Evolution to alternative levels of stable diversity leaves areas of niche space unexplored
by Ilan N. Rubin, Iaroslav Ispolatov, Michael Doebeli One of the oldest and most persistent questions in ecology and evolution is whether natural communities tend to evolve toward saturation and maximal diversity. Robert MacArthur’s classical theory of niche packing and the theory of adaptive radiations both imply that populations will diversify an d fully partition any available niche space. However, the saturation of natural populations is still very much an open area of debate and investigation. Additionally, recent evolutionary theory suggests the existence of alternative evolutionary stable states (ESSs), which...
Source: PLoS Computational Biology - July 28, 2021 Category: Biology Authors: Ilan N. Rubin Source Type: research

Modelling the visual world of a velvet worm
by Mikael Ljungholm, Dan-E. Nilsson In many animal phyla, eyes are small and provide only low-resolution vision for general orientation in the environment. Because these primitive eyes rarely have a defined image plane, traditional visual-optics principles cannot be applied. To assess the functional capacity of such eyes we have dev eloped modelling principles based on ray tracing in 3D reconstructions of eye morphology, where refraction on the way to the photoreceptors and absorption in the photopigment are calculated incrementally for ray bundles from all angles within the visual field. From the ray tracing, we calculat...
Source: PLoS Computational Biology - July 28, 2021 Category: Biology Authors: Mikael Ljungholm Source Type: research

Multidimensional analysis of immune responses identified biomarkers of recent < i > Mycobacterium tuberculosis < /i > infection
by Tessa Lloyd, Pia Steigler, Cheleka A. M. Mpande, Virginie Rozot, Boitumelo Mosito, Constance Schreuder, Timothy D. Reid, Mark Hatherill, Thomas J. Scriba, Francesca Little, Elisa Nemes, the ACS Study Team The risk of tuberculosis (TB) disease is higher in individuals with recentMycobacterium tuberculosis (M.tb) infection compared to individuals with more remote, established infection. We aimed to define blood-based biomarkers to distinguish between recent and remote infection, which would allow targeting of recently infected individuals for preventive TB treatment. We hypothesized that integration of multiple immune me...
Source: PLoS Computational Biology - July 28, 2021 Category: Biology Authors: Tessa Lloyd Source Type: research

Mathematical modeling of N-803 treatment in SIV-infected non-human primates
by Jonathan W. Cody, Amy L. Ellis-Connell, Shelby L. O ’Connor, Elsje Pienaar Immunomodulatory drugs could contribute to a functional cure for Human Immunodeficiency Virus (HIV). Interleukin-15 (IL-15) promotes expansion and activation of CD8+ T cell and natural killer (NK) cell populations. In one study, an IL-15 superagonist, N-803, suppressed Simian Immunodeficiency Virus (SIV) in non-human primates (NHPs) who had received prior SIV vaccination. However, viral suppression attenuated with continued N-803 treatment, partially returning after long treatment interruption. While there is evidence of concurrent drug to...
Source: PLoS Computational Biology - July 28, 2021 Category: Biology Authors: Jonathan W. Cody Source Type: research

Beyond the chemical master equation: Stochastic chemical kinetics coupled with auxiliary processes
by Davin Lunz, Gregory Batt, Jakob Ruess, J. Fr édéric Bonnans The chemical master equation and its continuum approximations are indispensable tools in the modeling of chemical reaction networks. These are routinely used to capture complex nonlinear phenomena such as multimodality as well as transient events such as first-passage times, that accurately charac terise a plethora of biological and chemical processes. However, some mechanisms, such as heterogeneous cellular growth or phenotypic selection at the population level, cannot be represented by the master equation and thus have been tackled separately. ...
Source: PLoS Computational Biology - July 28, 2021 Category: Biology Authors: Davin Lunz Source Type: research

Noise suppression in stochastic genetic circuits using PID controllers
by Saurabh Modi, Supravat Dey, Abhyudai Singh Inside individual cells, protein population counts are subject to molecular noise due to low copy numbers and the inherent probabilistic nature of biochemical processes. We investigate the effectiveness of proportional, integral and derivative (PID) based feedback controllers to suppress protein c ount fluctuations originating from two noise sources: bursty expression of the protein, and external disturbance in protein synthesis. Designs of biochemical reactions that function as PID controllers are discussed, with particular focus on individual controllers separately, and the ...
Source: PLoS Computational Biology - July 28, 2021 Category: Biology Authors: Saurabh Modi Source Type: research

