On the evolution and development of morphological complexity: A view from gene regulatory networks
This study suggests that the likelihood of mutations increasing phenotypic complexity becomes smaller when the phenotype itself is complex. In addition, the complexity of the genotype-phenotype map (GPM) also increases with the phenotypic complexity. We sh ow that complex GPMs and the above mutational asymmetry are inevitable consequences of how genes need to be wired in order to build complex and robust phenotypes during development. We randomly wired genes and cell behaviors into networks in EmbryoMaker. EmbryoMaker is a mathematical model of develo pment that can simulate any gene network, all animal cell behaviors (div...
Source: PLoS Computational Biology - February 24, 2021 Category: Biology Authors: Pascal F. Hagolani Source Type: research

Correction: Biophysically grounded mean-field models of neural populations under electrical stimulation
by Caglar Cakan, Klaus Obermayer (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - February 24, 2021 Category: Biology Authors: Caglar Cakan Source Type: research

Evolution of heterogeneous perceptual limits and indifference in competitive foraging
by Richard P. Mann The collective behaviour of animal and human groups emerges from the individual decisions and actions of their constituent members. Recent research has revealed many ways in which the behaviour of groups can be influenced by differences amongst their constituent individuals. The existence of indiv idual differences that have implications for collective behaviour raises important questions. How are these differences generated and maintained? Are individual differences driven by exogenous factors, or are they a response to the social dilemmas these groups face? Here I consider the classic case of patch se...
Source: PLoS Computational Biology - February 23, 2021 Category: Biology Authors: Richard P. Mann Source Type: research

Hybridized distance- and contact-based hierarchical structure modeling for folding soluble and membrane proteins
by Rahmatullah Roche, Sutanu Bhattacharya, Debswapna Bhattacharya Crystallography and NMR system (CNS) is currently a widely used method for fragment-freeab initio protein folding from inter-residue distance or contact maps. Despite its widespread use in protein structure prediction, CNS is a decade-old macromolecular structure determination system that was originally developed for solving macromolecular geometry from experimental restraints as opposed to predictive modeling driven by interaction map data. As such, the adaptation of the CNS experimental structure determination protocol forab initio protein folding is intr...
Source: PLoS Computational Biology - February 23, 2021 Category: Biology Authors: Rahmatullah Roche Source Type: research

Quantitative profiling of protease specificity
by Boris I. Ratnikov, Piotr Cieplak, Albert G. Remacle, Elise Nguyen, Jeffrey W. Smith Proteases are an important class of enzymes, whose activity is central to many physiologic and pathologic processes. Detailed knowledge of protease specificity is key to understanding their function. Although many methods have been developed to profile specificities of proteases, few have the dive rsity and quantitative grasp necessary to fully define specificity of a protease, both in terms of substrate numbers and their catalytic efficiencies. We have developed a concept of “selectome”; the set of substrate amino acid sequ...
Source: PLoS Computational Biology - February 22, 2021 Category: Biology Authors: Boris I. Ratnikov Source Type: research

Spectrally specific temporal analyses of spike-train responses to complex sounds: A unifying framework
by Satyabrata Parida, Hari Bharadwaj, Michael G. Heinz Significant scientific and translational questions remain in auditory neuroscience surrounding the neural correlates of perception. Relating perceptual and neural data collected from humans can be useful; however, human-based neural data are typically limited to evoked far-field responses, which l ack anatomical and physiological specificity. Laboratory-controlled preclinical animal models offer the advantage of comparing single-unit and evoked responses from the same animals. This ability provides opportunities to develop invaluable insight into proper interpretation...
Source: PLoS Computational Biology - February 22, 2021 Category: Biology Authors: Satyabrata Parida Source Type: research

A mathematical model of the role of aggregation in sonic hedgehog signalling
by Daniel J. A. Derrick, Kathryn Wolton, Richard A. Currie, Marcus John Tindall Effective regulation of the sonic hedgehog (Shh) signalling pathway is essential for normal development in a wide variety of species. Correct Shh signalling requires the formation of Shh aggregates on the surface of producing cells. Shh aggregates subsequently diffuse away and are recognised in re ceiving cells located elsewhere in the developing embryo. Various mechanisms have been postulated regarding how these aggregates form and what their precise role is in the overall signalling process. To understand the role of these mechanisms in the ...
Source: PLoS Computational Biology - February 22, 2021 Category: Biology Authors: Daniel J. A. Derrick Source Type: research

