In silico prediction of ARB resistance: A first step in creating personalized ARB therapy
by Shane D. Anderson, Asna Tabassum, Jae Kyung Yeon, Garima Sharma, Priscilla Santos, Tik Hang Soong, Yin Win Thu, Isaac Nies, Tomomi Kurita, Andrew Chandler, Abdelaziz Alsamarah, Rhye-Samuel Kanassatega, Yun L. Luo, Wesley M. Botello-Smith, Bradley T. Andresen Angiotensin II type 1 receptor (AT1R) blockers (ARBs) are among the most prescribed drugs. However, ARB effectiveness varies widely, which may be due to non-synonymous single nucleotide polymorphisms (nsSNPs) within the AT1R gene. The AT1R coding sequence contains over 100 nsSNPs; therefore, this study embarked on determining which nsSNPs may abrogate the binding o...
Source: PLoS Computational Biology - November 25, 2020 Category: Biology Authors: Shane D. Anderson Source Type: research

Transforming the study of organisms: Phenomic data models and knowledge bases
by Anne E. Thessen, Ramona L. Walls, Lars Vogt, Jessica Singer, Robert Warren, Pier Luigi Buttigieg, James P. Balhoff, Christopher J. Mungall, Deborah L. McGuinness, Brian J. Stucky, Matthew J. Yoder, Melissa A. Haendel The rapidly decreasing cost of gene sequencing has resulted in a deluge of genomic data from across the tree of life; however, outside a few model organism databases, genomic data are limited in their scientific impact because they are not accompanied by computable phenomic data. The majority of p henomic data are contained in countless small, heterogeneous phenotypic data sets that are very difficult or i...
Source: PLoS Computational Biology - November 24, 2020 Category: Biology Authors: Anne E. Thessen Source Type: research

Breaking the circularity in circular analyses: Simulations and formal treatment of the flattened average approach
by Howard Bowman, Joseph L. Brooks, Omid Hajilou, Alexia Zoumpoulaki, Vladimir Litvak There has been considerable debate and concern as to whether there is a replication crisis in the scientific literature. A likely cause of poor replication is the multiple comparisons problem. An important way in which this problem can manifest in the M/EEG context is through post hoc tailoring of analysis windows (a.k.a. regions-of-interest, ROIs) to landmarks in the collected data. Post hoc tailoring of ROIs is used because it allows researchers to adapt to inter-experiment variability and discover novel differences that fall outside o...
Source: PLoS Computational Biology - November 23, 2020 Category: Biology Authors: Howard Bowman Source Type: research

Integrative analysis of structural variations using short-reads and linked-reads yields highly specific and sensitive predictions
In this study, we performed a comprehensive analysis of different types and sizes of SVs predicted by both the technologies and validated with an independent PCR based approach. The SVs commonly identified by both t he technologies were highly specific, while validation rate dropped for uncommon events. A particularly high FDR was observed for SVs only found by 10XWGS. To improve FDR and sensitivity, statistical models for both the technologies were trained. Using our approach, we characterized SVs from the MCF 7 cell line and a primary breast cancer tumor with high precision. This approach improves SV prediction and can t...
Source: PLoS Computational Biology - November 23, 2020 Category: Biology Authors: Riccha Sethi Source Type: research

Within-host mechanisms of immune regulation explain the contrasting dynamics of two helminth species in both single and dual infections
by Chiara Vanalli, Lorenzo Mari, Lorenzo Righetto, Renato Casagrandi, Marino Gatto, Isabella M. Cattadori Variation in the intensity and duration of infections is often driven by variation in the network and strength of host immune responses. While many of the immune mechanisms and components are known for parasitic helminths, how these relationships change from single to multiple infections and impac t helminth dynamics remains largely unclear. Here, we used laboratory data from a rabbit-helminth system and developed a within-host model of infection to investigate different scenarios of immune regulation in rabbits infec...
Source: PLoS Computational Biology - November 23, 2020 Category: Biology Authors: Chiara Vanalli Source Type: research

A dual-feedback loop model of the mammalian circadian clock for multi-input control of circadian phase
by Lindsey S. Brown, Francis J. Doyle III The molecular circadian clock is driven by interlocked transcriptional-translational feedback loops, producing oscillations in the expressions of genes and proteins to coordinate the timing of biological processes throughout the body. Modeling this system gives insight into the underlying processe s driving oscillations in an activator-repressor architecture and allows us to make predictions about how to manipulate these oscillations. The knockdown or upregulation of different cellular components using small molecules can disrupt these rhythms, causing a phase shift, and we aim to...
Source: PLoS Computational Biology - November 23, 2020 Category: Biology Authors: Lindsey S. Brown Source Type: research

