectra with a finite sampling of tip-growing cells and organs that were obtained from voltage measurements of the elongating coleoptiles of maize in situ. The electromotive force (EMF) oscillations (~ 0.1 {\mu}V) were measured in a simple but highly sensitive RL circuit, in which the solenoid was initially placed at the tip of the specimen and then was moved thus changing its position in relation to growth (EMF can be measured first at the tip, then at the sub-apical part and finally at the shank). The influx- and efflux-induced oscillations of Ca$^{2+}$, along with H$^{+}$, K$^{+}$ and Cl$^{-}$ were densely sampled (preserving the Nyquist theorem in order to 'grasp the structure' of the pulse), the logarithmic amplitude of pulse spectrum was calculated, and the detected frequencies, which displayed a periodic sequence of pulses, were compared with the literature data. A band of life vital individual pulses was obtained in a single run of the experiment, which not only allowed the fundamental frequencies (and intensities of the processes) to be determined but also permitted the phase relations of the various transport processes in the plasma membrane and tonoplast to be established. A discrete frequency spectrum (like the hydrogen spectrum in quantum physics) was achieved for a growing plant for the first time, while all of the metabolic and enzymatic functions of the life cell cycle were preserved using this totally non-invasive treatment.
1801.02665
Wenpo Yao
Wenpo Yao Wenli Yao and Jun Wang
Symbolic relative entropy in quantifying nonlinear dynamics of equalities-involved heartbeats
The theory underlying the symbolic relative entropy on nonlinear dynamics in our manuscript might lead somewhat misleading and is needed further analysis and discussions
null
null
null
q-bio.QM nlin.CD
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Symbolic relative entropy, an efficient nonlinear complexity parameter measuring probabilistic divergences of symbolic sequences, is proposed in our nonlinear dynamics analysis of heart rates considering equal states. Equalities are not rare in discrete heartbeats because of the limits of resolution of signals collection, and more importantly equal states contain underlying important cardiac regulation information which is neglected by some chaotic deterministic parameters and temporal asymmetric measurements. The relative entropy of symbolization associated with equal states has satisfied nonlinear dynamics complexity detections in heartbeats and shows advantages to some nonlinear dynamics parameters without considering equalities. Researches on cardiac activities suggest the highest probabilistic divergence of the healthy young heart rates and highlight the facts that heart diseases and aging reduce the nonlinear dynamical complexity of heart rates.
[ { "created": "Tue, 2 Jan 2018 12:26:45 GMT", "version": "v1" }, { "created": "Sun, 21 Jan 2018 02:52:22 GMT", "version": "v2" }, { "created": "Mon, 28 Jan 2019 04:32:18 GMT", "version": "v3" } ]
2019-01-29
[ [ "Yao", "Wenpo Yao Wenli", "" ], [ "Wang", "Jun", "" ] ]
Symbolic relative entropy, an efficient nonlinear complexity parameter measuring probabilistic divergences of symbolic sequences, is proposed in our nonlinear dynamics analysis of heart rates considering equal states. Equalities are not rare in discrete heartbeats because of the limits of resolution of signals collection, and more importantly equal states contain underlying important cardiac regulation information which is neglected by some chaotic deterministic parameters and temporal asymmetric measurements. The relative entropy of symbolization associated with equal states has satisfied nonlinear dynamics complexity detections in heartbeats and shows advantages to some nonlinear dynamics parameters without considering equalities. Researches on cardiac activities suggest the highest probabilistic divergence of the healthy young heart rates and highlight the facts that heart diseases and aging reduce the nonlinear dynamical complexity of heart rates.
2104.11567
Aditya Sengar
Aditya Sengar, Thomas E. Ouldridge, Oliver Henrich, Lorenzo Rovigatti, Petr Sulc
A primer on the oxDNA model of DNA: When to use it, how to simulate it and how to interpret the results
null
Front. Mol. Biosci. 8, 693710 (2021)
10.3389/fmolb.2021.693710
null
q-bio.BM cond-mat.soft physics.bio-ph
http://creativecommons.org/licenses/by/4.0/
The oxDNA model of DNA has been applied widely to systems in biology, biophysics and nanotechnology. It is currently available via two independent open source packages. Here we present a set of clearly-documented exemplar simulations that simultaneously provide both an introduction to simulating the model, and a review of the model's fundamental properties. We outline how simulation results can be interpreted in terms of -- and feed into our understanding of -- less detailed models that operate at larger length scales, and provide guidance on whether simulating a system with oxDNA is worthwhile.
[ { "created": "Fri, 23 Apr 2021 12:49:59 GMT", "version": "v1" } ]
2022-09-26
[ [ "Sengar", "Aditya", "" ], [ "Ouldridge", "Thomas E.", "" ], [ "Henrich", "Oliver", "" ], [ "Rovigatti", "Lorenzo", "" ], [ "Sulc", "Petr", "" ] ]
The oxDNA model of DNA has been applied widely to systems in biology, biophysics and nanotechnology. It is currently available via two independent open source packages. Here we present a set of clearly-documented exemplar simulations that simultaneously provide both an introduction to simulating the model, and a review of the model's fundamental properties. We outline how simulation results can be interpreted in terms of -- and feed into our understanding of -- less detailed models that operate at larger length scales, and provide guidance on whether simulating a system with oxDNA is worthwhile.
2306.15428
Chris Jones
Chris Jones, Damaris Zurell and Karoline Wiesner
Evaluating The Impact Of Species Specialisation On Ecological Network Robustness Using Analytic Methods
22 pages, 12 figures, 2 tables
null
null
null
q-bio.PE math.CO physics.soc-ph
http://creativecommons.org/licenses/by/4.0/
Ecological networks describe the interactions between different species, informing us of how they rely on one another for food, pollination and survival. If a species in an ecosystem is under threat of extinction, it can affect other species in the system and possibly result in their secondary extinction as well. Understanding how (primary) extinctions cause secondary extinctions on ecological networks has been considered previously using computational methods. However, these methods do not provide an explanation for the properties which make ecological networks robust, and can be computationally expensive. We develop a new analytic model for predicting secondary extinctions which requires no non-deterministic computational simulation. Our model can predict secondary extinctions when primary extinctions occur at random or due to some targeting based on the number of links per species or risk of extinction, and can be applied to an ecological network of any number of layers. Using our model, we consider how false positives and negatives in network data affect predictions for network robustness. We have also extended the model to predict scenarios in which secondary extinctions occur once species lose a certain percentage of interaction strength, and to model the loss of interactions as opposed to just species extinction. From our model, it is possible to derive new analytic results such as how ecological networks are most robust when secondary species degree variance is minimised. Additionally, we show that both specialisation and generalisation in distribution of interaction strength can be advantageous for network robustness, depending upon the extinction scenario being considered.
[ { "created": "Tue, 27 Jun 2023 12:38:35 GMT", "version": "v1" }, { "created": "Wed, 5 Jul 2023 13:42:44 GMT", "version": "v2" } ]
2023-07-06
[ [ "Jones", "Chris", "" ], [ "Zurell", "Damaris", "" ], [ "Wiesner", "Karoline", "" ] ]
Ecological networks describe the interactions between different species, informing us of how they rely on one another for food, pollination and survival. If a species in an ecosystem is under threat of extinction, it can affect other species in the system and possibly result in their secondary extinction as well. Understanding how (primary) extinctions cause secondary extinctions on ecological networks has been considered previously using computational methods. However, these methods do not provide an explanation for the properties which make ecological networks robust, and can be computationally expensive. We develop a new analytic model for predicting secondary extinctions which requires no non-deterministic computational simulation. Our model can predict secondary extinctions when primary extinctions occur at random or due to some targeting based on the number of links per species or risk of extinction, and can be applied to an ecological network of any number of layers. Using our model, we consider how false positives and negatives in network data affect predictions for network robustness. We have also extended the model to predict scenarios in which secondary extinctions occur once species lose a certain percentage of interaction strength, and to model the loss of interactions as opposed to just species extinction. From our model, it is possible to derive new analytic results such as how ecological networks are most robust when secondary species degree variance is minimised. Additionally, we show that both specialisation and generalisation in distribution of interaction strength can be advantageous for network robustness, depending upon the extinction scenario being considered.
1502.02908
Stefan Engblom
Pavol Bauer, Stefan Engblom, Stefan Widgren
Fast event-based epidemiological simulations on national scales
27 pages, 5 figures
Int. J. High Perf. Comput. Appl. 30(4):438--453 (2016)
10.1177/1094342016635723
null
q-bio.PE cs.DC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present a computational modeling framework for data-driven simulations and analysis of infectious disease spread in large populations. For the purpose of efficient simulations, we devise a parallel solution algorithm targeting multi-socket shared memory architectures. The model integrates infectious dynamics as continuous-time Markov chains and available data such as animal movements or aging are incorporated as externally defined events. To bring out parallelism and accelerate the computations, we decompose the spatial domain and optimize cross-boundary communication using dependency-aware task scheduling. Using registered livestock data at a high spatio-temporal resolution, we demonstrate that our approach not only is resilient to varying model configurations, but also scales on all physical cores at realistic work loads. Finally, we show that these very features enable the solution of inverse problems on national scales.
[ { "created": "Tue, 10 Feb 2015 13:48:46 GMT", "version": "v1" }, { "created": "Wed, 4 Nov 2015 15:48:54 GMT", "version": "v2" }, { "created": "Wed, 27 Jan 2016 13:57:07 GMT", "version": "v3" } ]
2018-02-19
[ [ "Bauer", "Pavol", "" ], [ "Engblom", "Stefan", "" ], [ "Widgren", "Stefan", "" ] ]
We present a computational modeling framework for data-driven simulations and analysis of infectious disease spread in large populations. For the purpose of efficient simulations, we devise a parallel solution algorithm targeting multi-socket shared memory architectures. The model integrates infectious dynamics as continuous-time Markov chains and available data such as animal movements or aging are incorporated as externally defined events. To bring out parallelism and accelerate the computations, we decompose the spatial domain and optimize cross-boundary communication using dependency-aware task scheduling. Using registered livestock data at a high spatio-temporal resolution, we demonstrate that our approach not only is resilient to varying model configurations, but also scales on all physical cores at realistic work loads. Finally, we show that these very features enable the solution of inverse problems on national scales.
0707.0394
Davide Cora
Davide Cora, Ferdinando Di Cunto, Michele Caselle, Paolo Provero
Identification of candidate regulatory sequences in mammalian 3' UTRs by statistical analysis of oligonucleotide distributions
Added two references
BMC Bioinformatics. 2007 May 24;8:174. PMID: 17524134
null
null
q-bio.GN
null
3' untranslated regions (3' UTRs) contain binding sites for many regulatory elements, and in particular for microRNAs (miRNAs). The importance of miRNA-mediated post-transcriptional regulation has become increasingly clear in the last few years. We propose two complementary approaches to the statistical analysis of oligonucleotide frequencies in mammalian 3' UTRs aimed at the identification of candidate binding sites for regulatory elements. The first method is based on the identification of sets of genes characterized by evolutionarily conserved overrepresentation of an oligonucleotide. The second method is based on the identification of oligonucleotides showing statistically significant strand asymmetry in their distribution in 3' UTRs. Both methods are able to identify many previously known binding sites located in 3'UTRs, and in particular seed regions of known miRNAs. Many new candidates are proposed for experimental verification.
[ { "created": "Tue, 3 Jul 2007 11:39:13 GMT", "version": "v1" }, { "created": "Mon, 16 Jul 2007 23:30:34 GMT", "version": "v2" } ]
2007-07-17
[ [ "Cora", "Davide", "" ], [ "Di Cunto", "Ferdinando", "" ], [ "Caselle", "Michele", "" ], [ "Provero", "Paolo", "" ] ]
3' untranslated regions (3' UTRs) contain binding sites for many regulatory elements, and in particular for microRNAs (miRNAs). The importance of miRNA-mediated post-transcriptional regulation has become increasingly clear in the last few years. We propose two complementary approaches to the statistical analysis of oligonucleotide frequencies in mammalian 3' UTRs aimed at the identification of candidate binding sites for regulatory elements. The first method is based on the identification of sets of genes characterized by evolutionarily conserved overrepresentation of an oligonucleotide. The second method is based on the identification of oligonucleotides showing statistically significant strand asymmetry in their distribution in 3' UTRs. Both methods are able to identify many previously known binding sites located in 3'UTRs, and in particular seed regions of known miRNAs. Many new candidates are proposed for experimental verification.
1408.5803
Pu Tian
Kai Wang, Shiyang Long, Zhiming Zhang, Lanru Liu, Qimeng Wang and Pu Tian
Ideal gas behavior of rotamerically defined conformers in native globular proteins
6 figures in the main text
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Protein conformational transitions, which are essential for function, may be driven either by entropy or enthalpy when molecular systems comprising solute and solvent molecules are the focus. Revealing thermodynamic origin of a given molecular process is an important but difficult task, and general principles governing protein conformational distributions remain elusive. Here we demonstrate that when protein molecules are taken as thermodynamic systems and solvents being treated as the environment, conformational entropy is an excellent proxy for free energy and is sufficient to explain protein conformational distributions. Specifically, by defining each unique combination of side chain torsional state as a conformer, the population distribution (or free energy) on an arbitrarily given order parameter is approximately a linear function of conformational entropy. Additionally, span of various microscopic potential energy terms is observed to be highly correlated with both conformational entropy and free energy. Presently widely utilized free energy proxies, including minimum potential energy, average potential energy terms by themselves or in combination with vibrational entropy\cite, are found to correlate with free energy rather poorly. Therefore, our findings provide a fundamentally new theoretical base for development of significantly more reliable and efficient next generation computational tools, where the number of available conformers,rather than poential energy of microscopic configurations, is the central focus. We anticipate that many related research fields, including structure based drug design and discovery, protein design, docking and prediction of general intermolecular interactions involving proteins, are expected to benefit greatly.
[ { "created": "Mon, 25 Aug 2014 15:23:20 GMT", "version": "v1" }, { "created": "Thu, 30 Apr 2015 22:50:28 GMT", "version": "v2" } ]
2015-05-04
[ [ "Wang", "Kai", "" ], [ "Long", "Shiyang", "" ], [ "Zhang", "Zhiming", "" ], [ "Liu", "Lanru", "" ], [ "Wang", "Qimeng", "" ], [ "Tian", "Pu", "" ] ]
Protein conformational transitions, which are essential for function, may be driven either by entropy or enthalpy when molecular systems comprising solute and solvent molecules are the focus. Revealing thermodynamic origin of a given molecular process is an important but difficult task, and general principles governing protein conformational distributions remain elusive. Here we demonstrate that when protein molecules are taken as thermodynamic systems and solvents being treated as the environment, conformational entropy is an excellent proxy for free energy and is sufficient to explain protein conformational distributions. Specifically, by defining each unique combination of side chain torsional state as a conformer, the population distribution (or free energy) on an arbitrarily given order parameter is approximately a linear function of conformational entropy. Additionally, span of various microscopic potential energy terms is observed to be highly correlated with both conformational entropy and free energy. Presently widely utilized free energy proxies, including minimum potential energy, average potential energy terms by themselves or in combination with vibrational entropy\cite, are found to correlate with free energy rather poorly. Therefore, our findings provide a fundamentally new theoretical base for development of significantly more reliable and efficient next generation computational tools, where the number of available conformers,rather than poential energy of microscopic configurations, is the central focus. We anticipate that many related research fields, including structure based drug design and discovery, protein design, docking and prediction of general intermolecular interactions involving proteins, are expected to benefit greatly.
2112.04266
Simon Wein
Simon Wein, Alina Sch\"uller, Ana Maria Tom\'e, Wilhelm M. Malloni, Mark W. Greenlee, Elmar W. Lang
Forecasting Brain Activity Based on Models of Spatio-Temporal Brain Dynamics: A Comparison of Graph Neural Network Architectures
null
null
null
null
q-bio.NC stat.ML
http://creativecommons.org/licenses/by/4.0/
Comprehending the interplay between spatial and temporal characteristics of neural dynamics can contribute to our understanding of information processing in the human brain. Graph neural networks (GNNs) provide a new possibility to interpret graph structured signals like those observed in complex brain networks. In our study we compare different spatio-temporal GNN architectures and study their ability to model neural activity distributions obtained in functional MRI (fMRI) studies. We evaluate the performance of the GNN models on a variety of scenarios in MRI studies and also compare it to a VAR model, which is currently often used for directed functional connectivity analysis. We show that by learning localized functional interactions on the anatomical substrate, GNN based approaches are able to robustly scale to large network studies, even when available data are scarce. By including anatomical connectivity as the physical substrate for information propagation, such GNNs also provide a multi-modal perspective on directed connectivity analysis, offering a novel possibility to investigate the spatio-temporal dynamics in brain networks.
[ { "created": "Wed, 8 Dec 2021 12:57:13 GMT", "version": "v1" }, { "created": "Thu, 28 Apr 2022 12:59:58 GMT", "version": "v2" } ]
2022-04-29
[ [ "Wein", "Simon", "" ], [ "Schüller", "Alina", "" ], [ "Tomé", "Ana Maria", "" ], [ "Malloni", "Wilhelm M.", "" ], [ "Greenlee", "Mark W.", "" ], [ "Lang", "Elmar W.", "" ] ]
Comprehending the interplay between spatial and temporal characteristics of neural dynamics can contribute to our understanding of information processing in the human brain. Graph neural networks (GNNs) provide a new possibility to interpret graph structured signals like those observed in complex brain networks. In our study we compare different spatio-temporal GNN architectures and study their ability to model neural activity distributions obtained in functional MRI (fMRI) studies. We evaluate the performance of the GNN models on a variety of scenarios in MRI studies and also compare it to a VAR model, which is currently often used for directed functional connectivity analysis. We show that by learning localized functional interactions on the anatomical substrate, GNN based approaches are able to robustly scale to large network studies, even when available data are scarce. By including anatomical connectivity as the physical substrate for information propagation, such GNNs also provide a multi-modal perspective on directed connectivity analysis, offering a novel possibility to investigate the spatio-temporal dynamics in brain networks.
1805.01579
Iosif Lazaridis
Iosif Lazaridis
The evolutionary history of human populations in Europe
null
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by-nc-sa/4.0/
I review the evolutionary history of human populations in Europe with an emphasis on what has been learned in recent years through the study of ancient DNA. Human populations in Europe ~430-39kya (archaic Europeans) included Neandertals and their ancestors, who were genetically differentiated from other archaic Eurasians (such as the Denisovans of Siberia), as well as modern humans. Modern humans arrived to Europe by ~45kya, and are first genetically attested by ~39kya when they were still mixing with Neandertals. The first Europeans who were recognizably genetically related to modern ones appeared in the genetic record shortly thereafter at ~37kya. At ~15kya a largely homogeneous set of hunter-gatherers became dominant in most of Europe, but with some admixture from Siberian hunter-gatherers in the eastern part of the continent. These hunter-gatherers were joined by migrants from the Near East beginning at ~8kya: Anatolian farmers settled most of mainland Europe, and migrants from the Caucasus reached eastern Europe, forming steppe populations. After ~5kya there was migration from the steppe into mainland Europe and vice versa. Present-day Europeans (ignoring the long-distance migrations of the modern era) are largely the product of this Bronze Age collision of steppe pastoralists with Neolithic farmers.
[ { "created": "Fri, 4 May 2018 00:43:47 GMT", "version": "v1" } ]
2018-05-07
[ [ "Lazaridis", "Iosif", "" ] ]
I review the evolutionary history of human populations in Europe with an emphasis on what has been learned in recent years through the study of ancient DNA. Human populations in Europe ~430-39kya (archaic Europeans) included Neandertals and their ancestors, who were genetically differentiated from other archaic Eurasians (such as the Denisovans of Siberia), as well as modern humans. Modern humans arrived to Europe by ~45kya, and are first genetically attested by ~39kya when they were still mixing with Neandertals. The first Europeans who were recognizably genetically related to modern ones appeared in the genetic record shortly thereafter at ~37kya. At ~15kya a largely homogeneous set of hunter-gatherers became dominant in most of Europe, but with some admixture from Siberian hunter-gatherers in the eastern part of the continent. These hunter-gatherers were joined by migrants from the Near East beginning at ~8kya: Anatolian farmers settled most of mainland Europe, and migrants from the Caucasus reached eastern Europe, forming steppe populations. After ~5kya there was migration from the steppe into mainland Europe and vice versa. Present-day Europeans (ignoring the long-distance migrations of the modern era) are largely the product of this Bronze Age collision of steppe pastoralists with Neolithic farmers.
2402.11762
Tomoharu Suda
Tomoharu Suda
Effective Kinetics of Chemical Reaction Networks
19 pages, 0 figures. Added a reference and a remark
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Chemical reaction network theory is a powerful framework to describe and analyze chemical systems. While much about the concentration profile in an equilibrium state can be determined in terms of the graph structure, the overall reaction's time evolution depends on the network's kinetic rate function. In this article, we consider the problem of the effective kinetics of a chemical reaction network regarded as a conversion system from the feeding species to products. We define the notion of effective kinetics as a partial solution of a system of non-autonomous ordinary differential equations determined from a chemical reaction network. Examples of actual calculations include the Michaelis-Menten mechanism, for which it is confirmed that our notion of effective kinetics yields the classical formula. Further, we introduce the notion of straight-line solutions of non-autonomous ordinary differential equations to formalize the situation where a well-defined reaction rate exists and consider its relation with the quasi-stationary state approximation used in microkinetics. Our considerations here give a unified framework to formulate the reaction rate of chemical reaction networks.
[ { "created": "Mon, 19 Feb 2024 01:25:33 GMT", "version": "v1" }, { "created": "Wed, 28 Feb 2024 00:04:22 GMT", "version": "v2" } ]
2024-02-29
[ [ "Suda", "Tomoharu", "" ] ]
Chemical reaction network theory is a powerful framework to describe and analyze chemical systems. While much about the concentration profile in an equilibrium state can be determined in terms of the graph structure, the overall reaction's time evolution depends on the network's kinetic rate function. In this article, we consider the problem of the effective kinetics of a chemical reaction network regarded as a conversion system from the feeding species to products. We define the notion of effective kinetics as a partial solution of a system of non-autonomous ordinary differential equations determined from a chemical reaction network. Examples of actual calculations include the Michaelis-Menten mechanism, for which it is confirmed that our notion of effective kinetics yields the classical formula. Further, we introduce the notion of straight-line solutions of non-autonomous ordinary differential equations to formalize the situation where a well-defined reaction rate exists and consider its relation with the quasi-stationary state approximation used in microkinetics. Our considerations here give a unified framework to formulate the reaction rate of chemical reaction networks.
2003.12936
Yevgeniy Kovchegov
Evgenia Chunikhina, Paul Logan, Yevgeniy Kovchegov, Anatoly Yambartsev, Debashis Mondal, Andrey Morgun
The C-SHIFT algorithm for normalizing covariances
null
null
null
null
q-bio.GN q-bio.QM stat.AP stat.ME
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Omics technologies are powerful tools for analyzing patterns in gene expression data for thousands of genes. Due to a number of systematic variations in experiments, the raw gene expression data is often obfuscated by undesirable technical noises. Various normalization techniques were designed in an attempt to remove these non-biological errors prior to any statistical analysis. One of the reasons for normalizing data is the need for recovering the covariance matrix used in gene network analysis. In this paper, we introduce a novel normalization technique, called the covariance shift (C-SHIFT) method. This normalization algorithm uses optimization techniques together with the blessing of dimensionality philosophy and energy minimization hypothesis for covariance matrix recovery under additive noise (in biology, known as the bias). Thus, it is perfectly suited for the analysis of logarithmic gene expression data. Numerical experiments on synthetic data demonstrate the method's advantage over the classical normalization techniques. Namely, the comparison is made with Rank, Quantile, cyclic LOESS (locally estimated scatterplot smoothing), and MAD (median absolute deviation) normalization methods. We also evaluate the performance of C-SHIFT algorithm on real biological data.
[ { "created": "Sun, 29 Mar 2020 03:24:51 GMT", "version": "v1" }, { "created": "Thu, 5 Aug 2021 06:53:14 GMT", "version": "v2" } ]
2021-08-06
[ [ "Chunikhina", "Evgenia", "" ], [ "Logan", "Paul", "" ], [ "Kovchegov", "Yevgeniy", "" ], [ "Yambartsev", "Anatoly", "" ], [ "Mondal", "Debashis", "" ], [ "Morgun", "Andrey", "" ] ]
Omics technologies are powerful tools for analyzing patterns in gene expression data for thousands of genes. Due to a number of systematic variations in experiments, the raw gene expression data is often obfuscated by undesirable technical noises. Various normalization techniques were designed in an attempt to remove these non-biological errors prior to any statistical analysis. One of the reasons for normalizing data is the need for recovering the covariance matrix used in gene network analysis. In this paper, we introduce a novel normalization technique, called the covariance shift (C-SHIFT) method. This normalization algorithm uses optimization techniques together with the blessing of dimensionality philosophy and energy minimization hypothesis for covariance matrix recovery under additive noise (in biology, known as the bias). Thus, it is perfectly suited for the analysis of logarithmic gene expression data. Numerical experiments on synthetic data demonstrate the method's advantage over the classical normalization techniques. Namely, the comparison is made with Rank, Quantile, cyclic LOESS (locally estimated scatterplot smoothing), and MAD (median absolute deviation) normalization methods. We also evaluate the performance of C-SHIFT algorithm on real biological data.
1301.4247
Alfredo Rodriguez
R. Martin, R. Godinez, A. O. Rodriguez
Functional Magnetic Resonance Imaging: a study of malnourished rats
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Malnutrition is a main public health problem in developing countries. Incidence is increasing and the mortality rate is still high. Malnutrition can leads mayor problems that can be irreversible if it is present before brain development is completed. We used BOLD (blood oxygen level-dependent effect) Functional Magnetic Resonance Imaging to investigate the regions of brain activity in malnourished rats. The food competition method was applied to a rat model to provoke malnutrition during lactation. The weight increase is delayed even if there is plenty milk available. To localize those regions of activity resulting from the trigeminal nerve stimulation, the vibrissae-barrel axis was employed due to the functional and morphological correlation between the vibrissae and the barrels. BOLD response changes caused by the trigeminal nerve stimulation on brain activity of malnourished and control rats were obtained at 7T. Results showed a major neuronal activity in malnourished rats on regions like cerebellum, somatosensorial cortex, hippocampus, and hypothalamus. This is the first study in malnourished rats and illustrates BOLD activation in various brain structures.
[ { "created": "Wed, 16 Jan 2013 01:17:44 GMT", "version": "v1" } ]
2013-01-21
[ [ "Martin", "R.", "" ], [ "Godinez", "R.", "" ], [ "Rodriguez", "A. O.", "" ] ]
Malnutrition is a main public health problem in developing countries. Incidence is increasing and the mortality rate is still high. Malnutrition can leads mayor problems that can be irreversible if it is present before brain development is completed. We used BOLD (blood oxygen level-dependent effect) Functional Magnetic Resonance Imaging to investigate the regions of brain activity in malnourished rats. The food competition method was applied to a rat model to provoke malnutrition during lactation. The weight increase is delayed even if there is plenty milk available. To localize those regions of activity resulting from the trigeminal nerve stimulation, the vibrissae-barrel axis was employed due to the functional and morphological correlation between the vibrissae and the barrels. BOLD response changes caused by the trigeminal nerve stimulation on brain activity of malnourished and control rats were obtained at 7T. Results showed a major neuronal activity in malnourished rats on regions like cerebellum, somatosensorial cortex, hippocampus, and hypothalamus. This is the first study in malnourished rats and illustrates BOLD activation in various brain structures.
1409.4978
Iain Johnston
Ben P. Williams, Iain G. Johnston, Sarah Covshoff, Julian M. Hibberd
Phenotypic landscape inference reveals multiple evolutionary paths to C$_4$ photosynthesis
null
eLife 2 e00961 (2013)
10.7554/eLife.00961
null
q-bio.PE stat.ME
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
C$_4$ photosynthesis has independently evolved from the ancestral C$_3$ pathway in at least 60 plant lineages, but, as with other complex traits, how it evolved is unclear. Here we show that the polyphyletic appearance of C$_4$ photosynthesis is associated with diverse and flexible evolutionary paths that group into four major trajectories. We conducted a meta-analysis of 18 lineages containing species that use C$_3$, C$_4$, or intermediate C$_3$-C$_4$ forms of photosynthesis to parameterise a 16-dimensional phenotypic landscape. We then developed and experimentally verified a novel Bayesian approach based on a hidden Markov model that predicts how the C$_4$ phenotype evolved. The alternative evolutionary histories underlying the appearance of C$_4$ photosynthesis were determined by ancestral lineage and initial phenotypic alterations unrelated to photosynthesis. We conclude that the order of C$_4$ trait acquisition is flexible and driven by non-photosynthetic drivers. This flexibility will have facilitated the convergent evolution of this complex trait.