Rapid 3D phenotypic analysis of neurons and organoids using data-driven cell segmentation-free machine learning
by Philipp Mergenthaler, Santosh Hariharan, James M. Pemberton, Corey Lourenco, Linda Z. Penn, David W. Andrews Phenotypic profiling of large three-dimensional microscopy data sets has not been widely adopted due to the challenges posed by cell segmentation and feature selection. The computational demands of automated processing further limit analysis of hard-to-segment images such as of neurons and organoi ds. Here we describe a comprehensive shallow-learning framework for automated quantitative phenotyping of three-dimensional (3D) image data; using unsupervised data-driven voxel-based feature learning, which enables co...
Source: PLoS Computational Biology - February 22, 2021 Category: Biology Authors: Philipp Mergenthaler Source Type: research

Nonlinear effects of intrinsic dynamics on temporal encoding in a model of avian auditory cortex
by Christof Fehrman, Tyler D. Robbins, C. Daniel Meliza Neurons exhibit diverse intrinsic dynamics, which govern how they integrate synaptic inputs to produce spikes. Intrinsic dynamics are often plastic during development and learning, but the effects of these changes on stimulus encoding properties are not well known. To examine this relationship, we simulated auditory responses to zebra finch song using a linear-dynamical cascade model, which combines a linear spectrotemporal receptive field with a dynamical, conductance-based neuron model, then used generalized linear models to estimate encoding properties from the re...
Source: PLoS Computational Biology - February 22, 2021 Category: Biology Authors: Christof Fehrman Source Type: research

Calcium-vesicles perform active diffusion in the sea urchin embryo during larval biomineralization
by Mark R. Winter, Miri Morgulis, Tsvia Gildor, Andrew R. Cohen, Smadar Ben-Tabou de-Leon Biomineralization is the process by which organisms use minerals to harden their tissues and provide them with physical support. Biomineralizing cells concentrate the mineral in vesicles that they secret into a dedicated compartment where crystallization occurs. The dynamics of vesicle motion and the molecular mechanisms that control it, are not well understood. Sea urchin larval skeletogenesis provides an excellent platform for investigating the kinetics of mineral-bearing vesicles. Here we used lattice light-sheet microscopy to stu...
Source: PLoS Computational Biology - February 22, 2021 Category: Biology Authors: Mark R. Winter Source Type: research

Computational modeling of the gut microbiota reveals putative metabolic mechanisms of recurrent < i > Clostridioides difficile < /i > infection
In this study, anin silico pipeline was used to process 16S rRNA gene amplicon sequence data of 225 stool samples from 93 CDI patients into sample-specific models of bacterial community metabolism. Clustered metabolite production rates generated from post-diagnosis samples generated a highEnterobacteriaceae abundance cluster containing disproportionately large numbers of recurrent samples and patients. This cluster was predicted to have significantly reduced capabilities for secondary bile acid synthesis but elevated capabilities for aromatic amino acid catabolism. When applied to 16S sequence data of 40 samples from fecal...
Source: PLoS Computational Biology - February 22, 2021 Category: Biology Authors: Michael A. Henson Source Type: research

Efficient and flexible Integration of variant characteristics in rare variant association studies using integrated nested Laplace approximation
by Hana Susak, Laura Serra-Saurina, German Demidov, Raquel Rabionet, Laura Dom ènech, Mattia Bosio, Francesc Muyas, Xavier Estivill, Geòrgia Escaramís, Stephan Ossowski Rare variants are thought to play an important role in the etiology of complex diseases and may explain a significant fraction of the missing heritability in genetic disease studies. Next-generation sequencing facilitates the association of rare variants in coding or regulatory regions with comple x diseases in large cohorts at genome-wide scale. However, rare variant association studies (RVAS) still lack power when cohorts are small t...
Source: PLoS Computational Biology - February 19, 2021 Category: Biology Authors: Hana Susak Source Type: research

