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Divergent genome evolution caused by regional variation in DNA gain and loss between human and mouse
by Reuben M. Buckley, R. Daniel Kortschak, David L. Adelson The forces driving the accumulation and removal of non-coding DNA and ultimately the evolution of genome size in complex organisms are intimately linked to genome structure and organisation. Our analysis provides a novel method for capturing the regional variation of lineage-specific DNA gain and loss events in their respective genomic contexts. To further understand this connection we used comparative genomics to identify genome-wide individual DNA gain and loss events in the human and mouse genomes. Focusing on the distribution of DNA gains and losses, relation...
Source: PLoS Computational Biology - April 20, 2018 Category: Biology Authors: Reuben M. Buckley Source Type: research

Exploiting glycan topography for computational design of Env glycoprotein antigenicity
by Wen-Han Yu, Peng Zhao, Monia Draghi, Claudia Arevalo, Christina B. Karsten, Todd J. Suscovich, Bronwyn Gunn, Hendrik Streeck, Abraham L. Brass, Michael Tiemeyer, Michael Seaman, John R. Mascola, Lance Wells, Douglas A. Lauffenburger, Galit Alter Mounting evidence suggests that glycans, rather than merely serving as a “shield”, contribute critically to antigenicity of the HIV envelope (Env) glycoprotein, representing critical antigenic determinants for many broadly neutralizing antibodies (bNAbs). While many studies have focused on def ining the role of individual glycans or groups of proximal glycans in bNA...
Source: PLoS Computational Biology - April 20, 2018 Category: Biology Authors: Wen-Han Yu Source Type: research

Optimal dynamic control approach in a multi-objective therapeutic scenario: Application to drug delivery in the treatment of prostate cancer
by Itziar Irurzun-Arana, Alvaro Janda, Sergio Ardanza-Trevijano, I ñaki F. Trocóniz Numerous problems encountered in computational biology can be formulated as optimization problems. In this context, optimization of drug release characteristics or dosing schedules for anticancer agents has become a prominent area not only for the development of new drugs, but also for established drugs. However, in complex systems, optimization of drug exposure is not a trivial task and cannot be efficiently addressed through trial-error simulation exercises. Finding a solution to those problems is a challenging task which r...
Source: PLoS Computational Biology - April 19, 2018 Category: Biology Authors: Itziar Irurzun-Arana Source Type: research

Decision making improves sperm chemotaxis in the presence of noise
by Justus A. Kromer, Steffen M ärcker, Steffen Lange, Christel Baier, Benjamin M. Friedrich To navigate their surroundings, cells rely on sensory input that is corrupted by noise. In cells performing chemotaxis, such noise arises from the stochastic binding of signalling molecules at low chemoattractant concentrations. We reveal a fundamental relationship between the speed of chemotactic steering and the strength of directional fluctuations that result from the amplification of noise in a chemical input signal. This relation implies a trade-off between steering that is slow and reliable, and steering that is fast but...
Source: PLoS Computational Biology - April 19, 2018 Category: Biology Authors: Justus A. Kromer Source Type: research

Compositional clustering in task structure learning
by Nicholas T. Franklin, Michael J. Frank Humans are remarkably adept at generalizing knowledge between experiences in a way that can be difficult for computers. Often, this entails generalizing constituent pieces of experiences that do not fully overlap, but nonetheless share useful similarities with, previously acquired knowledge. Howev er, it is often unclear how knowledge gained in one context should generalize to another. Previous computational models and data suggest that rather than learning about each individual context, humans build latent abstract structures and learn to link these structures to arbitrary contex...
Source: PLoS Computational Biology - April 19, 2018 Category: Biology Authors: Nicholas T. Franklin Source Type: research

EmbryoMiner: A new framework for interactive knowledge discovery in large-scale cell tracking data of developing embryos
by Benjamin Schott, Manuel Traub, Cornelia Schlagenhauf, Masanari Takamiya, Thomas Antritter, Andreas Bartschat, Katharina L öffler, Denis Blessing, Jens C. Otte, Andrei Y. Kobitski, G. Ulrich Nienhaus, Uwe Strähle, Ralf Mikut, Johannes Stegmaier State-of-the-art light-sheet and confocal microscopes allow recording of entire embryos in 3D and over time (3D+t) for many hours. Fluorescently labeled structures can be segmented and tracked automatically in these terabyte-scale 3D+t images, resulting in thousands of cell migration trajectories that provide detailed insights to large-scale tissue reorganization at the...
Source: PLoS Computational Biology - April 19, 2018 Category: Biology Authors: Benjamin Schott Source Type: research