A model of resource partitioning between foraging bees based on learning
by Thibault Dubois, Cristian Pasquaretta, Andrew B. Barron, Jacques Gautrais, Mathieu Lihoreau Central place foraging pollinators tend to develop multi-destination routes (traplines) to exploit patchily distributed plant resources. While the formation of traplines by individual pollinators has been studied in detail, how populations of foragers use resources in a common area is an open ques tion, difficult to address experimentally. We explored conditions for the emergence of resource partitioning among traplining bees using agent-based models built from experimental data of bumblebees foraging on artificial flowers. In t...
Source: PLoS Computational Biology - July 28, 2021 Category: Biology Authors: Thibault Dubois Source Type: research

Perturbations in dynamical models of whole-brain activity dissociate between the level and stability of consciousness
by Yonatan Sanz Perl, Carla Pallavicini, Ignacio P érez Ipiña, Athena Demertzi, Vincent Bonhomme, Charlotte Martial, Rajanikant Panda, Jitka Annen, Agustin Ibañez, Morten Kringelbach, Gustavo Deco, Helmut Laufs, Jacobo Sitt, Steven Laureys, Enzo Tagliazucchi Consciousness transiently fades away during deep sleep, more stably under anesthesia, and sometimes permanently due to brain injury. The development of an index to quantify the level of consciousness across these different states is regarded as a key problem both in basic and clinical neuroscience . We argue that this problem is ill-defined since ...
Source: PLoS Computational Biology - July 27, 2021 Category: Biology Authors: Yonatan Sanz Perl Source Type: research

Modeling Na < sub > V < /sub > 1.1/ < i > SCN1A < /i > sodium channel mutations in a microcircuit with realistic ion concentration dynamics suggests differential GABAergic mechanisms leading to hyperexcitability in epilepsy and hemiplegic migraine
by Louisiane Lemaire, Mathieu Desroches, Martin Krupa, Lara Pizzamiglio, Paolo Scalmani, Massimo Mantegazza Loss of function mutations ofSCN1A, the gene coding for the voltage-gated sodium channel NaV1.1, cause different types of epilepsy, whereas gain of function mutations cause sporadic and familial hemiplegic migraine type 3 (FHM-3). However, it is not clear yet how these opposite effects can induce paroxysmal pathological activities involving neuronal networks ’ hyperexcitability that are specific of epilepsy (seizures) or migraine (cortical spreading depolarization, CSD). To better understand differential mecha...
Source: PLoS Computational Biology - July 27, 2021 Category: Biology Authors: Louisiane Lemaire Source Type: research

Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching
by Matthias Niemann, Nils Lachmann, Kirsten Geneugelijk, Eric Spierings The EuroTransplant Kidney Allocation System (ETKAS) aims at allocating organs to patients on the waiting list fairly whilst optimizing HLA match grades. ETKAS currently considers the number of HLA-A, -B, -DR mismatches. Evidently, epitope matching is biologically and clinically more relevant. We h ere executed ETKAS-based computer simulations to evaluate the impact of epitope matching on allocation and compared the strategies. A virtual population of 400,000 individuals was generated using the National Marrow Donor Program (NMDP) haplotype frequency d...
Source: PLoS Computational Biology - July 27, 2021 Category: Biology Authors: Matthias Niemann Source Type: research

The kinetic landscape of nucleosome assembly: A coarse-grained molecular dynamics study
In this study, employing coarse-grained molecular dynamics simulations and Markov state modeling, we characterized the complete kinetics of nucleosome assembly. On the nucleosome-positioning 601 DNA sequence, we observe a rich transition network among various canonical and non-canonical tetrasome, hexasome, and nucleosome conformations. A low salt environment makes nucleosomes stable, but the kinetic landscape becomes more rugged, so that the system is more likely to be trapped in off-pathway partially assembled intermediates. Finally, we find that the co-operativ ity between DNA bending and histone association enables pos...
Source: PLoS Computational Biology - July 27, 2021 Category: Biology Authors: Giovanni B. Brandani Source Type: research

Emergence of directional bias in tau deposition from axonal transport dynamics
by Justin Torok, Pedro D. Maia, Parul Verma, Christopher Mezias, Ashish Raj Defects in axonal transport may partly underpin the differences between the observed pathophysiology of Alzheimer’s disease (AD) and that of other non-amyloidogenic tauopathies. Particularly, pathological tau variants may have molecular properties that dysregulate motor proteins responsible for the anterograde-directed transport of tau in a disease-specific fashion. Here we develop the first computational model of tau-modified axonal transport that produces directional biases in the spread of tau pathology. We simulated the spatiotemporal pr...
Source: PLoS Computational Biology - July 27, 2021 Category: Biology Authors: Justin Torok Source Type: research