Poisson balanced spiking networks
by Camille E. Rull án Buxó, Jonathan W. Pillow An important problem in computational neuroscience is to understand how networks of spiking neurons can carry out various computations underlying behavior. Balanced spiking networks (BSNs) provide a powerful framework for implementing arbitrary linear dynamical systems in networks of integrate-and -fire neurons. However, the classic BSN model requires near-instantaneous transmission of spikes between neurons, which is biologically implausible. Introducing realistic synaptic delays leads to an pathological regime known as “ping-ponging”, in which diff...
Source: PLoS Computational Biology - November 20, 2020 Category: Biology Authors: Camille E. Rull án Buxó Source Type: research

< i > EventEpi < /i > —A natural language processing framework for event-based surveillance
by Auss Abbood, Alexander Ullrich, R üdiger Busche, Stéphane Ghozzi According to the World Health Organization (WHO), around 60% of all outbreaks are detected using informal sources. In many public health institutes, including the WHO and the Robert Koch Institute (RKI), dedicated groups of public health agents sift through numerous articles and newsletters to det ect relevant events. This media screening is one important part of event-based surveillance (EBS). Reading the articles, discussing their relevance, and putting key information into a database is a time-consuming process. To support EBS, but also to ...
Source: PLoS Computational Biology - November 20, 2020 Category: Biology Authors: Auss Abbood Source Type: research

Modeling HIV-1 infection in the brain
In this study we develop a novel mathematical model that describes HIV-1 infection in the brain and in the plasma coupled via the BBB. The model predictions are consistent with data from macaques infected with a mixture of simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV). Using our model, we estimate the rate of virus transport across the BBB as well as viral replication inside the brain, and we compute the basic reproduction number. We also carry out thorough sensitivity analysis to define the robustness of the model predictions on virus dynamics inside the brain. Our model provides usefu...
Source: PLoS Computational Biology - November 19, 2020 Category: Biology Authors: Colin T. Barker Source Type: research

Ten simple rules for increased lab resilience
by Matthias C. Rillig, Milos Bielcik, V. Bala Chaudhary, Leonie Gr ünfeld, Stefanie Maaß, India Mansour, Masahiro Ryo, Stavros D. Veresoglou When running a lab we do not think about calamities, since they are rare events for which we cannot plan while we are busy with the day-to-day management and intellectual challenges of a research lab. No lab team can be prepared for something like a pandemic such as COVID-19, which has led to shut tered labs around the globe. But many other types of crises can also arise that labs may have to weather during their lifetime. What can researchers do to make a lab more resilie...
Source: PLoS Computational Biology - November 19, 2020 Category: Biology Authors: Matthias C. Rillig Source Type: research

Ten simple rules for starting research in your late teens
by Cameron Mura, Mike Chalupa, Abigail M. Newbury, Jack Chalupa, Philip E. Bourne (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - November 19, 2020 Category: Biology Authors: Cameron Mura Source Type: research

Evolution of multicellular life cycles under costly fragmentation
by Yuriy Pichugin, Arne Traulsen A fascinating wealth of life cycles is observed in biology, from unicellularity to the concerted fragmentation of multicellular units. However, the understanding of factors driving their evolution is still limited. We show that costs of fragmentation have a major impact on the evolution of life cy cles due to their influence on the growth rates of the associated populations. We model a group structured population of undifferentiated cells, where cell clusters reproduce by fragmentation. Fragmentation events are associated with a cost expressed by either a fragmentation delay, an additional...
Source: PLoS Computational Biology - November 19, 2020 Category: Biology Authors: Yuriy Pichugin Source Type: research

Systems biology informed deep learning for inferring parameters and hidden dynamics
by Alireza Yazdani, Lu Lu, Maziar Raissi, George Em Karniadakis Mathematical models of biological reactions at the system-level lead to a set of ordinary differential equations with many unknown parameters that need to be inferred using relatively few experimental measurements. Having a reliable and robust algorithm for parameter inference and prediction of th e hidden dynamics has been one of the core subjects in systems biology, and is the focus of this study. We have developed a new systems-biology-informed deep learning algorithm that incorporates the system of ordinary differential equations into the neural networks....
Source: PLoS Computational Biology - November 18, 2020 Category: Biology Authors: Alireza Yazdani Source Type: research

