6,146 results match your criteria PLoS Computational Biology [Journal]


Structure and variability of delay activity in premotor cortex.

PLoS Comput Biol 2019 Feb 22;15(2):e1006808. Epub 2019 Feb 22.

Department of Electrical Engineering, Stanford University, Stanford, CA, United States of America.

Voluntary movements are widely considered to be planned before they are executed. Recent studies have hypothesized that neural activity in motor cortex during preparation acts as an 'initial condition' which seeds the proceeding neural dynamics. Here, we studied these initial conditions in detail by investigating 1) the organization of neural states for different reaches and 2) the variance of these neural states from trial to trial. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006808DOI Listing
February 2019

Integrated structural variation and point mutation signatures in cancer genomes using correlated topic models.

PLoS Comput Biol 2019 Feb 22;15(2):e1006799. Epub 2019 Feb 22.

Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.

Mutation signatures in cancer genomes reflect endogenous and exogenous mutational processes, offering insights into tumour etiology, features for prognostic and biologic stratification and vulnerabilities to be exploited therapeutically. We present a novel machine learning formalism for improved signature inference, based on multi-modal correlated topic models (MMCTM) which can at once infer signatures from both single nucleotide and structural variation counts derived from cancer genome sequencing data. We exemplify the utility of our approach on two hormone driven, DNA repair deficient cancers: breast and ovary (n = 755 samples total). Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006799DOI Listing
February 2019

Independent working memory resources for egocentric and allocentric spatial information.

PLoS Comput Biol 2019 Feb 21;15(2):e1006563. Epub 2019 Feb 21.

Department of Psychology, University of Cambridge, Cambridge, United Kingdom.

Visuospatial working memory enables us to maintain access to visual information for processing even when a stimulus is no longer present, due to occlusion, our own movements, or transience of the stimulus. Here we show that, when localizing remembered stimuli, the precision of spatial recall does not rely solely on memory for individual stimuli, but additionally depends on the relative distances between stimuli and visual landmarks in the surroundings. Across three separate experiments, we consistently observed a spatially selective improvement in the precision of recall for items located near a persistent landmark. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006563DOI Listing
February 2019

Machine learning analysis of gene expression data reveals novel diagnostic and prognostic biomarkers and identifies therapeutic targets for soft tissue sarcomas.

PLoS Comput Biol 2019 Feb 20;15(2):e1006826. Epub 2019 Feb 20.

Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

Based on morphology it is often challenging to distinguish between the many different soft tissue sarcoma subtypes. Moreover, outcome of disease is highly variable even between patients with the same disease. Machine learning on transcriptome sequencing data could be a valuable new tool to understand differences between and within entities. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006826DOI Listing
February 2019

A saturated reaction in repressor synthesis creates a daytime dead zone in circadian clocks.

PLoS Comput Biol 2019 Feb 19;15(2):e1006787. Epub 2019 Feb 19.

Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Japan.

Negative feedback loops (NFLs) for circadian clocks include light-responsive reactions that allow the clocks to shift their phase depending on the timing of light signals. Phase response curves (PRCs) for light signals in various organisms include a time interval called a dead zone where light signals cause no phase shift during daytime. Although the importance of the dead zone for robust light entrainment is known, how the dead zone arises from the biochemical reactions in an NFL underlying circadian gene expression rhythms remains unclear. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006787DOI Listing
February 2019

A component overlapping attribute clustering (COAC) algorithm for single-cell RNA sequencing data analysis and potential pathobiological implications.

PLoS Comput Biol 2019 Feb 19;15(2):e1006772. Epub 2019 Feb 19.

Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America.

Recent advances in next-generation sequencing and computational technologies have enabled routine analysis of large-scale single-cell ribonucleic acid sequencing (scRNA-seq) data. However, scRNA-seq technologies have suffered from several technical challenges, including low mean expression levels in most genes and higher frequencies of missing data than bulk population sequencing technologies. Identifying functional gene sets and their regulatory networks that link specific cell types to human diseases and therapeutics from scRNA-seq profiles are daunting tasks. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006772DOI Listing
February 2019

Graph Peak Caller: Calling ChIP-seq peaks on graph-based reference genomes.

PLoS Comput Biol 2019 Feb 19;15(2):e1006731. Epub 2019 Feb 19.

