Predicting precision grip grasp locations on three-dimensional objects
by Lina K. Klein, Guido Maiello, Vivian C. Paulun, Roland W. Fleming We rarely experience difficulty picking up objects, yet of all potential contact points on the surface, only a small proportion yield effective grasps. Here, we present extensive behavioral data alongside a normative model that correctly predicts human precision grasping of unfamiliar 3D objects. We tracked participants’ forefinger and thumb as they picked up objects of 10 wood and brass cubes configured to tease apart effects of shape, weight, orientation, and mass distribution. Grasps were highly systematic and consistent across repetitions and p...
Source: PLoS Computational Biology - August 4, 2020 Category: Biology Authors: Lina K. Klein Source Type: research

Task-evoked activity quenches neural correlations and variability across cortical areas
by Takuya Ito, Scott L. Brincat, Markus Siegel, Ravi D. Mill, Biyu J. He, Earl K. Miller, Horacio G. Rotstein, Michael W. Cole Many large-scale functional connectivity studies have emphasized the importance of communication through increased inter-region correlations during task states. In contrast, local circuit studies have demonstrated that task states primarily reduce correlations among pairs of neurons, likely enhanc ing their information coding by suppressing shared spontaneous activity. Here we sought to adjudicate between these conflicting perspectives, assessing whether co-active brain regions during task states ...
Source: PLoS Computational Biology - August 3, 2020 Category: Biology Authors: Takuya Ito Source Type: research

Optimising efficacy of antibiotics against systemic infection by varying dosage quantities and times
by Andy Hoyle, David Cairns, Iona Paterson, Stuart McMillan, Gabriela Ochoa, Andrew P. Desbois Mass production and use of antibiotics has led to the rise of resistant bacteria, a problem possibly exacerbated by inappropriate and non-optimal application. Antibiotic treatment often followsfixed-dose regimens, with a standard dose of antibiotic administered equally spaced in time. But are such fixed-dose regimens optimal or can alternative regimens be designed to increase efficacy? Yet, few mathematical models have aimed to identify optimal treatments based on biological data of infections inside a living host. In addition, ...
Source: PLoS Computational Biology - August 3, 2020 Category: Biology Authors: Andy Hoyle Source Type: research

Combining hypoxia-activated prodrugs and radiotherapy < i > in silico < /i > : Impact of treatment scheduling and the intra-tumoural oxygen landscape
by Sara Hamis, Mohammad Kohandel, Ludwig J. Dubois, Ala Yaromina, Philippe Lambin, Gibin G. Powathil Hypoxia-activated prodrugs (HAPs) present a conceptually elegant approach to not only overcome, but better yet, exploit intra-tumoural hypoxia. Despite being successfulin vitro andin vivo, HAPs are yet to achieve successful results in clinical settings. It has been hypothesised that this lack of clinical success can, in part, be explained by the insufficiently stringent clinical screening selection of determining which tumours are suitable for HAP treatments. Taking a mathematical modelling approach, we investigate how tum...
Source: PLoS Computational Biology - August 3, 2020 Category: Biology Authors: Sara Hamis Source Type: research

Multiplexing information flow through dynamic signalling systems
by Giorgos Minas, Dan J. Woodcock, Louise Ashall, Claire V. Harper, Michael R. H. White, David A. Rand We consider how a signalling system can act as an information hub by multiplexing information arising from multiple signals. We formally define multiplexing, mathematically characterise which systems can multiplex and how well they can do it. While the results of this paper are theoretical, to mot ivate the idea of multiplexing, we provide experimental evidence that tentatively suggests that the NF-κB transcription factor can multiplex information about changes in multiple signals. We believe that our theoretical r...
Source: PLoS Computational Biology - August 3, 2020 Category: Biology Authors: Giorgos Minas Source Type: research

Flexible neural connectivity under constraints on total connection strength
by Gabriel Koch Ocker, Michael A. Buice Neural computation is determined by neurons’ dynamics and circuit connectivity. Uncertain and dynamic environments may require neural hardware to adapt to different computational tasks, each requiring different connectivity configurations. At the same time, connectivity is subject to a variety o f constraints, placing limits on the possible computations a given neural circuit can perform. Here we examine the hypothesis that the organization of neural circuitry favors computational flexibility: that it makes many computational solutions available, given physiological constraint...
Source: PLoS Computational Biology - August 3, 2020 Category: Biology Authors: Gabriel Koch Ocker Source Type: research