Propagating annotations of molecular networks using < i > in silico < /i > fragmentation
by Ricardo R. da Silva, Mingxun Wang, Louis-F élix Nothias, Justin J. J. van der Hooft, Andrés Mauricio Caraballo-Rodríguez, Evan Fox, Marcy J. Balunas, Jonathan L. Klassen, Norberto Peporine Lopes, Pieter C. Dorrestein The annotation of small molecules is one of the most challenging and important steps in untargeted mass spectrometry analysis, as most of our biological interpretations rely on structural annotations. Molecular networking has emerged as a structured way to organize and mine data from untargeted ta ndem mass spectrometry (MS/MS) experiments and has been widely applied to propagate annot...
Source: PLoS Computational Biology - April 18, 2018 Category: Biology Authors: Ricardo R. da Silva Source Type: research

Biogeography and environmental conditions shape bacteriophage-bacteria networks across the human microbiome
This study quantified and contrasted the diversity of virome-microbiome networks across the human body and illustrated how environment al factors may influence phage-bacteria interactive dynamics. This work provides a baseline for future studies to better understand system perturbations, such as disease states, through ecological networks. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - April 18, 2018 Category: Biology Authors: Geoffrey D. Hannigan Source Type: research

Bayesian reconstruction of transmission within outbreaks using genomic variants
by Nicola De Maio, Colin J. Worby, Daniel J. Wilson, Nicole Stoesser Pathogen genome sequencing can reveal details of transmission histories and is a powerful tool in the fight against infectious disease. In particular, within-host pathogen genomic variants identified through heterozygous nucleotide base calls are a potential source of information to identify linke d cases and infer direction and time of transmission. However, using such data effectively to model disease transmission presents a number of challenges, including differentiating genuine variants from those observed due to sequencing error, as well as the spec...
Source: PLoS Computational Biology - April 18, 2018 Category: Biology Authors: Nicola De Maio Source Type: research

On the role of extrinsic noise in microRNA-mediated bimodal gene expression
by Marco Del Giudice, Stefano Bo, Silvia Grigolon, Carla Bosia Several studies highlighted the relevance of extrinsic noise in shaping cell decision making and differentiation in molecular networks. Bimodal distributions of gene expression levels provide experimental evidence of phenotypic differentiation, where the modes of the distribution often correspond to different physiological states of the system. We theoretically address the presence of bimodal phenotypes in the context of microRNA (miRNA)-mediated regulation. MiRNAs are small noncoding RNA molecules that downregulate the expression of their target mRNAs. The na...
Source: PLoS Computational Biology - April 17, 2018 Category: Biology Authors: Marco Del Giudice Source Type: research

A computational model of shared fine-scale structure in the human connectome
by J. Swaroop Guntupalli, Ma Feilong, James V. Haxby Variation in cortical connectivity profiles is typically modeled as having a coarse spatial scale parcellated into interconnected brain areas. We created a high-dimensional common model of the human connectome to search for fine-scale structure that is shared across brains. Projecting individual c onnectivity data into this new common model connectome accounts for substantially more variance in the human connectome than do previous models. This newly discovered shared structure is closely related to fine-scale distinctions in representations of information. These result...
Source: PLoS Computational Biology - April 17, 2018 Category: Biology Authors: J. Swaroop Guntupalli Source Type: research

Origins of scale invariance in vocalization sequences and speech
by Fatemeh Khatami, Markus W öhr, Heather L. Read, Monty A. Escabí To communicate effectively animals need to detect temporal vocalization cues that vary over several orders of magnitude in their amplitude and frequency content. This large range of temporal cues is evident in the power-law scale-invariant relationship between the power of temporal fluctuations in sounds and the sound modulation frequency (f). Though various forms of scale invariance have been described for natural sounds, the origins and implications of scale invariant phenomenon remain unknown. Using animal vocalization sequences, including c...
Source: PLoS Computational Biology - April 16, 2018 Category: Biology Authors: Fatemeh Khatami Source Type: research