Projecting contact matrices in 177 geographical regions: An update and comparison with empirical data for the COVID-19 era
In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the sy nthetic contact matrices show qualitative similarities to th...
Source: PLoS Computational Biology - July 26, 2021 Category: Biology Authors: Kiesha Prem Source Type: research

Insights into substrate recognition and specificity for IgG by Endoglycosidase S2
by Asaminew H. Aytenfisu, Daniel Deredge, Erik H. Klontz, Jonathan Du, Eric J. Sundberg, Alexander D. MacKerell Jr Antibodies bind foreign antigens with high affinity and specificity leading to their neutralization and/or clearance by the immune system. The conserved N-glycan on IgG has significant impact on antibody effector function, with the endoglycosidases ofStreptococcus pyogenes deglycosylating the IgG to evade the immune system, a process catalyzed by the endoglycosidase EndoS2. Studies have shown that two of the four domains of EndoS2, the carbohydrate binding module (CBM) and the glycoside hydrolase (GH) domain ...
Source: PLoS Computational Biology - July 26, 2021 Category: Biology Authors: Asaminew H. Aytenfisu Source Type: research

Covasim: An agent-based model of COVID-19 dynamics and interventions
by Cliff C. Kerr, Robyn M. Stuart, Dina Mistry, Romesh G. Abeysuriya, Katherine Rosenfeld, Gregory R. Hart, Rafael C. N úñez, Jamie A. Cohen, Prashanth Selvaraj, Brittany Hagedorn, Lauren George, Michał Jastrzębski, Amanda S. Izzo, Greer Fowler, Anna Palmer, Dominic Delport, Nick Scott, Sherrie L. Kelly, Caroline S. Bennette, Bradley G. Wagner, Stewart T. Chang, Assaf P. Oron, Edward A. Wenger, Jasmina Panovska-G riffiths, Michael Famulare, Daniel J. Klein The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource need...
Source: PLoS Computational Biology - July 26, 2021 Category: Biology Authors: Cliff C. Kerr Source Type: research

Dimeric allostery mechanism of the plant circadian clock photoreceptor ZEITLUPE
by Francesco Trozzi, Feng Wang, Gennady Verkhivker, Brian D. Zoltowski, Peng Tao InArabidopsis thaliana, the Light-Oxygen-Voltage (LOV) domain containing protein ZEITLUPE (ZTL) integrates light quality, intensity, and duration into regulation of the circadian clock. Recent structural and biochemical studies of ZTL indicate that the protein diverges from other members of the LOV superfamily in its allosteric mechanism, and that the divergent allosteric mechanism hinges upon conservation of two signaling residues G46 and V48 that alter dynamic motions of a Gln residue implicated in signal transduction in all LOV proteins. H...
Source: PLoS Computational Biology - July 26, 2021 Category: Biology Authors: Francesco Trozzi Source Type: research

Explaining distortions in metacognition with an attractor network model of decision uncertainty
by Nadim A. A. Atiya, Quentin J. M. Huys, Raymond J. Dolan, Stephen M. Fleming Metacognition is the ability to reflect on, and evaluate, our cognition and behaviour. Distortions in metacognition are common in mental health disorders, though the neural underpinnings of such dysfunction are unknown. One reason for this is that models of key components of metacognition, such as decision confidence, are generally specified at an algorithmic or process level. While such models can be used to relate brain function to psychopathology, they are difficult to map to a neurobiological mechanism. Here, we develop a biologically-plaus...
Source: PLoS Computational Biology - July 26, 2021 Category: Biology Authors: Nadim A. A. Atiya Source Type: research

Bridging cell-scale simulations and radiologic images to explain short-time intratumoral oxygen fluctuations
by Jessica L. Kingsley, James R. Costello, Natarajan Raghunand, Katarzyna A. Rejniak Radiologic images provide a way to monitor tumor development and its response to therapies in a longitudinal and minimally invasive fashion. However, they operate on a macroscopic scale (average value per voxel) and are not able to capture microscopic scale (cell-level) phenomena. Nevertheless, to examine the causes of frequent fast fluctuations in tissue oxygenation, models simulating individual cells’ behavior are needed. Here, we provide a link between the average data values recorded for radiologic images and the cellular and va...
Source: PLoS Computational Biology - July 26, 2021 Category: Biology Authors: Jessica L. Kingsley Source Type: research