Department of informatics, University of Oslo, Oslo, Norway.

Graph-based representations are considered to be the future for reference genomes, as they allow integrated representation of the steadily increasing data on individual variation. Currently available tools allow de novo assembly of graph-based reference genomes, alignment of new read sets to the graph representation as well as certain analyses like variant calling and haplotyping. We here present a first method for calling ChIP-Seq peaks on read data aligned to a graph-based reference genome. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006731DOI Listing
February 2019

Allosteric mechanism of the circadian protein Vivid resolved through Markov state model and machine learning analysis.

PLoS Comput Biol 2019 Feb 19;15(2):e1006801. Epub 2019 Feb 19.

Department of Chemistry, Center for Scientific Computation, Center for Drug Discovery, Design, and Delivery (CD4), Southern Methodist University, Dallas, Texas, United States of America.

The fungal circadian clock photoreceptor Vivid (VVD) contains a photosensitive allosteric light, oxygen, voltage (LOV) domain that undergoes a large N-terminal conformational change. The mechanism by which a blue-light driven covalent bond formation leads to a global conformational change remains unclear, which hinders the further development of VVD as an optogenetic tool. We answered this question through a novel computational platform integrating Markov state models, machine learning methods, and newly developed community analysis algorithms. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006801DOI Listing
February 2019

Multi-modality in gene regulatory networks with slow promoter kinetics.

PLoS Comput Biol 2019 Feb 19;15(2):e1006784. Epub 2019 Feb 19.

Departments of Electrical and Computer Engineering and of Bioengineering, Northeastern University, Boston, Massachusetts, United States of America.

Phenotypical variability in the absence of genetic variation often reflects complex energetic landscapes associated with underlying gene regulatory networks (GRNs). In this view, different phenotypes are associated with alternative states of complex nonlinear systems: stable attractors in deterministic models or modes of stationary distributions in stochastic descriptions. We provide theoretical and practical characterizations of these landscapes, specifically focusing on stochastic Slow Promoter Kinetics (SPK), a time scale relevant when transcription factor binding and unbinding are affected by epigenetic processes like DNA methylation and chromatin remodeling. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006784DOI Listing
February 2019

Multiscale modeling of influenza A virus replication in cell cultures predicts infection dynamics for highly different infection conditions.

PLoS Comput Biol 2019 Feb 19;15(2):e1006819. Epub 2019 Feb 19.

Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.

Influenza A viruses (IAV) are commonly used to infect animal cell cultures for research purposes and vaccine production. Their replication is influenced strongly by the multiplicity of infection (MOI), which ranges over several orders of magnitude depending on the respective application. So far, mathematical models of IAV replication have paid little attention to the impact of the MOI on infection dynamics and virus yields. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006819DOI Listing
February 2019

A numerical approach for a discrete Markov model for progressing drug resistance of cancer.

PLoS Comput Biol 2019 Feb 19;15(2):e1006770. Epub 2019 Feb 19.

Graduate School of Social Sciences, Tokyo Metropolitan University, Tokyo, Japan.

The presence of treatment-resistant cells is an important factor that limits the efficacy of cancer therapy, and the prospect of resistance is considered the major cause of the treatment strategy. Several recent studies have employed mathematical models to elucidate the dynamics of generating resistant cancer cells and attempted to predict the probability of emerging resistant cells. The purpose of this paper is to present numerical approach to compute the number of resistant cells and the emerging probability of resistance. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006770DOI Listing
February 2019

Identifying individual risk rare variants using protein structure guided local tests (POINT).

PLoS Comput Biol 2019 Feb 19;15(2):e1006722. Epub 2019 Feb 19.

Department of Statistics, North Carolina State University, Raleigh, North Carolina, United States of America.

Rare variants are of increasing interest to genetic association studies because of their etiological contributions to human complex diseases. Due to the rarity of the mutant events, rare variants are routinely analyzed on an aggregate level. While aggregation analyses improve the detection of global-level signal, they are not able to pinpoint causal variants within a variant set. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006722DOI Listing
February 2019

Verbalizing phylogenomic conflict: Representation of node congruence across competing reconstructions of the neoavian explosion.

PLoS Comput Biol 2019 Feb 15;15(2):e1006493. Epub 2019 Feb 15.