A computational study of astrocytic glutamate influence on post-synaptic neuronal excitability
by Bronac Flanagan, Liam McDaid, John Wade, KongFatt Wong-Lin, Jim Harkin The ability of astrocytes to rapidly clear synaptic glutamate and purposefully release the excitatory transmitter is critical in the functioning of synapses and neuronal circuits. Dysfunctions of these homeostatic functions have been implicated in the pathology of brain disorders such as mesial te mporal lobe epilepsy. However, the reasons for these dysfunctions are not clear from experimental data and computational models have been developed to provide further understanding of the implications of glutamate clearance from the extracellular space, as...
Source: PLoS Computational Biology - April 16, 2018 Category: Biology Authors: Bronac Flanagan Source Type: research

Whole-body iron transport and metabolism: Mechanistic, multi-scale model to improve treatment of anemia in chronic kidney disease
by Joydeep Sarkar, Alka A. Potdar, Gerald M. Saidel Iron plays vital roles in the human body including enzymatic processes, oxygen-transport via hemoglobin and immune response. Iron metabolism is characterized by ~95% recycling and minor replenishment through diet. Anemia of chronic kidney disease (CKD) is characterized by a lack of synthesis of er ythropoietin leading to reduced red blood cell (RBC) formation and aberrant iron recycling. Treatment of CKD anemia aims to normalize RBC count and serum hemoglobin. Clinically, the various fluxes of iron transport and accumulation are not measured so that changes during diseas...
Source: PLoS Computational Biology - April 16, 2018 Category: Biology Authors: Joydeep Sarkar Source Type: research

Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly
by Juan Francisco Viso, Patricia Belelli, Mat ías Machado, Humberto González, Sergio Pantano, María Julia Amundarain, Fernando Zamarreño, Maria Marta Branda, Diego M. A. Guérin, Marcelo D. Costabel In this work, we assess a previously advanced hypothesis that predicts the existence of ion channels in the capsid of small and non-enveloped icosahedral viruses. With this purpose we examineTriatoma Virus (TrV) as a case study. This virus has a stable capsid under highly acidic conditions but disassembles and releases the genome in alkaline environments. Our calculations range from a subtle s...
Source: PLoS Computational Biology - April 16, 2018 Category: Biology Authors: Juan Francisco Viso Source Type: research

Cell adhesion and fluid flow jointly initiate genotype spatial distribution in biofilms
by Ricardo Mart ínez-García, Carey D. Nadell, Raimo Hartmann, Knut Drescher, Juan A. Bonachela Biofilms are microbial collectives that occupy a diverse array of surfaces. It is well known that the function and evolution of biofilms are strongly influenced by the spatial arrangement of different strains and species within them, but how spatiotemporal distributions of different genotypes in b iofilm populations originate is still underexplored. Here, we study the origins of biofilm genetic structure by combining model development, numerical simulations, and microfluidic experiments using the human pathogenVibr...
Source: PLoS Computational Biology - April 16, 2018 Category: Biology Authors: Ricardo Mart ínez-García Source Type: research

Using pseudoalignment and base quality to accurately quantify microbial community composition
by Mark Reppell, John Novembre Pooled DNA from multiple unknown organisms arises in a variety of contexts, for example microbial samples from ecological or human health research. Determining the composition of pooled samples can be difficult, especially at the scale of modern sequencing data and reference databases. Here we pro pose a novel method for taxonomic profiling in pooled DNA that combines the speed and low-memory requirements of k-mer based pseudoalignment with a likelihood framework that uses base quality information to better resolve multiply mapped reads. We apply the method to the problem of classifying 16S ...
Source: PLoS Computational Biology - April 16, 2018 Category: Biology Authors: Mark Reppell Source Type: research

Backbone Brackets and Arginine Tweezers delineate Class I and Class II aminoacyl tRNA synthetases
by Florian Kaiser, Sebastian Bittrich, Sebastian Salentin, Christoph Leberecht, V. Joachim Haupt, Sarah Krautwurst, Michael Schroeder, Dirk Labudde The origin of the machinery that realizes protein biosynthesis in all organisms is still unclear. One key component of this machinery are aminoacyl tRNA synthetases (aaRS), which ligate tRNAs to amino acids while consuming ATP. Sequence analyses revealed that these enzymes can be divided into two complementary classes. Both classes differ significantly on a sequence and structural level, feature different reaction mechanisms, and occur in diverse oligomerization states. The on...
Source: PLoS Computational Biology - April 16, 2018 Category: Biology Authors: Florian Kaiser Source Type: research