An antigenic diversification threshold for falciparum malaria transmission at high endemicity
We present here the concept of a threshold in local pathogen diversification that defines a sharp transition in transmission intensity below which new antigen-encoding genes generated by either recombination or migration cannot establish. Transmission still occurs below this threshold, but diversity of these genes can neither accumulate nor recover from interventions that further reduce it. An analytical expectation for this threshold is derived and compared to numerical results from a stochastic individual-based model of malaria transmission that incorporates the major antigen-encoding multigene family known asvar. This t...
Source: PLoS Computational Biology - February 19, 2021 Category: Biology Authors: Qixin He Source Type: research

Margination and adhesion dynamics of tumor cells in a real microvascular network
by Sitong Wang, Ting Ye, Guansheng Li, Xuejiao Zhang, Huixin Shi In tumor metastasis, the margination and adhesion of tumor cells are two critical and closely related steps, which may determine the destination where the tumor cells extravasate to. We performed a direct three-dimensional simulation on the behaviors of the tumor cells in a real microvascular netw ork, by a hybrid method of the smoothed dissipative particle dynamics and immersed boundary method (SDPD-IBM). The tumor cells are found to adhere at the microvascular bifurcations more frequently, and there is a positive correlation between the adhesion of the tum...
Source: PLoS Computational Biology - February 19, 2021 Category: Biology Authors: Sitong Wang Source Type: research

Bayesian parameter estimation for automatic annotation of gene functions using observational data and phylogenetic trees
by George G. Vega Yon, Duncan C. Thomas, John Morrison, Huaiyu Mi, Paul D. Thomas, Paul Marjoram Gene function annotation is important for a variety of downstream analyses of genetic data. But experimental characterization of function remains costly and slow, making computational prediction an important endeavor. Phylogenetic approaches to prediction have been developed, but implementation of a practical Bayesian framework for parameter estimation remains an outstanding challenge. We have developed a computationally efficient model of evolution of gene annotations using phylogenies based on a Bayesian framework using Mark...
Source: PLoS Computational Biology - February 18, 2021 Category: Biology Authors: George G. Vega Yon Source Type: research

Ten simple rules for navigating the computational aspect of an interdisciplinary PhD
by Sabrina Islam, Christine A. Wells (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - February 18, 2021 Category: Biology Authors: Sabrina Islam Source Type: research

Brain-inspired model for early vocal learning and correspondence matching using free-energy optimization
by Alexandre Pitti, Mathias Quoy, Sofiane Boucenna, Catherine Lavandier We propose a developmental model inspired by the cortico-basal system (CX-BG) for vocal learning in babies and for solving the correspondence mismatch problem they face when they hear unfamiliar voices, with different tones and pitches. This model is based on the neural architecture INFERNO standi ng for Iterative Free-Energy Optimization of Recurrent Neural Networks. Free-energy minimization is used for rapidly exploring, selecting and learning the optimal choices of actions to perform (eg sound production) in order to reproduce and control as accura...
Source: PLoS Computational Biology - February 18, 2021 Category: Biology Authors: Alexandre Pitti Source Type: research

Ten simple rules for running and managing virtual internships
by Johannes Werner, Debora Jeske (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - February 18, 2021 Category: Biology Authors: Johannes Werner Source Type: research

Ten simple rules for starting (and sustaining) an academic data science initiative
by Micaela S. Parker, Arlyn E. Burgess, Philip E. Bourne (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - February 18, 2021 Category: Biology Authors: Micaela S. Parker Source Type: research

Ten simple rules for getting started with command-line bioinformatics
by Parice A. Brandies, Carolyn J. Hogg (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - February 18, 2021 Category: Biology Authors: Parice A. Brandies Source Type: research