Cortical ignition dynamics is tightly linked to the core organisation of the human connectome
by Samy Castro, Wael El-Deredy, Demian Battaglia, Patricio Orio The capability of cortical regions to flexibly sustain an “ignited” state of activity has been discussed in relation to conscious perception or hierarchical information processing. Here, we investigate how the intrinsic propensity of different regions to get ignited is determined by the specif ic topological organisation of the structural connectome. More specifically, we simulated the resting-state dynamics of mean-field whole-brain models and assessed how dynamic multi-stability and ignition differ between a reference model embedding a realistic...
Source: PLoS Computational Biology - July 31, 2020 Category: Biology Authors: Samy Castro Source Type: research

Regional sequence expansion or collapse in heterozygous genome assemblies
by Kathryn C. Asalone, Kara M. Ryan, Maryam Yamadi, Annastelle L. Cohen, William G. Farmer, Deborah J. George, Claudia Joppert, Kaitlyn Kim, Madeeha Froze Mughal, Rana Said, Metin Toksoz-Exley, Evgeny Bisk, John R. Bracht High levels of heterozygosity present a unique genome assembly challenge and can adversely impact downstream analyses, yet is common in sequencing datasets obtained from non-model organisms. Here we show that by re-assembling a heterozygous dataset with variant parameters and different assembly al gorithms, we are able to generate assemblies whose protein annotations are statistically enriched for specif...
Source: PLoS Computational Biology - July 31, 2020 Category: Biology Authors: Kathryn C. Asalone Source Type: research

Ten simple rules for reading a scientific paper
by Maureen A. Carey, Kevin L. Steiner, William A. Petri Jr (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - July 30, 2020 Category: Biology Authors: Maureen A. Carey Source Type: research

Quorum sensing via dynamic cytokine signaling comprehensively explains divergent patterns of effector choice among helper T cells
by Edward C. Schrom II, Simon A. Levin, Andrea L. Graham In the animal kingdom, various forms of swarming enable groups of autonomous individuals to transform uncertain information into unified decisions which are probabilistically beneficial. Crossing scales from individual to group decisions requires dynamically accumulating signals among individuals. In striking parallel, the mammalian immune system is also a group of decentralized autonomous units (i.e. cells) which collectively navigate uncertainty with the help of dynamically accumulating signals (i.e. cytokines). Therefore, we apply techniques of understanding swar...
Source: PLoS Computational Biology - July 30, 2020 Category: Biology Authors: Edward C. Schrom II Source Type: research

Electrical coupling controls dimensionality and chaotic firing of inferior olive neurons
by Huu Hoang, Eric J. Lang, Yoshito Hirata, Isao T. Tokuda, Kazuyuki Aihara, Keisuke Toyama, Mitsuo Kawato, Nicolas Schweighofer We previously proposed, on theoretical grounds, that the cerebellum must regulate the dimensionality of its neuronal activity during motor learning and control to cope with the low firing frequency of inferior olive neurons, which form one of two major inputs to the cerebellar cortex. Such dimensi onality regulation is possible via modulation of electrical coupling through the gap junctions between inferior olive neurons by inhibitory GABAergic synapses. In addition, we previously showed in simu...
Source: PLoS Computational Biology - July 30, 2020 Category: Biology Authors: Huu Hoang Source Type: research

ADP is the dominant controller of AMP-activated protein kinase activity dynamics in skeletal muscle during exercise
by Ian F. Coccimiglio, David C. Clarke Exercise training elicits profound metabolic adaptations in skeletal muscle cells. A key molecule in coordinating these adaptations is AMP-activated protein kinase (AMPK), whose activity increases in response to cellular energy demand. AMPK activity dynamics are primarily controlled by the adenine nucleotides ADP and AMP, but how each contributes to its control in skeletal muscle during exercise is unclear. We developed and validated a mathematical model of AMPK signaling dynamics, and then applied global parameter sensitivity analyses with data-informed constraints to predict that A...
Source: PLoS Computational Biology - July 30, 2020 Category: Biology Authors: Ian F. Coccimiglio Source Type: research