Allostery in the dengue virus NS3 helicase: Insights into the NTPase cycle from molecular simulations
by Russell B. Davidson, Josie Hendrix, Brian J. Geiss, Martin McCullagh The C-terminus domain of non-structural 3 (NS3) protein of theFlaviviridae viruses (e.g. HCV, dengue, West Nile, Zika) is a nucleotide triphosphatase (NTPase) -dependent superfamily 2 (SF2) helicase that unwinds double-stranded RNA while translocating along the nucleic polymer. Due to these functions, NS3 is an important target for antiviral development yet the biophysics of this enzyme are poorly understood. Microsecond-long molecular dynamic simulations of the dengue NS3 helicase domain are reported from which allosteric effects of RNA and NTPase su...
Source: PLoS Computational Biology - April 16, 2018 Category: Biology Authors: Russell B. Davidson Source Type: research

A modelling approach for exploring muscle dynamics during cyclic contractions
by Stephanie A. Ross, Nilima Nigam, James M. Wakeling Hill-type muscle models are widely used within the field of biomechanics to predict and understand muscle behaviour, and are often essential where muscle forces cannot be directly measured. However, these models have limited accuracy, particularly during cyclic contractions at the submaximal level s of activation that typically occur during locomotion. To address this issue, recent studies have incorporated effects into Hill-type models that are oftentimes neglected, such as size-dependent, history-dependent, and activation-dependent effects. However, the contribution ...
Source: PLoS Computational Biology - April 16, 2018 Category: Biology Authors: Stephanie A. Ross Source Type: research

Biobeam —Multiplexed wave-optical simulations of light-sheet microscopy
by Martin Weigert, Kaushikaram Subramanian, Sebastian T. Bundschuh, Eugene W. Myers, Moritz Kreysing Sample-induced image-degradation remains an intricate wave-optical problem in light-sheet microscopy. Here we presentbiobeam, an open-source software package that enables simulation of operational light-sheet microscopes by combining data from 105–106 multiplexed and GPU-accelerated point-spread-function calculations. The wave-optical nature of these simulations leads to the faithful reproduction of spatially varying aberrations, diffraction artifacts, geometric image distortions, adaptive optics, and emergent wave-o...
Source: PLoS Computational Biology - April 13, 2018 Category: Biology Authors: Martin Weigert Source Type: research

Ten simple rules for responsible referencing
by Bart Penders (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - April 12, 2018 Category: Biology Authors: Bart Penders Source Type: research

Eleven quick tips for finding research data
by Kathleen Gregory, Siri Jodha Khalsa, William K. Michener, Fotis E. Psomopoulos, Anita de Waard, Mingfang Wu (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - April 12, 2018 Category: Biology Authors: Kathleen Gregory Source Type: research

Physics-based simulations of aerial attacks by peregrine falcons reveal that stooping at high speed maximizes catch success against agile prey
by Robin Mills, Hanno Hildenbrandt, Graham K. Taylor, Charlotte K. Hemelrijk The peregrine falconFalco peregrinus is renowned for attacking its prey from high altitude in a fast controlled dive called a stoop. Many other raptors employ a similar mode of attack, but the functional benefits of stooping remain obscure. Here we investigate whether, when, and why stooping promotes catch success, using a three-dimensional, agent-based modeling approach to simulate attacks of falcons on aerial prey. We simulate avian flapping and gliding flight using an analytical quasi-steady model of the aerodynamic forces and moments, paramet...
Source: PLoS Computational Biology - April 12, 2018 Category: Biology Authors: Robin Mills Source Type: research

Assessing the durability and efficiency of landscape-based strategies to deploy plant resistance to pathogens
This article describes the model and its parameterisation for rust diseases of cereal crops, caused by fungi of the genusPuccinia. To illustrate the model, we use it to assess the epidemiological and evolutionary potential of the combination of a major gene and different traits of quantitative resistance. The comparison of the four major deployment strategies described above will be the objective of future studies. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - April 12, 2018 Category: Biology Authors: Loup Rimbaud Source Type: research