Sensing ecosystem dynamics via audio source separation: A case study of marine soundscapes off northeastern Taiwan
This study investigated the application of a seafloor acoustic observatory as a long-term plat form for observing marine ecosystem dynamics through audio source separation. A source separation model based on the assumption of source-specific periodicity was used to factorize time-frequency representations of long-duration underwater recordings. With minimal supervision, the model learned to d iscriminate source-specific spectral features and prove to be effective in the separation of sounds made by cetaceans, soniferous fish, and abiotic sources from the deep-water soundscapes off northeastern Taiwan. Results revealed phen...
Source: PLoS Computational Biology - February 18, 2021 Category: Biology Authors: Tzu-Hao Lin Source Type: research

Positive interactions within and between populations decrease the likelihood of evolutionary rescue
by Yaron Goldberg, Jonathan Friedman Positive interactions, including intraspecies cooperation and interspecies mutualisms, play crucial roles in shaping the structure and function of many ecosystems, ranging from plant communities to the human microbiome. While the evolutionary forces that form and maintain positive interactions hav e been investigated extensively, the influence of positive interactions on the ability of species to adapt to new environments is still poorly understood. Here, we use numerical simulations and theoretical analyses to study how positive interactions impact the likelihood that populations surv...
Source: PLoS Computational Biology - February 18, 2021 Category: Biology Authors: Yaron Goldberg Source Type: research

Cholinergic neuromodulation of inhibitory interneurons facilitates functional integration in whole-brain models
by Carlos Coronel-Oliveros, Rodrigo Cofr é, Patricio Orio Segregation and integration are two fundamental principles of brain structural and functional organization. Neuroimaging studies have shown that the brain transits between different functionally segregated and integrated states, and neuromodulatory systems have been proposed as key to facilitate t hese transitions. Although whole-brain computational models have reproduced this neuromodulatory effect, the role of local inhibitory circuits and their cholinergic modulation has not been studied. In this article, we consider a Jansen& Rit whole-brain model in...
Source: PLoS Computational Biology - February 18, 2021 Category: Biology Authors: Carlos Coronel-Oliveros Source Type: research

Deep6mA: A deep learning framework for exploring similar patterns in DNA N6-methyladenine sites across different species
by Zutan Li, Hangjin Jiang, Lingpeng Kong, Yuanyuan Chen, Kun Lang, Xiaodan Fan, Liangyun Zhang, Cong Pian N6-methyladenine (6mA) is an important DNA modification form associated with a wide range of biological processes. Identifying accurately 6mA sites on a genomic scale is crucial for under-standing of 6mA’s biological functions. However, the existing experimental techniques for detecting 6mA site s are cost-ineffective, which implies the great need of developing new computational methods for this problem. In this paper, we developed, without requiring any prior knowledge of 6mA and manually crafted sequence feat...
Source: PLoS Computational Biology - February 18, 2021 Category: Biology Authors: Zutan Li Source Type: research

Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural insights from a computational model
In this study, we investigate the mutual interactions between the tumor cells and the neutrophils that facilitate tumor invasion by developing a mathematical model that involves taxis-reaction-diffusion equations for the critical componen ts in the interaction. These include the densities of tumor and neutrophils, and the concentrations of signaling molecules and structure such as neutrophil extracellular traps (NETs). We apply the mathematical model to a Boyden invasion assay used in the experiments to demonstrate that the tumor-ass ociated neutrophils can enhance tumor cell invasion by secreting the neutrophil elastase. ...
Source: PLoS Computational Biology - February 17, 2021 Category: Biology Authors: Junho Lee Source Type: research

A comprehensive computational model of animal biosonar signal processing
by Chen Ming, Stephanie Haro, Andrea Megela Simmons, James A. Simmons Computational models of animal biosonar seek to identify critical aspects of echo processing responsible for the superior, real-time performance of echolocating bats and dolphins in target tracking and clutter rejection. The Spectrogram Correlation and Transformation (SCAT) model replicates aspect s of biosonar imaging in both species by processing wideband biosonar sounds and echoes with auditory mechanisms identified from experiments with bats. The model acquires broadband biosonar broadcasts and echoes, represents them as time-frequency spectrograms ...
Source: PLoS Computational Biology - February 17, 2021 Category: Biology Authors: Chen Ming Source Type: research