Emergent neutrality in consumer-resource dynamics
by Rafael D ’Andrea, Theo Gibbs, James P. O’Dwyer Neutral theory assumes all species and individuals in a community are ecologically equivalent. This controversial hypothesis has been tested across many taxonomic groups and environmental contexts, and successfully predicts species abundance distributions across multiple high-diversity communities . However, it has been critiqued for its failure to predict a broader range of community properties, particularly regarding community dynamics from generational to geological timescales. Moreover, it is unclear whether neutrality can ever be a true description of a co...
Source: PLoS Computational Biology - July 30, 2020 Category: Biology Authors: Rafael D ’Andrea Source Type: research

scPADGRN: A preconditioned ADMM approach for reconstructing dynamic gene regulatory network using single-cell RNA sequencing data
by Xiao Zheng, Yuan Huang, Xiufen Zou Disease development and cell differentiation both involve dynamic changes; therefore, the reconstruction of dynamic gene regulatory networks (DGRNs) is an important but difficult problem in systems biology. With recent technical advances in single-cell RNA sequencing (scRNA-seq), large volumes of scRNA-seq data are being obtained for various processes. However, most current methods of inferring DGRNs from bulk samples may not be suitable for scRNA-seq data. In this work, we present scPADGRN, a novel DGRN inference method using “time-series” scRNA-seq data. scPADGRN combine...
Source: PLoS Computational Biology - July 27, 2020 Category: Biology Authors: Xiao Zheng Source Type: research

A circuit model of auditory cortex
by Youngmin Park, Maria N. Geffen The mammalian sensory cortex is composed of multiple types of inhibitory and excitatory neurons, which form sophisticated microcircuits for processing and transmitting sensory information. Despite rapid progress in understanding the function of distinct neuronal populations, the parameters of conn ectivity that are required for the function of these microcircuits remain unknown. Recent studies found that two most common inhibitory interneurons, parvalbumin- (PV) and somatostatin-(SST) positive interneurons control sound-evoked responses, temporal adaptation and network dynamics in the aud...
Source: PLoS Computational Biology - July 27, 2020 Category: Biology Authors: Youngmin Park Source Type: research

Temperature-robust activity patterns arise from coordinated axonal Sodium channel properties
by Margaret L. DeMaegd, Wolfgang Stein Action potentials are a key component of neuronal communication and their precise timing is critical for processes like learning, memory, and complex behaviors. Action potentials propagate through long axons to their postsynaptic partners, which requires axons not only to faithfully transfer actio n potentials to distant synaptic regions but also to maintain their timing. This is particularly challenging when axons differ in their morphological and physiological properties, as timing is predicted to diverge between these axons when extrinsic conditions change. It is unknown if and ho...
Source: PLoS Computational Biology - July 27, 2020 Category: Biology Authors: Margaret L. DeMaegd Source Type: research

Spatial and temporal patterns of nitric oxide diffusion and degradation drive emergent cerebrovascular dynamics
by William Davis Haselden, Ravi Teja Kedarasetti, Patrick J. Drew Nitric oxide (NO) is a gaseous signaling molecule that plays an important role in neurovascular coupling. NO produced by neurons diffuses into the smooth muscle surrounding cerebral arterioles, driving vasodilation. However, the rate of NO degradation in hemoglobin is orders of magnitude higher th an in brain tissue, though how this might impact NO signaling dynamics is not completely understood. We used simulations to investigate how the spatial and temporal patterns of NO generation and degradation impacted dilation of a penetrating arteriole in cortex. W...
Source: PLoS Computational Biology - July 27, 2020 Category: Biology Authors: William Davis Haselden Source Type: research

An extended and generalized framework for the calculation of metabolic intervention strategies based on minimal cut sets
by Philipp Schneider, Axel von Kamp, Steffen Klamt The concept of minimal cut sets (MCS) provides a flexible framework for analyzing properties of metabolic networks and for computing metabolic intervention strategies. In particular, it has been used to support the targeted design of microbial strains for bio-based production processes. Herein we present a number of major extensions that generalize the existing MCS approach and broaden its scope for applications in metabolic engineering. We first introduce a modified approach to integrate gene-protein-reaction associations (GPR) in the metabolic network structure for the ...
Source: PLoS Computational Biology - July 27, 2020 Category: Biology Authors: Philipp Schneider Source Type: research

Depth in convolutional neural networks solves scene segmentation
by Noor Seijdel, Nikos Tsakmakidis, Edward H. F. de Haan, Sander M. Bohte, H. Steven Scholte Feedforward deep convolutional neural networks (DCNNs) are, under specific conditions, matching and even surpassing human performance in object recognition in natural scenes. This performance suggests that the analysis of a loose collection of image features could support the recognition of natura l object categories, without dedicated systems to solve specific visual subtasks. Research in humans however suggests that while feedforward activity may suffice for sparse scenes with isolated objects, additional visual operations ('rou...
Source: PLoS Computational Biology - July 24, 2020 Category: Biology Authors: Noor Seijdel Source Type: research

