Correction: Spatiotemporal network coding of physiological mossy fiber inputs by the cerebellar granular layer
by Shyam Kumar Sudhakar, Sungho Hong, Ivan Raikov, Rodrigo Publio, Claus Lang, Thomas Close, Daqing Guo, Mario Negrello, Erik de Schutter (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 22, 2019 Category: Biology Authors: Shyam Kumar Sudhakar Source Type: research

Correction: Bayesian hypothesis testing and experimental design for two-photon imaging data
by Luke E. Rogerson, Zhijian Zhao, Katrin Franke, Thomas Euler, Philipp Berens (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 22, 2019 Category: Biology Authors: Luke E. Rogerson Source Type: research

A multi-scale coevolutionary approach to predict interactions between protein domains
by Giancarlo Croce, Thomas Gueudr é, Maria Virginia Ruiz Cuevas, Victoria Keidel, Matteo Figliuzzi, Hendrik Szurmant, Martin Weigt Interacting proteins and protein domains coevolve on multiple scales, from their correlated presence across species, to correlations in amino-acid usage. Genomic databases provide rapidly growing data for variability in genomic protein content and in protein sequences, calling for computational pr edictions of unknown interactions. We first introduce the concept ofdirect phyletic couplings, based on global statistical models of phylogenetic profiles. They strongly increase the accuracy ...
Source: PLoS Computational Biology - October 21, 2019 Category: Biology Authors: Giancarlo Croce Source Type: research

LASSI: A lattice model for simulating phase transitions of multivalent proteins
by Jeong-Mo Choi, Furqan Dar, Rohit V. Pappu Many biomolecular condensates form via spontaneous phase transitions that are driven by multivalent proteins. These molecules are biological instantiations ofassociative polymers that conform to a so-calledstickers-and-spacers architecture. The stickers are protein-protein or protein-RNA interaction motifs and / or domains that can form reversible, non-covalent crosslinks with one another. Spacers are interspersed between stickers and their preferential interactions with solvent molecules determine the cooperativity of phase transitions. Here, we report the development of an op...
Source: PLoS Computational Biology - October 21, 2019 Category: Biology Authors: Jeong-Mo Choi Source Type: research

The folded X-pattern is not necessarily a statistical signature of decision confidence
by Manuel Rausch, Michael Zehetleitner Recent studies have traced the neural correlates of confidence in perceptual choices using statistical signatures of confidence. The most widely used statistical signature is the folded X-pattern, which was derived from a standard model of confidence assuming an objective definition of confidence as the posterior probability of making the correct choice given the evidence. The folded X-pattern entails that confidence as the subjective probability of being correct equals the probability of 0.75 if the stimulus in neutral about the choice options, increases with discriminability of the...
Source: PLoS Computational Biology - October 21, 2019 Category: Biology Authors: Manuel Rausch Source Type: research

Sequence specificity despite intrinsic disorder: How a disease-associated Val/Met polymorphism rearranges tertiary interactions in a long disordered protein
by Ruchi Lohia, Reza Salari, Grace Brannigan The role of electrostatic interactions and mutations that change charge states in intrinsically disordered proteins (IDPs) is well-established, but many disease-associated mutations in IDPs are charge-neutral. The Val66Met single nucleotide polymorphism (SNP) in precursor brain-derived neurotrophi c factor (BDNF) is one of the earliest SNPs to be associated with neuropsychiatric disorders, and the underlying molecular mechanism is unknown. Here we report on over 250μs of fully-atomistic, explicit solvent, temperature replica-exchange molecular dynamics (MD) simulations of th...
Source: PLoS Computational Biology - October 18, 2019 Category: Biology Authors: Ruchi Lohia Source Type: research