Data-driven method to infer the seizure propagation patterns in an epileptic brain from intracranial electroencephalography
by Viktor Sip, Meysam Hashemi, Anirudh N. Vattikonda, Marmaduke M. Woodman, Huifang Wang, Julia Scholly, Samuel Medina Villalon, Maxime Guye, Fabrice Bartolomei, Viktor K. Jirsa Surgical interventions in epileptic patients aimed at the removal of the epileptogenic zone have success rates at only 60-70%. This failure can be partly attributed to the insufficient spatial sampling by the implanted intracranial electrodes during the clinical evaluation, leading to an incomplet e picture of spatio-temporal seizure organization in the regions that are not directly observed. Utilizing the partial observations of the seizure sprea...
Source: PLoS Computational Biology - February 17, 2021 Category: Biology Authors: Viktor Sip Source Type: research

Computational prediction of drug response in short QT syndrome type 1 based on measurements of compound effect in stem cell-derived cardiomyocytes
by Karoline Horgmo J æger, Samuel Wall, Aslak Tveito Short QT (SQT) syndrome is a genetic cardiac disorder characterized by an abbreviated QT interval of the patient’s electrocardiogram. The syndrome is associated with increased risk of arrhythmia and sudden cardiac death and can arise from a number of ion channel mutations. Cardiomyocytes derived from induced pluripotent stem cells generated from SQT patients (SQT hiPSC-CMs) provide promising platforms for testing pharmacological treatments directly in human cardiac cells exhibiting mutations specific for the syndrome. However, a difficulty is posed by the re...
Source: PLoS Computational Biology - February 16, 2021 Category: Biology Authors: Karoline Horgmo J æger Source Type: research

A model of developmental canalization, applied to human cranial form
by Philipp Mitteroecker, Ekaterina Stansfield Developmental mechanisms that canalize or compensate perturbations of organismal development (targeted or compensatory growth) are widely considered a prerequisite of individual health and the evolution of complex life, but little is known about the nature of these mechanisms. It is even unclear i f and how a “target trajectory” of individual development is encoded in the organism’s genetic-developmental system or, instead, emerges as an epiphenomenon. Here we develop a statistical model of developmental canalization based on an extended autoregressive model....
Source: PLoS Computational Biology - February 16, 2021 Category: Biology Authors: Philipp Mitteroecker Source Type: research

Estimating the extrinsic incubation period of malaria using a mechanistic model of sporogony
by Isaac J. Stopard, Thomas S. Churcher, Ben Lambert During sporogony, malaria-causing parasites infect a mosquito, reproduce and migrate to the mosquito salivary glands where they can be transmitted the next time blood feeding occurs. The time required for sporogony, known as the extrinsic incubation period (EIP), is an important determinant of mal aria transmission intensity. The EIP is typically estimated as the time for a given percentile,x, of infected mosquitoes to develop salivary gland sporozoites (the infectious parasite life stage), which is denoted by EIPx. Many mechanisms, however, affect the observed sporozoi...
Source: PLoS Computational Biology - February 16, 2021 Category: Biology Authors: Isaac J. Stopard Source Type: research

Arrhythmogenic effects of ultra-long and bistable cardiac action potentials
by Stewart Heitmann, Anton Shpak, Jamie I. Vandenberg, Adam P. Hill Contemporary accounts of the initiation of cardiac arrhythmias typically rely on after-depolarizations as the trigger for reentrant activity. The after-depolarizations are usually triggered by calcium entry or spontaneous release within the cells of the myocardium or the conduction system. Here we propose an alternative mechanism whereby arrhythmias are triggered autonomously by cardiac cells that fail to repolarize after a normal heartbeat. We investigated the proposal by representing the heart as an excitable medium of FitzHugh-Nagumo cells where a prop...
Source: PLoS Computational Biology - February 16, 2021 Category: Biology Authors: Stewart Heitmann Source Type: research