[ { "created": "Wed, 17 Sep 2014 12:59:01 GMT", "version": "v1" } ]
2014-09-18
[ [ "Williams", "Ben P.", "" ], [ "Johnston", "Iain G.", "" ], [ "Covshoff", "Sarah", "" ], [ "Hibberd", "Julian M.", "" ] ]
C$_4$ photosynthesis has independently evolved from the ancestral C$_3$ pathway in at least 60 plant lineages, but, as with other complex traits, how it evolved is unclear. Here we show that the polyphyletic appearance of C$_4$ photosynthesis is associated with diverse and flexible evolutionary paths that group into four major trajectories. We conducted a meta-analysis of 18 lineages containing species that use C$_3$, C$_4$, or intermediate C$_3$-C$_4$ forms of photosynthesis to parameterise a 16-dimensional phenotypic landscape. We then developed and experimentally verified a novel Bayesian approach based on a hidden Markov model that predicts how the C$_4$ phenotype evolved. The alternative evolutionary histories underlying the appearance of C$_4$ photosynthesis were determined by ancestral lineage and initial phenotypic alterations unrelated to photosynthesis. We conclude that the order of C$_4$ trait acquisition is flexible and driven by non-photosynthetic drivers. This flexibility will have facilitated the convergent evolution of this complex trait.
1501.03578
Liang Liu
Liang Liu, Zhenxiang Xi, Shaoyuan Wu, Charles Davis, Scott V. Edwards
Estimating phylogenetic trees from genome-scale data
39 pages, 3 figures
null
10.1111/nyas.12747
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
As researchers collect increasingly large molecular data sets to reconstruct the Tree of Life, the heterogeneity of signals in the genomes of diverse organisms poses challenges for traditional phylogenetic analysis. A class of phylogenetic methods known as "species tree methods" have been proposed to directly address one important source of gene tree heterogeneity, namely the incomplete lineage sorting or deep coalescence that occurs when evolving lineages radiate rapidly, resulting in a diversity of gene trees from a single underlying species tree. Although such methods are gaining in popularity, they are being adopted with caution in some quarters, in part because of an increasing number of examples of strong phylogenetic conflict between concatenation or supermatrix methods and species tree methods. Here we review theory and empirical examples that help clarify these conflicts. Thinking of concatenation as a special case of the more general model provided by the multispecies coalescent can help explain a number of differences in the behavior of the two methods on phylogenomic data sets. Recent work suggests that species tree methods are more robust than concatenation approaches to some of the classic challenges of phylogenetic analysis, including rapidly evolving sites in DNA sequences, base compositional heterogeneity and long branch attraction. We show that approaches such as binning, designed to augment the signal in species tree analyses, can distort the distribution of gene trees and are inconsistent. Computationally efficient species tree methods that incorporate biological realism are a key to phylogenetic analysis of whole genome data.
[ { "created": "Thu, 15 Jan 2015 05:21:26 GMT", "version": "v1" } ]
2015-09-11
[ [ "Liu", "Liang", "" ], [ "Xi", "Zhenxiang", "" ], [ "Wu", "Shaoyuan", "" ], [ "Davis", "Charles", "" ], [ "Edwards", "Scott V.", "" ] ]
As researchers collect increasingly large molecular data sets to reconstruct the Tree of Life, the heterogeneity of signals in the genomes of diverse organisms poses challenges for traditional phylogenetic analysis. A class of phylogenetic methods known as "species tree methods" have been proposed to directly address one important source of gene tree heterogeneity, namely the incomplete lineage sorting or deep coalescence that occurs when evolving lineages radiate rapidly, resulting in a diversity of gene trees from a single underlying species tree. Although such methods are gaining in popularity, they are being adopted with caution in some quarters, in part because of an increasing number of examples of strong phylogenetic conflict between concatenation or supermatrix methods and species tree methods. Here we review theory and empirical examples that help clarify these conflicts. Thinking of concatenation as a special case of the more general model provided by the multispecies coalescent can help explain a number of differences in the behavior of the two methods on phylogenomic data sets. Recent work suggests that species tree methods are more robust than concatenation approaches to some of the classic challenges of phylogenetic analysis, including rapidly evolving sites in DNA sequences, base compositional heterogeneity and long branch attraction. We show that approaches such as binning, designed to augment the signal in species tree analyses, can distort the distribution of gene trees and are inconsistent. Computationally efficient species tree methods that incorporate biological realism are a key to phylogenetic analysis of whole genome data.
q-bio/0511022
Eytan Domany
Yuval Tabach, Michael Milyavsky, Igor Shats, Ran Brosh, Or Zuk, Assif Yitzhaky, Roberto Mantovani, Eytan Domany, Varda Rotter Yitzhak Pilpel
The promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation
To appear in Molecular Systems Biology
null
null
null
q-bio.MN q-bio.QM
null
Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here we analyzed genome-wide transcription profiling of an in-vitro transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16INK4A tumor suppressors inactivation. This cluster predominantly consists of cell cycle genes and constitutes a signature of a diversity of cancers. By linking expression profiles of the genes in the cluster with the dynamic behavior of p53 and p16INK4A, we identified a promoter architecture that integrates signals from the two tumor suppressive channels and that maps their activity onto distinct levels of expression of the cell cycle genes, which in turn, correspond to different cellular proliferation rates. Taking components of the mitotic spindle as an example, we experimentally verified our predictions that p53-mediated transcriptional repression of several of these novel targets is dependent on the activities of p21, NFY and E2F. Our study demonstrates how a well-controlled transformation process allows linking between gene expression, promoter architecture and activity of upstream signaling molecules.
[ { "created": "Tue, 15 Nov 2005 09:13:10 GMT", "version": "v1" } ]
2007-05-23
[ [ "Tabach", "Yuval", "" ], [ "Milyavsky", "Michael", "" ], [ "Shats", "Igor", "" ], [ "Brosh", "Ran", "" ], [ "Zuk", "Or", "" ], [ "Yitzhaky", "Assif", "" ], [ "Mantovani", "Roberto", "" ], [ "Domany"...
Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here we analyzed genome-wide transcription profiling of an in-vitro transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16INK4A tumor suppressors inactivation. This cluster predominantly consists of cell cycle genes and constitutes a signature of a diversity of cancers. By linking expression profiles of the genes in the cluster with the dynamic behavior of p53 and p16INK4A, we identified a promoter architecture that integrates signals from the two tumor suppressive channels and that maps their activity onto distinct levels of expression of the cell cycle genes, which in turn, correspond to different cellular proliferation rates. Taking components of the mitotic spindle as an example, we experimentally verified our predictions that p53-mediated transcriptional repression of several of these novel targets is dependent on the activities of p21, NFY and E2F. Our study demonstrates how a well-controlled transformation process allows linking between gene expression, promoter architecture and activity of upstream signaling molecules.
1910.08566
Chiara Villa
Chiara Villa, Mark A. J. Chaplain, Tommaso Lorenzi
Modelling the emergence of phenotypic heterogeneity in vascularised tumours
21 pages, 4 figures
null
null
null
q-bio.TO nlin.AO q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present a mathematical study of the emergence of phenotypic heterogeneity in vascularised tumours. Our study is based on formal asymptotic analysis and numerical simulations of a system of non-local parabolic equations that describes the phenotypic evolution of tumour cells and their nonlinear dynamic interactions with the oxygen, which is released from the intratumoural vascular network. Numerical simulations are carried out both in the case of arbitrary distributions of intratumour blood vessels and in the case where the intratumoural vascular network is reconstructed from clinical images obtained using dynamic optical coherence tomography. The results obtained support a more in-depth theoretical understanding of the eco-evolutionary process which underpins the emergence of phenotypic heterogeneity in vascularised tumours. In particular, our results offer a theoretical basis for empirical evidence indicating that the phenotypic properties of cancer cells in vascularised tumours vary with the distance from the blood vessels, and establish a relation between the degree of tumour tissue vascularisation and the level of intratumour phenotypic heterogeneity.
[ { "created": "Fri, 18 Oct 2019 18:00:23 GMT", "version": "v1" }, { "created": "Tue, 22 Sep 2020 21:53:54 GMT", "version": "v2" }, { "created": "Thu, 1 Oct 2020 08:25:35 GMT", "version": "v3" }, { "created": "Thu, 25 Mar 2021 12:54:17 GMT", "version": "v4" } ]
2021-03-26
[ [ "Villa", "Chiara", "" ], [ "Chaplain", "Mark A. J.", "" ], [ "Lorenzi", "Tommaso", "" ] ]
We present a mathematical study of the emergence of phenotypic heterogeneity in vascularised tumours. Our study is based on formal asymptotic analysis and numerical simulations of a system of non-local parabolic equations that describes the phenotypic evolution of tumour cells and their nonlinear dynamic interactions with the oxygen, which is released from the intratumoural vascular network. Numerical simulations are carried out both in the case of arbitrary distributions of intratumour blood vessels and in the case where the intratumoural vascular network is reconstructed from clinical images obtained using dynamic optical coherence tomography. The results obtained support a more in-depth theoretical understanding of the eco-evolutionary process which underpins the emergence of phenotypic heterogeneity in vascularised tumours. In particular, our results offer a theoretical basis for empirical evidence indicating that the phenotypic properties of cancer cells in vascularised tumours vary with the distance from the blood vessels, and establish a relation between the degree of tumour tissue vascularisation and the level of intratumour phenotypic heterogeneity.
2008.04849
Sarath Yasodharan
Shubhada Agrawal, Siddharth Bhandari, Anirban Bhattacharjee, Anand Deo, Narendra M. Dixit, Prahladh Harsha, Sandeep Juneja, Poonam Kesarwani, Aditya Krishna Swamy, Preetam Patil, Nihesh Rathod, Ramprasad Saptharishi, Sharad Shriram, Piyush Srivastava, Rajesh Sundaresan, Nidhin Koshy Vaidhiyan, Sarath Yasodharan
City-Scale Agent-Based Simulators for the Study of Non-Pharmaceutical Interventions in the Context of the COVID-19 Epidemic
56 pages
Journal of the Indian Institute of Science, volume 100, pages 809-847, 2020
10.1007/s41745-020-00211-3
null
q-bio.PE cs.OH physics.soc-ph q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We highlight the usefulness of city-scale agent-based simulators in studying various non-pharmaceutical interventions to manage an evolving pandemic. We ground our studies in the context of the COVID-19 pandemic and demonstrate the power of the simulator via several exploratory case studies in two metropolises, Bengaluru and Mumbai. Such tools become common-place in any city administration's tool kit in our march towards digital health.
[ { "created": "Tue, 11 Aug 2020 16:49:04 GMT", "version": "v1" } ]
2021-01-05
[ [ "Agrawal", "Shubhada", "" ], [ "Bhandari", "Siddharth", "" ], [ "Bhattacharjee", "Anirban", "" ], [ "Deo", "Anand", "" ], [ "Dixit", "Narendra M.", "" ], [ "Harsha", "Prahladh", "" ], [ "Juneja", "Sandeep", ...
We highlight the usefulness of city-scale agent-based simulators in studying various non-pharmaceutical interventions to manage an evolving pandemic. We ground our studies in the context of the COVID-19 pandemic and demonstrate the power of the simulator via several exploratory case studies in two metropolises, Bengaluru and Mumbai. Such tools become common-place in any city administration's tool kit in our march towards digital health.
1506.07314
Steven Frank
Steven A. Frank
d'Alembert's direct and inertial forces acting on populations: the Price equation and the fundamental theorem of natural selection
version 2: New Methods section, revised throughout for minor corrections and clarity, version 3: minor editing, publication information
Entropy 17:7087-7100 (2015)
10.3390/e17107087
null
q-bio.PE cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
I develop a framework for interpreting the forces that act on any population described by frequencies. The conservation of total frequency, or total probability, shapes the characteristics of force. I begin with Fisher's fundamental theorem of natural selection. That theorem partitions the total evolutionary change of a population into two components. The first component is the partial change caused by the direct force of natural selection, holding constant all aspects of the environment. The second component is the partial change caused by the changing environment. I demonstrate that Fisher's partition of total change into the direct force of selection and the forces from the changing environmental frame of reference is identical to d'Alembert's principle of mechanics, which separates the work done by the direct forces from the work done by the inertial forces associated with the changing frame of reference. In d'Alembert's principle, there exist inertial forces from a change in the frame of reference that exactly balance the direct forces. I show that the conservation of total probability strongly shapes the form of the balance between the direct and inertial forces. I then use the strong results for conserved probability to obtain general results for the change in any system quantity, such as biological fitness or energy. Those general results derive from simple coordinate changes between frequencies and system quantities. Ultimately, d'Alembert's separation of direct and inertial forces provides deep conceptual insight into the interpretation of forces and the unification of disparate fields of study.
[ { "created": "Wed, 24 Jun 2015 10:43:17 GMT", "version": "v1" }, { "created": "Fri, 4 Sep 2015 16:28:02 GMT", "version": "v2" }, { "created": "Tue, 20 Oct 2015 18:37:25 GMT", "version": "v3" } ]
2015-10-21
[ [ "Frank", "Steven A.", "" ] ]
I develop a framework for interpreting the forces that act on any population described by frequencies. The conservation of total frequency, or total probability, shapes the characteristics of force. I begin with Fisher's fundamental theorem of natural selection. That theorem partitions the total evolutionary change of a population into two components. The first component is the partial change caused by the direct force of natural selection, holding constant all aspects of the environment. The second component is the partial change caused by the changing environment. I demonstrate that Fisher's partition of total change into the direct force of selection and the forces from the changing environmental frame of reference is identical to d'Alembert's principle of mechanics, which separates the work done by the direct forces from the work done by the inertial forces associated with the changing frame of reference. In d'Alembert's principle, there exist inertial forces from a change in the frame of reference that exactly balance the direct forces. I show that the conservation of total probability strongly shapes the form of the balance between the direct and inertial forces. I then use the strong results for conserved probability to obtain general results for the change in any system quantity, such as biological fitness or energy. Those general results derive from simple coordinate changes between frequencies and system quantities. Ultimately, d'Alembert's separation of direct and inertial forces provides deep conceptual insight into the interpretation of forces and the unification of disparate fields of study.
2204.08525
Yasser Roudi
Iv\'an A. Davidovich, Yasser Roudi
Bayesian interpolation for power laws in neural data analysis
null
null
null
null
q-bio.NC q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Power laws arise in a variety of phenomena ranging from matter undergoing phase transition to the distribution of word frequencies in the English language. Usually, their presence is only apparent when data is abundant, and accurately determining their exponents often requires even larger amounts of data. As the scale of recordings in neuroscience becomes larger, an increasing number of studies attempt to characterise potential power-law relationships in neural data. In this paper, we aim to discuss the potential pitfalls that one faces in such efforts and to promote a Bayesian interpolation framework for this purpose. We apply this framework to synthetic data and to data from a recent study of large-scale recordings in mouse primary visual cortex (V1), where the exponent of a power-law scaling in the data played an important role: its value was argued to determine whether the population's stimulus-response relationship is smooth, and experimental data was provided to confirm that this is indeed so. Our analysis shows that with such data types and sizes as we consider here, the best-fit values found for the parameters of the power law and the uncertainty for these estimates are heavily dependent on the noise model assumed for the estimation, the range of the data chosen, and (with all other things being equal) the particular recordings. It is thus challenging to offer a reliable statement about the exponents of the power law. Our analysis, however, shows that this does not affect the conclusions regarding the smoothness of the population response to low-dimensional stimuli but casts doubt on those to natural images. We discuss the implications of this result for the neural code in the V1 and offer the approach discussed here as a framework that future studies, perhaps exploring larger ranges of data, can employ as their starting point to examine power-law scalings in neural data.
[ { "created": "Mon, 18 Apr 2022 19:14:27 GMT", "version": "v1" } ]
2022-04-20
[ [ "Davidovich", "Iván A.", "" ], [ "Roudi", "Yasser", "" ] ]
Power laws arise in a variety of phenomena ranging from matter undergoing phase transition to the distribution of word frequencies in the English language. Usually, their presence is only apparent when data is abundant, and accurately determining their exponents often requires even larger amounts of data. As the scale of recordings in neuroscience becomes larger, an increasing number of studies attempt to characterise potential power-law relationships in neural data. In this paper, we aim to discuss the potential pitfalls that one faces in such efforts and to promote a Bayesian interpolation framework for this purpose. We apply this framework to synthetic data and to data from a recent study of large-scale recordings in mouse primary visual cortex (V1), where the exponent of a power-law scaling in the data played an important role: its value was argued to determine whether the population's stimulus-response relationship is smooth, and experimental data was provided to confirm that this is indeed so. Our analysis shows that with such data types and sizes as we consider here, the best-fit values found for the parameters of the power law and the uncertainty for these estimates are heavily dependent on the noise model assumed for the estimation, the range of the data chosen, and (with all other things being equal) the particular recordings. It is thus challenging to offer a reliable statement about the exponents of the power law. Our analysis, however, shows that this does not affect the conclusions regarding the smoothness of the population response to low-dimensional stimuli but casts doubt on those to natural images. We discuss the implications of this result for the neural code in the V1 and offer the approach discussed here as a framework that future studies, perhaps exploring larger ranges of data, can employ as their starting point to examine power-law scalings in neural data.
1303.5986
Rory Donovan
Rory M. Donovan, Andrew J. Sedgewick, James R. Faeder, Daniel M. Zuckerman
Efficient Stochastic Simulation of Chemical Kinetics Networks using a Weighted Ensemble of Trajectories
11 pages, 6 figures, 4 supplemental files
J. Chem. Phys. 139, 115105 (2013)
10.1063/1.4821167
null
q-bio.MN physics.bio-ph physics.chem-ph q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We apply the "weighted ensemble" (WE) simulation strategy, previously employed in the context of molecular dynamics simulations, to a series of systems-biology models that range in complexity from one-dimensional to a system with 354 species and 3680 reactions. WE is relatively easy to implement, does not require extensive hand-tuning of parameters, does not depend on the details of the simulation algorithm, and can facilitate the simulation of extremely rare events. For the coupled stochastic reaction systems we study, WE is able to produce accurate and efficient approximations of the joint probability distribution for all chemical species for all time t. WE is also able to efficiently extract mean first passage times for the systems, via the construction of a steady-state condition with feedback. In all cases studied here, WE results agree with independent calculations, but significantly enhance the precision with which rare or slow processes can be characterized. Speedups over "brute-force" in sampling rare events via the Gillespie direct Stochastic Simulation Algorithm range from ~10^12 to ~10^20 for rare states in a distribution, and ~10^2 to ~10^4 for finding mean first passage times.
[ { "created": "Sun, 24 Mar 2013 20:04:18 GMT", "version": "v1" }, { "created": "Thu, 28 Mar 2013 20:48:20 GMT", "version": "v2" } ]
2015-03-11
[ [ "Donovan", "Rory M.", "" ], [ "Sedgewick", "Andrew J.", "" ], [ "Faeder", "James R.", "" ], [ "Zuckerman", "Daniel M.", "" ] ]
We apply the "weighted ensemble" (WE) simulation strategy, previously employed in the context of molecular dynamics simulations, to a series of systems-biology models that range in complexity from one-dimensional to a system with 354 species and 3680 reactions. WE is relatively easy to implement, does not require extensive hand-tuning of parameters, does not depend on the details of the simulation algorithm, and can facilitate the simulation of extremely rare events. For the coupled stochastic reaction systems we study, WE is able to produce accurate and efficient approximations of the joint probability distribution for all chemical species for all time t. WE is also able to efficiently extract mean first passage times for the systems, via the construction of a steady-state condition with feedback. In all cases studied here, WE results agree with independent calculations, but significantly enhance the precision with which rare or slow processes can be characterized. Speedups over "brute-force" in sampling rare events via the Gillespie direct Stochastic Simulation Algorithm range from ~10^12 to ~10^20 for rare states in a distribution, and ~10^2 to ~10^4 for finding mean first passage times.
1705.09347
Michael Margaliot
Yoram Zarai and Michael Margaliot and Tamir Tuller
Ribosome Flow Model with Extended Objects
null
null
null
null
q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We study a deterministic mechanistic model for the flow of ribosomes along the mRNA molecule, called the ribosome flow model with extended objects (RFMEO). This model encapsulates many realistic features of translation including non-homogeneous transition rates along the mRNA, the fact that every ribosome covers several codons, and the fact that ribosomes cannot overtake one another. The RFMEO is a mean-field approximation of an important model from statistical mechanics called the totally asymmetric simple exclusion process with extended objects (TASEPEO). We demonstrate that the RFMEO describes biophysical aspects of translation better than previous mean-field approximations, and that its predictions correlate well with those of TASEPEO. However, unlike TASEPEO, the RFMEO is amenable to rigorous analysis using tools from systems and control theory. We show that the ribosome density profile along the mRNA in the RFMEO converges to a unique steady-state density that depends on the length of the mRNA, the transition rates along it, and the number of codons covered by every ribosome, but not on the initial density of ribosomes along the mRNA. In particular, the protein production rate also converges to a unique steady-state. Furthermore, if the transition rates along the mRNA are periodic with a common period T then the ribosome density along the mRNA and the protein production rate converge to a unique periodic pattern with period T, that is, the model entrains to periodic excitations in the transition rates. We believe that the RFMEO could be useful for modeling, understanding, and re-engineering translation as well as other important biological processes.
[ { "created": "Thu, 25 May 2017 20:12:50 GMT", "version": "v1" } ]
2017-05-29
[ [ "Zarai", "Yoram", "" ], [ "Margaliot", "Michael", "" ], [ "Tuller", "Tamir", "" ] ]
We study a deterministic mechanistic model for the flow of ribosomes along the mRNA molecule, called the ribosome flow model with extended objects (RFMEO). This model encapsulates many realistic features of translation including non-homogeneous transition rates along the mRNA, the fact that every ribosome covers several codons, and the fact that ribosomes cannot overtake one another. The RFMEO is a mean-field approximation of an important model from statistical mechanics called the totally asymmetric simple exclusion process with extended objects (TASEPEO). We demonstrate that the RFMEO describes biophysical aspects of translation better than previous mean-field approximations, and that its predictions correlate well with those of TASEPEO. However, unlike TASEPEO, the RFMEO is amenable to rigorous analysis using tools from systems and control theory. We show that the ribosome density profile along the mRNA in the RFMEO converges to a unique steady-state density that depends on the length of the mRNA, the transition rates along it, and the number of codons covered by every ribosome, but not on the initial density of ribosomes along the mRNA. In particular, the protein production rate also converges to a unique steady-state. Furthermore, if the transition rates along the mRNA are periodic with a common period T then the ribosome density along the mRNA and the protein production rate converge to a unique periodic pattern with period T, that is, the model entrains to periodic excitations in the transition rates. We believe that the RFMEO could be useful for modeling, understanding, and re-engineering translation as well as other important biological processes.
1801.07130
Yifei Qi
Jingxue Wang, Huali Cao, and John Z.H. Zhang, and Yifei Qi
Computational Protein Design with Deep Learning Neural Networks
16 pages, 5 figures, 3 tables
Scientific Reports 8: 6349 (2018)
10.1038/s41598-018-24760-x
null
q-bio.QM q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Computational protein design has a wide variety of applications. Despite its remarkable success, designing a protein for a given structure and function is still a challenging task. On the other hand, the number of solved protein structures is rapidly increasing while the number of unique protein folds has reached a steady number, suggesting more structural information is being accumulated on each fold. Deep learning neural network is a powerful method to learn such big data set and has shown superior performance in many machine learning fields. In this study, we applied the deep learning neural network approach to computational protein design for predicting the probability of 20 natural amino acids on each residue in a protein. A large set of protein structures was collected and a multi-layer neural network was constructed. A number of structural properties were extracted as input features and the best network achieved an accuracy of 38.3%. Using the network output as residue type restraints was able to improve the average sequence identity in designing three natural proteins using Rosetta. Moreover, the predictions from our network show ~3% higher sequence identity than a previous method. Results from this study may benefit further development of computational protein design methods.
[ { "created": "Mon, 22 Jan 2018 14:59:18 GMT", "version": "v1" }, { "created": "Sat, 24 Feb 2018 03:15:40 GMT", "version": "v2" } ]
2018-04-26
[ [ "Wang", "Jingxue", "" ], [ "Cao", "Huali", "" ], [ "Zhang", "John Z. H.", "" ], [ "Qi", "Yifei", "" ] ]
Computational protein design has a wide variety of applications. Despite its remarkable success, designing a protein for a given structure and function is still a challenging task. On the other hand, the number of solved protein structures is rapidly increasing while the number of unique protein folds has reached a steady number, suggesting more structural information is being accumulated on each fold. Deep learning neural network is a powerful method to learn such big data set and has shown superior performance in many machine learning fields. In this study, we applied the deep learning neural network approach to computational protein design for predicting the probability of 20 natural amino acids on each residue in a protein. A large set of protein structures was collected and a multi-layer neural network was constructed. A number of structural properties were extracted as input features and the best network achieved an accuracy of 38.3%. Using the network output as residue type restraints was able to improve the average sequence identity in designing three natural proteins using Rosetta. Moreover, the predictions from our network show ~3% higher sequence identity than a previous method. Results from this study may benefit further development of computational protein design methods.
1804.00153
Cristiano Capone
Cristiano Capone, Guido Gigante, Paolo Del Giudice
Spontaneous activity emerging from an inferred network model captures complex temporal dynamics of spiking data
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The combination of new recording techniques in neuroscience and powerful inference methods recently held the promise to recover useful effective models, at the single neuron or network level, directly from observed data. The value of a model of course should critically depend on its ability to reproduce the dynamical behavior of the modeled system; however, few attempts have been made to inquire into the dynamics of inferred models in neuroscience, and none, to our knowledge, at the network level. Here we introduce a principled modification of a widely used generalized linear model (GLM), and learn its structural and dynamic parameters from ex-vivo spiking data. We show that the new model is able to capture the most prominent features of the highly non-stationary and non-linear dynamics displayed by the biological network, where the reference GLM largely fails. Two ingredients turn out to be key for success. The first one is a bounded transfer function that makes the single neuron able to respond to its input in a saturating fashion; beyond its biological plausibility such property, by limiting the capacity of the neuron to transfer information, makes the coding more robust in the face of the highly variable network activity, and noise. The second ingredient is a super-Poisson spikes generative probabilistic mechanism; this feature, that accounts for the fact that observations largely undersample the network, allows the model neuron to more flexibly incorporate the observed activity fluctuations. Taken together, the two ingredients, without increasing complexity, allow the model to capture the key dynamic elements. When left free to generate its spontaneous activity, the inferred model proved able to reproduce not only the non-stationary population dynamics of the network, but also part of the fine-grained structure of the dynamics at the single neuron level.
[ { "created": "Sat, 31 Mar 2018 10:48:34 GMT", "version": "v1" }, { "created": "Fri, 6 Apr 2018 09:06:53 GMT", "version": "v2" } ]
2018-04-09
[ [ "Capone", "Cristiano", "" ], [ "Gigante", "Guido", "" ], [ "Del Giudice", "Paolo", "" ] ]
The combination of new recording techniques in neuroscience and powerful inference methods recently held the promise to recover useful effective models, at the single neuron or network level, directly from observed data. The value of a model of course should critically depend on its ability to reproduce the dynamical behavior of the modeled system; however, few attempts have been made to inquire into the dynamics of inferred models in neuroscience, and none, to our knowledge, at the network level. Here we introduce a principled modification of a widely used generalized linear model (GLM), and learn its structural and dynamic parameters from ex-vivo spiking data. We show that the new model is able to capture the most prominent features of the highly non-stationary and non-linear dynamics displayed by the biological network, where the reference GLM largely fails. Two ingredients turn out to be key for success. The first one is a bounded transfer function that makes the single neuron able to respond to its input in a saturating fashion; beyond its biological plausibility such property, by limiting the capacity of the neuron to transfer information, makes the coding more robust in the face of the highly variable network activity, and noise. The second ingredient is a super-Poisson spikes generative probabilistic mechanism; this feature, that accounts for the fact that observations largely undersample the network, allows the model neuron to more flexibly incorporate the observed activity fluctuations. Taken together, the two ingredients, without increasing complexity, allow the model to capture the key dynamic elements. When left free to generate its spontaneous activity, the inferred model proved able to reproduce not only the non-stationary population dynamics of the network, but also part of the fine-grained structure of the dynamics at the single neuron level.