Principles that govern competition or co-existence in Rho-GTPase driven polarization
by Jian-Geng Chiou, Samuel A. Ramirez, Timothy C. Elston, Thomas P. Witelski, David G. Schaeffer, Daniel J. Lew Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating cell) or several clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for unipolar or multipolar outcomes is unclear. The design principles of Rho-GTPase circuits are captured by two-component r...
Source: PLoS Computational Biology - April 12, 2018 Category: Biology Authors: Jian-Geng Chiou Source Type: research

Cox-nnet: An artificial neural network method for prognosis prediction of high-throughput omics data
by Travers Ching, Xun Zhu, Lana X. Garmire Artificial neural networks (ANN) are computing architectures with many interconnections of simple neural-inspired computing elements, and have been applied to biomedical fields such as imaging analysis and diagnosis. We have developed a new ANN framework called Cox-nnet to predict patient prognosi s from high throughput transcriptomics data. In 10 TCGA RNA-Seq data sets, Cox-nnet achieves the same or better predictive accuracy compared to other methods, including Cox-proportional hazards regression (with LASSO, ridge, and mimimax concave penalty), Random Forests Survival and CoxB...
Source: PLoS Computational Biology - April 10, 2018 Category: Biology Authors: Travers Ching Source Type: research

A multitask clustering approach for single-cell RNA-seq analysis in Recessive Dystrophic Epidermolysis Bullosa
by Huanan Zhang, Catherine A. A. Lee, Zhuliu Li, John R. Garbe, Cindy R. Eide, Raphael Petegrosso, Rui Kuang, Jakub Tolar Single-cell RNA sequencing (scRNA-seq) has been widely applied to discover new cell types by detecting sub-populations in a heterogeneous group of cells. Since scRNA-seq experiments have lower read coverage/tag counts and introduce more technical biases compared to bulk RNA-seq experiments, the li mited number of sampled cells combined with the experimental biases and other dataset specific variations presents a challenge to cross-dataset analysis and discovery of relevant biological variations across ...
Source: PLoS Computational Biology - April 9, 2018 Category: Biology Authors: Huanan Zhang Source Type: research

Spatial modeling of the membrane-cytosolic interface in protein kinase signal transduction
by Wolfgang Giese, Gregor Milicic, Andreas Schr öder, Edda Klipp The spatial architecture of signaling pathways and the interaction with cell size and morphology are complex, but little understood. With the advances of single cell imaging and single cell biology, it becomes crucial to understand intracellular processes in time and space. Activation of cell surf ace receptors often triggers a signaling cascade including the activation of membrane-attached and cytosolic signaling components, which eventually transmit the signal to the cell nucleus. Signaling proteins can form steep gradients in the cytosol, which cause...
Source: PLoS Computational Biology - April 9, 2018 Category: Biology Authors: Wolfgang Giese Source Type: research

Toward a theory of coactivation patterns in excitable neural networks
by Arnaud Mess é, Marc-Thorsten Hütt, Claus C. Hilgetag The relationship between the structural connectivity (SC) and functional connectivity (FC) of neural systems is of central importance in brain network science. It is an open question, however, how the SC-FC relationship depends on specific topological features of brain networks or the models used for describing neural dynamics. Using a basic but general model of discrete excitable units that follow a susceptible—excited—refractory activity cycle (SER model), we here analyze how the network activity patterns underlying functional connectivity a...
Source: PLoS Computational Biology - April 9, 2018 Category: Biology Authors: Arnaud Mess é Source Type: research

Interactions of spatial strategies producing generalization gradient and blocking: A computational approach
We present a computational model of spatial navigation comprising different learning mechanisms in mammals, i.e., associative, cognitive mapping and parallel systems. This model is able to reproduce a large number of experimental results in different variants of the Morris water maze task, includi ng standard associative phenomena (spatial generalization gradient and blocking), as well as navigation based on cognitive mapping. Furthermore, we show that competitive and cooperative patterns between different navigation strategies in the model allow to explain previous apparently contradictory r esults supporting either assoc...
Source: PLoS Computational Biology - April 9, 2018 Category: Biology Authors: Laurent Doll é Source Type: research