A practical application of generative adversarial networks for RNA-seq analysis to predict the molecular progress of Alzheimer's disease
In this study, we applied a deep learning technique called generative adversarial networks (GANs) to predict the mole cular progress of Alzheimer’s disease (AD). We successfully applied GANs to analyze RNA-seq data from a 5xFAD mouse model of AD, which recapitulates major AD features of massive amyloid-β (Aβ) accumulation in the brain. We examined how the generator is featured to have specific-sample generation and biological gene association. Based on the above observations, we suggested virtual disease progress by latent space interpolation to yield the transition curves of various genes with pathological...
Source: PLoS Computational Biology - July 24, 2020 Category: Biology Authors: Jinhee Park Source Type: research

An < i > in vitro < /i > quantitative systems pharmacology approach for deconvolving mechanisms of drug-induced, multilineage cytopenias
by Jennifer L. Wilson, Dan Lu, Nick Corr, Aaron Fullerton, James Lu Myelosuppression is one of the most common and severe adverse events associated with anti-cancer therapies and can be a source of drug attrition. Current mathematical modeling methods for assessing cytopenia risk rely on indirect measurements of drug effects and primarily focus on single lineage r esponses to drugs. However, anti-cancer therapies have diverse mechanisms with varying degrees of effect across hematopoietic lineages. To improve predictive understanding of drug-induced myelosuppression, we developed a quantitative systems pharmacology (QSP) m...
Source: PLoS Computational Biology - July 23, 2020 Category: Biology Authors: Jennifer L. Wilson Source Type: research

A framework to assess the quality and impact of bioinformatics training across ELIXIR
by Kim T. Gurwitz, Prakash Singh Gaur, Louisa J. Bellis, Lee Larcombe, Eva Alloza, Balint Laszlo Balint, Alexander Botzki, Jure Dimec, Victoria Dominguez del Angel, Pedro L. Fernandes, Eija Korpelainen, Roland Krause, Mateusz Kuzak, Loredana Le Pera, Brane Lesko šek, Jessica M. Lindvall, Diana Marek, Paula A. Martinez, Tuur Muyldermans, Ståle Nygård, Patricia M. Palagi, Hedi Peterson, Fotis Psomopoulos, Vojtech Spiwok, Celia W. G. van Gelder, Allegra Via, Marko Vidak, Daniel Wibberg, Sarah L. Morgan, Gabriella Rustici ELIXIR is a pan-European intergovernmental organisation for life science that aims to ...
Source: PLoS Computational Biology - July 23, 2020 Category: Biology Authors: Kim T. Gurwitz Source Type: research

Nine quick tips for efficient bioinformatics curriculum development and training
by Susan McClatchy, Kristin M. Bass, Daniel M. Gatti, Adam Moylan, Gary Churchill Biomedical research is becoming increasingly data driven. New technologies that generate large-scale, complex data are continually emerging and evolving. As a result, there is a concurrent need for training researchers to use and understand new computational tools. Here we describe an efficient an d effective approach to developing curriculum materials that can be deployed in a research environment to meet this need. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - July 23, 2020 Category: Biology Authors: Susan McClatchy Source Type: research

Signaling models for dopamine-dependent temporal contiguity in striatal synaptic plasticity
by Hidetoshi Urakubo, Sho Yagishita, Haruo Kasai, Shin Ishii Animals remember temporal links between their actions and subsequent rewards. We previously discovered a synaptic mechanism underlying such reward learning in D1 receptor (D1R)-expressing spiny projection neurons (D1 SPN) of the striatum. Dopamine (DA) bursts promote dendritic spine enlargement in a time window of only a few seconds after paired pre- and post-synaptic spiking (pre–post pairing), which is termed as reinforcement plasticity (RP). The previous study has also identified underlying signaling pathways; however, it still remains unclear how the s...
Source: PLoS Computational Biology - July 23, 2020 Category: Biology Authors: Hidetoshi Urakubo Source Type: research

The location of the axon initial segment affects the bandwidth of spike initiation dynamics
by Christophe Verbist, Michael G. M üller, Huibert D. Mansvelder, Robert Legenstein, Michele Giugliano The dynamics and the sharp onset of action potential (AP) generation have recently been the subject of intense experimental and theoretical investigations. According to the resistive coupling theory, an electrotonic interplay between the site of AP initiation in the axon and the somato-dendritic l oad determines the AP waveform. This phenomenon not only alters the shape of AP recorded at the soma, but also determines the dynamics of excitability across a variety of time scales. Supporting this statement, here we gen...
Source: PLoS Computational Biology - July 23, 2020 Category: Biology Authors: Christophe Verbist Source Type: research