School of Information Sciences, University of Illinois at Urbana-Champaign, Champaign, Illinois, United States of America.

Phylogenomic research is accelerating the publication of landmark studies that aim to resolve deep divergences of major organismal groups. Meanwhile, systems for identifying and integrating the products of phylogenomic inference-such as newly supported clade concepts-have not kept pace. However, the ability to verbalize node concept congruence and conflict across multiple, in effect simultaneously endorsed phylogenomic hypotheses, is a prerequisite for building synthetic data environments for biological systematics and other domains impacted by these conflicting inferences. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006493DOI Listing
February 2019

Efficient neural decoding of self-location with a deep recurrent network.

PLoS Comput Biol 2019 Feb 15;15(2):e1006822. Epub 2019 Feb 15.

Computational Neuroscience Lab, Institute of Computer Science, University of Tartu, Tartu, Estonia.

Place cells in the mammalian hippocampus signal self-location with sparse spatially stable firing fields. Based on observation of place cell activity it is possible to accurately decode an animal's location. The precision of this decoding sets a lower bound for the amount of information that the hippocampal population conveys about the location of the animal. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006822DOI Listing
February 2019

Bioinformatics calls the school: Use of smartphones to introduce Python for bioinformatics in high schools.

PLoS Comput Biol 2019 Feb 14;15(2):e1006473. Epub 2019 Feb 14.

Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes - CONICET, Bernal, Buenos Aires, Argentina.

The dynamic nature of technological developments invites us to rethink the learning spaces. In this context, science education can be enriched by the contribution of new computational resources, making the educational process more up-to-date, challenging, and attractive. Bioinformatics is a key interdisciplinary field, contributing to the understanding of biological processes that is often underrated in secondary schools. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006473DOI Listing
February 2019

IRIS-EDA: An integrated RNA-Seq interpretation system for gene expression data analysis.

PLoS Comput Biol 2019 Feb 14;15(2):e1006792. Epub 2019 Feb 14.

Department of Agronomy, Horticulture, and Plant Science, BioSNTR, South Dakota State University, Brookings, SD, United States of America.

Next-Generation Sequencing has made available substantial amounts of large-scale Omics data, providing unprecedented opportunities to understand complex biological systems. Specifically, the value of RNA-Sequencing (RNA-Seq) data has been confirmed in inferring how gene regulatory systems will respond under various conditions (bulk data) or cell types (single-cell data). RNA-Seq can generate genome-scale gene expression profiles that can be further analyzed using correlation analysis, co-expression analysis, clustering, differential gene expression (DGE), among many other studies. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006792DOI Listing
February 2019

Identifying the mechanism for superdiffusivity in mouse fibroblast motility.

PLoS Comput Biol 2019 Feb 14;15(2):e1006732. Epub 2019 Feb 14.

Physics Department, Syracuse University, Syracuse, New York, United States of America.

We seek to characterize the motility of mouse fibroblasts on 2D substrates. Utilizing automated tracking techniques, we find that cell trajectories are super-diffusive, where displacements scale faster than t1/2 in all directions. Two mechanisms have been proposed to explain such statistics in other cell types: run and tumble behavior with Lévy-distributed run times, and ensembles of cells with heterogeneous speed and rotational noise. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006732DOI Listing
February 2019

Improving the reliability of model-based decision-making estimates in the two-stage decision task with reaction-times and drift-diffusion modeling.

PLoS Comput Biol 2019 Feb 13;15(2):e1006803. Epub 2019 Feb 13.

Wellcome Centre for Human Neuroimaging, University College London, London, United Kingdom.

A well-established notion in cognitive neuroscience proposes that multiple brain systems contribute to choice behaviour. These include: (1) a model-free system that uses values cached from the outcome history of alternative actions, and (2) a model-based system that considers action outcomes and the transition structure of the environment. The widespread use of this distinction, across a range of applications, renders it important to index their distinct influences with high reliability. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006803DOI Listing
February 2019

Convergent perturbation of the human domain-resolved interactome by viruses and mutations inducing similar disease phenotypes.

PLoS Comput Biol 2019 Feb 13;15(2):e1006762. Epub 2019 Feb 13.