BioAFMviewer: An interactive interface for simulated AFM scanning of biomolecular structures and dynamics
by Romain Amyot, Holger Flechsig We provide a stand-alone software, the BioAFMviewer, which transforms biomolecular structures into the graphical representation corresponding to the outcome of atomic force microscopy (AFM) experiments. The AFM graphics is obtained by performing simulated scanning over the molecular structure enco ded in the corresponding PDB file. A versatile molecular viewer integrates the visualization of PDB structures and control over their orientation, while synchronized simulated scanning with variable spatial resolution and tip-shape geometry produces the corresponding AFM graphics. We demonstrate ...
Source: PLoS Computational Biology - November 18, 2020 Category: Biology Authors: Romain Amyot Source Type: research

DeepPheno: Predicting single gene loss-of-function phenotypes using an ontology-aware hierarchical classifier
by Maxat Kulmanov, Robert Hoehndorf Predicting the phenotypes resulting from molecular perturbations is one of the key challenges in genetics. Both forward and reverse genetic screen are employed to identify the molecular mechanisms underlying phenotypes and disease, and these resulted in a large number of genotype–phenotype assoc iation being available for humans and model organisms. Combined with recent advances in machine learning, it may now be possible to predict human phenotypes resulting from particular molecular aberrations. We developed DeepPheno, a neural network based hierarchical multi-class multi-label ...
Source: PLoS Computational Biology - November 18, 2020 Category: Biology Authors: Maxat Kulmanov Source Type: research

Validation of DBFOLD: An efficient algorithm for computing folding pathways of complex proteins
by Amir Bitran, William M. Jacobs, Eugene Shakhnovich Atomistic simulations can provide valuable, experimentally-verifiable insights into protein folding mechanisms, but existingab initio simulation methods are restricted to only the smallest proteins due to severe computational speed limits. The folding of larger proteins has been studied using native-centric potential functions, but such models omit the potentially crucial role of non-native interactions. Here, we present an algorithm, entitled DBFOLD, which can predict folding pathways for a wide range of proteins while accounting for the effects of non-native contacts...
Source: PLoS Computational Biology - November 16, 2020 Category: Biology Authors: Amir Bitran Source Type: research

Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus
by Jingwei Ma, Myan Do, Mark. A. Le Gros, Charles S. Peskin, Carolyn A. Larabell, Yoichiro Mori, Samuel A. Isaacson For a chemical signal to propagate across a cell, it must navigate a tortuous environment involving a variety of organelle barriers. In this work we study mathematical models for a basic chemical signal, the arrival times at the nuclear membrane of proteins that are activated at the cell membrane and diffuse throughout the cytosol. Organelle surfaces within human B cells are reconstructed from soft X-ray tomographic images, and modeled as reflecting barriers to the molecules’ diffusion. We show that si...
Source: PLoS Computational Biology - November 16, 2020 Category: Biology Authors: Jingwei Ma Source Type: research

Speed of phototransduction in the microvillus regulates the accuracy and bandwidth of the rhabdomeric photoreceptor
by Roman V. Frolov, Irina I. Ignatova Phototransduction reactions in the rhabdomeric photoreceptor are profoundly stochastic due to the small number of participating molecules and small reaction space. The resulting quantum bumps (QBs) vary in their timing (latency), amplitudes and durations, and these variabilities within each cell a re not correlated. Using modeling and electrophysiological recordings, we investigated how the QB properties depend on the cascade speed and how they influence signal transfer. Parametric analysis in the model supported by experimental data revealed that faster cascades elicit larger and nar...
Source: PLoS Computational Biology - November 16, 2020 Category: Biology Authors: Roman V. Frolov Source Type: research

Twelve quick steps for genome assembly and annotation in the classroom
by Hyungtaek Jung, Tomer Ventura, J. Sook Chung, Woo-Jin Kim, Bo-Hye Nam, Hee Jeong Kong, Young-Ok Kim, Min-Seung Jeon, Seong-il Eyun Eukaryotic genome sequencing and de novo assembly, once the exclusive domain of well-funded international consortia, have become increasingly affordable, thus fitting the budgets of individual research groups. Third-generation long-read DNA sequencing technologies are increasingly used, providing extensive genomic toolkits that were once reserved for a few select model organisms. Generating high-quality genome assemblies and annotations for many aquatic species still presents significant ch...
Source: PLoS Computational Biology - November 12, 2020 Category: Biology Authors: Hyungtaek Jung Source Type: research