1310.5910
Michael Courtney
Joshua M. Courtney and Michael W. Courtney
Comments on "Analysis of permanent magnets as elasmobranch bycatch reduction devices in hook-and-line and longline trials"
null
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A recent study (Fish. Bull. 109:394-401 (2011)) purportedly tests two hypotheses: 1. that the capture of elasmobranchs would be reduced with hooks containing magnets in comparison with control hooks in hook-and-line and longline studies. 2. that the presence of permanent magnets on hooks would not alter teleost capture because teleosts lack the ampullary organ. Review of this paper shows some inconsistencies in the data supporting the first hypothesis and insufficient data and poor experimental design to adequately test the second hypothesis. Further, since several orders of teleosts are known to possess ampullary organs and demonstrate electroreception, grouping all teleosts in a study design or data analysis of magnetic hook catch rates is not warranted. Adequate tests of the hypothesis that permanent magnets or magnetized hooks do not alter teleost capture requires a more careful study design and much larger sample sizes than O'Connell et al. (Fish. Bull. 109:394-401 (2011)).
[ { "created": "Tue, 22 Oct 2013 13:25:56 GMT", "version": "v1" } ]
2013-10-23
[ [ "Courtney", "Joshua M.", "" ], [ "Courtney", "Michael W.", "" ] ]
A recent study (Fish. Bull. 109:394-401 (2011)) purportedly tests two hypotheses: 1. that the capture of elasmobranchs would be reduced with hooks containing magnets in comparison with control hooks in hook-and-line and longline studies. 2. that the presence of permanent magnets on hooks would not alter teleost capture because teleosts lack the ampullary organ. Review of this paper shows some inconsistencies in the data supporting the first hypothesis and insufficient data and poor experimental design to adequately test the second hypothesis. Further, since several orders of teleosts are known to possess ampullary organs and demonstrate electroreception, grouping all teleosts in a study design or data analysis of magnetic hook catch rates is not warranted. Adequate tests of the hypothesis that permanent magnets or magnetized hooks do not alter teleost capture requires a more careful study design and much larger sample sizes than O'Connell et al. (Fish. Bull. 109:394-401 (2011)).
1508.03354
Andre Chalom
Andr\'e Chalom and Paulo In\'acio de Knegt L\'opez de Prado
Uncertainty analysis and composite hypothesis under the likelihood paradigm
null
null
null
null
q-bio.QM stat.ME
http://creativecommons.org/licenses/by-sa/4.0/
The correct use and interpretation of models depends on several steps, two of which being the calibration by parameter estimation and the analysis of uncertainty. In the biological literature, these steps are seldom discussed together, but they can be seen as fitting pieces of the same puzzle. In particular, analytical procedures for uncertainty estimation may be masking a high degree of uncertainty coming from a model with a stable structure, but insufficient data. Under a likelihoodist approach, the problem of uncertainty estimation is closely related to the problem of composite hypothesis. In this paper, we present a brief historical background on the statistical school of Likelihoodism, and examine the complex relations between the law of likelihood and the problem of composite hypothesis, together with the existing proposals for coping with it. Then, we propose a new integrative methodology for the uncertainty estimation of models using the information in the collected data. We argue that this methodology is intuitively appealing under a likelihood paradigm.
[ { "created": "Thu, 13 Aug 2015 20:40:58 GMT", "version": "v1" } ]
2015-08-17
[ [ "Chalom", "André", "" ], [ "de Prado", "Paulo Inácio de Knegt López", "" ] ]
The correct use and interpretation of models depends on several steps, two of which being the calibration by parameter estimation and the analysis of uncertainty. In the biological literature, these steps are seldom discussed together, but they can be seen as fitting pieces of the same puzzle. In particular, analytical procedures for uncertainty estimation may be masking a high degree of uncertainty coming from a model with a stable structure, but insufficient data. Under a likelihoodist approach, the problem of uncertainty estimation is closely related to the problem of composite hypothesis. In this paper, we present a brief historical background on the statistical school of Likelihoodism, and examine the complex relations between the law of likelihood and the problem of composite hypothesis, together with the existing proposals for coping with it. Then, we propose a new integrative methodology for the uncertainty estimation of models using the information in the collected data. We argue that this methodology is intuitively appealing under a likelihood paradigm.
1911.00755
Fernando Racimo
Fernando Racimo, Martin Sikora, Hannes Schroeder, Carles Lalueza-Fox
Beyond broad strokes: sociocultural insights from the study of ancient genomes
null
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
The amount of sequence data obtained from ancient samples has dramatically expanded in the last decade, and so have the types of questions that can now be addressed using ancient DNA. In the field of human history, while ancient DNA has provided answers to long-standing debates about major movements of people, it has also recently begun to inform on other important facets of the human experience. The field is now moving from not only focusing on large-scale supra-regional studies to also taking a more local perspective, shedding light on socioeconomic processes, inheritance rules, marriage practices and technological diffusion. In this review, we summarize recent studies showcasing these types of insights, focusing on the methods used to infer sociocultural aspects of human behaviour. This work often involves working across disciplines that have, until recently, evolved in separation. We argue that multidisciplinary dialogue is crucial for a more integrated and richer reconstruction of human history, as it can yield extraordinary insights about past societies, reproductive behaviours and even lifestyle habits that would not have been possible to obtain otherwise.
[ { "created": "Sat, 2 Nov 2019 17:20:32 GMT", "version": "v1" }, { "created": "Tue, 7 Jan 2020 14:26:26 GMT", "version": "v2" } ]
2020-01-08
[ [ "Racimo", "Fernando", "" ], [ "Sikora", "Martin", "" ], [ "Schroeder", "Hannes", "" ], [ "Lalueza-Fox", "Carles", "" ] ]
The amount of sequence data obtained from ancient samples has dramatically expanded in the last decade, and so have the types of questions that can now be addressed using ancient DNA. In the field of human history, while ancient DNA has provided answers to long-standing debates about major movements of people, it has also recently begun to inform on other important facets of the human experience. The field is now moving from not only focusing on large-scale supra-regional studies to also taking a more local perspective, shedding light on socioeconomic processes, inheritance rules, marriage practices and technological diffusion. In this review, we summarize recent studies showcasing these types of insights, focusing on the methods used to infer sociocultural aspects of human behaviour. This work often involves working across disciplines that have, until recently, evolved in separation. We argue that multidisciplinary dialogue is crucial for a more integrated and richer reconstruction of human history, as it can yield extraordinary insights about past societies, reproductive behaviours and even lifestyle habits that would not have been possible to obtain otherwise.
1505.00116
David Steinsaltz
David Steinsaltz and Shripad Tuljapurkar
Stochastic growth rates for life histories with rare migration or diapause
32 pages, 4 figures
null
null
null
q-bio.PE math.PR
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The growth of a population divided among spatial sites, with migration between the sites, is sometimes modelled by a product of random matrices, with each diagonal elements representing the growth rate in a given time period, and off-diagonal elements the migration rate. If the sites are reinterpreted as age classes, the same model may apply to a single population with age-dependent mortality and reproduction. We consider the case where the off-diagonal elements are small, representing a situation where there is little migration or, alternatively, where a deterministic life-history has been slightly disrupted, for example by introducing a rare delay in development. We examine the asymptotic behaviour of the long-term growth rate. We show that when the highest growth rate is attained at two different sites in the absence of migration (which is always the case when modelling a single age-structured population) the increase in stochastic growth rate due to a migration rate $\epsilon$ is like $(\log \epsilon^{-1})^{-1}$ as $\epsilon\downarrow 0$, under fairly generic conditions. When there is a single site with the highest growth rate the behavior is more delicate, depending on the tails of the growth rates. For the case when the log growth rates have Gaussian-like tails we show that the behavior near zero is like a power of $\epsilon$, and derive upper and lower bounds for the power in terms of the difference in the growth rates and the distance between the sites.
[ { "created": "Fri, 1 May 2015 08:17:45 GMT", "version": "v1" } ]
2015-05-04
[ [ "Steinsaltz", "David", "" ], [ "Tuljapurkar", "Shripad", "" ] ]
The growth of a population divided among spatial sites, with migration between the sites, is sometimes modelled by a product of random matrices, with each diagonal elements representing the growth rate in a given time period, and off-diagonal elements the migration rate. If the sites are reinterpreted as age classes, the same model may apply to a single population with age-dependent mortality and reproduction. We consider the case where the off-diagonal elements are small, representing a situation where there is little migration or, alternatively, where a deterministic life-history has been slightly disrupted, for example by introducing a rare delay in development. We examine the asymptotic behaviour of the long-term growth rate. We show that when the highest growth rate is attained at two different sites in the absence of migration (which is always the case when modelling a single age-structured population) the increase in stochastic growth rate due to a migration rate $\epsilon$ is like $(\log \epsilon^{-1})^{-1}$ as $\epsilon\downarrow 0$, under fairly generic conditions. When there is a single site with the highest growth rate the behavior is more delicate, depending on the tails of the growth rates. For the case when the log growth rates have Gaussian-like tails we show that the behavior near zero is like a power of $\epsilon$, and derive upper and lower bounds for the power in terms of the difference in the growth rates and the distance between the sites.
1208.5350
Man Yi Yim
Man Yi Yim, Ad Aertsen, Stefan Rotter
Impact of intrinsic biophysical diversity on the activity of spiking neurons
4 pages, 5 figures
Phys. Rev. E 87, 032710 (2013)
10.1103/PhysRevE.87.032710
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We study the effect of intrinsic heterogeneity on the activity of a population of leaky integrate-and-fire neurons. By rescaling the dynamical equation, we derive mathematical relations between multiple neuronal parameters and a fluctuating input noise. To this end, common input to heterogeneous neurons is conceived as an identical noise with neuron-specific mean and variance. As a consequence, the neuronal output rates can differ considerably, and their relative spike timing becomes desynchronized. This theory can quantitatively explain some recent experimental findings.
[ { "created": "Mon, 27 Aug 2012 10:06:12 GMT", "version": "v1" }, { "created": "Wed, 16 Jan 2013 10:27:55 GMT", "version": "v2" }, { "created": "Thu, 31 Jan 2013 14:42:54 GMT", "version": "v3" }, { "created": "Tue, 19 Feb 2013 17:08:00 GMT", "version": "v4" } ]
2013-08-21
[ [ "Yim", "Man Yi", "" ], [ "Aertsen", "Ad", "" ], [ "Rotter", "Stefan", "" ] ]
We study the effect of intrinsic heterogeneity on the activity of a population of leaky integrate-and-fire neurons. By rescaling the dynamical equation, we derive mathematical relations between multiple neuronal parameters and a fluctuating input noise. To this end, common input to heterogeneous neurons is conceived as an identical noise with neuron-specific mean and variance. As a consequence, the neuronal output rates can differ considerably, and their relative spike timing becomes desynchronized. This theory can quantitatively explain some recent experimental findings.
2304.07273
Stefano Grasso
Nicol\`o Cangiotti and Stefano Grasso
Genus Comparisons in the Topological Analysis of RNA Structures
11 pages, 9 figures
null
null
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
RNA folding prediction remains challenging, but can be also studied using a topological mathematical approach. In the present paper, the mathematical method to compute the topological classification of RNA structures and based on matrix field theory is shortly reviewed, as well as a computational software, McGenus, used for topological and folding predictions. Additionally, two types of analysis are performed: the prediction results from McGenus are compared with topological information extracted from experimentally-determined RNA structures, and the topology of RNA structures is investigated for biological significance, in both evolutionary and functional terms. Lastly, we advocate for more research efforts to be performed at intersection of physics-mathematics and biology, and in particular about the possible contributions that topology can provide to the study of RNA folding and structure.
[ { "created": "Fri, 14 Apr 2023 17:35:44 GMT", "version": "v1" }, { "created": "Mon, 17 Apr 2023 19:41:36 GMT", "version": "v2" }, { "created": "Thu, 11 May 2023 16:14:43 GMT", "version": "v3" } ]
2023-05-12
[ [ "Cangiotti", "Nicolò", "" ], [ "Grasso", "Stefano", "" ] ]
RNA folding prediction remains challenging, but can be also studied using a topological mathematical approach. In the present paper, the mathematical method to compute the topological classification of RNA structures and based on matrix field theory is shortly reviewed, as well as a computational software, McGenus, used for topological and folding predictions. Additionally, two types of analysis are performed: the prediction results from McGenus are compared with topological information extracted from experimentally-determined RNA structures, and the topology of RNA structures is investigated for biological significance, in both evolutionary and functional terms. Lastly, we advocate for more research efforts to be performed at intersection of physics-mathematics and biology, and in particular about the possible contributions that topology can provide to the study of RNA folding and structure.
2007.08374
Markus D Schirmer
Markus D. Schirmer, Kathleen L. Donahue, Marco J. Nardin, Adrian V. Dalca, Anne-Katrin Giese, Mark R. Etherton, Steven J. T. Mocking, Elissa C. McIntosh, John W. Cole, Lukas Holmegaard, Katarina Jood, Jordi Jimenez-Conde, Steven J. Kittner, Robin Lemmens, James F. Meschia, Jonathan Rosand, Jaume Roquer, Tatjana Rundek, Ralph L. Sacco MD, Reinhold Schmidt, Pankaj Sharma, Agnieszka Slowik, Tara M. Stanne, Achala Vagal, Johan Wasselius, Daniel Woo, Stephen Bevan, Laura Heitsch, Chia-Ling Phuah, Daniel Strbian MD, Turgut Tatlisumak, Christopher R. Levi, John Attia, Patrick F. McArdle, Bradford B. Worrall, Ona Wu, Christina Jern, Arne Lindgren, Jane Maguire, Vincent Thijs, Natalia S. Rost
Brain volume: An important determinant of functional outcome after acute ischemic stroke
null
Mayo Clinic Proceedings. Vol. 95. No. 5. Elsevier, 2020
10.1016/j.mayocp.2020.01.027
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Objective: To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). Methods: We analyzed cross-sectional data of the multi-site, international hospital-based MRI-GENetics Interface Exploration (MRI-GENIE) study (July 1, 2014- March 16, 2019) with clinical brain magnetic resonance imaging (MRI) obtained on admission for index stroke and functional outcome assessment. Post-stroke outcome was determined using the modified Rankin Scale (mRS) score (0-6; 0: asymptomatic; 6 death) recorded between 60-190 days after stroke. Demographics and other clinical variables including acute stroke severity (measured as National Institutes of Health Stroke Scale score), vascular risk factors, and etiologic stroke subtypes (Causative Classification of Stroke) were recorded during index admission. Results: Utilizing the data from 912 acute ischemic stroke (AIS) patients (65+/-15 years of age, 58% male, 57% history of smoking, and 65% hypertensive) in a generalized linear model, brain volume (per 155.1cm^3 ) was associated with age (beta -0.3 (per 14.4 years)), male sex (beta 1.0) and prior stroke (beta -0.2). In the multivariable outcome model, brain volume was an independent predictor of mRS (beta -0.233), with reduced odds of worse long-term functional outcomes (OR: 0.8, 95% CI 0.7-0.9) in those with larger brain volumes. Conclusions: Larger brain volume quantified on clinical MRI of AIS patients at time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of mechanisms of post-stroke recovery.
[ { "created": "Thu, 16 Jul 2020 14:51:40 GMT", "version": "v1" } ]
2020-07-17
[ [ "Schirmer", "Markus D.", "" ], [ "Donahue", "Kathleen L.", "" ], [ "Nardin", "Marco J.", "" ], [ "Dalca", "Adrian V.", "" ], [ "Giese", "Anne-Katrin", "" ], [ "Etherton", "Mark R.", "" ], [ "Mocking", "Steven J...
Objective: To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). Methods: We analyzed cross-sectional data of the multi-site, international hospital-based MRI-GENetics Interface Exploration (MRI-GENIE) study (July 1, 2014- March 16, 2019) with clinical brain magnetic resonance imaging (MRI) obtained on admission for index stroke and functional outcome assessment. Post-stroke outcome was determined using the modified Rankin Scale (mRS) score (0-6; 0: asymptomatic; 6 death) recorded between 60-190 days after stroke. Demographics and other clinical variables including acute stroke severity (measured as National Institutes of Health Stroke Scale score), vascular risk factors, and etiologic stroke subtypes (Causative Classification of Stroke) were recorded during index admission. Results: Utilizing the data from 912 acute ischemic stroke (AIS) patients (65+/-15 years of age, 58% male, 57% history of smoking, and 65% hypertensive) in a generalized linear model, brain volume (per 155.1cm^3 ) was associated with age (beta -0.3 (per 14.4 years)), male sex (beta 1.0) and prior stroke (beta -0.2). In the multivariable outcome model, brain volume was an independent predictor of mRS (beta -0.233), with reduced odds of worse long-term functional outcomes (OR: 0.8, 95% CI 0.7-0.9) in those with larger brain volumes. Conclusions: Larger brain volume quantified on clinical MRI of AIS patients at time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of mechanisms of post-stroke recovery.
1807.01828
Dirson Jian Li
Dirson Jian Li
Observations and perspectives on the variation of biodiversity
39 pages, 8 figures
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by-nc-sa/4.0/
Based on statistical analysis of the complete genome sequences, a remote relationship has been observed between the evolution of the genetic code and the three domain tree of life. The existence of such a remote relationship need to be explained. The unity of the living system throughout the history of life relies on the common features of life: the homochirality, the genetic code and the universal genome format. The universal genome format has been observed in the genomic codon distributions as a common feature of life at the sequence level. A main aim of this article is to reconstruct and to explain the Phanerozoic biodiversity curve. It has been observed that the exponential growth rate of the Phanerozoic biodiversity curve is about equal to the exponential growth rate of genome size evolution. Hence it is strongly indicated that the expansion of genomes causes the exponential trend of the Phanerozoic biodiversity curve, where the conservative property during the evolution of life is guaranteed by the universal genome format at the sequence level. In addition, a consensus curve based on the climatic and eustatic data is obtained to explain the fluctuations of the Phanerozoic biodiversity curve. Thus, the reconstructed biodiversity curve based on genomic, climatic and eustatic data agrees with Sepkoski's curve based on fossil data. The five mass extinctions can be discerned in this reconstructed biodiversity curve, which indicates a tectonic cause of the mass extinctions. And the declining origination rate and extinction rate throughout the Phanerozoic eon might be due to the growth trend in genome size evolution.
[ { "created": "Thu, 5 Jul 2018 02:04:56 GMT", "version": "v1" } ]
2018-07-06
[ [ "Li", "Dirson Jian", "" ] ]
Based on statistical analysis of the complete genome sequences, a remote relationship has been observed between the evolution of the genetic code and the three domain tree of life. The existence of such a remote relationship need to be explained. The unity of the living system throughout the history of life relies on the common features of life: the homochirality, the genetic code and the universal genome format. The universal genome format has been observed in the genomic codon distributions as a common feature of life at the sequence level. A main aim of this article is to reconstruct and to explain the Phanerozoic biodiversity curve. It has been observed that the exponential growth rate of the Phanerozoic biodiversity curve is about equal to the exponential growth rate of genome size evolution. Hence it is strongly indicated that the expansion of genomes causes the exponential trend of the Phanerozoic biodiversity curve, where the conservative property during the evolution of life is guaranteed by the universal genome format at the sequence level. In addition, a consensus curve based on the climatic and eustatic data is obtained to explain the fluctuations of the Phanerozoic biodiversity curve. Thus, the reconstructed biodiversity curve based on genomic, climatic and eustatic data agrees with Sepkoski's curve based on fossil data. The five mass extinctions can be discerned in this reconstructed biodiversity curve, which indicates a tectonic cause of the mass extinctions. And the declining origination rate and extinction rate throughout the Phanerozoic eon might be due to the growth trend in genome size evolution.
1903.05979
Vince Grolmusz
Mate Fellner and Balint Varga and Vince Grolmusz
The Frequent Complete Subgraphs in the Human Connectome
null
null
10.1371/journal.pone.0236883
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
While it is still not possible to describe the neural-level connections of the human brain, we can map the human connectome with several hundred vertices, by the application of diffusion-MRI based techniques. In these graphs, the nodes correspond to anatomically identified gray matter areas of the brain, while the edges correspond to the axonal fibers, connecting these areas. In our previous contributions, we have described numerous graph-theoretical phenomena of the human connectomes. Here we map the frequent complete subgraphs of the human brain networks: in these subgraphs, every pair of vertices is connected by an edge. We also examine sex differences in the results. The mapping of the frequent subgraphs gives robust substructures in the graph: if a subgraph is present in the 80% of the graphs, then, most probably, it could not be an artifact of the measurement or the data processing workflow. We list here the frequent complete subgraphs of the human braingraphs of 414 subjects, each with 463 nodes, with a frequency threshold of 80%, and identify 812 complete subgraphs, which are more frequent in male and 224 complete subgraphs, which are more frequent in female connectomes.
[ { "created": "Thu, 14 Mar 2019 13:26:38 GMT", "version": "v1" }, { "created": "Wed, 27 Mar 2019 18:31:13 GMT", "version": "v2" } ]
2020-09-09
[ [ "Fellner", "Mate", "" ], [ "Varga", "Balint", "" ], [ "Grolmusz", "Vince", "" ] ]
While it is still not possible to describe the neural-level connections of the human brain, we can map the human connectome with several hundred vertices, by the application of diffusion-MRI based techniques. In these graphs, the nodes correspond to anatomically identified gray matter areas of the brain, while the edges correspond to the axonal fibers, connecting these areas. In our previous contributions, we have described numerous graph-theoretical phenomena of the human connectomes. Here we map the frequent complete subgraphs of the human brain networks: in these subgraphs, every pair of vertices is connected by an edge. We also examine sex differences in the results. The mapping of the frequent subgraphs gives robust substructures in the graph: if a subgraph is present in the 80% of the graphs, then, most probably, it could not be an artifact of the measurement or the data processing workflow. We list here the frequent complete subgraphs of the human braingraphs of 414 subjects, each with 463 nodes, with a frequency threshold of 80%, and identify 812 complete subgraphs, which are more frequent in male and 224 complete subgraphs, which are more frequent in female connectomes.
1707.08914
Anatoly Zhokhin
A.S. Zhokhin, V.P. Gachok
Transition to Chaos in the Kinetic Model of Cellulose Hydrolysis Under Enzyme Biosynthesis Control
3 pages, 7 figures
null
null
null
q-bio.CB nlin.AO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In the paper the kinetic model of the biochemical process of cellulose hydrolysis with cell application is presented. The model includes enzyme biosynthesis control and is open conditions it represents the dynamical system in the preturbulent regime. The limit cycle and its five consequence bifurcations of the doubling-period type are found. Also the limit regime of the system - the strange attractor - is presented.
[ { "created": "Thu, 27 Jul 2017 15:52:54 GMT", "version": "v1" } ]
2020-07-09
[ [ "Zhokhin", "A. S.", "" ], [ "Gachok", "V. P.", "" ] ]
In the paper the kinetic model of the biochemical process of cellulose hydrolysis with cell application is presented. The model includes enzyme biosynthesis control and is open conditions it represents the dynamical system in the preturbulent regime. The limit cycle and its five consequence bifurcations of the doubling-period type are found. Also the limit regime of the system - the strange attractor - is presented.
1510.07882
Mareike Fischer
Mareike Fischer, Volkmar Liebscher
On the Balance of Unrooted Trees
16 pages, 8 figures
null
null
null
q-bio.PE math.CO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We solve a class of optimization problems for (phylogenetic) $X$-trees or their shapes. These problems have recently appeared in different contexts, e.g. in the context of the impact of tree shapes on the size of TBR neighborhoods, but so far these problems have not been characterized and solved in a systematic way. In this work we generalize the concept and also present several applications. Moreover, our results give rise to a nice notion of balance for trees. Unsurprisingly, so-called caterpillars are the most unbalanced tree shapes, but it turns out that balanced tree shapes cannot be described so easily as they need not even be unique.
[ { "created": "Tue, 27 Oct 2015 12:31:44 GMT", "version": "v1" } ]
2015-10-28
[ [ "Fischer", "Mareike", "" ], [ "Liebscher", "Volkmar", "" ] ]
We solve a class of optimization problems for (phylogenetic) $X$-trees or their shapes. These problems have recently appeared in different contexts, e.g. in the context of the impact of tree shapes on the size of TBR neighborhoods, but so far these problems have not been characterized and solved in a systematic way. In this work we generalize the concept and also present several applications. Moreover, our results give rise to a nice notion of balance for trees. Unsurprisingly, so-called caterpillars are the most unbalanced tree shapes, but it turns out that balanced tree shapes cannot be described so easily as they need not even be unique.
1308.2273
Naoki Masuda Dr.
Yohei Nakajima and Naoki Masuda
Evolutionary dynamics in finite populations with zealots
1 table, 4 figures
Journal of Mathematical Biology, 70, 465-484 (2015)
10.1007/s00285-014-0770-2
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We investigate evolutionary dynamics of two-strategy matrix games with zealots in finite populations. Zealots are assumed to take either strategy regardless of the fitness. When the strategy selected by the zealots is the same, the fixation of the strategy selected by the zealots is a trivial outcome. We study fixation time in this scenario. We show that the fixation time is divided into three main regimes, in one of which the fixation time is short, and in the other two the fixation time is exponentially long in terms of the population size. Different from the case without zealots, there is a threshold selection intensity below which the fixation is fast for an arbitrary payoff matrix. We illustrate our results with examples of various social dilemma games.
[ { "created": "Sat, 10 Aug 2013 03:59:11 GMT", "version": "v1" }, { "created": "Thu, 17 Mar 2016 10:41:31 GMT", "version": "v2" } ]
2016-03-18
[ [ "Nakajima", "Yohei", "" ], [ "Masuda", "Naoki", "" ] ]
We investigate evolutionary dynamics of two-strategy matrix games with zealots in finite populations. Zealots are assumed to take either strategy regardless of the fitness. When the strategy selected by the zealots is the same, the fixation of the strategy selected by the zealots is a trivial outcome. We study fixation time in this scenario. We show that the fixation time is divided into three main regimes, in one of which the fixation time is short, and in the other two the fixation time is exponentially long in terms of the population size. Different from the case without zealots, there is a threshold selection intensity below which the fixation is fast for an arbitrary payoff matrix. We illustrate our results with examples of various social dilemma games.
1003.5828
Arne Traulsen
Chaitanya S. Gokhale, Yoh Iwasa, Martin A. Nowak and Arne Traulsen
The pace of evolution across fitness valleys
null
Journal of Theoretical Biology 259 (2009) 613-620
10.1016/j.jtbi.2009.04.011
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
How fast does a population evolve from one fitness peak to another? We study the dynamics of evolving, asexually reproducing populations in which a certain number of mutations jointly confer a fitness advantage. We consider the time until a population has evolved from one fitness peak to another one with a higher fitness. The order of mutations can either be fixed or random. If the order of mutations is fixed, then the population follows a metaphorical ridge, a single path. If the order of mutations is arbitrary, then there are many ways to evolve to the higher fitness state. We address the time required for fixation in such scenarios and study how it is affected by the order of mutations, the population size, the fitness values and the mutation rate.
[ { "created": "Tue, 30 Mar 2010 14:10:51 GMT", "version": "v1" } ]
2010-03-31
[ [ "Gokhale", "Chaitanya S.", "" ], [ "Iwasa", "Yoh", "" ], [ "Nowak", "Martin A.", "" ], [ "Traulsen", "Arne", "" ] ]
How fast does a population evolve from one fitness peak to another? We study the dynamics of evolving, asexually reproducing populations in which a certain number of mutations jointly confer a fitness advantage. We consider the time until a population has evolved from one fitness peak to another one with a higher fitness. The order of mutations can either be fixed or random. If the order of mutations is fixed, then the population follows a metaphorical ridge, a single path. If the order of mutations is arbitrary, then there are many ways to evolve to the higher fitness state. We address the time required for fixation in such scenarios and study how it is affected by the order of mutations, the population size, the fitness values and the mutation rate.