A mechanistic and data-driven reconstruction of the time-varying reproduction number: Application to the COVID-19 epidemic
by Bernard Cazelles, Clara Champagne, Benjamin Nguyen-Van-Yen, Catherine Comiskey, Elisabeta Vergu, Benjamin Roche The effective reproduction numberReff is a critical epidemiological parameter that characterizes the transmissibility of a pathogen. However, this parameter is difficult to estimate in the presence of silent transmission and/or significant temporal variation in case reporting. This variation can occur due to the lack of timely or appropriate testing, public health interventions and/or changes in human behavior during an epidemic. This is exactly the situation we are confronted with during this COVID-19 pandem...
Source: PLoS Computational Biology - July 26, 2021 Category: Biology Authors: Bernard Cazelles Source Type: research

Autoencoder based local T cell repertoire density can be used to classify samples and T cell receptors
We present ELATE–an En coder-based LocAl Tcr dEnsity and show that the resulting density of a sample can be used as a novel measure to study repertoire properties. The cross-density between two samples can be used as a similarity matrix to fully characterize samples from the same host. Finally, the same projection in comb ination with machine learning algorithms can be used to predict TCR-peptide binding through the local density of known TCRs binding a specific target. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - July 26, 2021 Category: Biology Authors: Shirit Dvorkin Source Type: research

A model explaining mRNA level fluctuations based on activity demands and RNA age
by Zhongneng Xu, Shuichi Asakawa Cellular RNA levels typically fluctuate and are influenced by different transcription rates and RNA degradation rates. However, the understanding of the fundamental relationships between RNA abundance, environmental stimuli, RNA activities, and RNA age distributions is incomplete. Furthermore, the rates of RNA degradation and transcription are difficult to measure in transcriptomic experiments in living organisms, especially in studies involving humans. A model based on activity demands and RNA age was developed to explore the mechanisms of RNA level fluctuations. Using single-cell time-se...
Source: PLoS Computational Biology - July 23, 2021 Category: Biology Authors: Zhongneng Xu Source Type: research

Machine learning reveals mesenchymal breast carcinoma cell adaptation in response to matrix stiffness
In this study, we developed a workflow using image-b ased cell profiling and machine learning to examine morphological, contextual and molecular states of individual breast carcinoma cells (MDA-MB-231). MDA-MB-231 heterogeneous response to the host organ microenvironment was modelled by substrates with controllable stiffness varying from 0.2kPa (soft tissues) to 64kPa (bone tissues). We identified 3 distinct morphological cell types (morphs) varying from compact round-shaped to flattened irregular-shaped cells with lamellipodia, predominantly populating 2-kPa and>16kPa substrates, respectively. These observations were a...
Source: PLoS Computational Biology - July 23, 2021 Category: Biology Authors: Vlada S. Rozova Source Type: research

Integrating systemic and molecular levels to infer  key drivers sustaining metabolic adaptations
by Pedro de Atauri, M íriam Tarrado-Castellarnau, Josep Tarragó-Celada, Carles Foguet, Effrosyni Karakitsou, Josep Joan Centelles, Marta Cascante Metabolic adaptations to complex perturbations, like the response to pharmacological treatments in multifactorial diseases such as cancer, can be described through measurements of part of the fluxes and concentrations at the systemic level and individual transporter and enzyme activities at the mo lecular level. In the framework of Metabolic Control Analysis (MCA), ensembles of linear constraints can be built integrating these measurements at both systemic and mole...
Source: PLoS Computational Biology - July 23, 2021 Category: Biology Authors: Pedro de Atauri Source Type: research

Optimizing testing for COVID-19 in India
by Philip Cherian, Sandeep Krishna, Gautam I. Menon COVID-19 testing across India uses a mix of two types of tests. Rapid Antigen Tests (RATs) are relatively inexpensive point-of-care lateral-flow-assay tests, but they are also less sensitive. The reverse-transcriptase polymerase-chain-reaction (RT-PCR) test has close to 100% sensitivity and specif icity in a laboratory setting, but delays in returning results, as well as increased costs relative to RATs, may vitiate this advantage. India-wide, about 49% of COVID-19 tests are RATs, but some Indian states, including the large states of Uttar Pradesh (pop. 227.9 million) an...
Source: PLoS Computational Biology - July 22, 2021 Category: Biology Authors: Philip Cherian Source Type: research