Dedicated transcriptomics combined with power analysis lead to functional understanding of genes with weak phenotypic changes in knockout lines
by Chen Xie, Cemalettin Bekpen, Sven K ünzel, Maryam Keshavarz, Rebecca Krebs-Wheaton, Neva Skrabar, Kristian K. Ullrich, Wenyu Zhang, Diethard Tautz Systematic knockout studies in mice have shown that a large fraction of the gene replacements show no lethal or other overt phenotypes. This has led to the development of more refined analysis schemes, including physiological, behavioral, developmental and cytological tests. However, transcriptomi c analyses have not yet been systematically evaluated for non-lethal knockouts. We conducted a power analysis to determine the experimental conditions under which even small c...
Source: PLoS Computational Biology - November 12, 2020 Category: Biology Authors: Chen Xie Source Type: research

Ten simple rules for writing a paper about scientific software
by Joseph D. Romano, Jason H. Moore Papers describing software are an important part of computational fields of scientific research. These “software papers” are unique in a number of ways, and they require special consideration to improve their impact on the scientific community and their efficacy at conveying important informat ion. Here, we discuss 10 specific rules for writing software papers, covering some of the different scenarios and publication types that might be encountered, and important questions from which all computational researchers would benefit by asking along the way. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - November 12, 2020 Category: Biology Authors: Joseph D. Romano Source Type: research

Machine learning assisted intraoperative assessment of brain tumor margins using HRMAS NMR spectroscopy
by Doruk Cakmakci, Emin Onur Karakaslar, Elisa Ruhland, Marie-Pierre Chenard, Francois Proust, Martial Piotto, Izzie Jacques Namer, A. Ercument Cicek Complete resection of the tumor is important for survival in glioma patients. Even if the gross total resection was achieved, left-over micro-scale tissue in the excision cavity risks recurrence. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) technique can distinguish healthy and malign tissue efficiently using peak intensities of biomarker metabolites. The method is fast, sensitive and can work with small and unprocessed samples, which makes it ...
Source: PLoS Computational Biology - November 11, 2020 Category: Biology Authors: Doruk Cakmakci Source Type: research

Few-shot learning for classification of novel macromolecular structures in cryo-electron tomograms
by Ran Li, Liangyong Yu, Bo Zhou, Xiangrui Zeng, Zhenyu Wang, Xiaoyan Yang, Jing Zhang, Xin Gao, Rui Jiang, Min Xu Cryo-electron tomography (cryo-ET) provides 3D visualization of subcellular components in the near-native state and at sub-molecular resolutions in single cells, demonstrating an increasingly important role in structural biologyin situ. However, systematic recognition and recovery of macromolecular structures in cryo-ET data remain challenging as a result of low signal-to-noise ratio (SNR), small sizes of macromolecules, and high complexity of the cellular environment. Subtomogram structural classification is...
Source: PLoS Computational Biology - November 11, 2020 Category: Biology Authors: Ran Li Source Type: research

Using B cell receptor lineage structures to predict affinity
by Duncan K. Ralph, Frederick A. Matsen IV CommentsPlease post comments or questions on this paper as new issues at https://git.io/Jvxkn. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - November 11, 2020 Category: Biology Authors: Duncan K. Ralph Source Type: research

Deep learning predicts short non-coding RNA functions from only raw sequence data
by Teresa Maria Rosaria Noviello, Francesco Ceccarelli, Michele Ceccarelli, Luigi Cerulo Small non-coding RNAs (ncRNAs) are short non-coding sequences involved in gene regulation in many biological processes and diseases. The lack of a complete comprehension of their biological functionality, especially in a genome-wide scenario, has demanded new computational approaches to annotate t heir roles. It is widely known that secondary structure is determinant to know RNA function and machine learning based approaches have been successfully proven to predict RNA function from secondary structure information. Here we show that R...
Source: PLoS Computational Biology - November 11, 2020 Category: Biology Authors: Teresa Maria Rosaria Noviello Source Type: research

Ten simple rules for writing Dockerfiles for reproducible data science
by Daniel N üst, Vanessa Sochat, Ben Marwick, Stephen J. Eglen, Tim Head, Tony Hirst, Benjamin D. Evans Computational science has been greatly improved by the use of containers for packaging software and data dependencies. In a scholarly context, the main drivers for using these containers are transparency and support of reproducibility; in turn, a workflow’s reproducibility can be greatly affecte d by the choices that are made with respect to building containers. In many cases, the build process for the container’s image is created from instructions provided in a Dockerfile format. In support of this app...
Source: PLoS Computational Biology - November 10, 2020 Category: Biology Authors: Daniel N üst Source Type: research