Color improves edge classification in human vision
In this study, we explore the role that color (chromatic) cues play in edge classification. We conducted a psychophysical experiment that required subjects to classify edges into illumination and material, in patches taken from images of natural scenes that either cont ained or did not contain color information. The edge images were of various sizes and were pre-classified into illumination and material, based on inspection of the edge in the context of the whole image from which the edge was extracted. Edge classification performance was found to be superior for the color compared to grayscale images, in keeping with colo...
Source: PLoS Computational Biology - October 18, 2019 Category: Biology Authors: Camille Breuil Source Type: research

Spectral tuning of adaptation supports coding of sensory context in auditory cortex
by Mateo Lopez Espejo, Zachary P. Schwartz, Stephen V. David Perception of vocalizations and other behaviorally relevant sounds requires integrating acoustic information over hundreds of milliseconds. Sound-evoked activity in auditory cortex typically has much shorter latency, but the acoustic context,i.e., sound history, can modulate sound evoked activity over longer periods. Contextual effects are attributed to modulatory phenomena, such as stimulus-specific adaption and contrast gain control. However, an encoding model that links context to natural sound processing has yet to be established. We tested whether a model i...
Source: PLoS Computational Biology - October 18, 2019 Category: Biology Authors: Mateo Lopez Espejo Source Type: research

Action potential propagation and synchronisation in myelinated axons
by Helmut Schmidt, Thomas R. Kn ösche With the advent of advanced MRI techniques it has become possible to study axonal white matter non-invasively and in great detail. Measuring the various parameters of the long-range connections of the brain opens up the possibility to build and refine detailed models of large-scale neuronal activi ty. One particular challenge is to find a mathematical description of action potential propagation that is sufficiently simple, yet still biologically plausible to model signal transmission across entire axonal fibre bundles. We develop a mathematical framework in which we replace the H...
Source: PLoS Computational Biology - October 17, 2019 Category: Biology Authors: Helmut Schmidt Source Type: research

Patient Dossier: Healthcare queries over distributed resources
by Miguel Vazquez, Alfonso Valencia As with many other aspects of the modern world, in healthcare, the explosion of data and resources opens new opportunities for the development of added-value services. Still, a number of specific conditions on this domain greatly hinders these developments, including ethical and legal issues, frag mentation of the relevant data in different locations, and a level of (meta)data complexity that requires great expertise across technical, clinical, and biological domains. We propose the Patient Dossier paradigm as a way to organize new innovative healthcare services that sorts the current l...
Source: PLoS Computational Biology - October 17, 2019 Category: Biology Authors: Miguel Vazquez Source Type: research

Ten simple rules to aid in achieving a vision
by Philip E. Bourne (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 17, 2019 Category: Biology Authors: Philip E. Bourne Source Type: research

Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation
by Alireza Kazemi, Bruno Louis, Daniel Isabey, Gary F. Nieman, Louis A. Gatto, Joshua Satalin, Sarah Baker, James B. Grotberg, Marcel Filoche Surfactant Replacement Therapy (SRT), which involves instillation of a liquid-surfactant mixture directly into the lung airway tree, is a major therapeutic treatment in neonatal patients with respiratory distress syndrome (RDS). This procedure has proved to be remarkably effective in premature new borns, inducing a five-fold decrease of mortality in the past 35 years. Disappointingly, its use in adults for treating acute respiratory distress syndrome (ARDS) experienced initial succe...
Source: PLoS Computational Biology - October 17, 2019 Category: Biology Authors: Alireza Kazemi Source Type: research

Detecting distant-homology protein structures by aligning deep neural-network based contact maps
In this study, we propose a new method, CEthreader, which first predicts residue-residue contacts by coupling evolutionary precision matrices with deep residual convolutional neural-networks. The predicted contact maps are then integrated with sequence profile alignments to recognize structural templates fr om the PDB. The method was tested on two independent benchmark sets consisting collectively of 1,153 non-homologous protein targets, where CEthreader detected 176% or 36% more correct templates with a TM-score>0.5 than the best state-of-the-art profile- or contact-based threading methods, respectively, for the Hard t...
Source: PLoS Computational Biology - October 17, 2019 Category: Biology Authors: Wei Zheng Source Type: research