Spatio-temporal modeling of the crowding conditions and metabolic variability in microbial communities
by Liliana Angeles-Martinez, Vassily Hatzimanikatis The metabolic capabilities of the species and the local environment shape the microbial interactions in a community either through the exchange of metabolic products or the competition for the resources. Cells are often arranged in close proximity to each other, creating a crowded environment that unevenly reduce the diffusion of nutrients. Herein, we investigated how the crowding conditions and metabolic variability among cells shape the dynamics of microbial communities. For this, we developed CROMICS, a spatio-temporal framework that combines techniques such as indivi...
Source: PLoS Computational Biology - July 22, 2021 Category: Biology Authors: Liliana Angeles-Martinez Source Type: research

The influence of the crowding assumptions in biofilm simulations
by Liliana Angeles-Martinez, Vassily Hatzimanikatis Microorganisms are frequently organized into crowded structures that affect the nutrients diffusion. This reduction in metabolite diffusion could modify the microbial dynamics, meaning that computational methods for studying microbial systems need accurate ways to model the crowding conditions. We previously developed a computational framework, termed CROMICS, that incorporates the effect of the (time-dependent) crowding conditions on the spatio-temporal modeling of microbial communities, and we used it to demonstrate the crowding influence on the community dynamics. To ...
Source: PLoS Computational Biology - July 22, 2021 Category: Biology Authors: Liliana Angeles-Martinez Source Type: research

ChIP-GSM: Inferring active transcription factor modules to predict functional regulatory elements
by Xi Chen, Andrew F. Neuwald, Leena Hilakivi-Clarke, Robert Clarke, Jianhua Xuan Transcription factors (TFs) often function as a module including both master factors and mediators binding at cis-regulatory regions to modulate nearby gene transcription. ChIP-seq profiling of multiple TFs makes it feasible to infer functional TF modules. However, when inferring TF modules based on co-localization of ChIP-seq peaks, often many weak binding events are missed, especially for mediators, resulting in incomplete identification of modules. To address this problem, we develop a ChIP-seq data-driven Gibbs Sampler to infer Modules (...
Source: PLoS Computational Biology - July 22, 2021 Category: Biology Authors: Xi Chen Source Type: research

PEDF, a pleiotropic WTC-LI biomarker: Machine learning biomarker identification and validation
by George Crowley, James Kim, Sophia Kwon, Rachel Lam, David J. Prezant, Mengling Liu, Anna Nolan Biomarkers predict World Trade Center-Lung Injury (WTC-LI); however, there remains unaddressed multicollinearity in our serum cytokines, chemokines, and high-throughput platform datasets used to phenotype WTC-disease. To address this concern, we used automated, machine-learning, high-dimensional d ata pruning, and validated identified biomarkers. The parent cohort consisted of male, never-smoking firefighters with WTC-LI (FEV1, %Pred (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - July 21, 2021 Category: Biology Authors: George Crowley Source Type: research

Spatially resolved simulations of the spread of COVID-19 in three European countries
by Andrea Parisi, Samuel P. C. Brand, Joe Hilton, Rabia Aziza, Matt J. Keeling, D. James Nokes We explore the spatial and temporal spread of the novel SARS-CoV-2 virus under containment measures in three European countries based on fits to data of the early outbreak. Using data from Spain and Italy, we estimate an age dependent infection fatality ratio for SARS-CoV-2, as well as risks of ho spitalization and intensive care admission. We use them in a model that simulates the dynamics of the virus using an age structured, spatially detailed agent based approach, that explicitly incorporates governmental interventions and c...
Source: PLoS Computational Biology - July 20, 2021 Category: Biology Authors: Andrea Parisi Source Type: research

Rigid-body fitting to atomic force microscopy images for inferring probe shape and biomolecular structure
by Toru Niina, Yasuhiro Matsunaga, Shoji Takada Atomic force microscopy (AFM) can visualize functional biomolecules near the physiological condition, but the observed data are limited to the surface height of specimens. Since the AFM images highly depend on the probe tip shape, for successful inference of molecular structures from the measureme nt, the knowledge of the probe shape is required, but is often missing. Here, we developed a method of the rigid-body fitting to AFM images, which simultaneously finds the shape of the probe tip and the placement of the molecular structure via an exhaustive search. First, we examin...
Source: PLoS Computational Biology - July 20, 2021 Category: Biology Authors: Toru Niina Source Type: research