Astrocyte-mediated spike-timing-dependent long-term depression modulates synaptic properties in the developing cortex
by Tiina Manninen, Ausra Saudargiene, Marja-Leena Linne Astrocytes have been shown to modulate synaptic transmission and plasticity in specific cortical synapses, but our understanding of the underlying molecular and cellular mechanisms remains limited. Here we present a new biophysicochemical model of a somatosensory cortical layer 4 to layer 2/3 syna pse to study the role of astrocytes in spike-timing-dependent long-term depression (t-LTD)in vivo. By applying the synapse model and electrophysiological data recorded from rodent somatosensory cortex, we show that a signal from a postsynaptic neuron, orchestrated by endoca...
Source: PLoS Computational Biology - November 10, 2020 Category: Biology Authors: Tiina Manninen Source Type: research

A semi-supervised Bayesian approach for simultaneous protein sub-cellular localisation assignment and novelty detection
by Oliver M. Crook, Aikaterini Geladaki, Daniel J. H. Nightingale, Owen Vennard, Kathryn S. Lilley, Laurent Gatto, Paul D. W. Kirk The cell is compartmentalised into complex micro-environments allowing an array of specialised biological processes to be carried out in synchrony. Determining a protein’s sub-cellular localisation to one or more of these compartments can therefore be a first step in determining its function. Hi gh-throughput and high-accuracy mass spectrometry-based sub-cellular proteomic methods can now shed light on the localisation of thousands of proteins at once. Machine learning algorithms are the...
Source: PLoS Computational Biology - November 9, 2020 Category: Biology Authors: Oliver M. Crook Source Type: research

The interplay between cancer type, panel size and tumor mutational burden threshold in patient selection for cancer immunotherapy
by Mahdi Golkaram, Chen Zhao, Kristina Kruglyak, Shile Zhang, Sven Bilke The tumor mutational burden (TMB) is increasingly recognized as an emerging biomarker that predicts improved outcomes or response to immune checkpoint inhibitors in cancer. A multitude of technical and biological factors make it difficult to compare TMB values across platforms, histologies, and tr eatments. Here, we present a mechanistic model that explains the association between panel size, histology, and TMB threshold with panel performance and survival outcome and demonstrate the limitations of existing methods utilized to harmonize TMB across pl...
Source: PLoS Computational Biology - November 9, 2020 Category: Biology Authors: Mahdi Golkaram Source Type: research

Arioc: High-concurrency short-read alignment on multiple GPUs
by Richard Wilton, Alexander S. Szalay In large DNA sequence repositories, archival data storage is often coupled with computers that provide 40 or more CPU threads and multiple GPU (general-purpose graphics processing unit) devices. This presents an opportunity for DNA sequence alignment software to exploit high-concurrency hardware t o generate short-read alignments at high speed. Arioc, a GPU-accelerated short-read aligner, can compute WGS (whole-genome sequencing) alignments ten times faster than comparable CPU-only alignment software. When two or more GPUs are available, Arioc's speed increases proportionately becaus...
Source: PLoS Computational Biology - November 9, 2020 Category: Biology Authors: Richard Wilton Source Type: research

Cancer classification based on chromatin accessibility profiles with deep adversarial learning model
In this study, based on the deep adversarial learning, we present an end-to-end approach ClusterATAC to leverage high-dimensional features and explore the classification results. On the ATAC-seq dataset and RNA-seq dataset, ClusterATAC has achieved exc ellent performance. Since ATAC-seq data plays a crucial role in the study of the effects of non-coding regions on the molecular classification of cancers, we explore the clustering solution obtained by ClusterATAC on the pan-cancer ATAC dataset. In this solution, more than 70% of the clustering are single-tumor-type-dominant, and the vast majority of the remaining clusters a...
Source: PLoS Computational Biology - November 9, 2020 Category: Biology Authors: Hai Yang Source Type: research