Spec2Vec: Improved mass spectral similarity scoring through learning of structural relationships
by Florian Huber, Lars Ridder, Stefan Verhoeven, Jurriaan H. Spaaks, Faruk Diblen, Simon Rogers, Justin J. J. van der Hooft Spectral similarity is used as a proxy for structural similarity in many tandem mass spectrometry (MS/MS) based metabolomics analyses such as library matching and molecular networking. Although weaknesses in the relationship between spectral similarity scores and the true structural similarities h ave been described, little development of alternative scores has been undertaken. Here, we introduce Spec2Vec, a novel spectral similarity score inspired by a natural language processing algorithm—Wor...
Source: PLoS Computational Biology - February 16, 2021 Category: Biology Authors: Florian Huber Source Type: research

On the importance of evolving phenotype distributions on evolutionary diversification
by Gil Jorge Barros Henriques, Koichi Ito, Christoph Hauert, Michael Doebeli Evolutionary branching occurs when a population with a unimodal phenotype distribution diversifies into a multimodally distributed population consisting of two or more strains. Branching results from frequency-dependent selection, which is caused by interactions between individuals. For example, a population performing a social task may diversify into a cooperator strain and a defector strain. Branching can also occur in multi-dimensional phenotype spaces, such as when two tasks are performed simultaneously. In such cases, the strains may diverge...
Source: PLoS Computational Biology - February 16, 2021 Category: Biology Authors: Gil Jorge Barros Henriques Source Type: research

Unsupervised manifold learning of collective behavior
by Mathew Titus, George Hagstrom, James R. Watson Collective behavior is an emergent property of numerous complex systems, from financial markets to cancer cells to predator-prey ecological systems. Characterizing modes of collective behavior is often done through human observation, training generative models, or other supervised learning techniq ues. Each of these cases requires knowledge of and a method for characterizing the macro-state(s) of the system. This presents a challenge for studying novel systems where there may be little prior knowledge. Here, we present a new unsupervised method of detecting emergent behavi...
Source: PLoS Computational Biology - February 12, 2021 Category: Biology Authors: Mathew Titus Source Type: research

Investigating the representation of uncertainty in neuronal circuits
by Guillaume P. Dehaene, Ruben Coen-Cagli, Alexandre Pouget Skilled behavior often displays signatures of Bayesian inference. In order for the brain to implement the required computations, neuronal activity must carry accurate information about the uncertainty of sensory inputs. Two major approaches have been proposed to study neuronal representations of u ncertainty. The first one, the Bayesian decoding approach, aims primarily at decoding the posterior probability distribution of the stimulus from population activity using Bayes’ rule, and indirectly yields uncertainty estimates as a by-product. The second one, wh...
Source: PLoS Computational Biology - February 12, 2021 Category: Biology Authors: Guillaume P. Dehaene Source Type: research

OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular simulations
We present OpenAWSEM and Open3SPN2, new cross-compatible implementations of coarse-grained models for protein (AWSEM) and DNA (3SPN2) molecular dynamics simulations within the OpenMM framework. These new implementations retain the chemical accuracy and intrinsic efficiency of the original models w hile adding GPU acceleration and the ease of forcefield modification provided by OpenMM’s Custom Forces software framework. By utilizing GPUs, we achieve around a 30-fold speedup in protein and protein-DNA simulations over the existing LAMMPS-based implementations running on a single CPU core. We showcase the benefits of Op...
Source: PLoS Computational Biology - February 12, 2021 Category: Biology Authors: Wei Lu Source Type: research

Evaluating epidemic forecasts in an interval format
This article provides an overview of how established methods for the evaluation of quantile and interval forecasts can be applied to epidemic forecasts in this format. Specifically, we discuss the computation and interpretation of the weighted interval score, which is a proper score that approximates the continuous ranked probability score. It can be interpreted as a generalization of the absolute error to probabilistic forecasts and allows for a decomposition into a measure of sharpness and penalties for over- and underprediction. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - February 12, 2021 Category: Biology Authors: Johannes Bracher Source Type: research