A Kuramoto model of self-other integration across interpersonal synchronization strategies
by Ole Adrian Heggli, Joana Cabral, Ivana Konvalinka, Peter Vuust, Morten L. Kringelbach Human social behaviour is complex, and the biological and neural mechanisms underpinning it remain debated. A particularly interesting social phenomenon is our ability and tendency to fall into synchronization with other humans. Our ability to coordinate actions and goals relies on the ability to distinguish between and integrate self and other, which when impaired can lead to devastating consequences. Interpersonal synchronization has been a widely used framework for studying action coordination and self-other integration, showing th...
Source: PLoS Computational Biology - October 16, 2019 Category: Biology Authors: Ole Adrian Heggli Source Type: research

Computational design and interpretation of single-RNA translation experiments
by Luis U. Aguilera, William Raymond, Zachary R. Fox, Michael May, Elliot Djokic, Tatsuya Morisaki, Timothy J. Stasevich, Brian Munsky Advances in fluorescence microscopy have introduced new assays to quantify live-cell translation dynamics at single-RNA resolution. We introduce a detailed, yet efficient sequence-based stochastic model that generates realistic synthetic data for several such assays, including Fluorescence Correla tion Spectroscopy (FCS), ribosome Run-Off Assays (ROA) after Harringtonine application, and Fluorescence Recovery After Photobleaching (FRAP). We simulate these experiments under multiple imaging...
Source: PLoS Computational Biology - October 16, 2019 Category: Biology Authors: Luis U. Aguilera Source Type: research

Transitions in information processing dynamics at the whole-brain network level are driven by alterations in neural gain
In this study, we advance these results by demonstrating that the gain-mediated phase transition is characterized by a shift in the underlying dynamics of neural information proc essing. Specifically, the dynamics of the subcritical (segregated) regime are dominated by information storage, whereas the supercritical (integrated) regime is associated with increased information transfer (measured via transfer entropy). Operating near to the critical regime with respect to modul ating neural gain parameters would thus appear to provide computational advantages, offering flexibility in the information processing that can be per...
Source: PLoS Computational Biology - October 15, 2019 Category: Biology Authors: Mike Li Source Type: research

TAPES: A tool for assessment and prioritisation in exome studies
by Alexandre Xavier, Rodney J. Scott, Bente A. Talseth-Palmer Next-generation sequencing continues to grow in importance for researchers. Exome sequencing became a widespread tool to further study the genomic basis of Mendelian diseases. In an effort to identify pathogenic variants, reject benign variants and better predict variant effects in downstream anal ysis, the American College of Medical Genetics (ACMG) published a set of criteria in 2015. While there are multiple publicly available software’s available to assign the ACMG criteria, most of them do not take into account multi-sample variant calling formats. H...
Source: PLoS Computational Biology - October 15, 2019 Category: Biology Authors: Alexandre Xavier Source Type: research

Categorical encoding of decision variables in orbitofrontal cortex
by Arno Onken, Jue Xie, Stefano Panzeri, Camillo Padoa-Schioppa A fundamental and recurrent question in systems neuroscience is that of assessing what variables are encoded by a given population of neurons. Such assessments are often challenging because neurons in one brain area may encode multiple variables, and because neuronal representations might be categ orical or non-categorical. These issues are particularly pertinent to the representation of decision variables in the orbitofrontal cortex (OFC)–an area implicated in economic choices. Here we present a new algorithm to assess whether a neuronal representation...
Source: PLoS Computational Biology - October 14, 2019 Category: Biology Authors: Arno Onken Source Type: research