Neural mass modeling of slow-fast dynamics of seizure initiation and abortion
by Elif K öksal Ersöz, Julien Modolo, Fabrice Bartolomei, Fabrice Wendling Epilepsy is a dynamic and complex neurological disease affecting about 1% of the worldwide population, among which 30% of the patients are drug-resistant. Epilepsy is characterized by recurrent episodes of paroxysmal neural discharges (the so-called seizures), which manifest themselves through a l arge-amplitude rhythmic activity observed in depth-EEG recordings, in particular in local field potentials (LFPs). The signature characterizing the transition to seizures involves complex oscillatory patterns, which could serve as a marker to pr...
Source: PLoS Computational Biology - November 9, 2020 Category: Biology Authors: Elif K öksal Ersöz Source Type: research

Maximizing the reusability of gene expression data by predicting missing metadata
In this study, we developed a framework to predict the missing metadata of gene expression datasets to maximize their reusability. We found that when using predicted data to conduct other analyses, it is not optimal to use all th e predicted data. Instead, one should only use the subset of data, which can be predicted accurately. We proposed a new metric called Proportion of Cases Accurately Predicted (PCAP), which is optimized in our specifically-designed machine learning pipeline. The new approach performed better than pip elines using commonly used metrics such as F1-score in terms of maximizing the reusability of data ...
Source: PLoS Computational Biology - November 6, 2020 Category: Biology Authors: Pei-Yau Lung Source Type: research

Interspike intervals within retinal spike bursts combinatorially encode multiple stimulus features
In this study, we demonstrate that such combinatorial coding occurs for retinal bursts. By recording ganglion cell spikes from isolated salamander retinae, we found that intraburst ISIs encode oscillatory light sequences that are much faster than the light intensity modulation encoded by the number of spikes. When a burst has three spikes, the two intraburst ISIs combinatorially encode the amplitude and phase of the oscillatory sequence. Analysis of trial-to-trial variability suggested that intraburst ISIs are regulated by two independent mechanisms responding to orthogonal oscillatory components, one of which is common to...
Source: PLoS Computational Biology - November 6, 2020 Category: Biology Authors: Toshiyuki Ishii Source Type: research

Quantitative comparison between sub-millisecond time resolution single-molecule FRET measurements and 10-second molecular simulations of a biosensor protein
by Dylan Girodat, Avik K. Pati, Daniel S. Terry, Scott C. Blanchard, Karissa Y. Sanbonmatsu Molecular Dynamics (MD) simulations seek to provide atomic-level insights into conformationally dynamic biological systems at experimentally relevant time resolutions, such as those afforded by single-molecule fluorescence measurements. However, limitations in the time scales of MD simulations and the time resolution of single-molecule measurements have challenged efforts to obtain overlapping temporal regimes required for close quantitative comparisons. Achieving such overlap has the potential to provide novel theories, hypotheses...
Source: PLoS Computational Biology - November 5, 2020 Category: Biology Authors: Dylan Girodat Source Type: research

Poly(A)-DG: A deep-learning-based domain generalization method to identify cross-species Poly(A) signal without prior knowledge from target species
by Yumin Zheng, Haohan Wang, Yang Zhang, Xin Gao, Eric P. Xing, Min Xu In eukaryotes, polyadenylation (poly(A)) is an essential process during mRNA maturation. Identifying thecis-determinants of poly(A) signal (PAS) on the DNA sequence is the key to understand the mechanism of translation regulation and mRNA metabolism. Although machine learning methods were widely used in computationally identifying PAS, the need for tremendous amounts of annotation data hinder applications of existing methods in species without experimental data on PAS. Therefore, cross-species PAS identification, which enables the possibility to predic...
Source: PLoS Computational Biology - November 5, 2020 Category: Biology Authors: Yumin Zheng Source Type: research

Using interactive digital notebooks for bioscience and informatics education
by Alan Davies, Frances Hooley, Peter Causey-Freeman, Iliada Eleftheriou, Georgina Moulton Interactive digital notebooks provide an opportunity for researchers and educators to carry out data analysis and report the results in a single digital format. Further to just being digital, the format allows for rich content to be created in order to interact with the code and data contained in such a notebook to form an educational narrative. This primer introduces some of the fundamental aspects involved in using Jupyter notebooks in an educational setting for teaching in the bio/health informatics disciplines. We also provide 2...
Source: PLoS Computational Biology - November 5, 2020 Category: Biology Authors: Alan Davies Source Type: research