1006.0019
Teruhiko Yoneyama
Teruhiko Yoneyama and Mukkai S. Krishnamoorthy
Simulating the Spread of Influenza Pandemic of 1918-1919 Considering the Effect of the First World War
null
null
null
null
q-bio.PE physics.soc-ph
http://creativecommons.org/licenses/by/3.0/
The Influenza Pandemic of 1918-1919, also called Spanish Flu Pandemic, was one of the severest pandemics in history. It is thought that the First World War much influenced the spread of the pandemic. In this paper, we model the pandemic considering both civil and military traffic. We propose a hybrid model to determine how the pandemic spread through the world. Our approach considers both the SEIR-based model for local areas and the network model for global connection between countries. First, we reproduce the situation in 12 countries. Then, we simulate another scenario: there was no military traffic during the pandemic, to determine the influence of the influenced of the war on the pandemic. By considering the simulation results, we find that the influence of the war varies in countries; in countries which were deeply involved in the war, the infections were much influenced by the war, while in countries which were not much engaged in the war, the infections were not influenced by the war.
[ { "created": "Tue, 11 May 2010 22:04:52 GMT", "version": "v1" } ]
2010-06-02
[ [ "Yoneyama", "Teruhiko", "" ], [ "Krishnamoorthy", "Mukkai S.", "" ] ]
The Influenza Pandemic of 1918-1919, also called Spanish Flu Pandemic, was one of the severest pandemics in history. It is thought that the First World War much influenced the spread of the pandemic. In this paper, we model the pandemic considering both civil and military traffic. We propose a hybrid model to determine how the pandemic spread through the world. Our approach considers both the SEIR-based model for local areas and the network model for global connection between countries. First, we reproduce the situation in 12 countries. Then, we simulate another scenario: there was no military traffic during the pandemic, to determine the influence of the influenced of the war on the pandemic. By considering the simulation results, we find that the influence of the war varies in countries; in countries which were deeply involved in the war, the infections were much influenced by the war, while in countries which were not much engaged in the war, the infections were not influenced by the war.
1103.4347
Ian Holmes
Oscar Westesson, Gerton Lunter, Benedict Paten, Ian Holmes
Phylogenetic automata, pruning, and multiple alignment
96 pages: background, informal tutorial, and formal definitions
null
null
null
q-bio.PE q-bio.GN q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present an extension of Felsenstein's algorithm to indel models defined on entire sequences, without the need to condition on one multiple alignment. The algorithm makes use of a generalization from probabilistic substitution matrices to weighted finite-state transducers. Our approach may equivalently be viewed as a probabilistic formulation of progressive multiple sequence alignment, using partial-order graphs to represent ensemble profiles of ancestral sequences. We present a hierarchical stochastic approximation technique which makes this algorithm tractable for alignment analyses of reasonable size.
[ { "created": "Tue, 22 Mar 2011 19:01:39 GMT", "version": "v1" }, { "created": "Fri, 17 Feb 2012 20:59:16 GMT", "version": "v2" }, { "created": "Thu, 23 Oct 2014 07:25:39 GMT", "version": "v3" } ]
2014-10-24
[ [ "Westesson", "Oscar", "" ], [ "Lunter", "Gerton", "" ], [ "Paten", "Benedict", "" ], [ "Holmes", "Ian", "" ] ]
We present an extension of Felsenstein's algorithm to indel models defined on entire sequences, without the need to condition on one multiple alignment. The algorithm makes use of a generalization from probabilistic substitution matrices to weighted finite-state transducers. Our approach may equivalently be viewed as a probabilistic formulation of progressive multiple sequence alignment, using partial-order graphs to represent ensemble profiles of ancestral sequences. We present a hierarchical stochastic approximation technique which makes this algorithm tractable for alignment analyses of reasonable size.
1901.11418
Weisi Guo
Zhuangkun Wei, Bin Li, Weisi Guo, Wenxiu Hu, Chenglin Zhao
Sequential Bayesian Detection of Spike Activities from Fluorescence Observations
null
null
null
null
q-bio.NC cs.LG eess.SP stat.ML
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Extracting and detecting spike activities from the fluorescence observations is an important step in understanding how neuron systems work. The main challenge lies in that the combination of the ambient noise with dynamic baseline fluctuation, often contaminates the observations, thereby deteriorating the reliability of spike detection. This may be even worse in the face of the nonlinear biological process, the coupling interactions between spikes and baseline, and the unknown critical parameters of an underlying physiological model, in which erroneous estimations of parameters will affect the detection of spikes causing further error propagation. In this paper, we propose a random finite set (RFS) based Bayesian approach. The dynamic behaviors of spike sequence, fluctuated baseline and unknown parameters are formulated as one RFS. This RFS state is capable of distinguishing the hidden active/silent states induced by spike and non-spike activities respectively, thereby \emph{negating the interaction role} played by spikes and other factors. Then, premised on the RFS states, a Bayesian inference scheme is designed to simultaneously estimate the model parameters, baseline, and crucial spike activities. Our results demonstrate that the proposed scheme can gain an extra $12\%$ detection accuracy in comparison with the state-of-the-art MLSpike method.
[ { "created": "Thu, 31 Jan 2019 15:14:28 GMT", "version": "v1" } ]
2019-02-01
[ [ "Wei", "Zhuangkun", "" ], [ "Li", "Bin", "" ], [ "Guo", "Weisi", "" ], [ "Hu", "Wenxiu", "" ], [ "Zhao", "Chenglin", "" ] ]
Extracting and detecting spike activities from the fluorescence observations is an important step in understanding how neuron systems work. The main challenge lies in that the combination of the ambient noise with dynamic baseline fluctuation, often contaminates the observations, thereby deteriorating the reliability of spike detection. This may be even worse in the face of the nonlinear biological process, the coupling interactions between spikes and baseline, and the unknown critical parameters of an underlying physiological model, in which erroneous estimations of parameters will affect the detection of spikes causing further error propagation. In this paper, we propose a random finite set (RFS) based Bayesian approach. The dynamic behaviors of spike sequence, fluctuated baseline and unknown parameters are formulated as one RFS. This RFS state is capable of distinguishing the hidden active/silent states induced by spike and non-spike activities respectively, thereby \emph{negating the interaction role} played by spikes and other factors. Then, premised on the RFS states, a Bayesian inference scheme is designed to simultaneously estimate the model parameters, baseline, and crucial spike activities. Our results demonstrate that the proposed scheme can gain an extra $12\%$ detection accuracy in comparison with the state-of-the-art MLSpike method.
2106.14509
Herv\'e Turlier
Mathieu Le-Verge-Serandour, Herv\'e Turlier
Blastocoel morphogenesis: a biophysics perspective
26 pages, 6 figures, review
null
null
null
q-bio.CB
http://creativecommons.org/licenses/by-nc-sa/4.0/
The blastocoel is a fluid-filled cavity characteristic of animal embryos at the blastula stage. Its emergence is commonly described as the result of cleavage patterning, but this historical view conceals a large diversity of mechanisms and overlooks many unsolved questions from a biophysics perspective. In this review, we describe generic mechanisms for blastocoel morphogenesis, rooted in biological literature and simple physical principles. We propose novel directions of study and emphasize the importance to study blastocoel morphogenesis as an evolutionary and physical continuum.
[ { "created": "Mon, 28 Jun 2021 09:51:03 GMT", "version": "v1" }, { "created": "Mon, 11 Oct 2021 12:33:43 GMT", "version": "v2" } ]
2021-10-12
[ [ "Le-Verge-Serandour", "Mathieu", "" ], [ "Turlier", "Hervé", "" ] ]
The blastocoel is a fluid-filled cavity characteristic of animal embryos at the blastula stage. Its emergence is commonly described as the result of cleavage patterning, but this historical view conceals a large diversity of mechanisms and overlooks many unsolved questions from a biophysics perspective. In this review, we describe generic mechanisms for blastocoel morphogenesis, rooted in biological literature and simple physical principles. We propose novel directions of study and emphasize the importance to study blastocoel morphogenesis as an evolutionary and physical continuum.
1006.4397
Ruriko Yoshida
Kai Xu and Ruriko Yoshida
Statistical analysis on detecting recombination sites in DNA-beta satellites associated with the old world geminiviruses
8 figures and 2 tables. To appear in Frontiers in Systems Biology
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Although an exchange of genetic information by recombination plays an important role in the evolution of viruses, it is not clear how it generates diversity. {\it Geminiviruses} are plant viruses which have ambisense single-stranded circular DNA genomes and one of the most economically important plant viruses in agricultural production. Small circular single-stranded DNA satellites, termed DNA-$\beta$, have recently been found associated with some geminivirus infections. In this paper we analyze a satellite molecule DNA-$\beta$ of geminiviruses for recombination events using phylogenetic and statistical analysis and we find that one strain from ToLCMaB has a recombination pattern and is possibly recombinant molecule between two strains from two species, PaLCuB-[IN:Chi:05] (major parent) and ToLCB-[IN:CP:04] (minor parent).
[ { "created": "Wed, 23 Jun 2010 00:15:33 GMT", "version": "v1" }, { "created": "Mon, 13 Sep 2010 03:13:42 GMT", "version": "v2" } ]
2010-09-14
[ [ "Xu", "Kai", "" ], [ "Yoshida", "Ruriko", "" ] ]
Although an exchange of genetic information by recombination plays an important role in the evolution of viruses, it is not clear how it generates diversity. {\it Geminiviruses} are plant viruses which have ambisense single-stranded circular DNA genomes and one of the most economically important plant viruses in agricultural production. Small circular single-stranded DNA satellites, termed DNA-$\beta$, have recently been found associated with some geminivirus infections. In this paper we analyze a satellite molecule DNA-$\beta$ of geminiviruses for recombination events using phylogenetic and statistical analysis and we find that one strain from ToLCMaB has a recombination pattern and is possibly recombinant molecule between two strains from two species, PaLCuB-[IN:Chi:05] (major parent) and ToLCB-[IN:CP:04] (minor parent).
2309.00061
Avigail Taylor
Avigail Taylor, Valentine M Macaulay, Anand K Maurya, Matthieu J Miossec and Francesca M Buffa
GeneFEAST: the pivotal, gene-centric step in functional enrichment analysis interpretation
Main text: 3 pages, 1 figure. Supplementary Information: 16 pages, 3 figures, 2 tables, 4 boxes
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by/4.0/
Summary: GeneFEAST, implemented in Python, is a gene-centric functional enrichment analysis summarisation and visualisation tool that can be applied to large functional enrichment analysis (FEA) results arising from upstream FEA pipelines. It produces a systematic, navigable HTML report, making it easy to identify sets of genes putatively driving multiple enrichments and to explore gene-level quantitative data first used to identify input genes. Further, GeneFEAST can compare FEA results from multiple studies, making it possible, for example, to highlight patterns of gene expression amongst genes commonly differentially expressed in two sets of conditions, and giving rise to shared enrichments under those conditions. GeneFEAST offers a novel, effective way to address the complexities of linking up many overlapping FEA results to their underlying genes and data, advancing gene-centric hypotheses, and providing pivotal information for downstream validation experiments. Availability: GeneFEAST is available at https://github.com/avigailtaylor/GeneFEAST Contact: avigail.taylor@well.ox.ac.uk
[ { "created": "Thu, 31 Aug 2023 18:05:20 GMT", "version": "v1" } ]
2023-09-04
[ [ "Taylor", "Avigail", "" ], [ "Macaulay", "Valentine M", "" ], [ "Maurya", "Anand K", "" ], [ "Miossec", "Matthieu J", "" ], [ "Buffa", "Francesca M", "" ] ]
Summary: GeneFEAST, implemented in Python, is a gene-centric functional enrichment analysis summarisation and visualisation tool that can be applied to large functional enrichment analysis (FEA) results arising from upstream FEA pipelines. It produces a systematic, navigable HTML report, making it easy to identify sets of genes putatively driving multiple enrichments and to explore gene-level quantitative data first used to identify input genes. Further, GeneFEAST can compare FEA results from multiple studies, making it possible, for example, to highlight patterns of gene expression amongst genes commonly differentially expressed in two sets of conditions, and giving rise to shared enrichments under those conditions. GeneFEAST offers a novel, effective way to address the complexities of linking up many overlapping FEA results to their underlying genes and data, advancing gene-centric hypotheses, and providing pivotal information for downstream validation experiments. Availability: GeneFEAST is available at https://github.com/avigailtaylor/GeneFEAST Contact: avigail.taylor@well.ox.ac.uk
1712.00407
K. Anton Feenstra
Sanne Abeln, Jaap Heringa, K. Anton Feenstra
Introduction to Protein Structure Prediction
null
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by/4.0/
This chapter gives a graceful introduction to problem of protein three- dimensional structure prediction, and focuses on how to make structural sense out of a single input sequence with unknown structure, the 'query' or 'target' sequence. We give an overview of the different classes of modelling techniques, notably template-based and template free. We also discuss the way in which structural predictions are validated within the global com- munity, and elaborate on the extent to which predicted structures may be trusted and used in practice. Finally we discuss whether the concept of a sin- gle fold pertaining to a protein structure is sustainable given recent insights. In short, we conclude that the general protein three-dimensional structure prediction problem remains unsolved, especially if we desire quantitative predictions. However, if a homologous structural template is available in the PDB model or reasonable to high accuracy may be generated.
[ { "created": "Fri, 1 Dec 2017 17:09:40 GMT", "version": "v1" } ]
2017-12-04
[ [ "Abeln", "Sanne", "" ], [ "Heringa", "Jaap", "" ], [ "Feenstra", "K. Anton", "" ] ]
This chapter gives a graceful introduction to problem of protein three- dimensional structure prediction, and focuses on how to make structural sense out of a single input sequence with unknown structure, the 'query' or 'target' sequence. We give an overview of the different classes of modelling techniques, notably template-based and template free. We also discuss the way in which structural predictions are validated within the global com- munity, and elaborate on the extent to which predicted structures may be trusted and used in practice. Finally we discuss whether the concept of a sin- gle fold pertaining to a protein structure is sustainable given recent insights. In short, we conclude that the general protein three-dimensional structure prediction problem remains unsolved, especially if we desire quantitative predictions. However, if a homologous structural template is available in the PDB model or reasonable to high accuracy may be generated.
2401.05470
Joaquim Estopinan
Joaquim Estopinan, Pierre Bonnet, Maximilien Servajean, Fran\c{c}ois Munoz, Alexis Joly
Modelling Species Distributions with Deep Learning to Predict Plant Extinction Risk and Assess Climate Change Impacts
18 pages, 5 figures. Coda and data: https://github.com/estopinj/IUCN_classification
null
null
null
q-bio.PE cs.LG stat.AP
http://creativecommons.org/licenses/by-nc-sa/4.0/
The post-2020 global biodiversity framework needs ambitious, research-based targets. Estimating the accelerated extinction risk due to climate change is critical. The International Union for Conservation of Nature (IUCN) measures the extinction risk of species. Automatic methods have been developed to provide information on the IUCN status of under-assessed taxa. However, these compensatory methods are based on current species characteristics, mainly geographical, which precludes their use in future projections. Here, we evaluate a novel method for classifying the IUCN status of species benefiting from the generalisation power of species distribution models based on deep learning. Our method matches state-of-the-art classification performance while relying on flexible SDM-based features that capture species' environmental preferences. Cross-validation yields average accuracies of 0.61 for status classification and 0.78 for binary classification. Climate change will reshape future species distributions. Under the species-environment equilibrium hypothesis, SDM projections approximate plausible future outcomes. Two extremes of species dispersal capacity are considered: unlimited or null. The projected species distributions are translated into features feeding our IUCN classification method. Finally, trends in threatened species are analysed over time and i) by continent and as a function of average ii) latitude or iii) altitude. The proportion of threatened species is increasing globally, with critical rates in Africa, Asia and South America. Furthermore, the proportion of threatened species is predicted to peak around the two Tropics, at the Equator, in the lowlands and at altitudes of 800-1,500 m.
[ { "created": "Wed, 10 Jan 2024 15:24:27 GMT", "version": "v1" } ]
2024-01-12
[ [ "Estopinan", "Joaquim", "" ], [ "Bonnet", "Pierre", "" ], [ "Servajean", "Maximilien", "" ], [ "Munoz", "François", "" ], [ "Joly", "Alexis", "" ] ]
The post-2020 global biodiversity framework needs ambitious, research-based targets. Estimating the accelerated extinction risk due to climate change is critical. The International Union for Conservation of Nature (IUCN) measures the extinction risk of species. Automatic methods have been developed to provide information on the IUCN status of under-assessed taxa. However, these compensatory methods are based on current species characteristics, mainly geographical, which precludes their use in future projections. Here, we evaluate a novel method for classifying the IUCN status of species benefiting from the generalisation power of species distribution models based on deep learning. Our method matches state-of-the-art classification performance while relying on flexible SDM-based features that capture species' environmental preferences. Cross-validation yields average accuracies of 0.61 for status classification and 0.78 for binary classification. Climate change will reshape future species distributions. Under the species-environment equilibrium hypothesis, SDM projections approximate plausible future outcomes. Two extremes of species dispersal capacity are considered: unlimited or null. The projected species distributions are translated into features feeding our IUCN classification method. Finally, trends in threatened species are analysed over time and i) by continent and as a function of average ii) latitude or iii) altitude. The proportion of threatened species is increasing globally, with critical rates in Africa, Asia and South America. Furthermore, the proportion of threatened species is predicted to peak around the two Tropics, at the Equator, in the lowlands and at altitudes of 800-1,500 m.
2205.05451
Ganesh Bagler Dr
Nishant Grover, Mansi Goel, Devansh Batra, Neelansh Garg, Rudraksh Tuwani, Apuroop Sethupathy and Ganesh Bagler
FlavorDB2: An Updated Database of Flavor Molecules
5 pages, 2 figures
null
null
null
q-bio.QM
http://creativecommons.org/licenses/by-nc-nd/4.0/
Flavor is expressed through interaction of molecules via gustatory and olfactory mechanisms. Knowing the utility of flavor molecules in food and fragrances, it is valuable to add a comprehensive repository of flavor compounds characterizing their flavor profile, chemical properties, regulatory status, consumption statistics, taste/aroma threshold values, reported uses in food categories, and synthesis. FlavorDB2 (https://cosylab.iiitd.edu.in/flavordb2/) is an updated database of flavor molecules with an user-friendly interface. This repository simplifies the search for flavor molecules, their attributes and offers a range of applications including food pairing. FlavorDB2 serves as a standard repository of flavor compounds.
[ { "created": "Tue, 10 May 2022 12:12:41 GMT", "version": "v1" } ]
2022-05-12
[ [ "Grover", "Nishant", "" ], [ "Goel", "Mansi", "" ], [ "Batra", "Devansh", "" ], [ "Garg", "Neelansh", "" ], [ "Tuwani", "Rudraksh", "" ], [ "Sethupathy", "Apuroop", "" ], [ "Bagler", "Ganesh", "" ] ]
Flavor is expressed through interaction of molecules via gustatory and olfactory mechanisms. Knowing the utility of flavor molecules in food and fragrances, it is valuable to add a comprehensive repository of flavor compounds characterizing their flavor profile, chemical properties, regulatory status, consumption statistics, taste/aroma threshold values, reported uses in food categories, and synthesis. FlavorDB2 (https://cosylab.iiitd.edu.in/flavordb2/) is an updated database of flavor molecules with an user-friendly interface. This repository simplifies the search for flavor molecules, their attributes and offers a range of applications including food pairing. FlavorDB2 serves as a standard repository of flavor compounds.
2007.14375
Ramachandran Vijayan
Ramachandran Vijayan, Samudrala Gourinath
Structure-based inhibitor screening of natural products against NSP15 of SARS- CoV-2 revealed Thymopentin and Oleuropein as potent inhibitors
21 pages, 7 figures
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by/4.0/
Coronaviruses are enveloped, non-segmented positive-sense RNA viruses that have the largest genome among RNA viruses. The genome contains a large replicase ORF encodes nonstructural proteins (NSPs), structural and accessory genes. NSP15 is a nidoviral RNA uridylate-specific endoribonuclease (NendoU) has C-terminal catalytic domain. The endoribonuclease activity of NSP15 interferes with the innate immune response of the host. Here, we screened Selleckchem Natural product database of compounds against the NSP15, Thymopentin and Oleuropein showed highest binding energies. The binding of these molecules was further validated by Molecular dynamic simulation and found very stable complexes. These drugs might serve as effective counter molecules in the reduction of virulence of this virus. Future validation of both these inhibitors are worth consideration for patients being treated for COVID -19.
[ { "created": "Tue, 28 Jul 2020 17:37:58 GMT", "version": "v1" } ]
2020-07-29
[ [ "Vijayan", "Ramachandran", "" ], [ "Gourinath", "Samudrala", "" ] ]
Coronaviruses are enveloped, non-segmented positive-sense RNA viruses that have the largest genome among RNA viruses. The genome contains a large replicase ORF encodes nonstructural proteins (NSPs), structural and accessory genes. NSP15 is a nidoviral RNA uridylate-specific endoribonuclease (NendoU) has C-terminal catalytic domain. The endoribonuclease activity of NSP15 interferes with the innate immune response of the host. Here, we screened Selleckchem Natural product database of compounds against the NSP15, Thymopentin and Oleuropein showed highest binding energies. The binding of these molecules was further validated by Molecular dynamic simulation and found very stable complexes. These drugs might serve as effective counter molecules in the reduction of virulence of this virus. Future validation of both these inhibitors are worth consideration for patients being treated for COVID -19.
2407.08812
Joan Carles Pons Mayol
Joan Carles Pons, Pau Vives L\'opez, Yukihiro Murakami, Leo Van Iersel
Fence decompositions and cherry covers in non-binary phylogenetic networks
16 pages
null
null
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Reticulate evolution can be modelled using phylogenetic networks. Tree-based networks, which are one of the more general classes of phylogenetic networks, have recently gained eminence for its ability to represent evolutionary histories with an underlying tree structure. To better understand tree-based networks, numerous characterizations have been proposed, based on tree embeddings, matchings, and arc partitions. Here, we build a bridge between two arc partition characterizations, namely maximal fence decompositions and cherry covers. Results on cherry covers have been found for general phylogenetic networks. We first show that the number of cherry covers is the same as the number of support trees (underlying tree structure of tree-based networks) for a given semibinary network. Maximal fence decompositions have only been defined thus far for binary networks (constraints on vertex degrees). We remedy this by generalizing fence decompositions to non-binary networks, and using this, we characterize semi-binary tree-based networks in terms of forbidden structures. Furthermore, we give an explicit enumeration of cherry covers of semi-binary networks, by studying its fence decomposition. Finally, we prove that it is possible to characterize semi-binary tree-child networks, a subclass of tree-based networks, in terms of the number of their cherry covers.
[ { "created": "Thu, 11 Jul 2024 18:50:53 GMT", "version": "v1" } ]
2024-07-15
[ [ "Pons", "Joan Carles", "" ], [ "López", "Pau Vives", "" ], [ "Murakami", "Yukihiro", "" ], [ "Van Iersel", "Leo", "" ] ]
Reticulate evolution can be modelled using phylogenetic networks. Tree-based networks, which are one of the more general classes of phylogenetic networks, have recently gained eminence for its ability to represent evolutionary histories with an underlying tree structure. To better understand tree-based networks, numerous characterizations have been proposed, based on tree embeddings, matchings, and arc partitions. Here, we build a bridge between two arc partition characterizations, namely maximal fence decompositions and cherry covers. Results on cherry covers have been found for general phylogenetic networks. We first show that the number of cherry covers is the same as the number of support trees (underlying tree structure of tree-based networks) for a given semibinary network. Maximal fence decompositions have only been defined thus far for binary networks (constraints on vertex degrees). We remedy this by generalizing fence decompositions to non-binary networks, and using this, we characterize semi-binary tree-based networks in terms of forbidden structures. Furthermore, we give an explicit enumeration of cherry covers of semi-binary networks, by studying its fence decomposition. Finally, we prove that it is possible to characterize semi-binary tree-child networks, a subclass of tree-based networks, in terms of the number of their cherry covers.
2310.15263
Chengrui Li
Chengrui Li, Soon Ho Kim, Chris Rodgers, Hannah Choi, Anqi Wu
One-hot Generalized Linear Model for Switching Brain State Discovery
null
null
null
null
q-bio.NC cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Exposing meaningful and interpretable neural interactions is critical to understanding neural circuits. Inferred neural interactions from neural signals primarily reflect functional interactions. In a long experiment, subject animals may experience different stages defined by the experiment, stimuli, or behavioral states, and hence functional interactions can change over time. To model dynamically changing functional interactions, prior work employs state-switching generalized linear models with hidden Markov models (i.e., HMM-GLMs). However, we argue they lack biological plausibility, as functional interactions are shaped and confined by the underlying anatomical connectome. Here, we propose a novel prior-informed state-switching GLM. We introduce both a Gaussian prior and a one-hot prior over the GLM in each state. The priors are learnable. We will show that the learned prior should capture the state-constant interaction, shedding light on the underlying anatomical connectome and revealing more likely physical neuron interactions. The state-dependent interaction modeled by each GLM offers traceability to capture functional variations across multiple brain states. Our methods effectively recover true interaction structures in simulated data, achieve the highest predictive likelihood with real neural datasets, and render interaction structures and hidden states more interpretable when applied to real neural data.
[ { "created": "Mon, 23 Oct 2023 18:10:22 GMT", "version": "v1" } ]
2023-10-25
[ [ "Li", "Chengrui", "" ], [ "Kim", "Soon Ho", "" ], [ "Rodgers", "Chris", "" ], [ "Choi", "Hannah", "" ], [ "Wu", "Anqi", "" ] ]
Exposing meaningful and interpretable neural interactions is critical to understanding neural circuits. Inferred neural interactions from neural signals primarily reflect functional interactions. In a long experiment, subject animals may experience different stages defined by the experiment, stimuli, or behavioral states, and hence functional interactions can change over time. To model dynamically changing functional interactions, prior work employs state-switching generalized linear models with hidden Markov models (i.e., HMM-GLMs). However, we argue they lack biological plausibility, as functional interactions are shaped and confined by the underlying anatomical connectome. Here, we propose a novel prior-informed state-switching GLM. We introduce both a Gaussian prior and a one-hot prior over the GLM in each state. The priors are learnable. We will show that the learned prior should capture the state-constant interaction, shedding light on the underlying anatomical connectome and revealing more likely physical neuron interactions. The state-dependent interaction modeled by each GLM offers traceability to capture functional variations across multiple brain states. Our methods effectively recover true interaction structures in simulated data, achieve the highest predictive likelihood with real neural datasets, and render interaction structures and hidden states more interpretable when applied to real neural data.
1011.0370
Sylvain Tollis
Sylvain Tollis, Anna E. Dart, George Tzircotis, and Robert G. Endres
The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape
Accepted for publication in BMC Systems Biology. 17 pages, 6 Figures, + supplementary information
null
null
null
q-bio.CB physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Phagocytosis is the fundamental cellular process by which eukaryotic cells bind and engulf particles by their cell membrane. Particle engulfment involves particle recognition by cell-surface receptors, signaling and remodeling of the actin cytoskeleton to guide the membrane around the particle in a zipper-like fashion. Despite the signaling complexity, phagocytosis also depends strongly on biophysical parameters, such as particle shape, and the need for actin-driven force generation remains poorly understood. Here, we propose a novel, three-dimensional and stochastic biophysical model of phagocytosis, and study the engulfment of particles of various sizes and shapes, including spiral and rod-shaped particles reminiscent of bacteria. Highly curved shapes are not taken up, in line with recent experimental results. Furthermore, we surprisingly find that even without actin-driven force generation, engulfment proceeds in a large regime of parameter values, albeit more slowly and with highly variable phagocytic cups. We experimentally confirm these predictions using fibroblasts, transfected with immunoreceptor FcyRIIa for engulfment of immunoglobulin G-opsonized particles. Specifically, we compare the wild-type receptor with a mutant receptor, unable to signal to the actin cytoskeleton. Based on the reconstruction of phagocytic cups from imaging data, we indeed show that cells are able to engulf small particles even without support from biological actin-driven processes. This suggests that biochemical pathways render the evolutionary ancient process of phagocytic highly robust, allowing cells to engulf even very large particles. The particle-shape dependence of phagocytosis makes a systematic investigation of host-pathogen interactions and an efficient design of a vehicle for drug delivery possible.