Phylogenetic correlations can suffice to infer protein partners from sequences
by Guillaume Marmier, Martin Weigt, Anne-Florence Bitbol Determining which proteins interact together is crucial to a systems-level understanding of the cell. Recently, algorithms based on Direct Coupling Analysis (DCA) pairwise maximum-entropy models have allowed to identify interaction partners among paralogous proteins from sequence data. This succes s of DCA at predicting protein-protein interactions could be mainly based on its known ability to identify pairs of residues that are in contact in the three-dimensional structure of protein complexes and that coevolve to remain physicochemically complementary. However, in...
Source: PLoS Computational Biology - October 14, 2019 Category: Biology Authors: Guillaume Marmier Source Type: research

Key residues in TLR4-MD2 tetramer formation identified by free energy simulations
by Alireza Tafazzol, Yong Duan Toll-like receptors (TLRs) play a central role in both the innate and adaptive immune systems by recognizing pathogen-associated molecular patterns and inducing the release of the effector molecules of the immune system. The dysregulation of the TLR system may cause various autoimmune diseases and septic shock. A series of molecular dynamics simulations and free energy calculations were performed to investigate the ligand-free, lipopolysaccharide (LPS)-bound, and neoseptin3-bound (TLR4-MD2)2 tetramers. Compared to earlier simulations done by others, our simulations showed that TLR4 structure...
Source: PLoS Computational Biology - October 14, 2019 Category: Biology Authors: Alireza Tafazzol Source Type: research

Combinations of low-level and high-level neural processes account for distinct patterns of context-dependent choice
by Mehran Spitmaan, Oihane Horno, Emily Chu, Alireza Soltani Context effects have been explained by either low-level neural adjustments or high-level cognitive processes but not their combination. It is currently unclear how these processes interact to shape individuals’ responses to context. Here, we used a large cohort of human subjects in experiments i nvolving choice between two or three gambles in order to study the dependence of context effects on neural adaptation and individuals’ risk attitudes. Our experiments did not provide any evidence that neural adaptation on long timescales (~100 trials) contrib...
Source: PLoS Computational Biology - October 14, 2019 Category: Biology Authors: Mehran Spitmaan Source Type: research

Evaluation of linear and non-linear activation dynamics models for insect muscle
by Nalin Harischandra, Anthony J. Clare, Jure Zakotnik, Laura M. L. Blackburn, Tom Matheson, Volker D ürr In computational modelling of sensory-motor control, the dynamics of muscle contraction is an important determinant of movement timing and joint stiffness. This is particularly so in animals with many slow muscles, as is the case in insects—many of which are important models for sensory-motor co ntrol. A muscle model is generally used to transform motoneuronal input into muscle force. Although standard models exist for vertebrate muscle innervated by many motoneurons, there is no agreement on a parametric m...
Source: PLoS Computational Biology - October 14, 2019 Category: Biology Authors: Nalin Harischandra Source Type: research

A computational account of threat-related attentional bias
by Toby Wise, Jochen Michely, Peter Dayan, Raymond J. Dolan Visual selective attention acts as a filter on perceptual information, facilitating learning and inference about important events in an agent’s environment. A role for visual attention in reward-based decisions has previously been demonstrated, but it remains unclear how visual attention is recr uited during aversive learning, particularly when learning about multiple stimuli concurrently. This question is of particular importance in psychopathology, where enhanced attention to threat is a putative feature of pathological anxiety. Using an aversive reversal...
Source: PLoS Computational Biology - October 10, 2019 Category: Biology Authors: Toby Wise Source Type: research

Consensus and uncertainty in the geographic range of < i > Aedes aegypti < /i > and < i > Aedes albopictus < /i > in the contiguous United States: Multi-model assessment and synthesis
by Andrew J. Monaghan, Rebecca J. Eisen, Lars Eisen, Janet McAllister, Harry M. Savage, John-Paul Mutebi, Michael A. JohanssonAedes (Stegomyia) aegypti (L.) andAe.(Stegomyia) albopictus (Skuse) mosquitoes can transmit dengue, chikungunya, yellow fever, and Zika viruses. Limited surveillance has led to uncertainty regarding the geographic ranges of these vectors globally, and particularly in regions at the present-day margins of habitat suitability such as the contiguous United States. Empirical habitat suitability models based on environmental conditions can augment surveillance gaps to describe the estimated potential spe...
Source: PLoS Computational Biology - October 10, 2019 Category: Biology Authors: Andrew J. Monaghan Source Type: research