The Moran process on 2-chromatic graphs
In this study, we represent a collection of properties affecting the fitness at a given location using a colo r. A green node is rich in resources while a red node is poorer. More colors can represent a broader spectrum of resource qualities. For a population evolving according to the birth-death Moran model, the first question we address is which structures, identified by graph connectivity and graph color ing, are evolutionarily equivalent. We prove that all properly two-colored, undirected, regular graphs are evolutionarily equivalent (where “properly colored” means that no two neighbors have the same color)...
Source: PLoS Computational Biology - November 5, 2020 Category: Biology Authors: Kamran Kaveh Source Type: research

Mathematical modeling of hepatitis C RNA replication, exosome secretion and virus release
by Carolin Zitzmann, Lars Kaderali, Alan S. Perelson Hepatitis C virus (HCV) causes acute hepatitis C and can lead to life-threating complications if it becomes chronic. The HCV genome is a single plus strand of RNA. Its intracellular replication is a spatiotemporally coordinated process of RNA translation upon cell infection, RNA synthesis within a replication compartment, and virus particle production. While HCV is mainly transmitted via mature infectious virus particles, it has also been suggested that HCV-infected cells can secrete HCV RNA carrying exosomes that can infect cells in a receptor independent manner. In or...
Source: PLoS Computational Biology - November 5, 2020 Category: Biology Authors: Carolin Zitzmann Source Type: research

PPM-Decay: A computational model of auditory prediction with memory decay
by Peter M. C. Harrison, Roberta Bianco, Maria Chait, Marcus T. Pearce Statistical learning and probabilistic prediction are fundamental processes in auditory cognition. A prominent computational model of these processes is Prediction by Partial Matching (PPM), a variable-order Markov model that learns by internalizingn-grams from training sequences. However, PPM has limitations as a cognitive model: in particular, it has a perfect memory that weights all historic observations equally, which is inconsistent with memory capacity constraints and recency effects observed in human cognition. We address these limitations with ...
Source: PLoS Computational Biology - November 4, 2020 Category: Biology Authors: Peter M. C. Harrison Source Type: research

Canard analysis reveals why a large Ca < sup > 2+ < /sup > window current promotes early afterdepolarizations in cardiac myocytes
by Joshua Kimrey, Theodore Vo, Richard Bertram The pumping of blood through the heart is due to a wave of muscle contractions that are in turn due to a wave of electrical activity initiated at the sinoatrial node. At the cellular level, this wave of electrical activity corresponds to the sequential excitation of electrically coupled cardiac ce lls. Under some conditions, the normally-long action potentials of cardiac cells are extended even further by small oscillations called early afterdepolarizations (EADs) that can occur either during the plateau phase or repolarizing phase of the action potential. Hence, cellular EAD...
Source: PLoS Computational Biology - November 4, 2020 Category: Biology Authors: Joshua Kimrey Source Type: research

Testing structural identifiability by a simple scaling method
by Mario Castro, Rob J. de Boer Successful mathematical modeling of biological processes relies on the expertise of the modeler to capture the essential mechanisms in the process at hand and on the ability to extract useful information from empirical data. A model is said to be structurally unidentifiable, if different quantitat ive sets of parameters provide the same observable outcome. This is typical (but not exclusive) of partially observed problems in which only a few variables can be experimentally measured. Most of the available methods to test the structural identifiability of a model are either too complex mathem...
Source: PLoS Computational Biology - November 3, 2020 Category: Biology Authors: Mario Castro Source Type: research

A recurrent neural network framework for flexible and adaptive decision making based on sequence learning
by Zhewei Zhang, Huzi Cheng, Tianming Yang The brain makes flexible and adaptive responses in a complicated and ever-changing environment for an organism’s survival. To achieve this, the brain needs to understand the contingencies between its sensory inputs, actions, and rewards. This is analogous to the statistical inference that has be en extensively studied in the natural language processing field, where recent developments of recurrent neural networks have found many successes. We wonder whether these neural networks, the gated recurrent unit (GRU) networks in particular, reflect how the brain solves the conting...
Source: PLoS Computational Biology - November 3, 2020 Category: Biology Authors: Zhewei Zhang Source Type: research

PhANNs, a fast and accurate tool and web server to classify phage structural proteins
by Vito Adrian Cantu, Peter Salamon, Victor Seguritan, Jackson Redfield, David Salamon, Robert A. Edwards, Anca M. Segall For any given bacteriophage genome or phage-derived sequences in metagenomic data sets, we are unable to assign a function to 50–90% of genes, or more. Structural protein-encoding genes constitute a large fraction of the average phage genome and are among the most divergent and difficult-to-iden tify genes using homology-based methods. To understand the functions encoded by phages, their contributions to their environments, and to help gauge their utility as potential phage therapy agents, we hav...
Source: PLoS Computational Biology - November 2, 2020 Category: Biology Authors: Vito Adrian Cantu Source Type: research