Need for speed: An optimized gridding approach for spatially explicit disease simulations
by Stefan Sellman, Kimberly Tsao, Michael J. Tildesley, Peter Brommesson, Colleen T. Webb, Uno Wennergren, Matt J. Keeling, Tom Lindstr öm Numerical models for simulating outbreaks of infectious diseases are powerful tools for informing surveillance and control strategy decisions. However, large-scale spatially explicit models can be limited by the amount of computational resources they require, which poses a problem when multiple sc enarios need to be explored to provide policy recommendations. We introduce an easily implemented method that can reduce computation time in a standard Susceptible-Exposed-Infectious-Rem...
Source: PLoS Computational Biology - April 6, 2018 Category: Biology Authors: Stefan Sellman Source Type: research

New computational approaches to understanding molecular protein function
by Jacquelyn S. Fetrow, Patricia C. Babbitt (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - April 5, 2018 Category: Biology Authors: Jacquelyn S. Fetrow Source Type: research

Automated plant species identification —Trends and future directions
by Jana W äldchen, Michael Rzanny, Marco Seeland, Patrick Mäder Current rates of species loss triggered numerous attempts to protect and conserve biodiversity. Species conservation, however, requires species identification skills, a competence obtained through intensive training and experience. Field researchers, land managers, educators, civil servants, and t he interested public would greatly benefit from accessible, up-to-date tools automating the process of species identification. Currently, relevant technologies, such as digital cameras, mobile devices, and remote access to databases, are ubiquitously avail...
Source: PLoS Computational Biology - April 5, 2018 Category: Biology Authors: Jana W äldchen Source Type: research

Ten quick tips for teaching programming
by Neil C. C. Brown, Greg Wilson (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - April 5, 2018 Category: Biology Authors: Neil C. C. Brown Source Type: research

A probabilistic, distributed, recursive mechanism for decision-making in the brain
by Javier A. Caballero, Mark D. Humphries, Kevin N. Gurney Decision formation recruits many brain regions, but the procedure they jointly execute is unknown. Here we characterize its essential composition, using as a framework a novel recursive Bayesian algorithm that makes decisions based on spike-trains with the statistics of those in sensory cortex (MT ). Using it to simulate the random-dot-motion task, we demonstrate it quantitatively replicates the choice behaviour of monkeys, whilst predicting losses of otherwise usable information from MT. Its architecture maps to the recurrent cortico-basal-ganglia-thalamo-cortica...
Source: PLoS Computational Biology - April 3, 2018 Category: Biology Authors: Javier A. Caballero Source Type: research

Computational analysis of the oscillatory behavior at the translation level induced by mRNA levels oscillations due to finite intracellular resources
In this study, based on a whole-cell model simulation of translation inS. cerevisiae, we evaluate for the first time the expected effect of mRNA levels fluctuations on translation due to the finite pool of ribosomes. We show that fluctuations of a single gene or a group of genes mRNA levels induce periodic behavior in allS. cerevisiae translation factors and aspects: the ribosomal densities and the translation rates of allS. cerevisiae mRNAs oscillate. We numerically measure the oscillation amplitudes demonstrating that fluctuations of endogenous and heterologous genes can cause a significant fluctuation of up to 50% in th...
Source: PLoS Computational Biology - April 3, 2018 Category: Biology Authors: Yoram Zarai Source Type: research

Spatial regularity control of phyllotaxis pattern generated by the mutual interaction between auxin and PIN1
by Hironori Fujita, Masayoshi Kawaguchi Phyllotaxis, the arrangement of leaves on a plant stem, is well known because of its beautiful geometric configuration, which is derived from the constant spacing between leaf primordia. This phyllotaxis is established by mutual interaction between a diffusible plant hormone auxin and its efflux c arrier PIN1, which cooperatively generate a regular pattern of auxin maxima, small regions with high auxin concentrations, leading to leaf primordia. However, the molecular mechanism of the regular pattern of auxin maxima is still largely unknown. To better understand how the phyllotaxis p...
Source: PLoS Computational Biology - April 3, 2018 Category: Biology Authors: Hironori Fujita Source Type: research

Effect of Ca < sup > 2+ < /sup > on the promiscuous target-protein binding of calmodulin
by Annie M. Westerlund, Lucie Delemotte Calmodulin (CaM) is a calcium sensing protein that regulates the function of a large number of proteins, thus playing a crucial part in many cell signaling pathways. CaM has the ability to bind more than 300 different target peptides in a Ca2+-dependent manner, mainly through the exposure of hydrophobic residues. How CaM can bind a large number of targets while retaining some selectivity is a fascinating open question. Here, we explore the mechanism of CaM selective promiscuity for selected target proteins. Analyzing enhanced sampling molecular dynamics simulations of Ca2+-bound and...
Source: PLoS Computational Biology - April 3, 2018 Category: Biology Authors: Annie M. Westerlund Source Type: research