[ { "created": "Mon, 1 Nov 2010 16:28:18 GMT", "version": "v1" } ]
2010-11-02
[ [ "Tollis", "Sylvain", "" ], [ "Dart", "Anna E.", "" ], [ "Tzircotis", "George", "" ], [ "Endres", "Robert G.", "" ] ]
Phagocytosis is the fundamental cellular process by which eukaryotic cells bind and engulf particles by their cell membrane. Particle engulfment involves particle recognition by cell-surface receptors, signaling and remodeling of the actin cytoskeleton to guide the membrane around the particle in a zipper-like fashion. Despite the signaling complexity, phagocytosis also depends strongly on biophysical parameters, such as particle shape, and the need for actin-driven force generation remains poorly understood. Here, we propose a novel, three-dimensional and stochastic biophysical model of phagocytosis, and study the engulfment of particles of various sizes and shapes, including spiral and rod-shaped particles reminiscent of bacteria. Highly curved shapes are not taken up, in line with recent experimental results. Furthermore, we surprisingly find that even without actin-driven force generation, engulfment proceeds in a large regime of parameter values, albeit more slowly and with highly variable phagocytic cups. We experimentally confirm these predictions using fibroblasts, transfected with immunoreceptor FcyRIIa for engulfment of immunoglobulin G-opsonized particles. Specifically, we compare the wild-type receptor with a mutant receptor, unable to signal to the actin cytoskeleton. Based on the reconstruction of phagocytic cups from imaging data, we indeed show that cells are able to engulf small particles even without support from biological actin-driven processes. This suggests that biochemical pathways render the evolutionary ancient process of phagocytic highly robust, allowing cells to engulf even very large particles. The particle-shape dependence of phagocytosis makes a systematic investigation of host-pathogen interactions and an efficient design of a vehicle for drug delivery possible.
2107.05388
Adrian Buganza Tepole
Vahidullah Tac, Vivek D. Sree, Manuel K. Rausch, Adrian B. Tepole
Data-driven Modeling of the Mechanical Behavior of Anisotropic Soft Biological Tissue
19 pages, 10 figures
null
null
null
q-bio.QM cond-mat.soft cs.CE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Constitutive models that describe the mechanical behavior of soft tissues have advanced greatly over the past few decades. These expert models are generalizable and require the calibration of a number of parameters to fit experimental data. However, inherent pitfalls stemming from the restriction to a specific functional form include poor fits to the data, non-uniqueness of fit, and high sensitivity to parameters. In this study we design and train fully connected neural networks as material models to replace or augment expert models. To guarantee objectivity, the neural network takes isochoric strain invariants as inputs, and outputs the value of strain energy and its derivatives with respect to the invariants. Convexity of the material model is enforced through the loss function. Direct prediction of the derivative functions -- rather than just predicting the energy -- serves two purposes: it provides flexibility during training, and it enables the calculation of the elasticity tensor through back-propagation. We showcase the ability of the neural network to learn the mechanical behavior of porcine and murine skin from biaxial test data. Crucially, we show that a multi-fidelity scheme which combines high fidelity experimental data with low fidelity analytical data yields the best performance. The neural network material model can then be interpreted as the best extension of an expert model: it learns the features that an expert has encoded in the analytical model while fitting the experimental data better. Finally, we implemented a general user material subroutine (UMAT) for the finite element software Abaqus and thereby make our advances available to the broader computational community. We expect that the methods and software generated in this work will broaden the use of data-driven constitutive models in biomedical applications.
[ { "created": "Thu, 8 Jul 2021 01:58:05 GMT", "version": "v1" } ]
2021-07-13
[ [ "Tac", "Vahidullah", "" ], [ "Sree", "Vivek D.", "" ], [ "Rausch", "Manuel K.", "" ], [ "Tepole", "Adrian B.", "" ] ]
Constitutive models that describe the mechanical behavior of soft tissues have advanced greatly over the past few decades. These expert models are generalizable and require the calibration of a number of parameters to fit experimental data. However, inherent pitfalls stemming from the restriction to a specific functional form include poor fits to the data, non-uniqueness of fit, and high sensitivity to parameters. In this study we design and train fully connected neural networks as material models to replace or augment expert models. To guarantee objectivity, the neural network takes isochoric strain invariants as inputs, and outputs the value of strain energy and its derivatives with respect to the invariants. Convexity of the material model is enforced through the loss function. Direct prediction of the derivative functions -- rather than just predicting the energy -- serves two purposes: it provides flexibility during training, and it enables the calculation of the elasticity tensor through back-propagation. We showcase the ability of the neural network to learn the mechanical behavior of porcine and murine skin from biaxial test data. Crucially, we show that a multi-fidelity scheme which combines high fidelity experimental data with low fidelity analytical data yields the best performance. The neural network material model can then be interpreted as the best extension of an expert model: it learns the features that an expert has encoded in the analytical model while fitting the experimental data better. Finally, we implemented a general user material subroutine (UMAT) for the finite element software Abaqus and thereby make our advances available to the broader computational community. We expect that the methods and software generated in this work will broaden the use of data-driven constitutive models in biomedical applications.
1105.0592
Joachim Krug
Johannes Neidhart and Joachim Krug
Adaptive walks and extreme value theory
4 pages, 2 figures; final version, to appear in Physical Review Letters
Physical Review Letters 107, 178102 (2011)
10.1103/PhysRevLett.107.178102
null
q-bio.PE cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We study biological evolution in a high-dimensional genotype space in the regime of rare mutations and strong selection. The population performs an uphill walk which terminates at local fitness maxima. Assigning fitness randomly to genotypes, we show that the mean walk length is logarithmic in the number of initially available beneficial mutations, with a prefactor determined by the tail of the fitness distribution. This result is derived analytically in a simplified setting where the mutational neighborhood is fixed during the adaptive process, and confirmed by numerical simulations.
[ { "created": "Tue, 3 May 2011 14:20:58 GMT", "version": "v1" }, { "created": "Tue, 20 Sep 2011 11:26:56 GMT", "version": "v2" } ]
2015-05-28
[ [ "Neidhart", "Johannes", "" ], [ "Krug", "Joachim", "" ] ]
We study biological evolution in a high-dimensional genotype space in the regime of rare mutations and strong selection. The population performs an uphill walk which terminates at local fitness maxima. Assigning fitness randomly to genotypes, we show that the mean walk length is logarithmic in the number of initially available beneficial mutations, with a prefactor determined by the tail of the fitness distribution. This result is derived analytically in a simplified setting where the mutational neighborhood is fixed during the adaptive process, and confirmed by numerical simulations.
2110.13951
Kirti Prakash
Johannes Hohlbein, Benedict Diederich, Barbora Marsikova, Emmanuel G. Reynaud, Seamus Holden, Wiebke Jahr, Robert Haase, and Kirti Prakash
Open microscopy in the life sciences: Quo Vadis?
28 pages, 2 figures
null
null
null
q-bio.OT physics.bio-ph physics.data-an physics.ins-det physics.optics
http://creativecommons.org/licenses/by-sa/4.0/
Light microscopy allows observing cellular features and objects with sub-micrometer resolution. As such, light microscopy has been playing a fundamental role in the life sciences for more than a hundred years. Fueled by the availability of mass-produced electronics and hardware, publicly shared documentation and building instructions, open-source software, wide access to rapid prototyping and 3D printing, and the enthusiasm of contributors and users involved, the concept of open microscopy has been gaining incredible momentum, bringing new sophisticated tools to an expanding user base. Here, we will first discuss the ideas behind open science and open microscopy before highlighting recent projects and developments in open microscopy. We argue that the availability of well-designed open hardware and software solutions targeting broad user groups or even non-experts, will increasingly be relevant to cope with the increasing complexity of cutting-edge imaging technologies. We will then extensively discuss the current and future challenges of open microscopy.
[ { "created": "Tue, 26 Oct 2021 18:31:34 GMT", "version": "v1" } ]
2021-10-28
[ [ "Hohlbein", "Johannes", "" ], [ "Diederich", "Benedict", "" ], [ "Marsikova", "Barbora", "" ], [ "Reynaud", "Emmanuel G.", "" ], [ "Holden", "Seamus", "" ], [ "Jahr", "Wiebke", "" ], [ "Haase", "Robert", ""...
Light microscopy allows observing cellular features and objects with sub-micrometer resolution. As such, light microscopy has been playing a fundamental role in the life sciences for more than a hundred years. Fueled by the availability of mass-produced electronics and hardware, publicly shared documentation and building instructions, open-source software, wide access to rapid prototyping and 3D printing, and the enthusiasm of contributors and users involved, the concept of open microscopy has been gaining incredible momentum, bringing new sophisticated tools to an expanding user base. Here, we will first discuss the ideas behind open science and open microscopy before highlighting recent projects and developments in open microscopy. We argue that the availability of well-designed open hardware and software solutions targeting broad user groups or even non-experts, will increasingly be relevant to cope with the increasing complexity of cutting-edge imaging technologies. We will then extensively discuss the current and future challenges of open microscopy.
1305.5803
Vladimir Privman
Sergii Domanskyi, Vladimir Privman
Design of Digital Response in Enzyme-Based Bioanalytical Systems for Information Processing Applications
null
J. Phys. Chem. B 116, 13690-13695 (2012)
10.1021/jp309001j
VP-250
q-bio.MN physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We investigate performance and optimization of the "digital" bioanalytical response. Specifically, we consider the recently introduced approach of a partial input conversion into inactive compounds, resulting in the "branch point effect" similar to that encountered in biological systems. This corresponds to an "intensity filter," which can yield a binary-type sigmoid-response output signal of interest in information and signal processing and in biosensing applications. We define measures for optimizing the response for information processing applications based on the kinetic modeling of the enzymatic reactions involved, and apply the developed approach to the recently published data for glucose detection.
[ { "created": "Fri, 24 May 2013 17:11:36 GMT", "version": "v1" } ]
2013-05-27
[ [ "Domanskyi", "Sergii", "" ], [ "Privman", "Vladimir", "" ] ]
We investigate performance and optimization of the "digital" bioanalytical response. Specifically, we consider the recently introduced approach of a partial input conversion into inactive compounds, resulting in the "branch point effect" similar to that encountered in biological systems. This corresponds to an "intensity filter," which can yield a binary-type sigmoid-response output signal of interest in information and signal processing and in biosensing applications. We define measures for optimizing the response for information processing applications based on the kinetic modeling of the enzymatic reactions involved, and apply the developed approach to the recently published data for glucose detection.
1406.5641
Cristiano Nisoli
Cristiano Nisoli and A. R. Bishop
Thermomechanical Stability and Mechanochemical Response of DNA: a Minimal Mesoscale Model
18 pages, 11 figures
The Journal of Chemical Physics 141 (11), 115101 (2014)
10.1063/1.4895724
null
q-bio.BM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We show that a mesoscale model, with a minimal number of parameters, can well describe the thermomechanical and mechanochemical behavior of homogeneous DNA at thermal equilibrium under tension and torque. We predict critical temperatures for denaturation under torque and stretch, phase diagrams for stable DNA, probe/response profiles under mechanical loads, and the density of dsDNA as a function of stretch and twist. We compare our predictions with available single molecule manipulation experiments and find strong agreement. In particular we elucidate the difference between angularly constrained and unconstrained overstretching. We propose that the smoothness of the angularly constrained overstreching transition is a consequence of the molecule being in the vicinity of criticality for a broad range of values of applied tension.
[ { "created": "Sat, 21 Jun 2014 18:17:52 GMT", "version": "v1" }, { "created": "Sat, 18 Oct 2014 14:45:47 GMT", "version": "v2" } ]
2015-06-22
[ [ "Nisoli", "Cristiano", "" ], [ "Bishop", "A. R.", "" ] ]
We show that a mesoscale model, with a minimal number of parameters, can well describe the thermomechanical and mechanochemical behavior of homogeneous DNA at thermal equilibrium under tension and torque. We predict critical temperatures for denaturation under torque and stretch, phase diagrams for stable DNA, probe/response profiles under mechanical loads, and the density of dsDNA as a function of stretch and twist. We compare our predictions with available single molecule manipulation experiments and find strong agreement. In particular we elucidate the difference between angularly constrained and unconstrained overstretching. We propose that the smoothness of the angularly constrained overstreching transition is a consequence of the molecule being in the vicinity of criticality for a broad range of values of applied tension.
1404.7591
Randall O'Reilly
Randall C. O'Reilly, Thomas E. Hazy, Jessica Mollick, Prescott Mackie, Seth Herd
Goal-Driven Cognition in the Brain: A Computational Framework
62 pages, 11 figures
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Current theoretical and computational models of dopamine-based reinforcement learning are largely rooted in the classical behaviorist tradition, and envision the organism as a purely reactive recipient of rewards and punishments, with resulting behavior that essentially reflects the sum of this reinforcement history. This framework is missing some fundamental features of the affective nervous system, most importantly, the central role of goals in driving and organizing behavior in a teleological manner. Even when goal-directed behaviors are considered in current frameworks, they are typically conceived of as arising in reaction to the environment, rather than being in place from the start. We hypothesize that goal-driven cognition is primary, and organized into two discrete phases: goal selection and goal engaged, which each have a substantially different effective value function. This dichotomy can potentially explain a wide range of phenomena, playing a central role in many clinical disorders, such as depression, OCD, ADHD, and PTSD, and providing a sensible account of the detailed biology and function of the dopamine system and larger limbic system, including critical ventral and medial prefrontal cortex. Computationally, reasoning backward from active goals to action selection is more tractable than projecting alternative action choices forward to compute possible outcomes. An explicit computational model of these brain areas and their function in this goal-driven framework is described, as are numerous testable predictions from this framework.
[ { "created": "Wed, 30 Apr 2014 05:04:13 GMT", "version": "v1" } ]
2014-05-01
[ [ "O'Reilly", "Randall C.", "" ], [ "Hazy", "Thomas E.", "" ], [ "Mollick", "Jessica", "" ], [ "Mackie", "Prescott", "" ], [ "Herd", "Seth", "" ] ]
Current theoretical and computational models of dopamine-based reinforcement learning are largely rooted in the classical behaviorist tradition, and envision the organism as a purely reactive recipient of rewards and punishments, with resulting behavior that essentially reflects the sum of this reinforcement history. This framework is missing some fundamental features of the affective nervous system, most importantly, the central role of goals in driving and organizing behavior in a teleological manner. Even when goal-directed behaviors are considered in current frameworks, they are typically conceived of as arising in reaction to the environment, rather than being in place from the start. We hypothesize that goal-driven cognition is primary, and organized into two discrete phases: goal selection and goal engaged, which each have a substantially different effective value function. This dichotomy can potentially explain a wide range of phenomena, playing a central role in many clinical disorders, such as depression, OCD, ADHD, and PTSD, and providing a sensible account of the detailed biology and function of the dopamine system and larger limbic system, including critical ventral and medial prefrontal cortex. Computationally, reasoning backward from active goals to action selection is more tractable than projecting alternative action choices forward to compute possible outcomes. An explicit computational model of these brain areas and their function in this goal-driven framework is described, as are numerous testable predictions from this framework.
2003.11376
Jagadish Kumar Dr.
Jagadish Kumar, K. P. S. S. Hembram
Epidemiological study of novel coronavirus (COVID-19)
9 pages, 8 figures
International Journal of Community Medicine and Public Health, Volume 8, Issue 3, Pages 1369, 2021
10.18203/2394-6040.ijcmph20210828
null
q-bio.PE physics.app-ph physics.bio-ph physics.med-ph
http://creativecommons.org/publicdomain/zero/1.0/
We report a statistical analysis of some highly infected countries by the novel coronavirus (COVID-19). The cumulative infected data were fitted with various growth models (e.g. Logistic equation, Weibull equation and Hill equation) and obtained the power index of top ten highly infected countries. The newly infected data were fitted with Gaussian distribution with the peak at ~40 days for the countries whose infection curves are seem to be saturated. The similarity in growth kinetics of infected people of different countries provides first-hand guidelines to take proper precautions to minimize human damage.
[ { "created": "Wed, 25 Mar 2020 12:54:40 GMT", "version": "v1" } ]
2021-04-16
[ [ "Kumar", "Jagadish", "" ], [ "Hembram", "K. P. S. S.", "" ] ]
We report a statistical analysis of some highly infected countries by the novel coronavirus (COVID-19). The cumulative infected data were fitted with various growth models (e.g. Logistic equation, Weibull equation and Hill equation) and obtained the power index of top ten highly infected countries. The newly infected data were fitted with Gaussian distribution with the peak at ~40 days for the countries whose infection curves are seem to be saturated. The similarity in growth kinetics of infected people of different countries provides first-hand guidelines to take proper precautions to minimize human damage.
1301.5277
Franck Rapaport
Franck Rapaport, Raya Khanin, Yupu Liang, Azra Krek, Paul Zumbo, Christopher E. Mason, Nicholas D. Socci, Doron Betel
Comprehensive evaluation of differential expression analysis methods for RNA-seq data
Manuscript includes supplementary figures
null
null
null
q-bio.GN q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
High-throughput sequencing of RNA transcripts (RNA-seq) has become the method of choice for detection of differential expression (DE). Concurrent with the growing popularity of this technology there has been a significant research effort devoted towards understanding the statistical properties of this data and the development of analysis methods. We report on a comprehensive evaluation of the commonly used DE methods using the SEQC benchmark data set. We evaluate a number of key features including: assessment of normalization, accuracy of DE detection, modeling of genes expressed in only one condition, and the impact of sequencing depth and number of replications on identifying DE genes. We find significant differences among the methods with no single method consistently outperforming the others. Furthermore, the performance of array-based approach is comparable to methods customized for RNA-seq data. Perhaps most importantly, our results demonstrate that increasing the number of replicate samples provides significantly more detection power than increased sequencing depth.
[ { "created": "Tue, 22 Jan 2013 19:06:32 GMT", "version": "v1" }, { "created": "Wed, 23 Jan 2013 03:26:19 GMT", "version": "v2" } ]
2013-01-24
[ [ "Rapaport", "Franck", "" ], [ "Khanin", "Raya", "" ], [ "Liang", "Yupu", "" ], [ "Krek", "Azra", "" ], [ "Zumbo", "Paul", "" ], [ "Mason", "Christopher E.", "" ], [ "Socci", "Nicholas D.", "" ], [ "...
High-throughput sequencing of RNA transcripts (RNA-seq) has become the method of choice for detection of differential expression (DE). Concurrent with the growing popularity of this technology there has been a significant research effort devoted towards understanding the statistical properties of this data and the development of analysis methods. We report on a comprehensive evaluation of the commonly used DE methods using the SEQC benchmark data set. We evaluate a number of key features including: assessment of normalization, accuracy of DE detection, modeling of genes expressed in only one condition, and the impact of sequencing depth and number of replications on identifying DE genes. We find significant differences among the methods with no single method consistently outperforming the others. Furthermore, the performance of array-based approach is comparable to methods customized for RNA-seq data. Perhaps most importantly, our results demonstrate that increasing the number of replicate samples provides significantly more detection power than increased sequencing depth.
q-bio/0607036
Andrew Tan
Andrew Y. Y. Tan, Craig A. Atencio, Daniel B. Polley, Michael M. Merzenich and Christoph E. Schreiner
Unbalanced synaptic inhibition can create intensity-tuned auditory cortex neurons
22 pages, 5 figures
Neuroscience 146: 449-462 (2007)
10.1016/j.neuroscience.2007.01.019
null
q-bio.NC
null
Intensity-tuned auditory cortex neurons may be formed by intensity-tuned synaptic excitation. Synaptic inhibition has also been shown to enhance, and possibly even create intensity-tuned neurons. Here we show, using in vivo whole cell recordings in pentobarbital-anesthetized rats, that some intensity-tuned neurons are indeed created solely through disproportionally large inhibition at high intensities, without any intensity-tuned excitation. Since inhibition is essentially cortical in origin, these neurons provide examples of auditory feature-selectivity arising de novo at the cortex.
[ { "created": "Fri, 21 Jul 2006 18:44:32 GMT", "version": "v1" } ]
2007-05-23
[ [ "Tan", "Andrew Y. Y.", "" ], [ "Atencio", "Craig A.", "" ], [ "Polley", "Daniel B.", "" ], [ "Merzenich", "Michael M.", "" ], [ "Schreiner", "Christoph E.", "" ] ]
Intensity-tuned auditory cortex neurons may be formed by intensity-tuned synaptic excitation. Synaptic inhibition has also been shown to enhance, and possibly even create intensity-tuned neurons. Here we show, using in vivo whole cell recordings in pentobarbital-anesthetized rats, that some intensity-tuned neurons are indeed created solely through disproportionally large inhibition at high intensities, without any intensity-tuned excitation. Since inhibition is essentially cortical in origin, these neurons provide examples of auditory feature-selectivity arising de novo at the cortex.
2308.03198
Shuyang Bian
Shuyang Bian, Yuanyuan Xie, Flora Zhang
Re-imagining the Future of Forest Management -- An Age-Dependent Approach towards Harvesting
null
null
null
null
q-bio.OT
http://creativecommons.org/licenses/by-sa/4.0/
Facing the drastic climate changes, current strategies for enhancing carbon dioxide stocks need to be thoroughly honed. To address the problem, we first built a carbon sequestration growth model driven by growth rate dependency (GRDM). We abstracted the carbon cycling system into the process of photosynthesis, the humidity fluctuation, and the original storage of carbon in the trees. In the photosynthesis model, we considered various factors, including transition rate of absorption and organic matter production. We also designed an Economic Return Evaluation Model (EREM) to estimate the optimal distribution of trees in the forest based on the utility function. Maximizing the utility brought by the amount of carbon storage, we derived the equation for profit optimization with the constraints of total economic expenses allowed. To assess its performance, we took an object-oriented approach, simulated an ideal forest by placing instances of trees and plotted a time-dependent forest composition graph. After proper normalization of climate and economic data, we also make predictions for 169 worldwide forest-covered countries. Our model further suggests high sensitivity and robustness with a similar trend of overall utility when environmental aridity or proportion of harvested woods are varied. Finally, we apply the model to Georgia temperate deciduous forest, and we evaluate the carbon storage ability to adjust the Red Spruce based on available biological literature research. We recognize that while the model is preliminary in its failure to identify a diverse array of variables, it has encapsulated key features of idealized forests.
[ { "created": "Sun, 6 Aug 2023 19:52:41 GMT", "version": "v1" } ]
2023-08-08
[ [ "Bian", "Shuyang", "" ], [ "Xie", "Yuanyuan", "" ], [ "Zhang", "Flora", "" ] ]
Facing the drastic climate changes, current strategies for enhancing carbon dioxide stocks need to be thoroughly honed. To address the problem, we first built a carbon sequestration growth model driven by growth rate dependency (GRDM). We abstracted the carbon cycling system into the process of photosynthesis, the humidity fluctuation, and the original storage of carbon in the trees. In the photosynthesis model, we considered various factors, including transition rate of absorption and organic matter production. We also designed an Economic Return Evaluation Model (EREM) to estimate the optimal distribution of trees in the forest based on the utility function. Maximizing the utility brought by the amount of carbon storage, we derived the equation for profit optimization with the constraints of total economic expenses allowed. To assess its performance, we took an object-oriented approach, simulated an ideal forest by placing instances of trees and plotted a time-dependent forest composition graph. After proper normalization of climate and economic data, we also make predictions for 169 worldwide forest-covered countries. Our model further suggests high sensitivity and robustness with a similar trend of overall utility when environmental aridity or proportion of harvested woods are varied. Finally, we apply the model to Georgia temperate deciduous forest, and we evaluate the carbon storage ability to adjust the Red Spruce based on available biological literature research. We recognize that while the model is preliminary in its failure to identify a diverse array of variables, it has encapsulated key features of idealized forests.
1903.07533
Konstantinos Michmizos
Ioannis E. Polykretis, Vladimir A. Ivanov, Konstantinos P. Michmizos
Computational Astrocyence: Astrocytes encode inhibitory activity into the frequency and spatial extent of their calcium elevations
4 pages, 3 figures, IEEE-EMBS International Conference on Biomedical and Health Informatics (BHI '19)
null
null
null
q-bio.CB cs.NE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Deciphering the complex interactions between neurotransmission and astrocytic $Ca^{2+}$ elevations is a target promising a comprehensive understanding of brain function. While the astrocytic response to excitatory synaptic activity has been extensively studied, how inhibitory activity results to intracellular $Ca^{2+}$ waves remains elusive. In this study, we developed a compartmental astrocytic model that exhibits distinct levels of responsiveness to inhibitory activity. Our model suggested that the astrocytic coverage of inhibitory terminals defines the spatial and temporal scale of their $Ca^{2+}$ elevations. Understanding the interplay between the synaptic pathways and the astrocytic responses will help us identify how astrocytes work independently and cooperatively with neurons, in health and disease.
[ { "created": "Mon, 18 Mar 2019 16:21:55 GMT", "version": "v1" } ]
2019-03-19
[ [ "Polykretis", "Ioannis E.", "" ], [ "Ivanov", "Vladimir A.", "" ], [ "Michmizos", "Konstantinos P.", "" ] ]
Deciphering the complex interactions between neurotransmission and astrocytic $Ca^{2+}$ elevations is a target promising a comprehensive understanding of brain function. While the astrocytic response to excitatory synaptic activity has been extensively studied, how inhibitory activity results to intracellular $Ca^{2+}$ waves remains elusive. In this study, we developed a compartmental astrocytic model that exhibits distinct levels of responsiveness to inhibitory activity. Our model suggested that the astrocytic coverage of inhibitory terminals defines the spatial and temporal scale of their $Ca^{2+}$ elevations. Understanding the interplay between the synaptic pathways and the astrocytic responses will help us identify how astrocytes work independently and cooperatively with neurons, in health and disease.
1401.5130
Aaron Darling
David Coil and Guillaume Jospin and Aaron E. Darling
A5-miseq: an updated pipeline to assemble microbial genomes from Illumina MiSeq data
This is a revision of a manuscript submitted to Bioinformatics as an application note
null
null
null
q-bio.QM q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Motivation: Open-source bacterial genome assembly remains inaccessible to many biologists due to its complexity. Few software solutions exist that are capable of automating all steps in the process of de novo genome assembly from Illumina data. Results: A5-miseq can produce high quality microbial genome assemblies from as little as 20-fold sequence data coverage on a laptop computer without any parameter tuning. A5-miseq does this by automating the process of adapter trimming, quality filtering, error correction, contig and scaffold generation, and detection of misassemblies. Unlike the original A5 pipeline, A5-miseq can use long reads from the Illumina MiSeq, use read pairing information during contig generation, and includes several improvements to read trimming. Together these changes result in substantially improved assemblies that recover a more complete set of reference genes than previous methods. Availability: A5-miseq is licensed under the GPL open source license. Source code and precompiled binaries for Mac OS X 10.6+ and Linux 2.6.15+ are available from http://sourceforge.net/projects/ngopt
[ { "created": "Tue, 21 Jan 2014 00:34:24 GMT", "version": "v1" }, { "created": "Wed, 4 Jun 2014 12:21:24 GMT", "version": "v2" } ]
2014-06-05
[ [ "Coil", "David", "" ], [ "Jospin", "Guillaume", "" ], [ "Darling", "Aaron E.", "" ] ]
Motivation: Open-source bacterial genome assembly remains inaccessible to many biologists due to its complexity. Few software solutions exist that are capable of automating all steps in the process of de novo genome assembly from Illumina data. Results: A5-miseq can produce high quality microbial genome assemblies from as little as 20-fold sequence data coverage on a laptop computer without any parameter tuning. A5-miseq does this by automating the process of adapter trimming, quality filtering, error correction, contig and scaffold generation, and detection of misassemblies. Unlike the original A5 pipeline, A5-miseq can use long reads from the Illumina MiSeq, use read pairing information during contig generation, and includes several improvements to read trimming. Together these changes result in substantially improved assemblies that recover a more complete set of reference genes than previous methods. Availability: A5-miseq is licensed under the GPL open source license. Source code and precompiled binaries for Mac OS X 10.6+ and Linux 2.6.15+ are available from http://sourceforge.net/projects/ngopt
2011.11742
Tatiana Yakushkina S.
Igor Samokhin and Tatiana Yakushkina and Alexander S. Bratus
Open Quasispecies Systems: New Approach to Evolutionary Adaptation
null
null
null
null
q-bio.PE math.DS nlin.AO
http://creativecommons.org/licenses/by/4.0/
Consider a mathematical model of evolutionary adaptation of fitness landscape and mutation matrix as a reaction to population changes. As a basis, we use an open quasispecies model, which is modified to include explicit death flow. We assume that evolutionary parameters of mutation and selection processes vary in a way to maximize the mean fitness of the system. From this standpoint, Fisher's theorem of natural selection is being rethought and discussed. Another assumption is that system dynamics has two significant timescales. According to our central hypothesis, major evolutionary transitions happen in the steady-state of the corresponding dynamical system, so the evolutionary time is much slower than the one of internal dynamics. For the specific cases of quasispecies systems, we show how our premises form the fitness landscape adaptation process.