miRWoods: Enhanced precursor detection and stacked random forests for the sensitive detection of microRNAs
by Jimmy Bell, Maureen Larson, Michelle Kutzler, Massimo Bionaz, Christiane V. L öhr, David Hendrix MicroRNAs are conserved, endogenous small RNAs with critical post-transcriptional regulatory functions throughout eukaryota, including prominent roles in development and disease. Despite much effort, microRNA annotations still contain errors and are incomplete due especially to challenges related to identifying valid miRs that have small numbers of reads, to properly locating hairpin precursors and to balancing precision and recall. Here, we present miRWoods, which solves these challenges using a duplex-focused precurs...
Source: PLoS Computational Biology - October 9, 2019 Category: Biology Authors: Jimmy Bell Source Type: research

Correction: Free energy profiles for unwrapping the outer superhelical turn of nucleosomal DNA
by Hidetoshi Kono, Shun Sakuraba, Hisashi Ishida (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 9, 2019 Category: Biology Authors: Hidetoshi Kono Source Type: research

Correction: Generation of Binary Tree-Child phylogenetic networks
by Gabriel Cardona, Joan Carles Pons, Celine Scornavacca (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 9, 2019 Category: Biology Authors: Gabriel Cardona Source Type: research

Correction: Modeling differentiation-state transitions linked to therapeutic escape in triple-negative breast cancer
by Margaret P. Chapman, Tyler Risom, Anil J. Aswani, Ellen M. Langer, Rosalie C. Sears, Claire J. Tomlin (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 9, 2019 Category: Biology Authors: Margaret P. Chapman Source Type: research

Dimensional reduction in networks of non-Markovian spiking neurons: Equivalence of synaptic filtering and heterogeneous propagation delays
by Maurizio Mattia, Matteo Biggio, Andrea Galluzzi, Marco Storace Message passing between components of a distributed physical system is non-instantaneous and contributes to determine the time scales of the emerging collective dynamics. In biological neuron networks this is due in part to local synaptic filtering of exchanged spikes, and in part to the distribut ion of the axonal transmission delays. How differently these two kinds of communication protocols affect the network dynamics is still an open issue due to the difficulties in dealing with the non-Markovian nature of synaptic transmission. Here, we develop a mean-...
Source: PLoS Computational Biology - October 8, 2019 Category: Biology Authors: Maurizio Mattia Source Type: research

Correction: A model for the origin and development of visual orientation selectivity
by The PLOS Computational Biology Staff (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 8, 2019 Category: Biology Authors: The PLOS Computational Biology Staff Source Type: research

Predicting gait adaptations due to ankle plantarflexor muscle weakness and contracture using physics-based musculoskeletal simulations
by Carmichael F. Ong, Thomas Geijtenbeek, Jennifer L. Hicks, Scott L. Delp Deficits in the ankle plantarflexor muscles, such as weakness and contracture, occur commonly in conditions such as cerebral palsy, stroke, muscular dystrophy, Charcot-Marie-Tooth disease, and sarcopenia. While these deficits likely contribute to observed gait pathologies, determining cause-effect relationships is difficult due to the often co-occurring biomechanical and neural deficits. To elucidate the effects of weakness and contracture, we systematically introduced isolated deficits into a musculoskeletal model and generated simulations of walk...
Source: PLoS Computational Biology - October 7, 2019 Category: Biology Authors: Carmichael F. Ong Source Type: research