Single-cell analysis reveals the pan-cancer invasiveness-associated transition of adipose-derived stromal cells into COL11A1-expressing cancer-associated fibroblasts
by Kaiyi Zhu, Lingyi Cai, Chenqian Cui, Juan R. de los Toyos, Dimitris Anastassiou During the last ten years, many research results have been referring to a particular type of cancer-associated fibroblasts associated with poor prognosis, invasiveness, metastasis and resistance to therapy in multiple cancer types, characterized by a gene expression signature with prominent presen ce of genesCOL11A1,THBS2 andINHBA. Identifying the underlying biological mechanisms responsible for their creation may facilitate the discovery of targets for potential pan-cancer therapeutics. Using a novel computational approach for single-cell ...
Source: PLoS Computational Biology - July 20, 2021 Category: Biology Authors: Kaiyi Zhu Source Type: research

Performance and scaling behavior of bioinformatic applications in virtualization environments to create awareness for the efficient use of compute resources
In this study we investigated the behavior of well-known applications in bioinformatics, regarding their performance in the terms of scaling, different virtual environments and different datasets with our benchmarking tool suiteBOOTABLE. The tool suite includes the tools BBMap, Bowtie2, BWA, Velvet, IDBA, SPAdes, Clustal Omega, MAFFT, SINA and GROMACS. In addition we added an application using the machine learning framework TensorFlow. Machine learning is not directly part of bioinformatics but applied to many biological problems, especially in the context of medical images (X-ray photographs). The mentioned tools have bee...
Source: PLoS Computational Biology - July 20, 2021 Category: Biology Authors: Maximilian Hanussek Source Type: research

Immune selection suppresses the emergence of drug resistance in malaria parasites but facilitates its spread
by Alexander O. B. Whitlock, Jonathan J. Juliano, Nicole Mideo Although drug resistance inPlasmodium falciparum typically evolves in regions of low transmission, resistance spreads readily following introduction to regions with a heavier disease burden. This suggests that the origin and the spread of resistance are governed by different processes, and that high transmission intensity specifically impedes the origin. Factors associated with high transmission, such as highly immune hosts and competition within genetically diverse infections, are associated with suppression of resistant lineages within hosts. However, intera...
Source: PLoS Computational Biology - July 19, 2021 Category: Biology Authors: Alexander O. B. Whitlock Source Type: research

From reaction kinetics to dementia: A simple dimer model of Alzheimer ’s disease etiology
by Michael R. Lindstrom, Manuel B. Chavez, Elijah A. Gross-Sable, Eric Y. Hayden, David B. Teplow Oligomers of the amyloidβ-protein (Aβ) have been implicated in the pathogenesis of Alzheimer ’s disease (AD) through their toxicity towards neurons. Understanding the process of oligomerization may contribute to the development of therapeutic agents, but this has been difficult due to the complexity of oligomerization and the metastability of the oligomers thus formed. To understand the k inetics of oligomer formation, and how that relates to the progression of AD, we developed models of the oligomerization pr...
Source: PLoS Computational Biology - July 19, 2021 Category: Biology Authors: Michael R. Lindstrom Source Type: research

Neuron tracing and quantitative analyses of dendritic architecture reveal symmetrical three-way-junctions and phenotypes of < i > git-1 < /i > in < i > C < /i > . < i > elegans < /i >
by Omer Yuval, Yael Iosilevskii, Anna Meledin, Benjamin Podbilewicz, Tom Shemesh Complex dendritic trees are a distinctive feature of neurons. Alterations to dendritic morphology are associated with developmental, behavioral and neurodegenerative changes. The highly-arborized PVD neuron ofC.elegans serves as a model to study dendritic patterning; however, quantitative, objective and automated analyses of PVD morphology are missing. Here, we present a method for neuronal feature extraction, based on deep-learning and fitting algorithms. The extracted neuronal architecture is represented by a database of structural elements...
Source: PLoS Computational Biology - July 19, 2021 Category: Biology Authors: Omer Yuval Source Type: research

The effect of natural selection on the propagation of protein expression noise to bacterial growth
by Laurens H. J. Krah, Rutger Hermsen In bacterial cells, protein expression is a highly stochastic process. Gene expression noise moreover propagates through the cell and adds to fluctuations in the cellular growth rate. A common intuition is that, due to their relatively high noise amplitudes, proteins with a low mean expression lev el are the most important drivers of fluctuations in physiological variables. In this work, we challenge this intuition by considering the effect of natural selection on noise propagation. Mathematically, the contribution of each protein species to the noise in the growth rate depends on two...
Source: PLoS Computational Biology - July 19, 2021 Category: Biology Authors: Laurens H. J. Krah Source Type: research