[ { "created": "Mon, 23 Nov 2020 21:36:15 GMT", "version": "v1" } ]
2020-11-25
[ [ "Samokhin", "Igor", "" ], [ "Yakushkina", "Tatiana", "" ], [ "Bratus", "Alexander S.", "" ] ]
Consider a mathematical model of evolutionary adaptation of fitness landscape and mutation matrix as a reaction to population changes. As a basis, we use an open quasispecies model, which is modified to include explicit death flow. We assume that evolutionary parameters of mutation and selection processes vary in a way to maximize the mean fitness of the system. From this standpoint, Fisher's theorem of natural selection is being rethought and discussed. Another assumption is that system dynamics has two significant timescales. According to our central hypothesis, major evolutionary transitions happen in the steady-state of the corresponding dynamical system, so the evolutionary time is much slower than the one of internal dynamics. For the specific cases of quasispecies systems, we show how our premises form the fitness landscape adaptation process.
2211.08503
Erin Ellefsen
Erin Ellefsen and Nancy Rodriguez
Nonlocal Mechanistic Models in Ecology: Numerical Methods and Parameter Inferencing
29 pages, 21 figures
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
Animals use various processes to inform themselves about their environment and make decisions about how to move and form their territory. In some cases, populations inform themselves of competing groups through observations at distances, scent markings, or memories of locations where an individual has encountered competing populations. As the process of gathering this information is inherently nonlocal, mechanistic models that include nonlocal terms have been proposed to investigate the movement of species. Naturally, these models present analytical and computational challenges. In this work we study a multi-species model with nonlocal advection. We introduce an efficient numerical scheme using spectral methods to compute solutions of a nonlocal reaction-advection-diffusion system for a large number of interacting species. Moreover, we investigate the effects that the parameters and interaction potentials have on the population densities. Finally, we propose a method using maximum likelihood estimation to determine the most important factors driving species' movements and test this method using synthetic data.
[ { "created": "Tue, 15 Nov 2022 21:01:19 GMT", "version": "v1" } ]
2022-11-17
[ [ "Ellefsen", "Erin", "" ], [ "Rodriguez", "Nancy", "" ] ]
Animals use various processes to inform themselves about their environment and make decisions about how to move and form their territory. In some cases, populations inform themselves of competing groups through observations at distances, scent markings, or memories of locations where an individual has encountered competing populations. As the process of gathering this information is inherently nonlocal, mechanistic models that include nonlocal terms have been proposed to investigate the movement of species. Naturally, these models present analytical and computational challenges. In this work we study a multi-species model with nonlocal advection. We introduce an efficient numerical scheme using spectral methods to compute solutions of a nonlocal reaction-advection-diffusion system for a large number of interacting species. Moreover, we investigate the effects that the parameters and interaction potentials have on the population densities. Finally, we propose a method using maximum likelihood estimation to determine the most important factors driving species' movements and test this method using synthetic data.
2209.08267
Te Wu
Te Wu, Feng Fu, and Long Wang
Evolutionary games and spatial periodicity
35 pages, 10 figures, and supplementary information
null
null
null
q-bio.PE nlin.AO
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We establish a theoretical framework to address evolutionary dynamics of spatial games under strong selection. As the selection intensity tends to infinity, strategy competition unfolds in the deterministic way of winners taking all. We rigorously prove that the evolutionary process soon or later either enters a cycle and from then on repeats the cycle periodically, or stabilizes at some state almost everywhere. This conclusion holds for any population graph and a large class of finite games. This framework suffices to reveal the underlying mathematical rationale for the kaleidoscopic cooperation of Nowak and May's pioneering work on spatial games: highly symmetric starting configuration causes a very long transient phase covering a large number of extremely beautiful spatial patterns. For all starting configurations, spatial patterns transit definitely over generations, so cooperators and defectors persist definitely. This framework can be extended to explore games including the snowdrift game, the public goods games (with or without loner, punishment), and repeated games on graphs. Aspiration dynamics can also be fully addressed when players deterministically switch strategy for unmet aspirations by virtue of our framework. Our results have potential implications for exploring the dynamics of a large variety of spatially extended systems in biology and physics.
[ { "created": "Sat, 17 Sep 2022 07:06:56 GMT", "version": "v1" } ]
2022-09-20
[ [ "Wu", "Te", "" ], [ "Fu", "Feng", "" ], [ "Wang", "Long", "" ] ]
We establish a theoretical framework to address evolutionary dynamics of spatial games under strong selection. As the selection intensity tends to infinity, strategy competition unfolds in the deterministic way of winners taking all. We rigorously prove that the evolutionary process soon or later either enters a cycle and from then on repeats the cycle periodically, or stabilizes at some state almost everywhere. This conclusion holds for any population graph and a large class of finite games. This framework suffices to reveal the underlying mathematical rationale for the kaleidoscopic cooperation of Nowak and May's pioneering work on spatial games: highly symmetric starting configuration causes a very long transient phase covering a large number of extremely beautiful spatial patterns. For all starting configurations, spatial patterns transit definitely over generations, so cooperators and defectors persist definitely. This framework can be extended to explore games including the snowdrift game, the public goods games (with or without loner, punishment), and repeated games on graphs. Aspiration dynamics can also be fully addressed when players deterministically switch strategy for unmet aspirations by virtue of our framework. Our results have potential implications for exploring the dynamics of a large variety of spatially extended systems in biology and physics.
2109.00824
Tsvi Tlusty
Somya Mani and Tsvi Tlusty
de novo gene birth as an inevitable consequence of adaptive evolution
null
null
null
null
q-bio.PE physics.bio-ph q-bio.GN
http://creativecommons.org/licenses/by-nc-nd/4.0/
Phylostratigraphy suggests that new genes are continually born de novo from non-genic sequences, and the genes that persist found new lineages, contributing to the adaptive evolution of organisms. While recent evidence supports the view that de novo gene birth is frequent and widespread, the mechanisms underlying this process are yet to be discovered. Here we hypothesize and examine a potential general mechanism of gene birth driven by the accumulation of beneficial mutations at non-genic loci. To demonstrate this possibility, we model this mechanism within the boundaries set by current knowledge on mutation effects. Estimates from this analysis are in line with observations of recurrent and extensive gene birth in genomics studies. Thus, we propose that, rather than being inactive and silent, non-genic regions are likely to be dynamic storehouses of potential genes.
[ { "created": "Thu, 2 Sep 2021 10:09:41 GMT", "version": "v1" }, { "created": "Mon, 20 Sep 2021 10:34:54 GMT", "version": "v2" }, { "created": "Wed, 6 Oct 2021 04:40:30 GMT", "version": "v3" } ]
2021-10-07
[ [ "Mani", "Somya", "" ], [ "Tlusty", "Tsvi", "" ] ]
Phylostratigraphy suggests that new genes are continually born de novo from non-genic sequences, and the genes that persist found new lineages, contributing to the adaptive evolution of organisms. While recent evidence supports the view that de novo gene birth is frequent and widespread, the mechanisms underlying this process are yet to be discovered. Here we hypothesize and examine a potential general mechanism of gene birth driven by the accumulation of beneficial mutations at non-genic loci. To demonstrate this possibility, we model this mechanism within the boundaries set by current knowledge on mutation effects. Estimates from this analysis are in line with observations of recurrent and extensive gene birth in genomics studies. Thus, we propose that, rather than being inactive and silent, non-genic regions are likely to be dynamic storehouses of potential genes.
0906.5173
Bob Eisenberg
Bob Eisenberg
Self-organized Models of Selectivity in Ca and Na Channels
Version of http://www.ima.umn.edu/2008-2009/W12.8-12.08/abstracts.html, talk given at the Institute for Mathematics and its Applications, University of Minnesota, November 19, 2008. Abstract published in Biophysical Journal, Volume 96, Issue 3, 253a
null
10.1016/j.bpj.2008.12.1247
null
q-bio.SC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
A simple pillbox model with two adjustable parameters accounts for the selectivity of both DEEA Ca channels and DEKA Na channels in many ionic solutions of different composition and concentration. Only the side chains are different in the model of the Ca and Na channels. Parameters are the same for both channels in all solutions. 'Pauling' radii are used for ions. No information from crystal structures is used in the model. Side chains are grossly approximated as spheres. The predicted properties of the Na and Ca channels are very different. How can such a simple model give such powerful results when chemical intuition says that selectivity depends on the precise relation of ions and side chains? We use Monte Carlo simulations of this model that determine the most stable-lowest free energy-structure of the ions and side chains. Structure is the computed consequence of the forces in this model. The relationship of ions and side chains vary with ionic solution and are very different in simulations of the Na and Ca channels. Selectivity is a consequence of the 'induced fit' of side chains to ions and depends on the flexibility (entropy) of the side chains as well as their location. The model captures the relation of side chains and ions well enough to account for selectivity of both Na channels and Ca channels in the wide range of conditions measured in experiments. Evidently, the structures in the real Na and Ca channels responsible for selectivity are self-organized, at their free energy minimum. Oversimplified models are enough to account for selectivity if the models calculate the 'most stable' structure as it changes from solution to solution, and mutation to mutation.
[ { "created": "Sun, 28 Jun 2009 22:17:44 GMT", "version": "v1" } ]
2015-05-13
[ [ "Eisenberg", "Bob", "" ] ]
A simple pillbox model with two adjustable parameters accounts for the selectivity of both DEEA Ca channels and DEKA Na channels in many ionic solutions of different composition and concentration. Only the side chains are different in the model of the Ca and Na channels. Parameters are the same for both channels in all solutions. 'Pauling' radii are used for ions. No information from crystal structures is used in the model. Side chains are grossly approximated as spheres. The predicted properties of the Na and Ca channels are very different. How can such a simple model give such powerful results when chemical intuition says that selectivity depends on the precise relation of ions and side chains? We use Monte Carlo simulations of this model that determine the most stable-lowest free energy-structure of the ions and side chains. Structure is the computed consequence of the forces in this model. The relationship of ions and side chains vary with ionic solution and are very different in simulations of the Na and Ca channels. Selectivity is a consequence of the 'induced fit' of side chains to ions and depends on the flexibility (entropy) of the side chains as well as their location. The model captures the relation of side chains and ions well enough to account for selectivity of both Na channels and Ca channels in the wide range of conditions measured in experiments. Evidently, the structures in the real Na and Ca channels responsible for selectivity are self-organized, at their free energy minimum. Oversimplified models are enough to account for selectivity if the models calculate the 'most stable' structure as it changes from solution to solution, and mutation to mutation.
0909.3691
Yaniv Erlich
Yaniv Erlich, Assaf Gordon, Michael Brand, Gregory J. Hannon and Partha P. Mitra
Compressed Genotyping
Submitted to IEEE Transaction on Information Theory - Special Issue on Molecular Biology and Neuroscience
null
10.1109/TIT.2009.2037043
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Significant volumes of knowledge have been accumulated in recent years linking subtle genetic variations to a wide variety of medical disorders from Cystic Fibrosis to mental retardation. Nevertheless, there are still great challenges in applying this knowledge routinely in the clinic, largely due to the relatively tedious and expensive process of DNA sequencing. Since the genetic polymorphisms that underlie these disorders are relatively rare in the human population, the presence or absence of a disease-linked polymorphism can be thought of as a sparse signal. Using methods and ideas from compressed sensing and group testing, we have developed a cost-effective genotyping protocol. In particular, we have adapted our scheme to a recently developed class of high throughput DNA sequencing technologies, and assembled a mathematical framework that has some important distinctions from 'traditional' compressed sensing ideas in order to address different biological and technical constraints.
[ { "created": "Mon, 21 Sep 2009 05:53:20 GMT", "version": "v1" } ]
2016-11-17
[ [ "Erlich", "Yaniv", "" ], [ "Gordon", "Assaf", "" ], [ "Brand", "Michael", "" ], [ "Hannon", "Gregory J.", "" ], [ "Mitra", "Partha P.", "" ] ]
Significant volumes of knowledge have been accumulated in recent years linking subtle genetic variations to a wide variety of medical disorders from Cystic Fibrosis to mental retardation. Nevertheless, there are still great challenges in applying this knowledge routinely in the clinic, largely due to the relatively tedious and expensive process of DNA sequencing. Since the genetic polymorphisms that underlie these disorders are relatively rare in the human population, the presence or absence of a disease-linked polymorphism can be thought of as a sparse signal. Using methods and ideas from compressed sensing and group testing, we have developed a cost-effective genotyping protocol. In particular, we have adapted our scheme to a recently developed class of high throughput DNA sequencing technologies, and assembled a mathematical framework that has some important distinctions from 'traditional' compressed sensing ideas in order to address different biological and technical constraints.
2205.14747
Valeriy Ginzburg
Anne V. Ginzburg (Michigan State University), Valeriy V. Ginzburg (Michigan State University and VVG Consulting LLC), Julia O. Ginzburg (VVG Physics Consulting LLC), Ana Garcia Arias (Central Michigan University), and Leela Rakesh (Central Michigan University)
Modeling the Dynamics of the Coronavirus SARS-CoV-2 Pandemic using Modified SIR Model with the 'Damped-Oscillator' Dynamics of the Effective Reproduction Number
null
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
The COVID-19 pandemic has been a great catastrophe that upended human lives and caused millions of deaths all over the world. The rapid spread of the virus, with its early-stage exponential growth and subsequent 'waves', caught many medical professionals and decision-makers unprepared. Even though epidemiological models have been known for almost a century (since the 'Spanish Influenza' pandemic of 1918-20), the real-life spread of the SARS-CoV-2 virus often confounded the modelers. While the general framework of epidemiological models like SEIR (susceptible-exposed-infected-recovered) or SIR (susceptible-exposed-infected) was not in question, the behavior of model parameters turned out to be unpredictable and complicated. In particular, while the 'basic' reproduction number, R0, can be considered a constant (for the original SARS-CoV-2 virus, prior to the emergence of variants, R0 is between 2.5 and 3.0), the 'effective' reproduction number, R(t), was a complex function of time, influenced by human behavior in response to the pandemic (e.g., masking, lockdowns, transition to remote work, etc.) To better understand these phenomena, we model the first year of the pandemic (between February 2020 and February 2021) for a number of localities (fifty US states, as well as several countries) using a simple SIR model. We show that the evolution of the pandemic can be described quite successfully by assuming that R(t) behaves in a 'viscoelastic' manner, as a sum of two or three 'damped oscillators' with different natural frequencies and damping coefficients. These oscillators likely correspond to different sub-populations having different reactions to proposed mitigation measures. The proposed approach can offer future data modelers new ways to fit the reproduction number evolution with time (as compared to the purely data-driven approaches most prevalent today).
[ { "created": "Sun, 29 May 2022 19:42:23 GMT", "version": "v1" } ]
2022-05-31
[ [ "Ginzburg", "Anne V.", "", "Michigan State University" ], [ "Ginzburg", "Valeriy V.", "", "Michigan State University and VVG Consulting LLC" ], [ "Ginzburg", "Julia O.", "", "VVG\n Physics Consulting LLC" ], [ "Arias", "Ana Garcia", "", ...
The COVID-19 pandemic has been a great catastrophe that upended human lives and caused millions of deaths all over the world. The rapid spread of the virus, with its early-stage exponential growth and subsequent 'waves', caught many medical professionals and decision-makers unprepared. Even though epidemiological models have been known for almost a century (since the 'Spanish Influenza' pandemic of 1918-20), the real-life spread of the SARS-CoV-2 virus often confounded the modelers. While the general framework of epidemiological models like SEIR (susceptible-exposed-infected-recovered) or SIR (susceptible-exposed-infected) was not in question, the behavior of model parameters turned out to be unpredictable and complicated. In particular, while the 'basic' reproduction number, R0, can be considered a constant (for the original SARS-CoV-2 virus, prior to the emergence of variants, R0 is between 2.5 and 3.0), the 'effective' reproduction number, R(t), was a complex function of time, influenced by human behavior in response to the pandemic (e.g., masking, lockdowns, transition to remote work, etc.) To better understand these phenomena, we model the first year of the pandemic (between February 2020 and February 2021) for a number of localities (fifty US states, as well as several countries) using a simple SIR model. We show that the evolution of the pandemic can be described quite successfully by assuming that R(t) behaves in a 'viscoelastic' manner, as a sum of two or three 'damped oscillators' with different natural frequencies and damping coefficients. These oscillators likely correspond to different sub-populations having different reactions to proposed mitigation measures. The proposed approach can offer future data modelers new ways to fit the reproduction number evolution with time (as compared to the purely data-driven approaches most prevalent today).
1902.09345
Thomas McGrath
Thomas M McGrath, Eleanor Spreckley, Aina Fernandez Rodriguez, Carlo Viscomi, Amin Alamshah, Elina Akalestou, Kevin G Murphy, Nick S Jones
The homeostatic dynamics of feeding behaviour identify novel mechanisms of anorectic agents
null
null
null
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Better understanding of feeding behaviour will be vital in reducing obesity and metabolic syndrome, but we lack a standard model that captures the complexity of feeding behaviour. We construct an accurate stochastic model of rodent feeding at the bout level in order to perform quantitative behavioural analysis. Analysing the different effects on feeding behaviour of PYY 3-36, lithium chloride, GLP-1 and leptin shows the precise behavioural changes caused by each anorectic agent, and demonstrates that these changes do not mimic satiety. In the ad libitum fed state during the light period, meal initiation is governed by complete stomach emptying, whereas in all other conditions there is a graduated response. We show how robust homeostatic control of feeding thwarts attempts to reduce food intake, and how this might be overcome. In silico experiments suggest that introducing a minimum intermeal interval or modulating gastric emptying can be as effective as anorectic drug administration.
[ { "created": "Fri, 22 Feb 2019 11:57:59 GMT", "version": "v1" }, { "created": "Thu, 14 Mar 2019 16:47:53 GMT", "version": "v2" }, { "created": "Thu, 9 May 2019 09:16:59 GMT", "version": "v3" } ]
2019-05-10
[ [ "McGrath", "Thomas M", "" ], [ "Spreckley", "Eleanor", "" ], [ "Rodriguez", "Aina Fernandez", "" ], [ "Viscomi", "Carlo", "" ], [ "Alamshah", "Amin", "" ], [ "Akalestou", "Elina", "" ], [ "Murphy", "Kevin G", ...
Better understanding of feeding behaviour will be vital in reducing obesity and metabolic syndrome, but we lack a standard model that captures the complexity of feeding behaviour. We construct an accurate stochastic model of rodent feeding at the bout level in order to perform quantitative behavioural analysis. Analysing the different effects on feeding behaviour of PYY 3-36, lithium chloride, GLP-1 and leptin shows the precise behavioural changes caused by each anorectic agent, and demonstrates that these changes do not mimic satiety. In the ad libitum fed state during the light period, meal initiation is governed by complete stomach emptying, whereas in all other conditions there is a graduated response. We show how robust homeostatic control of feeding thwarts attempts to reduce food intake, and how this might be overcome. In silico experiments suggest that introducing a minimum intermeal interval or modulating gastric emptying can be as effective as anorectic drug administration.
2007.09780
Anurag Mishra
Abhishek Srivastava, Anurag Mishra, Trusha Jayant Parekh, Sampreeti Jena
Implementing Stepped Pooled Testing for Rapid COVID-19 Detection
6 pages, including three tables and four figures
null
null
null
q-bio.PE stat.AP
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
COVID-19, a viral respiratory pandemic, has rapidly spread throughout the globe. Large scale and rapid testing of the population is required to contain the disease, but such testing is prohibitive in terms of resources, cost and time. Recently RT-PCR based pooled testing has emerged as a promising way to boost testing efficiency. We introduce a stepped pooled testing strategy, a probability driven approach which significantly reduces the number of tests required to identify infected individuals in a large population. Our comprehensive methodology incorporates the effect of false negative and positive rates to accurately determine not only the efficiency of pooling but also it's accuracy. Under various plausible scenarios, we show that this approach significantly reduces the cost of testing and also reduces the effective false positive rate of tests when compared to a strategy of testing every individual of a population. We also outline an optimization strategy to obtain the pool size that maximizes the efficiency of pooling given the diagnostic protocol parameters and local infection conditions.
[ { "created": "Sun, 19 Jul 2020 20:47:02 GMT", "version": "v1" } ]
2020-07-21
[ [ "Srivastava", "Abhishek", "" ], [ "Mishra", "Anurag", "" ], [ "Parekh", "Trusha Jayant", "" ], [ "Jena", "Sampreeti", "" ] ]
COVID-19, a viral respiratory pandemic, has rapidly spread throughout the globe. Large scale and rapid testing of the population is required to contain the disease, but such testing is prohibitive in terms of resources, cost and time. Recently RT-PCR based pooled testing has emerged as a promising way to boost testing efficiency. We introduce a stepped pooled testing strategy, a probability driven approach which significantly reduces the number of tests required to identify infected individuals in a large population. Our comprehensive methodology incorporates the effect of false negative and positive rates to accurately determine not only the efficiency of pooling but also it's accuracy. Under various plausible scenarios, we show that this approach significantly reduces the cost of testing and also reduces the effective false positive rate of tests when compared to a strategy of testing every individual of a population. We also outline an optimization strategy to obtain the pool size that maximizes the efficiency of pooling given the diagnostic protocol parameters and local infection conditions.
0811.3315
Farshid Mohammad-Rafiee
Davood Norouzi, Farshid Mohammad-Rafiee, Ramin Golestanian
Effect of Bending Anisotropy on the 3D Conformation of Short DNA Loops
null
Phys. Rev. Lett. 101, 168103 (2008)
10.1103/PhysRevLett.101.168103
null
q-bio.BM cond-mat.soft
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The equilibrium three dimensional shape of relatively short loops of DNA is studied using an elastic model that takes into account anisotropy in bending rigidities. Using a reasonable estimate for the anisotropy, it is found that cyclized DNA with lengths that are not integer multiples of the pitch take on nontrivial shapes that involve bending out of planes and formation of kinks. The effect of sequence inhomogeneity on the shape of DNA is addressed, and shown to enhance the geometrical features. These findings could shed some light on the role of DNA conformation in protein--DNA interactions.
[ { "created": "Thu, 20 Nov 2008 11:40:43 GMT", "version": "v1" } ]
2008-11-24
[ [ "Norouzi", "Davood", "" ], [ "Mohammad-Rafiee", "Farshid", "" ], [ "Golestanian", "Ramin", "" ] ]
The equilibrium three dimensional shape of relatively short loops of DNA is studied using an elastic model that takes into account anisotropy in bending rigidities. Using a reasonable estimate for the anisotropy, it is found that cyclized DNA with lengths that are not integer multiples of the pitch take on nontrivial shapes that involve bending out of planes and formation of kinks. The effect of sequence inhomogeneity on the shape of DNA is addressed, and shown to enhance the geometrical features. These findings could shed some light on the role of DNA conformation in protein--DNA interactions.
1907.00118
Colin Targonski
Colin Targonski, Benjamin T. Shealy, Melissa C. Smith, F. Alex Feltus
Cellular State Transformations using Generative Adversarial Networks
11 pages, 5 figures
null
null
null
q-bio.QM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We introduce a novel method to unite deep learning with biology by which generative adversarial networks (GANs) generate transcriptome perturbations and reveal condition-defining gene expression patterns. We find that a generator conditioned to perturb any input gene expression profile simulates a realistic transition between source and target RNA expression states. The perturbed samples follow a similar distribution to original samples from the dataset, also suggesting these are biologically meaningful perturbations. Finally, we show that it is possible to identify the genes most positively and negatively perturbed by the generator and that the enriched biological function of the perturbed genes are realistic. We call the framework the Transcriptome State Perturbation Generator (TSPG), which is open source software available at https://github.com/ctargon/TSPG.
[ { "created": "Fri, 28 Jun 2019 23:59:57 GMT", "version": "v1" } ]
2019-07-02
[ [ "Targonski", "Colin", "" ], [ "Shealy", "Benjamin T.", "" ], [ "Smith", "Melissa C.", "" ], [ "Feltus", "F. Alex", "" ] ]
We introduce a novel method to unite deep learning with biology by which generative adversarial networks (GANs) generate transcriptome perturbations and reveal condition-defining gene expression patterns. We find that a generator conditioned to perturb any input gene expression profile simulates a realistic transition between source and target RNA expression states. The perturbed samples follow a similar distribution to original samples from the dataset, also suggesting these are biologically meaningful perturbations. Finally, we show that it is possible to identify the genes most positively and negatively perturbed by the generator and that the enriched biological function of the perturbed genes are realistic. We call the framework the Transcriptome State Perturbation Generator (TSPG), which is open source software available at https://github.com/ctargon/TSPG.
1805.05696
Luka Ribar
Luka Ribar, Rodolphe Sepulchre
Neuromodulation of Neuromorphic Circuits
null
IEEE Transactions on Circuits and Systems I: Regular Papers, vol. 66, no. 8, pp. 3028-3040, Aug. 2019
10.1109/TCSI.2019.2907113
null
q-bio.NC cs.NE cs.SY eess.SY
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We present a novel methodology to enable control of a neuromorphic circuit in close analogy with the physiological neuromodulation of a single neuron. The methodology is general in that it only relies on a parallel interconnection of elementary voltage-controlled current sources. In contrast to controlling a nonlinear circuit through the parameter tuning of a state-space model, our approach is purely input-output. The circuit elements are controlled and interconnected to shape the current-voltage characteristics (I-V curves) of the circuit in prescribed timescales. In turn, shaping those I-V curves determines the excitability properties of the circuit. We show that this methodology enables both robust and accurate control of the circuit behavior and resembles the biophysical mechanisms of neuromodulation. As a proof of concept, we simulate a SPICE model composed of MOSFET transconductance amplifiers operating in the weak inversion regime.
[ { "created": "Tue, 15 May 2018 10:43:18 GMT", "version": "v1" }, { "created": "Thu, 25 Oct 2018 14:13:15 GMT", "version": "v2" }, { "created": "Thu, 21 Mar 2019 19:49:20 GMT", "version": "v3" } ]
2020-11-19
[ [ "Ribar", "Luka", "" ], [ "Sepulchre", "Rodolphe", "" ] ]
We present a novel methodology to enable control of a neuromorphic circuit in close analogy with the physiological neuromodulation of a single neuron. The methodology is general in that it only relies on a parallel interconnection of elementary voltage-controlled current sources. In contrast to controlling a nonlinear circuit through the parameter tuning of a state-space model, our approach is purely input-output. The circuit elements are controlled and interconnected to shape the current-voltage characteristics (I-V curves) of the circuit in prescribed timescales. In turn, shaping those I-V curves determines the excitability properties of the circuit. We show that this methodology enables both robust and accurate control of the circuit behavior and resembles the biophysical mechanisms of neuromodulation. As a proof of concept, we simulate a SPICE model composed of MOSFET transconductance amplifiers operating in the weak inversion regime.
1512.00843
Sheng Wang
Sheng Wang, Jian Peng, Jianzhu Ma and Jinbo Xu
Protein secondary structure prediction using deep convolutional neural fields
null
null
null
null
q-bio.BM cs.LG q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Protein secondary structure (SS) prediction is important for studying protein structure and function. When only the sequence (profile) information is used as input feature, currently the best predictors can obtain ~80% Q3 accuracy, which has not been improved in the past decade. Here we present DeepCNF (Deep Convolutional Neural Fields) for protein SS prediction. DeepCNF is a Deep Learning extension of Conditional Neural Fields (CNF), which is an integration of Conditional Random Fields (CRF) and shallow neural networks. DeepCNF can model not only complex sequence-structure relationship by a deep hierarchical architecture, but also interdependency between adjacent SS labels, so it is much more powerful than CNF. Experimental results show that DeepCNF can obtain ~84% Q3 accuracy, ~85% SOV score, and ~72% Q8 accuracy, respectively, on the CASP and CAMEO test proteins, greatly outperforming currently popular predictors. As a general framework, DeepCNF can be used to predict other protein structure properties such as contact number, disorder regions, and solvent accessibility.