An open source tool for automatic spatiotemporal assessment of calcium transients and local ‘signal-close-to-noise’ activity in calcium imaging data
by Juan Prada, Manju Sasi, Corinna Martin, Sibylle Jablonka, Thomas Dandekar, Robert Blum Local and spontaneous calcium signals play important roles in neurons and neuronal networks. Spontaneous or cell-autonomous calcium signals may be difficult to assess because they appear in an unpredictable spatiotemporal pattern and in very small neuronal loci of axons or dendrites. We developed an open source bioinformatics tool for an unbiased assessment of calcium signals in x,y-t imaging series. The tool bases its algorithm on a continuous wavelet transform-guided peak detection to identify calcium signal candidates. The highly ...
Source: PLoS Computational Biology - March 30, 2018 Category: Biology Authors: Juan Prada Source Type: research

Eleven quick tips for architecting biomedical informatics workflows with cloud computing
by Brian S. Cole, Jason H. Moore Cloud computing has revolutionized the development and operations of hardware and software across diverse technological arenas, yet academic biomedical research has lagged behind despite the numerous and weighty advantages that cloud computing offers. Biomedical researchers who embrace cloud compu ting can reap rewards in cost reduction, decreased development and maintenance workload, increased reproducibility, ease of sharing data and software, enhanced security, horizontal and vertical scalability, high availability, a thriving technology partner ecosystem, and much more. Despite these a...
Source: PLoS Computational Biology - March 29, 2018 Category: Biology Authors: Brian S. Cole Source Type: research

Eleven quick tips for running an interdisciplinary short course for new graduate students
by Timothy E. Saunders, Cynthia Y. He, Patrice Koehl, L. L. Sharon Ong, Peter T. C. So Quantitative reasoning and techniques are increasingly ubiquitous across the life sciences. However, new graduate researchers with a biology background are often not equipped with the skills that are required to utilize such techniques correctly and efficiently. In parallel, there are increasing n umbers of engineers, mathematicians, and physical scientists interested in studying problems in biology with only basic knowledge of this field. Students from such varied backgrounds can struggle to engage proactively together to tackle proble...
Source: PLoS Computational Biology - March 29, 2018 Category: Biology Authors: Timothy E. Saunders Source Type: research

SARNAclust: Semi-automatic detection of RNA protein binding motifs from immunoprecipitation data
by Ivan Dotu, Scott I. Adamson, Benjamin Coleman, Cyril Fournier, Emma Ricart-Altimiras, Eduardo Eyras, Jeffrey H. Chuang RNA-protein binding is critical to gene regulation, controlling fundamental processes including splicing, translation, localization and stability, and aberrant RNA-protein interactions are known to play a role in a wide variety of diseases. However, molecular understanding of RNA-protein interacti ons remains limited; in particular, identification of RNA motifs that bind proteins has long been challenging, especially when such motifs depend on both sequence and structure. Moreover, although RNA binding...
Source: PLoS Computational Biology - March 29, 2018 Category: Biology Authors: Ivan Dotu Source Type: research

Astrocytic Kir4.1 channels and gap junctions account for spontaneous epileptic seizure
by Mengmeng Du, Jiajia Li, Liang Chen, Yuguo Yu, Ying Wu Experimental recordings in hippocampal slices indicate that astrocytic dysfunction may cause neuronal hyper-excitation or seizures. Considering that astrocytes play important roles in mediating local uptake and spatial buffering of K+ in the extracellular space of the cortical circuit, we constructed a novel model of an astrocyte-neuron network module consisting of a single compartment neuron and 4 surrounding connected astrocytes and including extracellular potassium dynamics. Next, we developed a new model function for the astrocyte gap junctions, connecting two a...
Source: PLoS Computational Biology - March 28, 2018 Category: Biology Authors: Mengmeng Du Source Type: research