Department of Bioengineering, McGill University, Montreal, Quebec, Canada.

An important goal of systems medicine is to study disease in the context of genetic and environmental perturbations to the human interactome network. For diseases with both genetic and infectious contributors, a key postulate is that similar perturbations of the human interactome by either disease mutations or pathogens can have similar disease consequences. This postulate has so far only been tested for a few viral species at the level of whole proteins. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006762DOI Listing
February 2019

Maps of variability in cell lineage trees.

PLoS Comput Biol 2019 Feb 12;15(2):e1006745. Epub 2019 Feb 12.

Centre for Micro-Photonics, Department of Physics and Astronomy, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia.

New approaches to lineage tracking have allowed the study of differentiation in multicellular organisms over many generations of cells. Understanding the phenotypic variability observed in these lineage trees requires new statistical methods. Whereas an invariant cell lineage, such as that for the nematode Caenorhabditis elegans, can be described by a lineage map, defined as the pattern of phenotypes overlaid onto the binary tree, a traditional lineage map is static and does not describe the variability inherent in the cell lineages of higher organisms. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006745DOI Listing
February 2019

Cell geometry determines symmetric and asymmetric division plane selection in Arabidopsis early embryos.

PLoS Comput Biol 2019 Feb 11;15(2):e1006771. Epub 2019 Feb 11.

Institut Jean-Pierre Bourgin, INRA, AgroParisTech, CNRS, Université Paris-Saclay, 78000 Versailles, France.

Plant tissue architecture and organ morphogenesis rely on the proper orientation of cell divisions. Previous attempts to predict division planes from cell geometry in plants mostly focused on 2D symmetric divisions. Using the stereotyped division patterns of Arabidopsis thaliana early embryogenesis, we investigated geometrical principles underlying plane selection in symmetric and in asymmetric divisions within complex 3D cell shapes. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006771DOI Listing
February 2019

How good are pathogenicity predictors in detecting benign variants?

PLoS Comput Biol 2019 Feb 11;15(2):e1006481. Epub 2019 Feb 11.

Protein Structure and Bioinformatics, Department of Experimental Medical Science, Lund University, Lund, Sweden.

Computational tools are widely used for interpreting variants detected in sequencing projects. The choice of these tools is critical for reliable variant impact interpretation for precision medicine and should be based on systematic performance assessment. The performance of the methods varies widely in different performance assessments, for example due to the contents and sizes of test datasets. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006481DOI Listing
February 2019

A hierarchical sparse coding model predicts acoustic feature encoding in both auditory midbrain and cortex.

PLoS Comput Biol 2019 Feb 11;15(2):e1006766. Epub 2019 Feb 11.

Department of Computer Science and Technology, Tsinghua University, Beijing, China.

The auditory pathway consists of multiple stages, from the cochlear nucleus to the auditory cortex. Neurons acting at different stages have different functions and exhibit different response properties. It is unclear whether these stages share a common encoding mechanism. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006766DOI Listing
February 2019

Assessing the performance of real-time epidemic forecasts: A case study of Ebola in the Western Area region of Sierra Leone, 2014-15.

PLoS Comput Biol 2019 Feb 11;15(2):e1006785. Epub 2019 Feb 11.

Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Real-time forecasts based on mathematical models can inform critical decision-making during infectious disease outbreaks. Yet, epidemic forecasts are rarely evaluated during or after the event, and there is little guidance on the best metrics for assessment. Here, we propose an evaluation approach that disentangles different components of forecasting ability using metrics that separately assess the calibration, sharpness and bias of forecasts. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006785DOI Listing
February 2019

Network-guided prediction of aromatase inhibitor response in breast cancer.

PLoS Comput Biol 2019 Feb 11;15(2):e1006730. Epub 2019 Feb 11.

Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.

Prediction of response to specific cancer treatments is complicated by significant heterogeneity between tumors in terms of mutational profiles, gene expression, and clinical measures. Here we focus on the response of Estrogen Receptor (ER)+ post-menopausal breast cancer tumors to aromatase inhibitors (AI). We use a network smoothing algorithm to learn novel features that integrate several types of high throughput data and new cell line experiments. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006730DOI Listing
February 2019

Correlation Structure in Micro-ECoG Recordings is Described by Spatially Coherent Components.