Tracking and predicting U.S. influenza activity with a real-time surveillance network
by Sequoia I. Leuba, Reza Yaesoubi, Marina Antillon, Ted Cohen, Christoph Zimmer Each year in the United States, influenza causes illness in 9.2 to 35.6 million individuals and is responsible for 12,000 to 56,000 deaths. The U.S. Centers for Disease Control and Prevention (CDC) tracks influenza activity through a national surveillance network. These data are only available aft er a delay of 1 to 2 weeks, and thus influenza epidemiologists and transmission modelers have explored the use of other data sources to produce more timely estimates and predictions of influenza activity. We evaluated whether data collected from a n...
Source: PLoS Computational Biology - November 2, 2020 Category: Biology Authors: Sequoia I. Leuba Source Type: research

Galaxy and Apollo as a biologist-friendly interface for high-quality cooperative phage genome annotation
We describe in detail programs for finding Shine-Dalgarno sequences, resources used for confident identification of lysis genes such as spanins, and methods used for identifying interrupted genes that contain frameshifts or intro ns. At the CPT, genome annotation is separated into two robust segments that are facilitated through the automated execution of many tools chained together in an operation called a workflow. First, the structural annotation workflow results in gene and other feature calls. This is followed by a func tional annotation workflow that combines sequence comparisons and conserved domain searching, which...
Source: PLoS Computational Biology - November 2, 2020 Category: Biology Authors: Jolene Ramsey Source Type: research

Leveraging functional annotation to identify genes associated with complex diseases
by Wei Liu, Mo Li, Wenfeng Zhang, Geyu Zhou, Xing Wu, Jiawei Wang, Qiongshi Lu, Hongyu Zhao To increase statistical power to identify genes associated with complex traits, a number of transcriptome-wide association study (TWAS) methods have been proposed using gene expression as a mediating trait linking genetic variations and diseases. These methods first predict expression levels based on inferred expression quantitative trait loci (eQTLs) and then identify expression-mediated genetic effects on diseases by associating phenotypes with predicted expression levels. The success of these methods critically depends on the id...
Source: PLoS Computational Biology - November 2, 2020 Category: Biology Authors: Wei Liu Source Type: research

Learning and interpreting the gene regulatory grammar in a deep learning framework
by Ling Chen, John A. Capra Deep neural networks (DNNs) have achieved state-of-the-art performance in identifying gene regulatory sequences, but they have provided limited insight into the biology of regulatory elements due to the difficulty of interpreting the complex features they learn. Several models of how combinatorial binding of transcription factors, i.e. the regulatory grammar, drives enhancer activity have been proposed, ranging from the flexible TF billboard model to the stringent enhanceosome model. However, there is limited knowledge of the prevalence of these (or other) sequence architectures across enhan ce...
Source: PLoS Computational Biology - November 2, 2020 Category: Biology Authors: Ling Chen Source Type: research

Quantification of Ebola virus replication kinetics in vitro
by Laura E. Liao, Jonathan Carruthers, Sophie J. Smither, CL4 Virology Team , Simon A. Weller, Diane Williamson, Thomas R. Laws, Isabel Garc ía-Dorival, Julian Hiscox, Benjamin P. Holder, Catherine A. A. Beauchemin, Alan S. Perelson, Martín López-García, Grant Lythe, John Barr, Carmen Molina-París Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola modelling efforts have primarily focused onin vivo ...
Source: PLoS Computational Biology - November 2, 2020 Category: Biology Authors: Laura E. Liao Source Type: research

Stochastic colonization of hosts with a finite lifespan can drive individual host microbes out of equilibrium
We present a mathematical model of this process with a particular emphasis on the effect of ecological drift and a finite host lifespan. Our results indicate the host lifespan becomes especially relevant for short-living organisms (e.g.Caenorhabditis elegans,Drosophila melanogaster, andDanio rerio). In this case, alternative microbiome states (often called enterotypes), the coexistence of microbe-free and colonized hosts, and a reduced probability of colonization can be observed in our model. These results unify multiple reported observations around colonization and suggest that no selective or deterministic drivers are ne...
Source: PLoS Computational Biology - November 2, 2020 Category: Biology Authors: Rom án Zapién-Campos Source Type: research