Modeling the dynamics of oligodendrocyte precursor cells and the genesis of gliomas
We present three possible scenarios of disruption of the equilibrium: the appearance of an over-proliferating cell, of a deadless/non-differentiating cell, or of a cell that lost any contact-inhibition. We show that the appearance of an over-proliferating cell is sufficient to trigger the growth of a tumor that has low-grade glioma features: an invasive behaviour, a linear radial growth of the tumor with a corresponding growth velocity of less t han 2 mm per year, as well a cell density at the center which exceeds the one in normal tissue by a factor of less than two. The loss of contact inhibition leads to a more high-gra...
Source: PLoS Computational Biology - March 28, 2018 Category: Biology Authors: Aloys Dufour Source Type: research

Bamgineer: Introduction of simulated allele-specific copy number variants into exome and targeted sequence data sets
by Soroush Samadian, Jeff P. Bruce, Trevor J. Pugh Somatic copy number variations (CNVs) play a crucial role in development of many human cancers. The broad availability of next-generation sequencing data has enabled the development of algorithms to computationally infer CNV profiles from a variety of data types including exome and targeted sequen ce data; currently the most prevalent types of cancer genomics data. However, systemic evaluation and comparison of these tools remains challenging due to a lack of ground truth reference sets. To address this need, we have developed Bamgineer, a tool written in Python to introd...
Source: PLoS Computational Biology - March 28, 2018 Category: Biology Authors: Soroush Samadian Source Type: research

Dynamic cues for whisker-based object localization: An analytical solution to vibration during active whisker touch
by Roman Vaxenburg, Isis Wyche, Karel Svoboda, Alexander L. Efros, Samuel Andrew Hires Vibrations are important cues for tactile perception across species. Whisker-based sensation in mice is a powerful model system for investigating mechanisms of tactile perception. However, the role vibration plays in whisker-based sensation remains unsettled, in part due to difficulties in modelin g the vibration of whiskers. Here, we develop an analytical approach to calculate the vibrations of whiskers striking objects. We use this approach to quantify vibration forces during active whisker touch at a range of locations along the whis...
Source: PLoS Computational Biology - March 27, 2018 Category: Biology Authors: Roman Vaxenburg Source Type: research

Dynamic combination of sensory and reward information under time pressure
by Shiva Farashahi, Chih-Chung Ting, Chang-Hao Kao, Shih-Wei Wu, Alireza Soltani When making choices, collecting more information is beneficial but comes at the cost of sacrificing time that could be allocated to making other potentially rewarding decisions. To investigate how the brain balances these costs and benefits, we conducted a series of novel experiments in humans and simulated various computational models. Under six levels of time pressure, subjects made decisions either by integrating sensory information over time or by dynamically combining sensory and reward information over time. We found that during sensory...
Source: PLoS Computational Biology - March 27, 2018 Category: Biology Authors: Shiva Farashahi Source Type: research

A mechanistic pan-cancer pathway model informed by multi-omics data interprets stochastic cell fate responses to drugs and mitogens
by Mehdi Bouhaddou, Anne Marie Barrette, Alan D. Stern, Rick J. Koch, Matthew S. DiStefano, Eric A. Riesel, Luis C. Santos, Annie L. Tan, Alex E. Mertz, Marc R. Birtwistle Most cancer cells harbor multiple drivers whose epistasis and interactions with expression context clouds drug and drug combination sensitivity prediction. We constructed a mechanistic computational model that is context-tailored by omics data to capture regulation of stochastic proliferation and death by pan-cancer driver pathways. Simulations and experiments explore how the coordinated dynamics of RAF/MEK/ERK and PI-3K/AKT kinase activities in respons...
Source: PLoS Computational Biology - March 26, 2018 Category: Biology Authors: Mehdi Bouhaddou Source Type: research

Scabies in residential care homes: Modelling, inference and interventions for well-connected population sub-units
by Timothy Kinyanjui, Jo Middleton, Stefan G üttel, Jackie Cassell, Joshua Ross, Thomas House In the context of an ageing population, understanding the transmission of infectious diseases such as scabies through well-connected sub-units of the population, such as residential care homes, is particularly important for the design of efficient interventions to mitigate against the effects of t hose diseases. Here, we present a modelling methodology based on the efficient solution of a large-scale system of linear differential equations that allows statistical calibration of individual-based random models to real data on ...
Source: PLoS Computational Biology - March 26, 2018 Category: Biology Authors: Timothy Kinyanjui Source Type: research