PLoS Comput Biol 2019 Feb 11;15(2):e1006769. Epub 2019 Feb 11.

Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, United States of America.

Electrocorticography (ECoG) is becoming more prevalent due to improvements in fabrication and recording technology as well as its ease of implantation compared to intracortical electrophysiology, larger cortical coverage, and potential advantages for use in long term chronic implantation. Given the flexibility in the design of ECoG grids, which is only increasing, it remains an open question what geometry of the electrodes is optimal for an application. Conductive polymer, PEDOT:PSS, coated microelectrodes have an advantage that they can be made very small without losing low impedance. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006769DOI Listing
February 2019

BioJava 5: A community driven open-source bioinformatics library.

PLoS Comput Biol 2019 Feb 8;15(2):e1006791. Epub 2019 Feb 8.

Research Collaboratory for Structural Bioinformatics Protein Data Bank, San Diego Supercomputer Center, University of California, San Diego, La Jolla, CA 92093, USA.

BioJava is an open-source project that provides a Java library for processing biological data. The project aims to simplify bioinformatic analyses by implementing parsers, data structures, and algorithms for common tasks in genomics, structural biology, ontologies, phylogenetics, and more. Since 2012, we have released two major versions of the library (4 and 5) that include many new features to tackle challenges with increasingly complex macromolecular structure data. Read More

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http://dx.plos.org/10.1371/journal.pcbi.1006791
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http://dx.doi.org/10.1371/journal.pcbi.1006791DOI Listing
February 2019
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Information integration in large brain networks.

PLoS Comput Biol 2019 Feb 7;15(2):e1006807. Epub 2019 Feb 7.

Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, United States of America.

An outstanding problem in neuroscience is to understand how information is integrated across the many modules of the brain. While classic information-theoretic measures have transformed our understanding of feedforward information processing in the brain's sensory periphery, comparable measures for information flow in the massively recurrent networks of the rest of the brain have been lacking. To address this, recent work in information theory has produced a sound measure of network-wide "integrated information", which can be estimated from time-series data. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006807DOI Listing
February 2019

A local measure of symmetry and orientation for individual spikes of grid cells.

PLoS Comput Biol 2019 Feb 7;15(2):e1006804. Epub 2019 Feb 7.

Modelling of Cognitive Processes, Institute of Software Engineering and Theoretical Computer Science, Technische Universität Berlin, Germany.

Grid cells have attracted broad attention because of their highly symmetric hexagonal firing patterns. Recently, research has shifted its focus from the global symmetry of grid cell activity to local distortions both in space and time, such as drifts in orientation, local defects of the hexagonal symmetry, and the decay and reappearance of grid patterns after changes in lighting condition. Here, we introduce a method that allows to visualize and quantify such local distortions, by assigning both a local grid score and a local orientation to each individual spike of a neuronal recording. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006804DOI Listing
February 2019

Population dynamics and entrainment of basal ganglia pacemakers are shaped by their dendritic arbors.

PLoS Comput Biol 2019 Feb 7;15(2):e1006782. Epub 2019 Feb 7.

Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, The Faculty of Medicine, Jerusalem, Israel.

The theory of phase oscillators is an essential tool for understanding population dynamics of pacemaking neurons. GABAergic pacemakers in the substantia nigra pars reticulata (SNr), a main basal ganglia (BG) output nucleus, receive inputs from the direct and indirect pathways at distal and proximal regions of their dendritic arbors, respectively. We combine theory, optogenetic stimulation and electrophysiological experiments in acute brain slices to ask how dendritic properties impact the propensity of the various inputs, arriving at different locations along the dendrite, to recruit or entrain SNr pacemakers. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006782DOI Listing
February 2019

A data-driven interactome of synergistic genes improves network-based cancer outcome prediction.

PLoS Comput Biol 2019 Feb 6;15(2):e1006657. Epub 2019 Feb 6.

Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Robustly predicting outcome for cancer patients from gene expression is an important challenge on the road to better personalized treatment. Network-based outcome predictors (NOPs), which considers the cellular wiring diagram in the classification, hold much promise to improve performance, stability and interpretability of identified marker genes. Problematically, reports on the efficacy of NOPs are conflicting and for instance suggest that utilizing random networks performs on par to networks that describe biologically relevant interactions. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006657DOI Listing
February 2019
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Apollo: Democratizing genome annotation.