Scalable phylogenetic profiling using MinHash uncovers likely eukaryotic sexual reproduction genes
by David Moi, Laurent Kilchoer, Pablo S. Aguilar, Christophe Dessimoz Phylogenetic profiling is a computational method to predict genes involved in the same biological process by identifying protein families which tend to be jointly lost or retained across the tree of life. Phylogenetic profiling has customarily been more widely used with prokaryotes than eukaryotes , because the method is thought to require many diverse genomes. There are now many eukaryotic genomes available, but these are considerably larger, and typical phylogenetic profiling methods require at least quadratic time as a function of the number of genes...
Source: PLoS Computational Biology - July 22, 2020 Category: Biology Authors: David Moi Source Type: research

Beyond ranking nodes: Predicting epidemic outbreak sizes by network centralities
by Doina Bucur, Petter Holme Identifying important nodes for disease spreading is a central topic in network epidemiology. We investigate how well the position of a node, characterized by standard network measures, can predict its epidemiological importance in any graph of a given number of nodes. This is in contrast to other studies that deal with the easier prediction problem of ranking nodes by their epidemic importance in given graphs. As a benchmark for epidemic importance, we calculate the exact expected outbreak size given a node as the source. We study exhaustively all graphs of a given size, so do not restrict ou...
Source: PLoS Computational Biology - July 22, 2020 Category: Biology Authors: Doina Bucur Source Type: research

Multidimensional phenotyping predicts lifespan and quantifies health in < i > Caenorhabditis elegans < /i >
by C éline N. Martineau, André E. X. Brown, Patrick Laurent Ageing affects a wide range of phenotypes at all scales, but an objective measure of ageing remains challenging, even in simple model organisms. To measure the ageing process, we characterized the sequence of alterations of multiple phenotypes at organismal scale. Hundreds of morphological, postur al, and behavioral features were extracted from high-resolution videos. Out of the 1019 features extracted, 896 are ageing biomarkers, defined as those that show a significant correlation with relative age (age divided by lifespan). We used support vector ...
Source: PLoS Computational Biology - July 21, 2020 Category: Biology Authors: C éline N. Martineau Source Type: research

Bayesian modelling of high-throughput sequencing assays with malacoda
by Andrew R. Ghazi, Xianguo Kong, Ed S. Chen, Leonard C. Edelstein, Chad A. Shaw NGS studies have uncovered an ever-growing catalog of human variation while leaving an enormous gap between observed variation and experimental characterization of variant function. High-throughput screens powered by NGS have greatly increased the rate of variant functionalization, but the develop ment of comprehensive statistical methods to analyze screen data has lagged. In the massively parallel reporter assay (MPRA), short barcodes are counted by sequencing DNA libraries transfected into cells and the cell’s output RNA in order to s...
Source: PLoS Computational Biology - July 21, 2020 Category: Biology Authors: Andrew R. Ghazi Source Type: research

Predicting lymphatic filariasis elimination in data-limited settings: A  reconstructive computational framework for combining data generation and model discovery
by Morgan E. Smith, Emily Griswold, Brajendra K. Singh, Emmanuel Miri, Abel Eigege, Solomon Adelamo, John Umaru, Kenrick Nwodu, Yohanna Sambo, Jonathan Kadimbo, Jacob Danyobi, Frank O. Richards, Edwin Michael Although there is increasing importance placed on the use of mathematical models for the effective design and management of long-term parasite elimination, it is becoming clear that transmission models are most useful when they reflect the processes pertaining to local infection dynamics as oppose d to generalized dynamics. Such localized models must also be developed even when the data required for characterizing lo...
Source: PLoS Computational Biology - July 21, 2020 Category: Biology Authors: Morgan E. Smith Source Type: research

Multidimensional phenotyping predicts lifespan and quantifies health in < i > C < /i > . < i > elegans < /i >
by C éline N. Martineau, André E. X. Brown, Patrick Laurent Ageing affects a wide range of phenotypes at all scales, but an objective measure of ageing remains challenging, even in simple model organisms. To measure the ageing process, we characterized the sequence of alterations of multiple phenotypes at organismal scale. Hundreds of morphological, postur al, and behavioral features were extracted from high-resolution videos. Out of the 1019 features extracted, 896 are ageing biomarkers, defined as those that show a significant correlation with relative age (age divided by lifespan). We used support vector ...
Source: PLoS Computational Biology - July 21, 2020 Category: Biology Authors: C éline N. Martineau Source Type: research