TranSynergy: Mechanism-driven interpretable deep neural network for the synergistic prediction and pathway deconvolution of drug combinations
by Qiao Liu, Lei Xie Drug combinations have demonstrated great potential in cancer treatments. They alleviate drug resistance and improve therapeutic efficacy. The fast-growing number of anti-cancer drugs has caused the experimental investigation of all drug combinations to become costly and time-consuming. Computatio nal techniques can improve the efficiency of drug combination screening. Despite recent advances in applying machine learning to synergistic drug combination prediction, several challenges remain. First, the performance of existing methods is suboptimal. There is still much space for improvement. Se cond, bi...
Source: PLoS Computational Biology - February 12, 2021 Category: Biology Authors: Qiao Liu Source Type: research

The impact of phenotypic heterogeneity of tumour cells on treatment and relapse dynamics
by Michael Raatz, Saumil Shah, Guranda Chitadze, Monika Br üggemann, Arne Traulsen Intratumour heterogeneity is increasingly recognized as a frequent problem for cancer treatment as it allows for the evolution of resistance against treatment. While cancer genotyping becomes more and more established and allows to determine the genetic heterogeneity, less is known about the pheno typic heterogeneity among cancer cells. We investigate how phenotypic differences can impact the efficiency of therapy options that select on this diversity, compared to therapy options that are independent of the phenotype. We employ the eco...
Source: PLoS Computational Biology - February 12, 2021 Category: Biology Authors: Michael Raatz Source Type: research

From heterogeneous healthcare data to disease-specific biomarker networks: A hierarchical Bayesian network approach
We present an optimization algorithm for the adaptive refinement of such group Bayesian networks to account for a specific target variable, like a disease. T he combination of Bayesian networks, clustering, and refinement yields low-dimensional but disease-specific interaction networks. These networks provide easily interpretable, yet accurate models of biomarker interdependencies. We test our method extensively on simulated data, as well as on data from the Study of Health in Pomerania (SHIP-TREND), and demonstrate its effectiveness using non-alcoholic fatty liver disease and hypertension as examples. We show that the gro...
Source: PLoS Computational Biology - February 12, 2021 Category: Biology Authors: Ann-Kristin Becker Source Type: research

The intrinsically disordered N-terminus of the voltage-dependent anion channel
by Jordane Preto, Isabelle Krimm The voltage-dependent anion channel (VDAC) is a critical β-barrel membrane protein of the mitochondrial outer membrane, which regulates the transport of ions and ATP between mitochondria and the cytoplasm. In addition, VDAC plays a central role in the control of apoptosis and is therefore of grea t interest in both cancer and neurodegenerative diseases. Although not fully understood, it is presumed that the gating mechanism of VDAC is governed by its N-terminal region which, in the open state of the channel, exhibits an α-helical structure positioned midway inside the pore and s...
Source: PLoS Computational Biology - February 12, 2021 Category: Biology Authors: Jordane Preto Source Type: research

State-dependent protein-lipid interactions of a pentameric ligand-gated ion channel in a neuronal membrane
by Marc A. D ämgen, Philip C. Biggin Pentameric ligand-gated ion channels (pLGICs) are receptor proteins that are sensitive to their membrane environment, but the mechanism for how lipids modulate function under physiological conditions in a state dependent manner is not known. The glycine receptor is a pLGIC whose structure has been resolved in different functional states. Using a realistic model of a neuronal membrane coupled with coarse-grained molecular dynamics simulations, we demonstrate that some key lipid-protein interactions are dependent on the receptor state, suggesting that lipids may regulate the recepto...
Source: PLoS Computational Biology - February 11, 2021 Category: Biology Authors: Marc A. D ämgen Source Type: research

Ten simple rules for engaging with artificial intelligence in biomedicine
by Avni Malik, Paranjay Patel, Lubaina Ehsan, Shan Guleria, Thomas Hartka, Sodiq Adewole, Sana Syed (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - February 11, 2021 Category: Biology Authors: Avni Malik Source Type: research

The role of children in the spread of COVID-19: Using household data from Bnei Brak, Israel, to estimate the relative susceptibility and infectivity of children
This study uses data on infections within households in order to estimate the susceptibility and infectivity of children compared to those of adults. The data were collected fro m households in the city of Bnei Brak, Israel, in which all household members were tested for COVID-19 using PCR (637 households, average household size of 5.3). In addition, serological tests were performed on a subset of the individuals in the study. Inspection of the PCR data shows that children are less likely to be tested positive compared to adults (25% of children positive over all households, 44% of adults positive over all households, excl...
Source: PLoS Computational Biology - February 11, 2021 Category: Biology Authors: Itai Dattner Source Type: research