PLoS Comput Biol 2019 Feb 6;15(2):e1006790. Epub 2019 Feb 6.

Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.

Genome annotation is the process of identifying the location and function of a genome's encoded features. Improving the biological accuracy of annotation is a complex and iterative process requiring researchers to review and incorporate multiple sources of information such as transcriptome alignments, predictive models based on sequence profiles, and comparisons to features found in related organisms. Because rapidly decreasing costs are enabling an ever-growing number of scientists to incorporate sequencing as a routine laboratory technique, there is widespread demand for tools that can assist in the deliberative analytical review of genomic information. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006790DOI Listing
February 2019

Available energy fluxes drive a transition in the diversity, stability, and functional structure of microbial communities.

PLoS Comput Biol 2019 Feb 5;15(2):e1006793. Epub 2019 Feb 5.

Department of Physics, Boston University, Boston, MA, USA.

A fundamental goal of microbial ecology is to understand what determines the diversity, stability, and structure of microbial ecosystems. The microbial context poses special conceptual challenges because of the strong mutual influences between the microbes and their chemical environment through the consumption and production of metabolites. By analyzing a generalized consumer resource model that explicitly includes cross-feeding, stochastic colonization, and thermodynamics, we show that complex microbial communities generically exhibit a transition as a function of available energy fluxes from a "resource-limited" regime where community structure and stability is shaped by energetic and metabolic considerations to a diverse regime where the dominant force shaping microbial communities is the overlap between species' consumption preferences. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006793DOI Listing
February 2019

Noise-resistant developmental reproducibility in vertebrate somite formation.

PLoS Comput Biol 2019 Feb 4;15(2):e1006579. Epub 2019 Feb 4.

Gene Regulation Research, Division of Biological Science, Nara Institute of Science and Technology, Takayama, Nara, Japan.

The reproducibility of embryonic development is remarkable, although molecular processes are intrinsically stochastic at the single-cell level. How the multicellular system resists the inevitable noise to acquire developmental reproducibility constitutes a fundamental question in developmental biology. Toward this end, we focused on vertebrate somitogenesis as a representative system, because somites are repeatedly reproduced within a single embryo whereas such reproducibility is lost in segmentation clock gene-deficient embryos. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361423PMC
February 2019
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Utilizing longitudinal microbiome taxonomic profiles to predict food allergy via Long Short-Term Memory networks.

PLoS Comput Biol 2019 Feb 4;15(2):e1006693. Epub 2019 Feb 4.

Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, United States of America.

Food allergy is usually difficult to diagnose in early life, and the inability to diagnose patients with atopic diseases at an early age may lead to severe complications. Numerous studies have suggested an association between the infant gut microbiome and development of allergy. In this work, we investigated the capacity of Long Short-Term Memory (LSTM) networks to predict food allergies in early life (0-3 years) from subjects' longitudinal gut microbiome profiles. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361419PMC
February 2019
1 Read

DeepDrug3D: Classification of ligand-binding pockets in proteins with a convolutional neural network.

PLoS Comput Biol 2019 Feb 4;15(2):e1006718. Epub 2019 Feb 4.

Department of Biological Sciences, Louisiana State University, Baton Rouge, LA, United States of America.

Comprehensive characterization of ligand-binding sites is invaluable to infer molecular functions of hypothetical proteins, trace evolutionary relationships between proteins, engineer enzymes to achieve a desired substrate specificity, and develop drugs with improved selectivity profiles. These research efforts pose significant challenges owing to the fact that similar pockets are commonly observed across different folds, leading to the high degree of promiscuity of ligand-protein interactions at the system-level. On that account, novel algorithms to accurately classify binding sites are needed. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006718DOI Listing
February 2019
2 Reads

Characteristics of measles epidemics in China (1951-2004) and implications for elimination: A case study of three key locations.

PLoS Comput Biol 2019 Feb 4;15(2):e1006806. Epub 2019 Feb 4.

Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States.

Measles is a highly infectious, severe viral disease. The disease is targeted for global eradication; however, this result has proven challenging. In China, where countrywide vaccination coverage for the last decade has been above 95% (the threshold for measles elimination), measles continues to cause large epidemics. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006806DOI Listing
February 2019
1 Read

Mapping DNA sequence to transcription factor binding energy in vivo.