[ { "created": "Wed, 2 Dec 2015 01:53:57 GMT", "version": "v1" }, { "created": "Thu, 10 Dec 2015 17:01:59 GMT", "version": "v2" }, { "created": "Fri, 11 Dec 2015 03:16:55 GMT", "version": "v3" } ]
2015-12-14
[ [ "Wang", "Sheng", "" ], [ "Peng", "Jian", "" ], [ "Ma", "Jianzhu", "" ], [ "Xu", "Jinbo", "" ] ]
Protein secondary structure (SS) prediction is important for studying protein structure and function. When only the sequence (profile) information is used as input feature, currently the best predictors can obtain ~80% Q3 accuracy, which has not been improved in the past decade. Here we present DeepCNF (Deep Convolutional Neural Fields) for protein SS prediction. DeepCNF is a Deep Learning extension of Conditional Neural Fields (CNF), which is an integration of Conditional Random Fields (CRF) and shallow neural networks. DeepCNF can model not only complex sequence-structure relationship by a deep hierarchical architecture, but also interdependency between adjacent SS labels, so it is much more powerful than CNF. Experimental results show that DeepCNF can obtain ~84% Q3 accuracy, ~85% SOV score, and ~72% Q8 accuracy, respectively, on the CASP and CAMEO test proteins, greatly outperforming currently popular predictors. As a general framework, DeepCNF can be used to predict other protein structure properties such as contact number, disorder regions, and solvent accessibility.
q-bio/0507043
Heiko Rieger
D.-S. Lee, H. Rieger, K. Bartha
Flow correlated percolation during vascular network formation in tumors
4 pages, 3 figures (higher resolution at http://www.uni-saarland.de/fak7/rieger/HOMEPAGE/flow.eps)
Phys. Rev. Lett. 96, 058104 (2006)
10.1103/PhysRevLett.96.058104
null
q-bio.TO
null
A theoretical model based on the molecular interactions between a growing tumor and a dynamically evolving blood vessel network describes the transformation of the regular vasculature in normal tissues into a highly inhomogeneous tumor specific capillary network. The emerging morphology, characterized by the compartmentalization of the tumor into several regions differing in vessel density, diameter and necrosis, is in accordance with experimental data for human melanoma. Vessel collapse due to a combination of severely reduced blood flow and solid stress exerted by the tumor, leads to a correlated percolation process that is driven towards criticality by the mechanism of hydrodynamic vessel stabilization.
[ { "created": "Thu, 28 Jul 2005 13:53:44 GMT", "version": "v1" } ]
2007-05-23
[ [ "Lee", "D. -S.", "" ], [ "Rieger", "H.", "" ], [ "Bartha", "K.", "" ] ]
A theoretical model based on the molecular interactions between a growing tumor and a dynamically evolving blood vessel network describes the transformation of the regular vasculature in normal tissues into a highly inhomogeneous tumor specific capillary network. The emerging morphology, characterized by the compartmentalization of the tumor into several regions differing in vessel density, diameter and necrosis, is in accordance with experimental data for human melanoma. Vessel collapse due to a combination of severely reduced blood flow and solid stress exerted by the tumor, leads to a correlated percolation process that is driven towards criticality by the mechanism of hydrodynamic vessel stabilization.
1001.4972
Elke Markert
Elke K. Markert, Nils Baas, Arnold J. Levine, Alexei Vazquez
Higher Order Boolean networks as models of cell state dynamics
26 pages, 5 figures
null
null
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The regulation of the cell state is a complex process involving several components. These complex dynamics can be modeled using Boolean networks, allowing us to explain the existence of different cell states and the transition between them. Boolean models have been introduced both as specific examples and as ensemble or distribution network models. However, current ensemble Boolean network models do not make a systematic distinction between different cell components such as epigenetic factors, gene and transcription factors. Consequently, we still do not understand their relative contributions in controlling the cell fate. In this work we introduce and study higher order Boolean networks, which feature an explicit distinction between the different cell components and the types of interactions between them. We show that the stability of the cell state dynamics can be determined solving the eigenvalue problem of a matrix representing the regulatory interactions and their strengths. The qualitative analysis of this problem indicates that, in addition to the classification into stable and chaotic regimes, the cell state can be simple or complex depending on whether it can be deduced from the independent study of its components or not. Finally, we illustrate how the model can be expanded considering higher levels and higher order dynamics.
[ { "created": "Wed, 27 Jan 2010 15:29:27 GMT", "version": "v1" } ]
2010-01-28
[ [ "Markert", "Elke K.", "" ], [ "Baas", "Nils", "" ], [ "Levine", "Arnold J.", "" ], [ "Vazquez", "Alexei", "" ] ]
The regulation of the cell state is a complex process involving several components. These complex dynamics can be modeled using Boolean networks, allowing us to explain the existence of different cell states and the transition between them. Boolean models have been introduced both as specific examples and as ensemble or distribution network models. However, current ensemble Boolean network models do not make a systematic distinction between different cell components such as epigenetic factors, gene and transcription factors. Consequently, we still do not understand their relative contributions in controlling the cell fate. In this work we introduce and study higher order Boolean networks, which feature an explicit distinction between the different cell components and the types of interactions between them. We show that the stability of the cell state dynamics can be determined solving the eigenvalue problem of a matrix representing the regulatory interactions and their strengths. The qualitative analysis of this problem indicates that, in addition to the classification into stable and chaotic regimes, the cell state can be simple or complex depending on whether it can be deduced from the independent study of its components or not. Finally, we illustrate how the model can be expanded considering higher levels and higher order dynamics.
1701.07940
Pavel Sumazin
Matteo Manica, Hyunjae Ryan Kim, Roland Mathis, Philippe Chouvarine, Dorothea Rutishauser, Laura De Vargas Roditi, Bence Szalai, Ulrich Wagner, Kathrin Oehl, Karim Saba, Arati Pati, Julio Saez-Rodriguez, Angshumoy Roy, Donald W. Parsons, Peter J. Wild, Mar\'ia Rodr\'iguez Mart\'inez, Pavel Sumazin
Inferring clonal composition from multiple tumor biopsies
null
null
null
null
q-bio.GN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Explicit accounting for copy number alterations can dramatically improve mutation frequency estimates, leading to more accurate phylogeny reconstructions and subclone characterizations.
[ { "created": "Fri, 27 Jan 2017 04:32:45 GMT", "version": "v1" }, { "created": "Fri, 22 Nov 2019 19:22:19 GMT", "version": "v2" } ]
2019-11-26
[ [ "Manica", "Matteo", "" ], [ "Kim", "Hyunjae Ryan", "" ], [ "Mathis", "Roland", "" ], [ "Chouvarine", "Philippe", "" ], [ "Rutishauser", "Dorothea", "" ], [ "Roditi", "Laura De Vargas", "" ], [ "Szalai", "Bence"...
Explicit accounting for copy number alterations can dramatically improve mutation frequency estimates, leading to more accurate phylogeny reconstructions and subclone characterizations.
2008.09597
Nicole Eikmeier
Riti Bahl, Nicole Eikmeier, Alexandra Fraser, Matthew Junge, Felicia Keesing, Kukai Nakahata, and Lily Z. Wang
Modeling COVID-19 Spread in Small Colleges
17 pages, 8 figures, 5 tables
null
10.1371/journal.pone.0255654
null
q-bio.PE physics.soc-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We develop an agent-based model on a network meant to capture features unique to COVID-19 spread through a small residential college. We find that a safe reopening requires strong policy from administrators combined with cautious behavior from students. Strong policy includes weekly screening tests with quick turnaround and halving the campus population. Cautious behavior from students means wearing facemasks, socializing less, and showing up for COVID-19 testing. We also find that comprehensive testing and facemasks are the most effective single interventions, building closures can lead to infection spikes in other areas depending on student behavior, and faster return of test results significantly reduces total infections.
[ { "created": "Fri, 21 Aug 2020 17:52:27 GMT", "version": "v1" } ]
2021-09-15
[ [ "Bahl", "Riti", "" ], [ "Eikmeier", "Nicole", "" ], [ "Fraser", "Alexandra", "" ], [ "Junge", "Matthew", "" ], [ "Keesing", "Felicia", "" ], [ "Nakahata", "Kukai", "" ], [ "Wang", "Lily Z.", "" ] ]
We develop an agent-based model on a network meant to capture features unique to COVID-19 spread through a small residential college. We find that a safe reopening requires strong policy from administrators combined with cautious behavior from students. Strong policy includes weekly screening tests with quick turnaround and halving the campus population. Cautious behavior from students means wearing facemasks, socializing less, and showing up for COVID-19 testing. We also find that comprehensive testing and facemasks are the most effective single interventions, building closures can lead to infection spikes in other areas depending on student behavior, and faster return of test results significantly reduces total infections.
1104.4235
Pau Ru\'e
Pau Ru\'e, G\"urol M. S\"uel and Jordi Garcia-Ojalvo
Optimizing periodicity and polymodality in noise-induced genetic oscillators
9 pages, 6 figures
Phys. Rev. E 83, 061904 (2011)
10.1103/PhysRevE.83.061904
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Many cellular functions are based on the rhythmic organization of biological processes into self-repeating cascades of events. Some of these periodic processes, such as the cell cycles of several species, exhibit conspicuous irregularities in the form of period skippings, which lead to polymodal distributions of cycle lengths. A recently proposed mechanism that accounts for this quantized behavior is the stabilization of a Hopf-unstable state by molecular noise. Here we investigate the effect of varying noise in a model system, namely an excitable activator-repressor genetic circuit, that displays this noise-induced stabilization effect. Our results show that an optimal noise level enhances the regularity (coherence) of the cycles, in a form of coherence resonance. Similar noise levels also optimize the multimodal nature of the cycle lengths. Together, these results illustrate how molecular noise within a minimal gene regulatory motif confers robust generation of polymodal patterns of periodicity.
[ { "created": "Thu, 21 Apr 2011 11:36:19 GMT", "version": "v1" } ]
2011-09-30
[ [ "Rué", "Pau", "" ], [ "Süel", "Gürol M.", "" ], [ "Garcia-Ojalvo", "Jordi", "" ] ]
Many cellular functions are based on the rhythmic organization of biological processes into self-repeating cascades of events. Some of these periodic processes, such as the cell cycles of several species, exhibit conspicuous irregularities in the form of period skippings, which lead to polymodal distributions of cycle lengths. A recently proposed mechanism that accounts for this quantized behavior is the stabilization of a Hopf-unstable state by molecular noise. Here we investigate the effect of varying noise in a model system, namely an excitable activator-repressor genetic circuit, that displays this noise-induced stabilization effect. Our results show that an optimal noise level enhances the regularity (coherence) of the cycles, in a form of coherence resonance. Similar noise levels also optimize the multimodal nature of the cycle lengths. Together, these results illustrate how molecular noise within a minimal gene regulatory motif confers robust generation of polymodal patterns of periodicity.
1212.3888
Jeremy Sumner
Jeremy G. Sumner, Peter D. Jarvis, and Barbara R. Holland
A tensorial approach to the inversion of group-based phylogenetic models
24 pages, 2 figures
null
null
null
q-bio.PE math.ST stat.TH
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Using a tensorial approach, we show how to construct a one-one correspondence between pattern probabilities and edge parameters for any group-based model. This is a generalisation of the "Hadamard conjugation" and is equivalent to standard results that use Fourier analysis. In our derivation we focus on the connections to group representation theory and emphasize that the inversion is possible because, under their usual definition, group-based models are defined for abelian groups only. We also argue that our approach is elementary in the sense that it can be understood as simple matrix multiplication where matrices are rectangular and indexed by ordered-partitions of varying sizes.
[ { "created": "Mon, 17 Dec 2012 05:09:34 GMT", "version": "v1" } ]
2012-12-18
[ [ "Sumner", "Jeremy G.", "" ], [ "Jarvis", "Peter D.", "" ], [ "Holland", "Barbara R.", "" ] ]
Using a tensorial approach, we show how to construct a one-one correspondence between pattern probabilities and edge parameters for any group-based model. This is a generalisation of the "Hadamard conjugation" and is equivalent to standard results that use Fourier analysis. In our derivation we focus on the connections to group representation theory and emphasize that the inversion is possible because, under their usual definition, group-based models are defined for abelian groups only. We also argue that our approach is elementary in the sense that it can be understood as simple matrix multiplication where matrices are rectangular and indexed by ordered-partitions of varying sizes.
1408.3940
David A. Kessler
David A. Kessler and Nadav M. Shnerb
A generalized model of island biodiversity
null
null
10.1103/PhysRevE.91.042705
null
q-bio.PE cond-mat.stat-mech
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The dynamics of a local community of competing species with weak immigration from a static regional pool is studied. Implementing the generalized competitive Lotka-Volterra model with demographic noise, a rich dynamics structure with four qualitatively distinct phases is unfolded. When the overall interspecies competition is weak, the island species are a sample of the mainland species. For higher values of the competition parameter the system still admit an equilibrium community, but now some of the mainland species are absent on the island. Further increase in competition leads to an intermittent "chaotic" phase, where the dynamics is controlled by invadable combinations of species and the turnover rate is governed by the migration. Finally, the strong competition phase is glassy, dominated by uninvadable state and noise-induced transitions. Our model contains, as a spatial case, the celebrated neutral island theories of Wilson-MacArthur and Hubbell. Moreover, we show that slight deviations from perfect neutrality may lead to each of the phases, as the Hubbell point appears to be quadracritical.
[ { "created": "Mon, 18 Aug 2014 09:03:57 GMT", "version": "v1" } ]
2015-06-22
[ [ "Kessler", "David A.", "" ], [ "Shnerb", "Nadav M.", "" ] ]
The dynamics of a local community of competing species with weak immigration from a static regional pool is studied. Implementing the generalized competitive Lotka-Volterra model with demographic noise, a rich dynamics structure with four qualitatively distinct phases is unfolded. When the overall interspecies competition is weak, the island species are a sample of the mainland species. For higher values of the competition parameter the system still admit an equilibrium community, but now some of the mainland species are absent on the island. Further increase in competition leads to an intermittent "chaotic" phase, where the dynamics is controlled by invadable combinations of species and the turnover rate is governed by the migration. Finally, the strong competition phase is glassy, dominated by uninvadable state and noise-induced transitions. Our model contains, as a spatial case, the celebrated neutral island theories of Wilson-MacArthur and Hubbell. Moreover, we show that slight deviations from perfect neutrality may lead to each of the phases, as the Hubbell point appears to be quadracritical.
1411.1528
Roger Guimera
Roger Guimera, Marta Sales-Pardo
A network inference method for large-scale unsupervised identification of novel drug-drug interactions
null
PLoS Comput Biol 9(12): e1003374 (2013)
10.1371/journal.pcbi.1003374
null
q-bio.MN cond-mat.dis-nn physics.bio-ph physics.data-an
http://creativecommons.org/licenses/by/3.0/
Characterizing interactions between drugs is important to avoid potentially harmful combinations, to reduce off-target effects of treatments and to fight antibiotic resistant pathogens, among others. Here we present a network inference algorithm to predict uncharacterized drug-drug interactions. Our algorithm takes, as its only input, sets of previously reported interactions, and does not require any pharmacological or biochemical information about the drugs, their targets or their mechanisms of action. Because the models we use are abstract, our approach can deal with adverse interactions, synergistic/antagonistic/suppressing interactions, or any other type of drug interaction. We show that our method is able to accurately predict interactions, both in exhaustive pairwise interaction data between small sets of drugs, and in large-scale databases. We also demonstrate that our algorithm can be used efficiently to discover interactions of new drugs as part of the drug discovery process.
[ { "created": "Thu, 6 Nov 2014 08:32:47 GMT", "version": "v1" } ]
2014-11-07
[ [ "Guimera", "Roger", "" ], [ "Sales-Pardo", "Marta", "" ] ]
Characterizing interactions between drugs is important to avoid potentially harmful combinations, to reduce off-target effects of treatments and to fight antibiotic resistant pathogens, among others. Here we present a network inference algorithm to predict uncharacterized drug-drug interactions. Our algorithm takes, as its only input, sets of previously reported interactions, and does not require any pharmacological or biochemical information about the drugs, their targets or their mechanisms of action. Because the models we use are abstract, our approach can deal with adverse interactions, synergistic/antagonistic/suppressing interactions, or any other type of drug interaction. We show that our method is able to accurately predict interactions, both in exhaustive pairwise interaction data between small sets of drugs, and in large-scale databases. We also demonstrate that our algorithm can be used efficiently to discover interactions of new drugs as part of the drug discovery process.
2108.04951
Farzaneh Esmaili
Farzaneh Esmaili, Mahdi Pourmirzaei, Shahin Ramazi, Elham Yavari
A Brief Review of Machine Learning Techniques for Protein Phosphorylation Sites Prediction
null
null
null
null
q-bio.QM cs.LG
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Post-translational modifications (PTMs) have vital roles in extending the functional diversity of proteins and as a result, regulating diverse cellular processes in prokaryotic and eukaryotic organisms. Phosphorylation modification is a vital PTM that occurs in most proteins and plays significant roles in many biological processes. Disorders in the phosphorylation process lead to multiple diseases including neurological disorders and cancers. At first, this study comprehensively reviewed all databases related to phosphorylation sites (p-sites). Secondly, we introduced all steps regarding dataset creation, data preprocessing and method evaluation in p-sites prediction. Next, we investigated p-sites prediction methods which fall into two computational and Machine Learning (ML) groups. Additionally, it was shown that there are basically two main approaches for p-sites prediction by ML: conventional and End-to-End learning, which were given an overview for both of them. Moreover, this study introduced the most important feature extraction techniques which have mostly been used in ML approaches. Finally, we created three test sets from new proteins related to the 2022th released version of the dbPTM database based on general and human species. After evaluating available online tools on the test sets, results showed that the performance of online tools for p-sites prediction are quite weak on new reported phospho-proteins.
[ { "created": "Tue, 10 Aug 2021 22:23:30 GMT", "version": "v1" }, { "created": "Sun, 6 Feb 2022 21:33:46 GMT", "version": "v2" } ]
2022-02-08
[ [ "Esmaili", "Farzaneh", "" ], [ "Pourmirzaei", "Mahdi", "" ], [ "Ramazi", "Shahin", "" ], [ "Yavari", "Elham", "" ] ]
Post-translational modifications (PTMs) have vital roles in extending the functional diversity of proteins and as a result, regulating diverse cellular processes in prokaryotic and eukaryotic organisms. Phosphorylation modification is a vital PTM that occurs in most proteins and plays significant roles in many biological processes. Disorders in the phosphorylation process lead to multiple diseases including neurological disorders and cancers. At first, this study comprehensively reviewed all databases related to phosphorylation sites (p-sites). Secondly, we introduced all steps regarding dataset creation, data preprocessing and method evaluation in p-sites prediction. Next, we investigated p-sites prediction methods which fall into two computational and Machine Learning (ML) groups. Additionally, it was shown that there are basically two main approaches for p-sites prediction by ML: conventional and End-to-End learning, which were given an overview for both of them. Moreover, this study introduced the most important feature extraction techniques which have mostly been used in ML approaches. Finally, we created three test sets from new proteins related to the 2022th released version of the dbPTM database based on general and human species. After evaluating available online tools on the test sets, results showed that the performance of online tools for p-sites prediction are quite weak on new reported phospho-proteins.
2210.15207
Lucie Pellissier
Anil Annamneedi (PRC, BIOS), Caroline Gora (PRC, BIOS), Ana Dudas (PRC, BIOS), Xavier Leray (PRC, BIOS), V\'eronique Bozon (PRC, BIOS), Pascale Crepieux (PRC, BIOS), Lucie P. Pellissier (PRC, BIOS)
Towards the convergent therapeutic potential of GPCRs in autism spectrum disorders
null
null
null
null
q-bio.NC
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Changes in genetic and/or environmental factors to developing neural circuits and subsequent synaptic functions are known to be a causative underlying the varied socio-emotional behavioural patterns associated with autism spectrum disorders (ASD). Seven transmembrane G protein-coupled receptors (GPCRs) comprising the largest family of cell-surface receptors, mediate the transfer of extracellular signals to downstream cellular responses. Disruption of GPCR and their signalling have been implicated as a convergent pathologic mechanism of ASD. Here, we aim to review the literature about the 23 GPCRs that are genetically associated to ASD pathology according to Simons Foundation Autism Research Initiative (SFARI) database such as oxytocin (OXTR) and vasopressin (V1A, V1B) receptors, metabotropic glutamate (mGlu5, mGlu7) and gamma-aminobutyric acid (GABAB) receptors, dopamine (D1, D2), serotoninergic (5-HT1B and additionally included the 5-HT2A, 5-HT7 receptors for their strong relevance to ASD), adrenergic ($\beta$2) and cholinergic (M3) receptors, adenosine (A2A, A3) receptors, angiotensin (AT2) receptors, cannabinoid (CB1) receptors, chemokine (CX3CR1) receptors, orphan (GPR37, GPR85) and olfactory (OR1C1, OR2M4, OR2T10, OR52M1) receptors. We discussed the genetic variants, relation to core ASD behavioural deficits and update on pharmacological compounds targeting these 23 GPCRs. Of these OTR, V1A, mGlu5, D2, 5-HT2A, CB1, and GPR37 serve as the best therapeutic targets and have potential towards core domains of ASD pathology. With a functional crosstalk between different GPCRs and converging pharmacological responses, there is an urge to develop novel therapeutic strategies based on multiple GPCRs to reduce the socioeconomic burden associated with ASD and we strongly emphasize the need to prioritize the increased clinical trials targeting the multiple GPCRs.
[ { "created": "Thu, 27 Oct 2022 06:40:50 GMT", "version": "v1" } ]
2022-10-28
[ [ "Annamneedi", "Anil", "", "PRC, BIOS" ], [ "Gora", "Caroline", "", "PRC, BIOS" ], [ "Dudas", "Ana", "", "PRC, BIOS" ], [ "Leray", "Xavier", "", "PRC, BIOS" ], [ "Bozon", "Véronique", "", "PRC, BIOS" ], [ "Crepi...
Changes in genetic and/or environmental factors to developing neural circuits and subsequent synaptic functions are known to be a causative underlying the varied socio-emotional behavioural patterns associated with autism spectrum disorders (ASD). Seven transmembrane G protein-coupled receptors (GPCRs) comprising the largest family of cell-surface receptors, mediate the transfer of extracellular signals to downstream cellular responses. Disruption of GPCR and their signalling have been implicated as a convergent pathologic mechanism of ASD. Here, we aim to review the literature about the 23 GPCRs that are genetically associated to ASD pathology according to Simons Foundation Autism Research Initiative (SFARI) database such as oxytocin (OXTR) and vasopressin (V1A, V1B) receptors, metabotropic glutamate (mGlu5, mGlu7) and gamma-aminobutyric acid (GABAB) receptors, dopamine (D1, D2), serotoninergic (5-HT1B and additionally included the 5-HT2A, 5-HT7 receptors for their strong relevance to ASD), adrenergic ($\beta$2) and cholinergic (M3) receptors, adenosine (A2A, A3) receptors, angiotensin (AT2) receptors, cannabinoid (CB1) receptors, chemokine (CX3CR1) receptors, orphan (GPR37, GPR85) and olfactory (OR1C1, OR2M4, OR2T10, OR52M1) receptors. We discussed the genetic variants, relation to core ASD behavioural deficits and update on pharmacological compounds targeting these 23 GPCRs. Of these OTR, V1A, mGlu5, D2, 5-HT2A, CB1, and GPR37 serve as the best therapeutic targets and have potential towards core domains of ASD pathology. With a functional crosstalk between different GPCRs and converging pharmacological responses, there is an urge to develop novel therapeutic strategies based on multiple GPCRs to reduce the socioeconomic burden associated with ASD and we strongly emphasize the need to prioritize the increased clinical trials targeting the multiple GPCRs.
1305.4333
Nachol Chaiyaratana PhD
Anunchai Assawamakin, Nachol Chaiyaratana, Chanin Limwongse, Saravudh Sinsomros, Pa-thai Yenchitsomanus, Prakarnkiat Youngkong
Variable-length haplotype construction for gene-gene interaction studies
7 pages, 2 figures
IEEE Engineering in Medicine and Biology Magazine, 28(4), 25-31
10.1109/MEMB.2009.932902
null
q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This paper presents a non-parametric classification technique for identifying a candidate bi-allelic genetic marker set that best describes disease susceptibility in gene-gene interaction studies. The developed technique functions by creating a mapping between inferred haplotypes and case/control status. The technique cycles through all possible marker combination models generated from the available marker set where the best interaction model is determined from prediction accuracy and two auxiliary criteria including low-to-high order haplotype propagation capability and model parsimony. Since variable-length haplotypes are created during the best model identification, the developed technique is referred to as a variable-length haplotype construction for gene-gene interaction (VarHAP) technique. VarHAP has been benchmarked against a multifactor dimensionality reduction (MDR) program and a haplotype interaction technique embedded in a FAMHAP program in various two-locus interaction problems. The results reveal that VarHAP is suitable for all interaction situations with the presence of weak and strong linkage disequilibrium among genetic markers.
[ { "created": "Sun, 19 May 2013 07:11:22 GMT", "version": "v1" } ]
2013-05-21
[ [ "Assawamakin", "Anunchai", "" ], [ "Chaiyaratana", "Nachol", "" ], [ "Limwongse", "Chanin", "" ], [ "Sinsomros", "Saravudh", "" ], [ "Yenchitsomanus", "Pa-thai", "" ], [ "Youngkong", "Prakarnkiat", "" ] ]
This paper presents a non-parametric classification technique for identifying a candidate bi-allelic genetic marker set that best describes disease susceptibility in gene-gene interaction studies. The developed technique functions by creating a mapping between inferred haplotypes and case/control status. The technique cycles through all possible marker combination models generated from the available marker set where the best interaction model is determined from prediction accuracy and two auxiliary criteria including low-to-high order haplotype propagation capability and model parsimony. Since variable-length haplotypes are created during the best model identification, the developed technique is referred to as a variable-length haplotype construction for gene-gene interaction (VarHAP) technique. VarHAP has been benchmarked against a multifactor dimensionality reduction (MDR) program and a haplotype interaction technique embedded in a FAMHAP program in various two-locus interaction problems. The results reveal that VarHAP is suitable for all interaction situations with the presence of weak and strong linkage disequilibrium among genetic markers.
2208.05204
Jana Massing
Jana C. Massing, Ashkaan Fahimipour, Carina Bunse, Jarone Pinhassi, Thilo Gross
Quantification of metabolic niche occupancy dynamics in a Baltic Sea bacterial community
20 pages, 7 figures
null
null
null
q-bio.PE
http://creativecommons.org/licenses/by/4.0/
Progress in molecular methods has enabled the monitoring of bacterial populations in time. Nevertheless, understanding community dynamics and its links with ecosystem functioning remains challenging due to the tremendous diversity of microorganisms. Conceptual frameworks that make sense of time-series of taxonomically-rich bacterial communities, regarding their potential ecological function, are needed. A key concept for organizing ecological functions is the niche, the set of strategies that enable a population to persist and define its impacts on the surroundings. Here we present a framework based on manifold learning, to organize genomic information into potentially occupied bacterial metabolic niches over time. We apply the method to re-construct the dynamics of putatively occupied metabolic niches using a long-term bacterial time-series from the Baltic Sea, the Linnaeus Microbial Observatory (LMO). The results reveal a relatively low-dimensional space of occupied metabolic niches comprising groups of taxa with similar functional capabilities. Time patterns of occupied niches were strongly driven by seasonality. Some metabolic niches were dominated by one bacterial taxon whereas others were occupied by multiple taxa, and this depended on season. These results illustrate the power of manifold learning approaches to advance our understanding of the links between community composition and functioning in microbial systems.
[ { "created": "Wed, 10 Aug 2022 07:57:49 GMT", "version": "v1" } ]
2022-08-11
[ [ "Massing", "Jana C.", "" ], [ "Fahimipour", "Ashkaan", "" ], [ "Bunse", "Carina", "" ], [ "Pinhassi", "Jarone", "" ], [ "Gross", "Thilo", "" ] ]
Progress in molecular methods has enabled the monitoring of bacterial populations in time. Nevertheless, understanding community dynamics and its links with ecosystem functioning remains challenging due to the tremendous diversity of microorganisms. Conceptual frameworks that make sense of time-series of taxonomically-rich bacterial communities, regarding their potential ecological function, are needed. A key concept for organizing ecological functions is the niche, the set of strategies that enable a population to persist and define its impacts on the surroundings. Here we present a framework based on manifold learning, to organize genomic information into potentially occupied bacterial metabolic niches over time. We apply the method to re-construct the dynamics of putatively occupied metabolic niches using a long-term bacterial time-series from the Baltic Sea, the Linnaeus Microbial Observatory (LMO). The results reveal a relatively low-dimensional space of occupied metabolic niches comprising groups of taxa with similar functional capabilities. Time patterns of occupied niches were strongly driven by seasonality. Some metabolic niches were dominated by one bacterial taxon whereas others were occupied by multiple taxa, and this depended on season. These results illustrate the power of manifold learning approaches to advance our understanding of the links between community composition and functioning in microbial systems.