Capsule networks as recurrent models of grouping and segmentation
by Adrien Doerig, Lynn Schmittwilken, Bilge Sayim, Mauro Manassi, Michael H. Herzog Classically, visual processing is described as a cascade of local feedforward computations. Feedforward Convolutional Neural Networks (ffCNNs) have shown how powerful such models can be. However, using visual crowding as a well-controlled challenge, we previously showed that no classic model of vi sion, including ffCNNs, can explain human global shape processing. Here, we show that Capsule Neural Networks (CapsNets), combining ffCNNs with recurrent grouping and segmentation, solve this challenge. We also show that ffCNNs and standard recur...
Source: PLoS Computational Biology - July 21, 2020 Category: Biology Authors: Adrien Doerig Source Type: research

Mathematical modeling of plant cell fate transitions controlled by hormonal signals
by Filip Z. Klawe, Thomas Stiehl, Peter Bastian, Christophe Gaillochet, Jan U. Lohmann, Anna Marciniak-Czochra Coordination of fate transition and cell division is crucial to maintain the plant architecture and to achieve efficient production of plant organs. In this paper, we analysed the stem cell dynamics at the shoot apical meristem (SAM) that is one of the plant stem cells locations. We designed a mat hematical model to elucidate the impact of hormonal signaling on the fate transition rates between different zones corresponding to slowly dividing stem cells and fast dividing transit amplifying cells. The model is bas...
Source: PLoS Computational Biology - July 20, 2020 Category: Biology Authors: Filip Z. Klawe Source Type: research

A novel riboswitch classification based on imbalanced sequences achieved by machine learning
by Solomon Shiferaw Beyene, Tianyi Ling, Blagoj Ristevski, Ming Chen Riboswitch, a part of regulatory mRNA (50–250nt in length), has two main classes: aptamer and expression platform. One of the main challenges raised during the classification of riboswitch is imbalanced data. That is a circumstance in which the records of a sequences of one group are very small compared to the others. Such circumstances lead classifier to ignore minority group and emphasize on majority ones, which results in a skewed classification. We considered sixteen riboswitch families, to be in accord with recent riboswitch classification wor...
Source: PLoS Computational Biology - July 20, 2020 Category: Biology Authors: Solomon Shiferaw Beyene Source Type: research

Cross-species regulatory sequence activity prediction
by David R. Kelley Machine learning algorithms trained to predict the regulatory activity of nucleic acid sequences have revealed principles of gene regulation and guided genetic variation analysis. While the human genome has been extensively annotated and studied, model organisms have been less explored. Model orga nism genomes offer both additional training sequences and unique annotations describing tissue and cell states unavailable in humans. Here, we develop a strategy to train deep convolutional neural networks simultaneously on multiple genomes and apply it to learn sequence predictors for large compend ia of huma...
Source: PLoS Computational Biology - July 20, 2020 Category: Biology Authors: David R. Kelley Source Type: research

AlbaTraDIS: Comparative analysis of large datasets from parallel transposon mutagenesis experiments
by Andrew J. Page, Sarah Bastkowski, Muhammad Yasir, A. Keith Turner, Thanh Le Viet, George M. Savva, Mark A. Webber, Ian G. Charles Bacteria need to survive in a wide range of environments. Currently, there is an incomplete understanding of the genetic basis for mechanisms underpinning survival in stressful conditions, such as the presence of anti-microbials. Transposon directed insertion-site sequencing (TraDIS) is a powerful tool to identify genes and networks which are involved in survival and fitness under a given condition by simultaneously assaying the fitness of millions of mutants, thereby relating genotype to ph...
Source: PLoS Computational Biology - July 17, 2020 Category: Biology Authors: Andrew J. Page Source Type: research

Interactions between calmodulin and neurogranin govern the dynamics of CaMKII as a leaky integrator
by Mariam Ordyan, Tom Bartol, Mary Kennedy, Padmini Rangamani, Terrence Sejnowski Calmodulin-dependent kinase II (CaMKII) has long been known to play an important role in learning and memory as well as long term potentiation (LTP). More recently it has been suggested that it might be involved in the time averaging of synaptic signals, which can then lead to the high precision o f information stored at a single synapse. However, the role of the scaffolding molecule, neurogranin (Ng), in governing the dynamics of CaMKII is not yet fully understood. In this work, we adopt a rule-based modeling approach through the Monte Carl...
Source: PLoS Computational Biology - July 17, 2020 Category: Biology Authors: Mariam Ordyan Source Type: research