Hamming-shifting graph of genomic short reads: Efficient construction and its application for compression
We present a novel graph definition named Hamming-Shifting graph to address this problem. The definition originates from the technological characteristics of next-generation sequencing machines, aiming to link all pairs of distinct reads that have a small Hamming distance or a small shifting offset or both. We compute multiple lexicographically minimalk-mers to index the reads for an efficient search of the weight-lightest edges, and we prove a very high probability of successfully detecting these edges. The resulted graph creates a full mutual reference of the reads to cascade a code-minimized transfer of every child-read...
Source: PLoS Computational Biology - July 19, 2021 Category: Biology Authors: Yuansheng Liu Source Type: research

Multi-scale simulations of the T cell receptor reveal its lipid interactions, dynamics and the arrangement of its cytoplasmic region
by Dheeraj Prakaash, Graham P. Cook, Oreste Acuto, Antreas C. Kalli The T cell receptor (TCR-CD3) initiates T cell activation by binding to peptides of Major Histocompatibility Complexes (pMHC). The TCR-CD3 topology is well understood but the arrangement and dynamics of its cytoplasmic tails remains unknown, limiting our grasp of the signalling mechanism. Here, we use molecular dynamics simulations and modelling to investigate the entire TCR-CD3 embedded in a model membrane. Our study demonstrates conformational changes in the extracellular and transmembrane domains, and the arrangement of the TCR-CD3 cytoplasmic tails. T...
Source: PLoS Computational Biology - July 19, 2021 Category: Biology Authors: Dheeraj Prakaash Source Type: research

An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain
by Marte J. S ætra, Gaute T. Einevoll, Geir Halnes Within the computational neuroscience community, there has been a focus on simulating the electrical activity of neurons, while other components of brain tissue, such as glia cells and the extracellular space, are often neglected. Standard models of extracellular potentials are based on a combinat ion of multicompartmental models describing neural electrodynamics and volume conductor theory. Such models cannot be used to simulate the slow components of extracellular potentials, which depend on ion concentration dynamics, and the effect that this has on extracellular...
Source: PLoS Computational Biology - July 16, 2021 Category: Biology Authors: Marte J. S ætra Source Type: research

Prioritizing and characterizing functionally relevant genes across human tissues
by Gowthami Somepalli, Sarthak Sahoo, Arashdeep Singh, Sridhar Hannenhalli Knowledge of genes that are critical to a tissue’s function remains difficult to ascertain and presents a major bottleneck toward a mechanistic understanding of genotype-phenotype links. Here, we present the first machine learning model–FUGUE–combining transcriptional and network features, t o predict tissue-relevant genes across 30 human tissues. FUGUE achieves an average cross-validation auROC of 0.86 and auPRC of 0.50 (expected 0.09). In independent datasets, FUGUE accurately distinguishes tissue or cell type-specific genes, si...
Source: PLoS Computational Biology - July 16, 2021 Category: Biology Authors: Gowthami Somepalli Source Type: research

An association between prediction errors and risk-seeking: Theory and behavioral evidence
by Moritz Moeller, Jan Grohn, Sanjay Manohar, Rafal Bogacz Reward prediction errors (RPEs) and risk preferences have two things in common: both can shape decision making behavior, and both are commonly associated with dopamine. RPEs drive value learning and are thought to be represented in the phasic release of striatal dopamine. Risk preferences bias cho ices towards or away from uncertainty; they can be manipulated with drugs that target the dopaminergic system. Based on the common neural substrate, we hypothesize that RPEs and risk preferences are linked on the level of behavior as well. Here, we develop this hypothesi...
Source: PLoS Computational Biology - July 16, 2021 Category: Biology Authors: Moritz Moeller Source Type: research

A novel stochastic simulation approach enables exploration of mechanisms for regulating polarity site movement
by Samuel A. Ramirez, Michael Pablo, Sean Burk, Daniel J. Lew, Timothy C. Elston Cells polarize their movement or growth toward external directional cues in many different contexts. For example, budding yeast cells grow toward potential mating partners in response to pheromone gradients. Directed growth is controlled by polarity factors that assemble into clusters at the cell membrane. The clusters assemble, disassemble, and move between different regions of the membrane before eventually forming a stable polarity site directed toward the pheromone source. Pathways that regulate clustering have been identified but the mol...
Source: PLoS Computational Biology - July 15, 2021 Category: Biology Authors: Samuel A. Ramirez Source Type: research