Deriving fine-scale models of human mobility from aggregated origin-destination flow data
by Constanze Ciavarella, Neil M. Ferguson The spatial dynamics of epidemics are fundamentally affected by patterns of human mobility. Mobile phone call detail records (CDRs) are a rich source of mobility data, and allow semi-mechanistic models of movement to be parameterised even for resource poor settings. While the gravity model typical ly reproduces human movement reasonably well at the administrative level spatial scale, past studies suggest that parameter estimates vary with the level of spatial discretisation at which models are fitted. Given that privacy concerns usually preclude public release of very fine-scale m...
Source: PLoS Computational Biology - February 11, 2021 Category: Biology Authors: Constanze Ciavarella Source Type: research

When to wake up? The optimal waking-up strategies for starvation-induced persistence
by Yusuke Himeoka, Namiko Mitarai Prolonged lag time can be induced by starvation contributing to the antibiotic tolerance of bacteria. We analyze the optimal lag time to survive and grow the iterative and stochastic application of antibiotics. A simple model shows that the optimal lag time can exhibit a discontinuous transition w hen the severeness of the antibiotic application, such as the probability to be exposed the antibiotic, the death rate under the exposure, and the duration of the exposure, is increased. This suggests the possibility of reducing tolerant bacteria by controlled usage of antibiotics application. W...
Source: PLoS Computational Biology - February 11, 2021 Category: Biology Authors: Yusuke Himeoka Source Type: research

FastTrack: An open-source software for tracking varying numbers of deformable objects
by Benjamin Gallois, Rapha ël Candelier Analyzing the dynamical properties of mobile objects requires to extract trajectories from recordings, which is often done by tracking movies. We compiled a database of two-dimensional movies for very different biological and physical systems spanning a wide range of length scales and developed a general-purpose, optimized, open-source, cross-platform, easy to install and use, self-updating software called FastTrack. It can handle a changing number of deformable objects in a region of interest, and is particularly suitable for animal and cell tracking in two-dimensions. Further...
Source: PLoS Computational Biology - February 11, 2021 Category: Biology Authors: Benjamin Gallois Source Type: research

Signatures of neutral evolution in exponentially growing tumors: A theoretical perspective
by Hwai-Ray Tung, Rick Durrett Recent work of Sottoriva, Graham, and collaborators have led to the controversial claim that exponentially growing tumors have a site frequency spectrum that follows the 1/f law consistent with neutral evolution. This conclusion has been criticized based on data quality issues, statistical considerations, and simulation results. Here, we use rigorous mathematical arguments to investigate the site frequency spectrum in the two-type model of clonal evolution. If the fitnesses of the two types are λ0 (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - February 11, 2021 Category: Biology Authors: Hwai-Ray Tung Source Type: research

On the open-source landscape of < i > PLOS Computational Biology < /i >
by Mathieu Boudreau, Jean-Baptiste Poline, Pierre Bellec, Nikola Stikov (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - February 11, 2021 Category: Biology Authors: Mathieu Boudreau Source Type: research

DEXOM: Diversity-based enumeration of optimal context-specific metabolic networks
by Pablo Rodr íguez-Mier, Nathalie Poupin, Carlo de Blasio, Laurent Le Cam, Fabien Jourdan The correct identification of metabolic activity in tissues or cells under different conditions can be extremely elusive due to mechanisms such as post-transcriptional modification of enzymes or different rates in protein degradation, making difficult to perform predictions on the basis of gene ex pression alone. Context-specific metabolic network reconstruction can overcome some of these limitations by leveraging the integration of multi-omics data into genome-scale metabolic networks (GSMN). Using the experimental informati...
Source: PLoS Computational Biology - February 11, 2021 Category: Biology Authors: Pablo Rodr íguez-Mier Source Type: research