Computational principles of neural adaptation for binaural signal integration
by Timo Oess, Marc O. Ernst, Heiko Neumann Adaptation to statistics of sensory inputs is an essential ability of neural systems and extends their effective operational range. Having a broad operational range facilitates to react to sensory inputs of different granularities, thus is a crucial factor for survival. The computation of auditory cues for spatial localization of sound sources, particularly the interaural level difference (ILD), has long been considered as a static process. Novel findings suggest that this process of ipsi- and contra-lateral signal integration is highly adaptive and depends strongly on recent sti...
Source: PLoS Computational Biology - July 17, 2020 Category: Biology Authors: Timo Oess Source Type: research

Data-driven contact structures: From homogeneous mixing to multilayer networks
by Alberto Aleta, Guilherme Ferraz de Arruda, Yamir Moreno The modeling of the spreading of communicable diseases has experienced significant advances in the last two decades or so. This has been possible due to the proliferation of data and the development of new methods to gather, mine and analyze it. A key role has also been played by the latest advanc es in new disciplines like network science. Nonetheless, current models still lack a faithful representation of all possible heterogeneities and features that can be extracted from data. Here, we bridge a current gap in the mathematical modeling of infectious diseases an...
Source: PLoS Computational Biology - July 16, 2020 Category: Biology Authors: Alberto Aleta Source Type: research

Estimation of neuron parameters from imperfect observations
by Joseph D. Taylor, Samuel Winnall, Alain Nogaret The estimation of parameters controlling the electrical properties of biological neurons is essential to determine their complement of ion channels and to understand the function of biological circuits. By synchronizing conductance models to time series observations of the membrane voltage, one ma y construct models capable of predicting neuronal dynamics. However, identifying the actual set of parameters of biological ion channels remains a formidable theoretical challenge. Here, we present a regularization method that improves convergence towards this optimal solution w...
Source: PLoS Computational Biology - July 16, 2020 Category: Biology Authors: Joseph D. Taylor Source Type: research

Towards optogenetic vision restoration with high resolution
by Ulisse Ferrari, St éphane Deny, Abhishek Sengupta, Romain Caplette, Francesco Trapani, José-Alain Sahel, Deniz Dalkara, Serge Picaud, Jens Duebel, Olivier Marre In many cases of inherited retinal degenerations, ganglion cells are spared despite photoreceptor cell death, making it possible to stimulate them to restore visual function. Several studies have shown that it is possible to express an optogenetic protein in ganglion cells and make them light sens itive, a promising strategy to restore vision. However the spatial resolution of optogenetically-reactivated retinas has rarely been measured, especiall...
Source: PLoS Computational Biology - July 15, 2020 Category: Biology Authors: Ulisse Ferrari Source Type: research

Perturbation biology links temporal protein changes to drug responses in a melanoma cell line
by Elin Nyman, Richard R. Stein, Xiaohong Jing, Weiqing Wang, Benjamin Marks, Ioannis K. Zervantonakis, Anil Korkut, Nicholas P. Gauthier, Chris Sander Cancer cells have genetic alterations that often directly affect intracellular protein signaling processes allowing them to bypass control mechanisms for cell death, growth and division. Cancer drugs targeting these alterations often work initially, but resistance is common. Combinations of target ed drugs may overcome or prevent resistance, but their selection requires context-specific knowledge of signaling pathways including complex interactions such as feedback loops a...
Source: PLoS Computational Biology - July 15, 2020 Category: Biology Authors: Elin Nyman Source Type: research

A mathematical model for persistent post-CSD vasoconstriction
by Shixin Xu, Joshua C. Chang, Carson C. Chow, Kevin C. Brennan, Huaxiong Huang Cortical spreading depression (CSD) is the propagation of a relatively slow wave in cortical brain tissue that is linked to a number of pathological conditions such as stroke and migraine. Most of the existing literature investigates the dynamics of short term phenomena such as the depolarization and repolarization of membrane potentials or large ion shifts. Here, we focus on the clinically-relevant hour-long state of neurovascular malfunction in the wake of CSDs. This dysfunctional state involves widespread vasoconstriction and a general disr...
Source: PLoS Computational Biology - July 15, 2020 Category: Biology Authors: Shixin Xu Source Type: research

iDrug: Integration of drug repositioning and drug-target prediction via cross-network embedding
by Huiyuan Chen, Feixiong Cheng, Jing Li Computational drug repositioning and drug-target prediction have become essential tasks in the early stage of drug discovery. In previous studies, these two tasks have often been considered separately. However, the entities studied in these two tasks (i.e., drugs, targets, and diseases) are inhere ntly related. On one hand, drugs interact with targets in cells to modulate target activities, which in turn alter biological pathways to promote healthy functions and to treat diseases. On the other hand, both drug repositioning and drug-target prediction involve the same drug feature sp...
Source: PLoS Computational Biology - July 15, 2020 Category: Biology Authors: Huiyuan Chen Source Type: research