Large-scale, dynamin-like motions of the human guanylate binding protein 1 revealed by multi-resolution simulations
by Bogdan Barz, Jennifer Loschwitz, Birgit Strodel Guanylate binding proteins (GBPs) belong to the dynamin-related superfamily and exhibit various functions in the fight against infections. The functions of the human guanylate binding protein 1 (hGBP1) are tightly coupled to GTP hydrolysis and dimerization. Despite known crystal structures of the hGBP1 monomer and GTPase domain dimer, little is known about the dynamics of hGBP1. To gain a mechanistic understanding of hGBP1, we performed sub-millisecond multi-resolution molecular dynamics simulations of both the hGBP1 monomer and dimer. We found that hGBP1 is a highly flex...
Source: PLoS Computational Biology - October 7, 2019 Category: Biology Authors: Bogdan Barz Source Type: research

A simulation of the random and directed motion of dendritic cells in chemokine fields
by Avery Parr, Nicholas R. Anderson, Daniel A. Hammer Dendritic cells (DCs) are the most effective professional antigen-presenting cell. They ferry antigen from the extremities to T cells and are essential for the initiation of an adaptive immune response. Despite interest in how DCs respond to chemical stimuli, there have been few attempts to model DC migration. In this paper, we simulate the motility of DCs by modeling the generation of forces by filopodia and a force balance on the cell. The direction of fliopodial extension is coupled to differential occupancy of cognate chemokine receptors across the cell. Our model ...
Source: PLoS Computational Biology - October 7, 2019 Category: Biology Authors: Avery Parr Source Type: research

Correction: Frontal cortex tracks surprise separately for different sensory modalities but engages a common inhibitory control mechanism
by The PLOS Computational Biology Staff (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 7, 2019 Category: Biology Authors: The PLOS Computational Biology Staff Source Type: research

Ten simple rules for providing optimal administrative support to research teams
by Romina Garrido, Casandra A. Trowbridge, Nana Tamura (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 3, 2019 Category: Biology Authors: Romina Garrido Source Type: research

Using text-mined trait data to test for cooperate-and-radiate co-evolution between ants and plants
by Katrina M. Kaur, Pierre-Jean G. Mal é, Erik Spence, Crisanto Gomez, Megan E. Frederickson Mutualisms may be “key innovations” that spur lineage diversification by augmenting niche breadth, geographic range, or population size, thereby increasing speciation rates or decreasing extinction rates. Whether mutualism accelerates diversification in both interacting lineages is an open que stion. Research suggests that plants that attract ant mutualists have higher diversification rates than non-ant associated lineages. We ask whether the reciprocal is true: does the interaction between ants and plants also ...
Source: PLoS Computational Biology - October 3, 2019 Category: Biology Authors: Katrina M. Kaur Source Type: research

Constrained inference in sparse coding reproduces contextual effects and predicts laminar neural dynamics
by Federica Capparelli, Klaus Pawelzik, Udo Ernst When probed with complex stimuli that extend beyond their classical receptive field, neurons in primary visual cortex display complex and non-linear response characteristics. Sparse coding models reproduce some of the observed contextual effects, but still fail to provide a satisfactory explanatio n in terms of realistic neural structures and cortical mechanisms, since the connection scheme they propose consists only of interactions among neurons with overlapping input fields. Here we propose an extended generative model for visual scenes that includes spatial dependencies...
Source: PLoS Computational Biology - October 3, 2019 Category: Biology Authors: Federica Capparelli Source Type: research

Competition-driven evolution of organismal complexity
We present a detailed quantitative description of this process using a microevolutionary com petition model as an example. The model exhibits sequential increases in phenotypic complexity driven by diversification at existing levels of complexity and a resulting increase in competitive pressure, which can push an evolving species over the barrier of physiological costs of new phenotypic fea tures. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 3, 2019 Category: Biology Authors: Iaroslav Ispolatov Source Type: research