Accumulation of continuously time-varying sensory evidence constrains neural and behavioral responses in human collision threat detection
by Gustav Markkula, Zeynep Uluda ğ, Richard McGilchrist Wilkie, Jac Billington Evidence accumulation models provide a dominant account of human decision-making, and have been particularly successful at explaining behavioral and neural data in laboratory paradigms using abstract, stationary stimuli. It has been proposed, but with limited in-depth investigation so far, that si milar decision-making mechanisms are involved in tasks of a more embodied nature, such as movement and locomotion, by directly accumulating externally measurable sensory quantities of which the precise, typically continuously time-varying, magnitudes...
Source: PLoS Computational Biology - July 15, 2021 Category: Biology Authors: Gustav Markkula Source Type: research

Sperm migration in the genital tract — < i > In silico < /i > experiments identify key factors for reproductive success
by Jorin Diemer, Jens Hahn, Bj örn Goldenbogen, Karin Müller, Edda Klipp Sperm migration in the female genital tract controls sperm selection and, therefore, reproductive success as male gametes are conditioned for fertilization while their number is dramatically reduced. Mechanisms underlying sperm migration are mostly unknown, sincein vivo investigations are mostly unfeasible for ethical or practical reasons. By presenting a spatio-temporal model of the mammalian female genital tract combined with agent-based description of sperm motion and interaction as well as parameterizing it with bovine data, we offer an...
Source: PLoS Computational Biology - July 15, 2021 Category: Biology Authors: Jorin Diemer Source Type: research

Ten simple rules to improve academic work –life balance
by Michael John Bartlett, Feyza Nur Arslan, Adriana Bankston, Sarvenaz Sarabipour (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - July 15, 2021 Category: Biology Authors: Michael John Bartlett Source Type: research

Ten simple rules for attending your first conference
by Elizabeth Leininger, Kelly Shaw, Niema Moshiri, Kelly Neiles, Getiria Onsongo, Anna Ritz (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - July 15, 2021 Category: Biology Authors: Elizabeth Leininger Source Type: research

Responses to 10 common criticisms of anti-racism action in STEMM
by Maya L. Gosztyla, Lydia Kwong, Naomi A. Murray, Claire E. Williams, Nicholas Behnke, Porsia Curry, Kevin D. Corbett, Karen N. DSouza, Julia Gala de Pablo, Joanina Gicobi, Monica Javidnia, Navina Lotay, Sidney Madison Prescott, James P. Quinn, Zeena M. G. Rivera, Markia A. Smith, Karen T. Y. Tang, Aarya Venkat, Megan A. Yamoah (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - July 15, 2021 Category: Biology Authors: Maya L. Gosztyla Source Type: research

Data integration uncovers the metabolic bases of phenotypic variation in yeast
by Marianyela Sabina Petrizzelli, Dominique de Vienne, Thibault Nidelet, Camille No ûs, Christine Dillmann The relationship between different levels of integration is a key feature for understanding the genotype-phenotype map. Here, we describe a novel method of integrated data analysis that incorporates protein abundance data into constraint-based modeling to elucidate the biological mechanisms underl ying phenotypic variation. Specifically, we studied yeast genetic diversity at three levels of phenotypic complexity in a population of yeast obtained by pairwise crosses of eleven strains belonging to two species,Sac...
Source: PLoS Computational Biology - July 15, 2021 Category: Biology Authors: Marianyela Sabina Petrizzelli Source Type: research

Risk sensitivity and theory of mind in human coordination
by Pedro L. Ferreira, Francisco C. Santos, S érgio Pequito What humans do when exposed to uncertainty, incomplete information, and a dynamic environment influenced by other agents remains an open scientific challenge with important implications in both science and engineering applications. In these contexts, humans handle social situations by employing el aborate cognitive mechanisms such as theory of mind and risk sensitivity. Here we resort to a novel theoretical model, showing that both mechanisms leverage coordinated behaviors among self-regarding individuals. Particularly, we resort to cumulative prospect theo...
Source: PLoS Computational Biology - July 15, 2021 Category: Biology Authors: Pedro L. Ferreira Source Type: research

Three-dimensional stochastic simulation of chemoattractant-mediated excitability in cells
by Debojyoti Biswas, Peter N. Devreotes, Pablo A. Iglesias During the last decade, a consensus has emerged that the stochastic triggering of an excitable system drives pseudopod formation and subsequent migration of amoeboid cells. The presence of chemoattractant stimuli alters the threshold for triggering this activity and can bias the direction of migra tion. Though noise plays an important role in these behaviors, mathematical models have typically ignored its origin and merely introduced it as an external signal into a series of reaction-diffusion equations. Here we consider a more realistic description based on a rea...
Source: PLoS Computational Biology - July 14, 2021 Category: Biology Authors: Debojyoti Biswas Source Type: research