PLoS Comput Biol 2019 Feb 4;15(2):e1006226. Epub 2019 Feb 4.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America.

Despite the central importance of transcriptional regulation in biology, it has proven difficult to determine the regulatory mechanisms of individual genes, let alone entire gene networks. It is particularly difficult to decipher the biophysical mechanisms of transcriptional regulation in living cells and determine the energetic properties of binding sites for transcription factors and RNA polymerase. In this work, we present a strategy for dissecting transcriptional regulatory sequences using in vivo methods (massively parallel reporter assays) to formulate quantitative models that map a transcription factor binding site's DNA sequence to transcription factor-DNA binding energy. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006226DOI Listing
February 2019

Social evolution under demographic stochasticity.

PLoS Comput Biol 2019 Feb 4;15(2):e1006739. Epub 2019 Feb 4.

Department of Mathematics and Statistics, Department of Biology Queen's University, Kingston, ON, Canada.

How social traits such as altruism and spite evolve remains an open question in evolutionary biology. One factor thought to be potentially important is demographic stochasticity. Here we provide a general theoretical analysis of the role of demographic stochasticity in social evolution. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006739DOI Listing
February 2019

Even a good influenza forecasting model can benefit from internet-based nowcasts, but those benefits are limited.

PLoS Comput Biol 2019 Feb 1;15(2):e1006599. Epub 2019 Feb 1.

Los Alamos National Laboratory, Los Alamos, New Mexico, USA.

The ability to produce timely and accurate flu forecasts in the United States can significantly impact public health. Augmenting forecasts with internet data has shown promise for improving forecast accuracy and timeliness in controlled settings, but results in practice are less convincing, as models augmented with internet data have not consistently outperformed models without internet data. In this paper, we perform a controlled experiment, taking into account data backfill, to improve clarity on the benefits and limitations of augmenting an already good flu forecasting model with internet-based nowcasts. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006599DOI Listing
February 2019

RedCom: A strategy for reduced metabolic modeling of complex microbial communities and its application for analyzing experimental datasets from anaerobic digestion.

PLoS Comput Biol 2019 Feb 1;15(2):e1006759. Epub 2019 Feb 1.

Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.

Constraint-based modeling (CBM) is increasingly used to analyze the metabolism of complex microbial communities involved in ecology, biomedicine, and various biotechnological processes. While CBM is an established framework for studying the metabolism of single species with linear stoichiometric models, CBM of communities with balanced growth is more complicated, not only due to the larger size of the multi-species metabolic network but also because of the bilinear nature of the resulting community models. Moreover, the solution space of these community models often contains biologically unrealistic solutions, which, even with model linearization and under application of certain objective functions, cannot easily be excluded. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006759DOI Listing
February 2019

Predicting change: Approximate inference under explicit representation of temporal structure in changing environments.

PLoS Comput Biol 2019 01 31;15(1):e1006707. Epub 2019 Jan 31.

Department of Psychology, Technische Universität Dresden, Dresden, Germany.

In our daily lives timing of our actions plays an essential role when we navigate the complex everyday environment. It is an open question though how the representations of the temporal structure of the world influence our behavior. Here we propose a probabilistic model with an explicit representation of state durations which may provide novel insights in how the brain predicts upcoming changes. Read More

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http://dx.plos.org/10.1371/journal.pcbi.1006707
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January 2019
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Dynamical differential expression (DyDE) reveals the period control mechanisms of the Arabidopsis circadian oscillator.

PLoS Comput Biol 2019 01 31;15(1):e1006674. Epub 2019 Jan 31.

Department of Plant Sciences, University of Cambridge, Cambridge, United Kingdom.

The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The mechanistic basis underlying the adjustment of circadian rhythms to changing external conditions, however, has yet to be clearly elucidated. We explored the mechanism of action of nicotinamide in Arabidopsis thaliana, a metabolite that lengthens the period of circadian rhythms, to understand the regulation of circadian period. Read More

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January 2019

Social dynamics modeling of chrono-nutrition.

PLoS Comput Biol 2019 01 30;15(1):e1006714. Epub 2019 Jan 30.