A computational model of postprandial adipose tissue lipid metabolism derived using human arteriovenous stable isotope tracer data
In this study, we use arte riovenous measurement across the subcutaneous adipose tissue during a mixed meal challenge test to evaluate the performance and underlying assumptions of three existing models of adipose tissue metabolism and construct a new, refined model of adipose tissue metabolism. Our model introduces new terms , explicitly accounting for the conversion of glucose to glyceraldehye-3-phosphate, the postprandial influx of glycerol into the adipose tissue, and several physiologically relevant delays in insulin signalling in order to better describe the measured adipose tissues fluxes. We then applied our refi n...
Source: PLoS Computational Biology - October 3, 2019 Category: Biology Authors: Shauna D. O ’Donovan Source Type: research

Correction: A unifying Bayesian account of contextual effects in value-based choice
by Francesco Rigoli, Christoph Mathys, Karl J. Friston, Raymond J. Dolan (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 2, 2019 Category: Biology Authors: Francesco Rigoli Source Type: research

Estimating influenza incidence using search query deceptiveness and generalized ridge regression
by Reid Priedhorsky, Ashlynn R. Daughton, Martha Barnard, Fiona O ’Connell, Dave Osthus Seasonal influenza is a sometimes surprisingly impactful disease, causing thousands of deaths per year along with much additional morbidity. Timely knowledge of the outbreak state is valuable for managing an effective response. The current state of the art is to gather this knowledge using in-pers on patient contact. While accurate, this is time-consuming and expensive. This has motivated inquiry into new approaches using internet activity traces, based on the theory that lay observations of health status lead to informative feat...
Source: PLoS Computational Biology - October 1, 2019 Category: Biology Authors: Reid Priedhorsky Source Type: research

Evolving generalists in switching rugged landscapes
We present a generative model to estimate the propensity of evolving generalists in rugged landscapes that are tunably related and alternating relatively slowly. We find that e nvironmental cycling can substantially facilitate the search for fit generalists by dynamically enlarging their effective basins of attraction. Importantly, these high performers are most likely to emerge at intermediate levels of ruggedness and environmental relatedness. Our approach allows one to estimate correlations across environments from the topography of experimental fitness landscapes. Our work provides a conceptual framework to study evolu...
Source: PLoS Computational Biology - October 1, 2019 Category: Biology Authors: Shenshen Wang Source Type: research

Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression
We present Telescope, a computational software tool that provides accurate estimation of transpos able element expression (retrotranscriptome) resolved to specific genomic locations. Telescope directly addresses uncertainty in fragment assignment by reassigning ambiguously mapped fragments to the most probable source transcript as determined within a Bayesian statistical model. We demonstrate th e utility of our approach through single locus analysis of HERV expression in 13 ENCODE cell types. When examined at this resolution, we find that the magnitude and breadth of the retrotranscriptome can be vastly different among ce...
Source: PLoS Computational Biology - September 30, 2019 Category: Biology Authors: Matthew L. Bendall Source Type: research

Computational modelling predicts substantial carbon assimilation gains for C < sub > 3 < /sub > plants with a single-celled C < sub > 4 < /sub > biochemical pump
by Ivan Juri ć, Julian M. Hibberd, Mike Blatt, Nigel J. Burroughs Achieving global food security for the estimated 9 billion people by 2050 is a major scientific challenge. Crop productivity is fundamentally restricted by the rate of fixation of atmospheric carbon. The dedicated enzyme, RubisCO, has a low turnover and poor specificity for CO2. This limitation of C3 photosynthesis (the basic carbon-assimilation pathway present in all plants) is alleviated in some lineages by use of carbon-concentrating-mechanisms, such as the C4 cycle —a biochemical pump that concentrates CO2 near RubisCO increasing assimilation eff...
Source: PLoS Computational Biology - September 30, 2019 Category: Biology Authors: Ivan Juri ć Source Type: research

LOTUS: A single- and multitask machine learning algorithm for the prediction of cancer driver genes
by Olivier Collier, V éronique Stoven, Jean-Philippe Vert Cancer driver genes,i.e., oncogenes and tumor suppressor genes, are involved in the acquisition of important functions in tumors, providing a selective growth advantage, allowing uncontrolled proliferation and avoiding apoptosis. It is therefore important to identify these driver genes, both for the fundamental understanding of cancer and to help finding new therapeutic targets or biomarkers. Although the most frequently mutated driver genes have been identified, it is believed that many more remain to be discovered, particularly for driver genes specific to...
Source: PLoS Computational Biology - September 30, 2019 Category: Biology Authors: Olivier Collier Source Type: research