Heterogeneous, delayed-onset killing by multiple-hitting T cells: Stochastic simulations to assess methods for analysis of imaging data
by Richard J. Beck, Dario I. Bijker, Joost B. Beltman Although quantitative insights into the killing behaviour of Cytotoxic T Lymphocytes (CTLs) are necessary for the rational design of immune-based therapies, CTL killing function remains insufficiently characterised. One established model of CTL killing treats CTL cytotoxicity as a Poisson process, based on the assumption that CTLs serially kill antigen-presenting target cells via delivery of lethal hits, each lethal hit corresponding to a single injection of cytotoxic proteins into the target cell cytoplasm. Contradicting this model, a recentin vitro study of individua...
Source: PLoS Computational Biology - July 13, 2020 Category: Biology Authors: Richard J. Beck Source Type: research

Assessing the performance of methods for copy number aberration detection from single-cell DNA sequencing data
by Xian F. Mallory, Mohammadamin Edrisi, Nicholas Navin, Luay Nakhleh Single-cell DNA sequencing technologies are enabling the study of mutations and their evolutionary trajectories in cancer. Somatic copy number aberrations (CNAs) have been implicated in the development and progression of various types of cancer. A wide array of methods for CNA detection has been e ither developed specifically for or adapted to single-cell DNA sequencing data. Understanding the strengths and limitations that are unique to each of these methods is very important for obtaining accurate copy number profiles from single-cell DNA sequencing d...
Source: PLoS Computational Biology - July 13, 2020 Category: Biology Authors: Xian F. Mallory Source Type: research

Heart failure-induced atrial remodelling promotes electrical and conduction alternans
In this study, we investigated the effects of how HF-induced atrial cellular electrophysiological (with prolonged AP duration) and tissue stru ctural (reduced cell-to-cell coupling caused by atrial fibrosis) remodelling can have an effect on the generation of atrial AP alternans and their conduction at the cellular and one-dimensional (1D) tissue levels. Simulation results showed that HF-induced atrial electrical remodelling prolonged AP d uration, which was accompanied by an increased sarcoplasmic reticulum (SR) Ca2+ content and Ca2+ transient amplitude. Further analysis demonstrated that HF-induced atrial electrical remo...
Source: PLoS Computational Biology - July 13, 2020 Category: Biology Authors: Na Zhao Source Type: research

AncesTree: An interactive immunoglobulin lineage tree visualizer
by Mathilde Foglierini, Leontios Pappas, Antonio Lanzavecchia, Davide Corti, Laurent Perez High-throughput sequencing of human immunoglobulin genes allows analysis of antibody repertoires and the reconstruction of clonal lineage evolution. The study of antibodies (Abs) affinity maturation is of specific interest to understand the generation of Abs with high affinity or broadly neutraliz ing activities. Moreover, phylogenic analysis enables the identification of the key somatic mutations required to achieve optimal antigen binding. The Immcantation framework provides a start-to-finish set of analytical methods for high-thr...
Source: PLoS Computational Biology - July 10, 2020 Category: Biology Authors: Mathilde Foglierini Source Type: research

The interplay between somatic and dendritic inhibition promotes the emergence and stabilization of place fields
by Victor Pedrosa, Claudia Clopath During the exploration of novel environments, place fields are rapidly formed in hippocampal CA1 neurons. Place cell firing rate increases in early stages of exploration of novel environments but returns to baseline levels in familiar environments. Although similar in amplitude and width, place fi elds in familiar environments are more stable than in novel environments. We propose a computational model of the hippocampal CA1 network, which describes the formation, dynamics and stabilization of place fields. We show that although somatic disinhibition is sufficient to form place fields, d...
Source: PLoS Computational Biology - July 10, 2020 Category: Biology Authors: Victor Pedrosa Source Type: research

Whole cell biophysical modeling of codon-tRNA competition reveals novel insights related to translation dynamics
We describe a whole cell model of translation forE.coli. The model simulates all major translation components in the cell: ribosomes, mRNAs and tRNAs. It also includes, for the first time, fundamental aspects of translation, such as competition for ribosomes and tRNAs at a codon resolution while considering tRNAs wobble interactions and tRNA recycling. The model uses parameters that are tightly inferred from large scale measurements of translation. Furthermore, we demonstrate a robust modelling approach which relies on state-of-the-art practices of translation modelling and also provides a framework for easy generalization...
Source: PLoS Computational Biology - July 10, 2020 Category: Biology Authors: Doron Levin Source Type: research