Computer Laboratory, University of Cambridge, Cambridge, United Kingdom.

Gut microbiota and human relationships are strictly connected to each other. What we eat reflects our body-mind connection and synchronizes with people around us. However, how this impacts on gut microbiota and, conversely, how gut bacteria influence our dietary behaviors has not been explored yet. Read More

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http://dx.plos.org/10.1371/journal.pcbi.1006714
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January 2019
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Inherent versus induced protein flexibility: Comparisons within and between apo and holo structures.

PLoS Comput Biol 2019 01 30;15(1):e1006705. Epub 2019 Jan 30.

Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, United States of America.

Understanding how ligand binding influences protein flexibility is important, especially in rational drug design. Protein flexibility upon ligand binding is analyzed herein using 305 proteins with 2369 crystal structures with ligands (holo) and 1679 without (apo). Each protein has at least two apo and two holo structures for analysis. Read More

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January 2019
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Prediction of ultra-high-order antibiotic combinations based on pairwise interactions.

PLoS Comput Biol 2019 01 30;15(1):e1006774. Epub 2019 Jan 30.

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Drug combinations are a promising approach to achieve high efficacy at low doses and to overcome resistance. Drug combinations are especially useful when drugs cannot achieve effectiveness at tolerable doses, as occurs in cancer and tuberculosis (TB). However, discovery of effective drug combinations faces the challenge of combinatorial explosion, in which the number of possible combinations increases exponentially with the number of drugs and doses. Read More

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http://dx.plos.org/10.1371/journal.pcbi.1006774
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January 2019
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Mechanistic framework predicts drug-class specific utility of antiretrovirals for HIV prophylaxis.

PLoS Comput Biol 2019 01 30;15(1):e1006740. Epub 2019 Jan 30.

Department of Mathematics & Computer Science, Freie Universität Berlin, Germany.

Currently, there is no effective vaccine to halt HIV transmission. However, pre-exposure prophylaxis (PrEP) with the drug combination Truvada can substantially decrease HIV transmission in individuals at risk. Despite its benefits, Truvada-based PrEP is expensive and needs to be taken once-daily, which often leads to inadequate adherence and incomplete protection. Read More

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January 2019

Learning the sequence of influenza A genome assembly during viral replication using point process models and fluorescence in situ hybridization.

PLoS Comput Biol 2019 01 28;15(1):e1006199. Epub 2019 Jan 28.

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

Within influenza virus infected cells, viral genomic RNA are selectively packed into progeny virions, which predominantly contain a single copy of 8 viral RNA segments. Intersegmental RNA-RNA interactions are thought to mediate selective packaging of each viral ribonucleoprotein complex (vRNP). Clear evidence of a specific interaction network culminating in the full genomic set has yet to be identified. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006199DOI Listing
January 2019

A low-threshold potassium current enhances sparseness and reliability in a model of avian auditory cortex.

PLoS Comput Biol 2019 01 28;15(1):e1006723. Epub 2019 Jan 28.

Department of Psychology, University of Virginia, Charlottesville, VA, USA.

Birdsong is a complex vocal communication signal, and like humans, birds need to discriminate between similar sequences of sound with different meanings. The caudal mesopallium (CM) is a cortical-level auditory area implicated in song discrimination. CM neurons respond sparsely to conspecific song and are tolerant of production variability. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006723DOI Listing
January 2019

Designing and running an advanced Bioinformatics and genome analyses course in Tunisia.

PLoS Comput Biol 2019 01 28;15(1):e1006373. Epub 2019 Jan 28.

Institut Pasteur Paris, 28 rue du Dr Roux, 75724 Paris cedex 15, France.

Genome data, with underlying new knowledge, are accumulating at exponential rate thanks to ever-improving sequencing technologies and the parallel development of dedicated efficient Bioinformatics methods and tools. Advanced Education in Bioinformatics and Genome Analyses is to a large extent not accessible to students in developing countries where endeavors to set up Bioinformatics courses concern most often only basic levels. Here, we report a pioneering pilot experience concerning the design and implementation, from scratch, of a three-months advanced and extensive course in Bioinformatics and Genome Analyses in the Institut Pasteur de Tunis. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349305PMC
January 2019