Invariant neural responses for sensory categories revealed by the time-varying information for communication calls
by Julie E. Elie, Fr édéric E. Theunissen Although information theoretic approaches have been used extensively in the analysis of the neural code, they have yet to be used to describe how information is accumulated in time while sensory systems are categorizing dynamic sensory stimuli such as speech sounds or visual objects. Here, we pres ent a novel method to estimate the cumulative information for stimuli or categories. We further define a time-varying categorical information index that, by comparing the information obtained for stimuli versus categories of these same stimuli, quantifies invariant neural r...
Source: PLoS Computational Biology - September 26, 2019 Category: Biology Authors: Julie E. Elie Source Type: research

Ten simple rules to create biological network figures for communication
by G. Elisabeta Marai, Bruno Pinaud, Katja B ühler, Alexander Lex, John H. Morris Biological network figures are ubiquitous in the biology and medical literature. On the one hand, a good network figure can quickly provide information about the nature and degree of interactions between items and enable inferences about the reason for those interactions. On the other hand, good n etwork figures are difficult to create. In this paper, we outline 10 simple rules for creating biological network figures for communication, from choosing layouts, to applying color or other channels to show attributes, to the use of layering ...
Source: PLoS Computational Biology - September 26, 2019 Category: Biology Authors: G. Elisabeta Marai Source Type: research

On measuring selection in cancer from subclonal mutation frequencies
by Ivana Bozic, Chay Paterson, Bartlomiej Waclaw Recently available cancer sequencing data have revealed a complex view of the cancer genome containing a multitude of mutations, including drivers responsible for cancer progression and neutral passengers. Measuring selection in cancer and distinguishing drivers from passengers have important impl ications for development of novel treatment strategies. It has recently been argued that a third of cancers are evolving neutrally, as their mutational frequency spectrum follows a 1/f power law expected from neutral evolution in a particular intermediate frequency range. We study...
Source: PLoS Computational Biology - September 26, 2019 Category: Biology Authors: Ivana Bozic Source Type: research

Heterogeneous responses to low level death receptor activation are explained by random molecular assembly of the Caspase-8 activation platform
by Anna Matveeva, Michael Fichtner, Katherine McAllister, Christopher McCann, Marc Sturrock, Daniel B. Longley, Jochen H. M. Prehn Ligand binding to death receptors activates apoptosis in cancer cells. Stimulation of death receptors results in the formation of intracellular multiprotein platforms that either activate the apoptotic initiator Caspase-8 to trigger cell death, or signal through kinases to initiate inflammatory an d cell survival signalling. Two of these platforms, the Death-Inducing Signalling Complex (DISC) and the RIPoptosome, also initiate necroptosis by building filamentous scaffolds that lead to the acti...
Source: PLoS Computational Biology - September 25, 2019 Category: Biology Authors: Anna Matveeva Source Type: research

A scale-free analysis of the HIV-1 genome demonstrates multiple conserved regions of structural and functional importance
by Jordan P. Skittrall, Carin K. Ingemarsdotter, Julia R. Gog, Andrew M. L. Lever HIV-1 replicates via a low-fidelity polymerase with a high mutation rate; strong conservation of individual nucleotides is highly indicative of the presence of critical structural or functional properties. Identifying such conservation can reveal novel insights into viral behaviour. We analysed 36 51 publicly available sequences for the presence of nucleic acid conservation beyond that required by amino acid constraints, using a novel scale-free method that identifies regions of outlying score together with a codon scoring algorithm. Sequenc...
Source: PLoS Computational Biology - September 23, 2019 Category: Biology Authors: Jordan P. Skittrall Source Type: research