1610.03427
Nicholas Battista
Nicholas A. Battista, Andrea N. Lane, Laura A. Miller
On the dynamic suction pumping of blood cells in tubular hearts
21 pages, 19 figures
null
10.1007/978-3-319-60304-9
null
q-bio.TO physics.flu-dyn
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Around the third week after gestation in embryonic development, the human heart consists only of a valvless tube, unlike a fully developed adult heart, which is multi-chambered. At this stage in development, the heart valves have not formed and so net flow of blood through the heart must be driven by a different mechanism. It is hypothesized that there are two possible mechanisms that drive blood flow at this stage - Liebau pumping (dynamic suction pumping or valveless pumping) and peristaltic pumping. We implement the immersed boundary method with adaptive mesh refinement (IBAMR) to numerically study the effect of hematocrit on the circulation around a valveless. Both peristalsis and dynamic suction pumping are considered. In the case of dynamic suction pumping, the heart and circulatory system is simplified as a flexible tube attached to a relatively rigid racetrack. For some Womersley number (Wo) regimes, there is significant net flow around the racetrack. We find that the addition of flexible blood cells does not significantly affect flow rates within the tube for Wo $\leq$ 10. On the other hand, peristalsis consistently drives blood around the racetrack for all Wo and for all hematocrit considered.
[ { "created": "Tue, 11 Oct 2016 17:08:46 GMT", "version": "v1" } ]
2018-09-19
[ [ "Battista", "Nicholas A.", "" ], [ "Lane", "Andrea N.", "" ], [ "Miller", "Laura A.", "" ] ]
Around the third week after gestation in embryonic development, the human heart consists only of a valvless tube, unlike a fully developed adult heart, which is multi-chambered. At this stage in development, the heart valves have not formed and so net flow of blood through the heart must be driven by a different mechanism. It is hypothesized that there are two possible mechanisms that drive blood flow at this stage - Liebau pumping (dynamic suction pumping or valveless pumping) and peristaltic pumping. We implement the immersed boundary method with adaptive mesh refinement (IBAMR) to numerically study the effect of hematocrit on the circulation around a valveless. Both peristalsis and dynamic suction pumping are considered. In the case of dynamic suction pumping, the heart and circulatory system is simplified as a flexible tube attached to a relatively rigid racetrack. For some Womersley number (Wo) regimes, there is significant net flow around the racetrack. We find that the addition of flexible blood cells does not significantly affect flow rates within the tube for Wo $\leq$ 10. On the other hand, peristalsis consistently drives blood around the racetrack for all Wo and for all hematocrit considered.
2004.00217
Arun Sharma Dr
Arun Dev Sharma and Inderjeet Kaur
Molecular docking studies on Jensenone from eucalyptus essential oil as a potential inhibitor of COVID 19 corona virus infection
10 p. Research and reviews in biotechnology and biosciences 2020,7,59-66
null
null
null
q-bio.BM
http://creativecommons.org/licenses/by/4.0/
COVID-19, a member of corona virus family is spreading its tentacles across the world due to lack of drugs at present. However, the main viral proteinase (Mpro/3CLpro) has recently been regarded as a suitable target for drug design against SARS infection due to its vital role in polyproteins processing necessary for coronavirus reproduction. The present in silico study was designed to evaluate the effect of Jensenone, a essential oil component from eucalyptus oil, on Mpro by docking study. In the present study, molecular docking studies were conducted by using 1-click dock and swiss dock tools. Protein interaction mode was calculated by Protein Interactions Calculator.The calculated parameters such as binding energy, and binding site similarity indicated effective binding of Jensenone to COVID-19 proteinase. Active site prediction further validated the role of active site residues in ligand binding. PIC results indicated that, Mpro/ Jensenone complexes forms hydrophobic interactions, hydrogen bond interactions and strong ionic interactions. Therefore, Jensenone may represent potential treatment potential to act as COVID-19 Mpro inhibitor. However, further research is necessary to investigate their potential medicinal use.
[ { "created": "Wed, 1 Apr 2020 03:50:53 GMT", "version": "v1" }, { "created": "Fri, 17 Apr 2020 21:22:11 GMT", "version": "v2" } ]
2020-04-21
[ [ "Sharma", "Arun Dev", "" ], [ "Kaur", "Inderjeet", "" ] ]
COVID-19, a member of corona virus family is spreading its tentacles across the world due to lack of drugs at present. However, the main viral proteinase (Mpro/3CLpro) has recently been regarded as a suitable target for drug design against SARS infection due to its vital role in polyproteins processing necessary for coronavirus reproduction. The present in silico study was designed to evaluate the effect of Jensenone, a essential oil component from eucalyptus oil, on Mpro by docking study. In the present study, molecular docking studies were conducted by using 1-click dock and swiss dock tools. Protein interaction mode was calculated by Protein Interactions Calculator.The calculated parameters such as binding energy, and binding site similarity indicated effective binding of Jensenone to COVID-19 proteinase. Active site prediction further validated the role of active site residues in ligand binding. PIC results indicated that, Mpro/ Jensenone complexes forms hydrophobic interactions, hydrogen bond interactions and strong ionic interactions. Therefore, Jensenone may represent potential treatment potential to act as COVID-19 Mpro inhibitor. However, further research is necessary to investigate their potential medicinal use.
q-bio/0506006
Olga Issaeva
O.G. Isaeva and V.A. Osipov
Modeling of anti-tumor immune response: immunocorrective effect of weak centimeter electromagnetic waves
23 pages, 7 figures. This is a final version of our e-print that was accepted for publication in the Journal of Computational and Mathematical Methods in Medicine on July 24,2008
null
null
null
q-bio.CB q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
We formulate the dynamical model for the anti-tumor immune response based on intercellular cytokine-mediated interactions with the interleukin-2 (IL-2) taken into account. The analysis shows that the expression level of tumor antigens on antigen presenting cells has a distinct influence on the tumor dynamics. At low antigen presentation a progressive tumor growth takes place to the highest possible value. At high antigen presentation there is a decrease in tumor size to some value when the dynamical equilibrium between the tumor and the immune system is reached. In the case of the medium antigen presentation both these regimes can be realized depending on the initial tumor size and the condition of the immune system. A pronounced immunomodulating effect (the suppression of tumor growth and the normalization of IL-2 concentration) is established by considering the influence of low-intensity electromagnetic microwaves as a parametric perturbation of the dynamical system. This finding is in qualitative agreement with the recent experimental results on immunocorrective effects of centimeter electromagnetic waves in tumor-bearing mice.
[ { "created": "Tue, 7 Jun 2005 14:04:44 GMT", "version": "v1" }, { "created": "Mon, 10 Oct 2005 13:44:16 GMT", "version": "v2" }, { "created": "Tue, 17 Jul 2007 21:28:59 GMT", "version": "v3" }, { "created": "Sat, 26 Jul 2008 11:37:13 GMT", "version": "v4" } ]
2008-07-26
[ [ "Isaeva", "O. G.", "" ], [ "Osipov", "V. A.", "" ] ]
We formulate the dynamical model for the anti-tumor immune response based on intercellular cytokine-mediated interactions with the interleukin-2 (IL-2) taken into account. The analysis shows that the expression level of tumor antigens on antigen presenting cells has a distinct influence on the tumor dynamics. At low antigen presentation a progressive tumor growth takes place to the highest possible value. At high antigen presentation there is a decrease in tumor size to some value when the dynamical equilibrium between the tumor and the immune system is reached. In the case of the medium antigen presentation both these regimes can be realized depending on the initial tumor size and the condition of the immune system. A pronounced immunomodulating effect (the suppression of tumor growth and the normalization of IL-2 concentration) is established by considering the influence of low-intensity electromagnetic microwaves as a parametric perturbation of the dynamical system. This finding is in qualitative agreement with the recent experimental results on immunocorrective effects of centimeter electromagnetic waves in tumor-bearing mice.
2011.01069
Natasha Savage Dr
Natasha S. Savage
Describing the movement of molecules in reduced-dimension models
Main Text. Methods. Supplementary Text. References
null
10.1038/s42003-021-02200-3
null
q-bio.QM
http://creativecommons.org/licenses/by-nc-sa/4.0/
When addressing spatial biological questions using mathematical models, symmetries within the system are often exploited to simplify the problem by reducing its physical dimension. In a reduced-dimension model molecular movement is restricted to the reduced dimension, changing the nature of molecular movement. This change in molecular movement can lead to quantitatively and even qualitatively different results in the full and reduced systems. Within this manuscript we discuss the condition under which restricted molecular movement in reduced-dimension models accurately approximates molecular movement in the full system. For those systems which do not satisfy the condition, we present a general method for approximating unrestricted molecular movement in reduced-dimension models. We will derive a mathematically robust, finite difference method for solving the 2D diffusion equation within a 1D reduced-dimension model. The methods described here can be used to improve the accuracy of many reduced-dimension models while retaining benefits of system simplification.
[ { "created": "Mon, 2 Nov 2020 15:55:56 GMT", "version": "v1" }, { "created": "Sat, 13 Feb 2021 15:27:00 GMT", "version": "v2" }, { "created": "Tue, 16 Feb 2021 10:16:43 GMT", "version": "v3" } ]
2022-08-24
[ [ "Savage", "Natasha S.", "" ] ]
When addressing spatial biological questions using mathematical models, symmetries within the system are often exploited to simplify the problem by reducing its physical dimension. In a reduced-dimension model molecular movement is restricted to the reduced dimension, changing the nature of molecular movement. This change in molecular movement can lead to quantitatively and even qualitatively different results in the full and reduced systems. Within this manuscript we discuss the condition under which restricted molecular movement in reduced-dimension models accurately approximates molecular movement in the full system. For those systems which do not satisfy the condition, we present a general method for approximating unrestricted molecular movement in reduced-dimension models. We will derive a mathematically robust, finite difference method for solving the 2D diffusion equation within a 1D reduced-dimension model. The methods described here can be used to improve the accuracy of many reduced-dimension models while retaining benefits of system simplification.
2011.05862
Caner Ercan
Yetkin Agackiran, Funda Aksu, Nalan Akyurek, Caner Ercan, Mustafa Demiroz, Kurtulus Aksu
Programmed death ligand 1 expression levels, clinicopathologic features, and survival in surgically resected sarcomatoid lung carcinoma
null
Asia Pac J Clin Oncol 2020 1 9
10.1111/ajco.13460
null
q-bio.TO
http://creativecommons.org/licenses/by-nc-sa/4.0/
Aim: To determine the programmed death ligand-1 (PD-L1) expression rates in sarcomatoid lung carcinomas and to compare clinicopathologic features and survival rates of PD-L1-positive and negative patients. Methods: PD-L1 expression was evaluated in 65 surgically resected sarcomatoid carcinomas. The clinicopathologic features of cases with PD-L1-positive and negative tumors were compared. Kaplan-Meier survival analysis was performed. Multiple Cox proportional hazard regression analysis was performed to determine independent predictors of overall survival. Results: PD-L1 antibody positivity was found in 72.3% of surgically resected sarcomatoid lung carcinomas. Regarding histopathologic subtypes, PD-L1 expression was positive in 80.4% of pleomorphic carcinomas, 62.5% of spindle- and/or giant-cell carcinomas, and 16.7% of carcinosarcomas. Pleural invasion was observed in 68.1% of PD-L1-positive cases and 27.8% of PD-L1-negative cases (p = 0.008). No difference in survival was found between PD-L1-positive and negative tumors. The only factor significantly associated with poor survival was the pathological stage of the tumor. Conclusions: This study reveals a high rate of PD-L1 positivity in a large number of sarcomatoid lung carcinoma cases with pleomorphic carcinoma, spindle- and/or giantcell carcinoma, and carcinosarcoma subtypes. The only significantly different clinicopathologic feature in PD-L1-positive cases is pleural invasion. PD-L1 positivity is not a significant predictor of survival in sarcomatoid lung carcinomas.
[ { "created": "Sun, 8 Nov 2020 18:59:24 GMT", "version": "v1" } ]
2020-11-12
[ [ "Agackiran", "Yetkin", "" ], [ "Aksu", "Funda", "" ], [ "Akyurek", "Nalan", "" ], [ "Ercan", "Caner", "" ], [ "Demiroz", "Mustafa", "" ], [ "Aksu", "Kurtulus", "" ] ]
Aim: To determine the programmed death ligand-1 (PD-L1) expression rates in sarcomatoid lung carcinomas and to compare clinicopathologic features and survival rates of PD-L1-positive and negative patients. Methods: PD-L1 expression was evaluated in 65 surgically resected sarcomatoid carcinomas. The clinicopathologic features of cases with PD-L1-positive and negative tumors were compared. Kaplan-Meier survival analysis was performed. Multiple Cox proportional hazard regression analysis was performed to determine independent predictors of overall survival. Results: PD-L1 antibody positivity was found in 72.3% of surgically resected sarcomatoid lung carcinomas. Regarding histopathologic subtypes, PD-L1 expression was positive in 80.4% of pleomorphic carcinomas, 62.5% of spindle- and/or giant-cell carcinomas, and 16.7% of carcinosarcomas. Pleural invasion was observed in 68.1% of PD-L1-positive cases and 27.8% of PD-L1-negative cases (p = 0.008). No difference in survival was found between PD-L1-positive and negative tumors. The only factor significantly associated with poor survival was the pathological stage of the tumor. Conclusions: This study reveals a high rate of PD-L1 positivity in a large number of sarcomatoid lung carcinoma cases with pleomorphic carcinoma, spindle- and/or giantcell carcinoma, and carcinosarcoma subtypes. The only significantly different clinicopathologic feature in PD-L1-positive cases is pleural invasion. PD-L1 positivity is not a significant predictor of survival in sarcomatoid lung carcinomas.
1511.01958
Thierry Mora
Thierry Mora, Aleksandra M. Walczak, Lorenzo Del Castello, Francesco Ginelli, Stefania Melillo, Leonardo Parisi, Massimiliano Viale, Andrea Cavagna, and Irene Giardina
Local equilibrium in bird flocks
null
Nature Physics 12, 1153-1157 (2016)
10.1038/nphys3846
null
q-bio.PE cond-mat.stat-mech physics.bio-ph q-bio.QM
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The correlated motion of flocks is an instance of global order emerging from local interactions. An essential difference with analogous ferromagnetic systems is that flocks are active: animals move relative to each other, dynamically rearranging their interaction network. The effect of this off-equilibrium element is well studied theoretically, but its impact on actual biological groups deserves more experimental attention. Here, we introduce a novel dynamical inference technique, based on the principle of maximum entropy, which accodomates network rearrangements and overcomes the problem of slow experimental sampling rates. We use this method to infer the strength and range of alignment forces from data of starling flocks. We find that local bird alignment happens on a much faster timescale than neighbour rearrangement. Accordingly, equilibrium inference, which assumes a fixed interaction network, gives results consistent with dynamical inference. We conclude that bird orientations are in a state of local quasi-equilibrium over the interaction length scale, providing firm ground for the applicability of statistical physics in certain active systems.
[ { "created": "Fri, 6 Nov 2015 00:00:52 GMT", "version": "v1" }, { "created": "Mon, 27 Jun 2016 22:15:11 GMT", "version": "v2" } ]
2016-12-26
[ [ "Mora", "Thierry", "" ], [ "Walczak", "Aleksandra M.", "" ], [ "Del Castello", "Lorenzo", "" ], [ "Ginelli", "Francesco", "" ], [ "Melillo", "Stefania", "" ], [ "Parisi", "Leonardo", "" ], [ "Viale", "Massimili...
The correlated motion of flocks is an instance of global order emerging from local interactions. An essential difference with analogous ferromagnetic systems is that flocks are active: animals move relative to each other, dynamically rearranging their interaction network. The effect of this off-equilibrium element is well studied theoretically, but its impact on actual biological groups deserves more experimental attention. Here, we introduce a novel dynamical inference technique, based on the principle of maximum entropy, which accodomates network rearrangements and overcomes the problem of slow experimental sampling rates. We use this method to infer the strength and range of alignment forces from data of starling flocks. We find that local bird alignment happens on a much faster timescale than neighbour rearrangement. Accordingly, equilibrium inference, which assumes a fixed interaction network, gives results consistent with dynamical inference. We conclude that bird orientations are in a state of local quasi-equilibrium over the interaction length scale, providing firm ground for the applicability of statistical physics in certain active systems.
1605.05371
Ronan M.T. Fleming Dr
Hulda S. Haraldsd\'ottir and Ronan M. T. Fleming
Identification of conserved moieties in metabolic networks by graph theoretical analysis of atom transition networks
28 pages, 11 figures
null
10.1371/journal.pcbi.1004999
null
q-bio.MN
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network. Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling. All moiety conservation relations can be represented as nonnegative integer vectors in the left null space of the stoichiometric matrix corresponding to a biochemical network. Algorithms exist to compute such vectors based only on reaction stoichiometry but their computational complexity has limited their application to relatively small metabolic networks. Moreover, the vectors returned by existing algorithms do not, in general, represent conservation of a specific moiety with a defined atomic structure. Here, we show that identification of conserved moieties requires data on reaction atom mappings in addition to stoichiometry. We present a novel method to identify conserved moieties in metabolic networks by graph theoretical analysis of their underlying atom transition networks. Our method returns the exact group of atoms belonging to each conserved moiety as well as the corresponding vector in the left null space of the stoichiometric matrix. It can be implemented as a pipeline of polynomial time algorithms. Our implementation completes in under five minutes on a metabolic network with more than 4,000 mass balanced reactions. The scalability of the method enables extension of existing applications for moiety conservation relations to genome-scale metabolic networks. We also give examples of new applications made possible by elucidating the atomic structure of conserved moieties.
[ { "created": "Tue, 17 May 2016 21:30:54 GMT", "version": "v1" } ]
2017-02-08
[ [ "Haraldsdóttir", "Hulda S.", "" ], [ "Fleming", "Ronan M. T.", "" ] ]
Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network. Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling. All moiety conservation relations can be represented as nonnegative integer vectors in the left null space of the stoichiometric matrix corresponding to a biochemical network. Algorithms exist to compute such vectors based only on reaction stoichiometry but their computational complexity has limited their application to relatively small metabolic networks. Moreover, the vectors returned by existing algorithms do not, in general, represent conservation of a specific moiety with a defined atomic structure. Here, we show that identification of conserved moieties requires data on reaction atom mappings in addition to stoichiometry. We present a novel method to identify conserved moieties in metabolic networks by graph theoretical analysis of their underlying atom transition networks. Our method returns the exact group of atoms belonging to each conserved moiety as well as the corresponding vector in the left null space of the stoichiometric matrix. It can be implemented as a pipeline of polynomial time algorithms. Our implementation completes in under five minutes on a metabolic network with more than 4,000 mass balanced reactions. The scalability of the method enables extension of existing applications for moiety conservation relations to genome-scale metabolic networks. We also give examples of new applications made possible by elucidating the atomic structure of conserved moieties.
2302.13753
Leroy Cronin Prof
Michael Jirasek, Abhishek Sharma, Jessica R. Bame, S. Hessam M. Mehr, Nicola Bell, Stuart M. Marshall, Cole Mathis, Alasdair Macleod, Geoffrey J. T. Cooper, Marcel Swart, Rosa Mollfulleda, Leroy Cronin
Determining Molecular Complexity using Assembly Theory and Spectroscopy
27 pages, 7 figures plus supplementary data
null
null
null
q-bio.QM physics.bio-ph physics.chem-ph
http://creativecommons.org/licenses/by-nc-sa/4.0/
Determining the complexity of molecules has important applications from molecular design to understanding the history of the process that led to the formation of the molecule. Currently, it is not possible to experimentally determine, without full structure elucidation, how complex a molecule is. Assembly Theory has been developed to quantify the complexity of a molecule by finding the shortest path to construct the molecule from building blocks, revealing its molecular assembly index (MA). In this study, we present an approach to rapidly and exhaustively calculate the MA of molecules from the spectroscopic measurements. We demonstrate that molecular complexity (MA) can be experimentally estimated using three independent techniques: nuclear magnetic resonance (NMR), tandem mass spectrometry (MS/MS), and infrared spectroscopy (IR), and these give consistent results with good correlations with the theoretically determined values from assembly theory. By identifying and analysing the number of absorbances in IR spectra, carbon resonances in NMR, or molecular fragments in tandem MS, the molecular assembly of an unknown molecule can be reliably estimated from experimental data. This represents the first experimentally quantifiable approach to defining molecular assembly, a reliable metric for complexity, as an intrinsic property of molecules and can also be performed on complex mixtures. This paves the way to use spectroscopic and spectrometric techniques to unambiguously detect alien life in the solar system, and beyond on exoplanets.
[ { "created": "Fri, 24 Feb 2023 12:05:57 GMT", "version": "v1" }, { "created": "Tue, 7 Nov 2023 13:42:37 GMT", "version": "v2" } ]
2023-11-08
[ [ "Jirasek", "Michael", "" ], [ "Sharma", "Abhishek", "" ], [ "Bame", "Jessica R.", "" ], [ "Mehr", "S. Hessam M.", "" ], [ "Bell", "Nicola", "" ], [ "Marshall", "Stuart M.", "" ], [ "Mathis", "Cole", "" ],...
Determining the complexity of molecules has important applications from molecular design to understanding the history of the process that led to the formation of the molecule. Currently, it is not possible to experimentally determine, without full structure elucidation, how complex a molecule is. Assembly Theory has been developed to quantify the complexity of a molecule by finding the shortest path to construct the molecule from building blocks, revealing its molecular assembly index (MA). In this study, we present an approach to rapidly and exhaustively calculate the MA of molecules from the spectroscopic measurements. We demonstrate that molecular complexity (MA) can be experimentally estimated using three independent techniques: nuclear magnetic resonance (NMR), tandem mass spectrometry (MS/MS), and infrared spectroscopy (IR), and these give consistent results with good correlations with the theoretically determined values from assembly theory. By identifying and analysing the number of absorbances in IR spectra, carbon resonances in NMR, or molecular fragments in tandem MS, the molecular assembly of an unknown molecule can be reliably estimated from experimental data. This represents the first experimentally quantifiable approach to defining molecular assembly, a reliable metric for complexity, as an intrinsic property of molecules and can also be performed on complex mixtures. This paves the way to use spectroscopic and spectrometric techniques to unambiguously detect alien life in the solar system, and beyond on exoplanets.
1106.3791
Shanika Kuruppu Ms
Shanika Kuruppu, Simon Puglisi and Justin Zobel
Reference Sequence Construction for Relative Compression of Genomes
12 pages, 2 figures, to appear in the Proceedings of SPIRE2011 as a short paper
null
null
null
q-bio.QM cs.CE cs.IT math.IT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Relative compression, where a set of similar strings are compressed with respect to a reference string, is a very effective method of compressing DNA datasets containing multiple similar sequences. Relative compression is fast to perform and also supports rapid random access to the underlying data. The main difficulty of relative compression is in selecting an appropriate reference sequence. In this paper, we explore using the dictionary of repeats generated by Comrad, Re-pair and Dna-x algorithms as reference sequences for relative compression. We show this technique allows better compression and supports random access just as well. The technique also allows more general repetitive datasets to be compressed using relative compression.
[ { "created": "Mon, 20 Jun 2011 01:10:01 GMT", "version": "v1" } ]
2011-06-21
[ [ "Kuruppu", "Shanika", "" ], [ "Puglisi", "Simon", "" ], [ "Zobel", "Justin", "" ] ]
Relative compression, where a set of similar strings are compressed with respect to a reference string, is a very effective method of compressing DNA datasets containing multiple similar sequences. Relative compression is fast to perform and also supports rapid random access to the underlying data. The main difficulty of relative compression is in selecting an appropriate reference sequence. In this paper, we explore using the dictionary of repeats generated by Comrad, Re-pair and Dna-x algorithms as reference sequences for relative compression. We show this technique allows better compression and supports random access just as well. The technique also allows more general repetitive datasets to be compressed using relative compression.
2401.03095
Andrew Baumgartner
Andrew Baumgartner, Sui Huang, Jennifer Hadlock, and Cory Funk
Dimensional reduction of gradient-like stochastic systems with multiplicative noise via Fokker-Planck diffusion maps
null
null
null
null
q-bio.QM physics.bio-ph q-bio.CB q-bio.GN
http://creativecommons.org/licenses/by-sa/4.0/
Dimensional reduction techniques have long been used to visualize the structure and geometry of high dimensional data. However, most widely used techniques are difficult to interpret due to nonlinearities and opaque optimization processes. Here we present a specific graph based construction for dimensionally reducing continuous stochastic systems with multiplicative noise moving under the influence of a potential. To achieve this, we present a specific graph construction which generates the Fokker-Planck equation of the stochastic system in the continuum limit. The eigenvectors and eigenvalues of the normalized graph Laplacian are used as a basis for the dimensional reduction and yield a low dimensional representation of the dynamics which can be used for downstream analysis such as spectral clustering. We focus on the use case of single cell RNA sequencing data and show how current diffusion map implementations popular in the single cell literature fit into this framework.
[ { "created": "Fri, 5 Jan 2024 23:59:07 GMT", "version": "v1" } ]
2024-01-09
[ [ "Baumgartner", "Andrew", "" ], [ "Huang", "Sui", "" ], [ "Hadlock", "Jennifer", "" ], [ "Funk", "Cory", "" ] ]
Dimensional reduction techniques have long been used to visualize the structure and geometry of high dimensional data. However, most widely used techniques are difficult to interpret due to nonlinearities and opaque optimization processes. Here we present a specific graph based construction for dimensionally reducing continuous stochastic systems with multiplicative noise moving under the influence of a potential. To achieve this, we present a specific graph construction which generates the Fokker-Planck equation of the stochastic system in the continuum limit. The eigenvectors and eigenvalues of the normalized graph Laplacian are used as a basis for the dimensional reduction and yield a low dimensional representation of the dynamics which can be used for downstream analysis such as spectral clustering. We focus on the use case of single cell RNA sequencing data and show how current diffusion map implementations popular in the single cell literature fit into this framework.
2207.00330
Alexander Gorban
A.N. Gorban, T.A. Tyukina, L.I. Pokidysheva, E.V. Smirnova
It is useful to analyze correlation graphs
Mini-review, 9 pages, 62 bibliography
Physics of Life Reviews, Volume 40, March 2022, Pages 15-23
10.1016/j.plrev.2021.10.002
null
q-bio.TO
http://creativecommons.org/licenses/by-sa/4.0/
In 1987, we analyzed the changes in correlation graphs between various features of the organism during stress and adaptation. After 33 years of research of many authors, discoveries and rediscoveries, we can say with complete confidence: It is useful to analyze correlation graphs. In addition, we should add that the concept of adaptability ('adaptation energy') introduced by Selye is useful, especially if it is supplemented by 'adaptation entropy' and free energy, as well as an analysis of limiting factors. Our review of these topics, Dynamic and Thermodynamic Adaptation Models" (Phys Life Rev, 2021, arXiv:2103.01959 [q-bio.OT]), attracted many comments from leading experts, with new ideas and new problems, from the dynamics of aging and the training of athletes to single-cell omics. Methodological backgrounds, like free energy analysis, were also discussed in depth. In this article, we provide an analytical overview of twelve commenting papers and some related publications.
[ { "created": "Fri, 1 Jul 2022 10:48:18 GMT", "version": "v1" } ]
2022-07-04
[ [ "Gorban", "A. N.", "" ], [ "Tyukina", "T. A.", "" ], [ "Pokidysheva", "L. I.", "" ], [ "Smirnova", "E. V.", "" ] ]
In 1987, we analyzed the changes in correlation graphs between various features of the organism during stress and adaptation. After 33 years of research of many authors, discoveries and rediscoveries, we can say with complete confidence: It is useful to analyze correlation graphs. In addition, we should add that the concept of adaptability ('adaptation energy') introduced by Selye is useful, especially if it is supplemented by 'adaptation entropy' and free energy, as well as an analysis of limiting factors. Our review of these topics, Dynamic and Thermodynamic Adaptation Models" (Phys Life Rev, 2021, arXiv:2103.01959 [q-bio.OT]), attracted many comments from leading experts, with new ideas and new problems, from the dynamics of aging and the training of athletes to single-cell omics. Methodological backgrounds, like free energy analysis, were also discussed in depth. In this article, we provide an analytical overview of twelve commenting papers and some related publications.