Computational biology and bioinformatics articles within Nature Communications

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  • Article
    | Open Access

    Tumours frequently metastasize to multiple anatomical sites and understanding how these different metastases evolve may be important for therapy. Here, the authors develop a method—Treeomics—that can construct phylogenies from multiple metastases from next-generation sequencing data.

    • Johannes G. Reiter
    • , Alvin P. Makohon-Moore
    •  & Martin A. Nowak

  • Article
    | Open Access

    Fission yeastSchizosaccharomyces pombe has diverse traits. Jeffares et al. characterize large copy number variations (CNVs) and rearrangements in S. pombe, and show that CNVs are transient with effects on quantitative traits and gene expression, whereas rearrangements influence intrinsic reproductive isolation.

    • Daniel C. Jeffares
    • , Clemency Jolly
    •  & Fritz J. Sedlazeck

  • Article
    | Open Access

    Embryonic development is a complex process where genetic and biochemical information direct morphogenesis. Here the authors describe MecaGen, an agent-based model and simulation platform of multicellular development designed to allow a quantitative comparison between simulations and real biological data.

    • Julien Delile
    • , Matthieu Herrmann
    •  & René Doursat

  • Article
    | Open Access

    Currently available metagenomic data analysis relies on reference genomes. Here, the authors describe a newde novometagenomic assembly method, metaSort, that constructs bacterial genomes from metagenomic samples to reduce microbial community complexity while increasing genome recovery and assembly.

    • Peifeng Ji
    • , Yanming Zhang
    •  & Fangqing Zhao

  • Article
    | Open Access

    Experience constantly shapes perception, but the neural mechanisms of this rapid plasticity are unclear. Here, Holdgraf et al. record neural activity in the human auditory cortex and show that listening to normal speech elicits rapid plasticity that increases the neural gain for features of sound that are key for speech intelligibility.

    • Christopher R. Holdgraf
    • , Wendy de Heer
    •  & Frédéric E. Theunissen

  • Article
    | Open Access

    Altered DNA methylation is a feature of cancer and between-patient variability is prevalent. Here, the authors integrate data on thousands of human tumours, and find that expression levels of methionine metabolism genes are predictive of methylation features, and that the breakdown of this relationship is a negative prognostic marker.

    • Mahya Mehrmohamadi
    • , Lucas K. Mentch
    •  & Jason W. Locasale

  • Article
    | Open Access

    Formation and reinforcement of E-cadherin-mediated adhesion depends on intracellular trafficking and interactions with the actin cytoskeleton, but how these are coordinated is not known. Here the authors conduct a focused phenotypic screen to identify new pathways regulating cell–cell junction homeostasis.

    • J. C. Erasmus
    • , S. Bruche
    •  & V. M. M. Braga

  • Article
    | Open Access

    Experimenter scoring of cellular imaging data can be biased. This study describes an automated and unbiased multidimensional phenotyping method that relies on machine learning and complex feature computation of imaging data, and identifies weak alleles affecting synapse morphology in live C. elegans.

    • Adriana San-Miguel
    • , Peri T. Kurshan
    •  & Hang Lu

  • Article
    | Open Access

    mTORC1 is known to mediate the signalling activity of amino acids. Here, the authors combine modelling with experiments and find that amino acids acutely stimulate mTORC2, IRS/PI3K and AMPK, independently of mTORC1. AMPK activation through CaMKKβ sustains autophagy under non-starvation conditions.

    • Piero Dalle Pezze
    • , Stefanie Ruf
    •  & Kathrin Thedieck

  • Article
    | Open Access

    Identification of the function of proteins is difficult when there are no structurally or biochemically characterized homologs. Here, the authors present an approach that allows the prediction of nucleic-acid binding proteins based on sequence alone, and they are able to experimentally validate their method.

    • Sapir Peled
    • , Olga Leiderman
    •  & Yanay Ofran

  • Article
    | Open Access

    Early embryonic cell fate and lineage specification is tightly regulated in the preimplantation mammalian embryo. Here, the authors quantitatively examine the ratio of epiblast to primitive endoderm lineages in the blastocyst and show composition of the inner cell mass is conserved, independent of its size.

    • Néstor Saiz
    • , Kiah M. Williams
    •  & Anna-Katerina Hadjantonakis

  • Article
    | Open Access

    Protein repeats may be considered a paradox, being evolutionarily conserved yet also hotspots of protein evolution associated with innovation. Here, the authors use a novel method to show that new repeats undergo rapid divergence within species, but are then fixed and conserved between species.

    • Erez Persi
    • , Yuri I. Wolf
    •  & Eugene V Koonin

  • Article
    | Open Access

    Pathway analysis aids interpretation of large-scale gene expression data, but existing algorithms fall short of providing robust pathway identification. The method introduced here includes coexpression analysis and gene importance estimation to robustly identify relevant pathways and biomarkers for patient stratification.

    • Ivan V. Ozerov
    • , Ksenia V. Lezhnina
    •  & Alex Zhavoronkov

  • Article
    | Open Access

    Currently available methods for phenotype to genetic markers association need to account for population structure. Here, Klasen et al. devise a statistical method called Quantitative Trait Cluster Association Test (QTCAT) that overcomes the need for population structure correction.

    • Jonas R. Klasen
    • , Elke Barbez
    •  & Korbinian Schneeberger

  • Article
    | Open Access

    Knockout collections provide a valuable tool to explore gene function, yet are expensive and technically challenging to produce at a genome-wide scale. Here Baym et al. devise a cost-effective transposon-based method to quickly develop a knockout collection for the electroactive microbe Shewanella oneidensis.

    • Michael Baym
    • , Lev Shaket
    •  & Buz Barstow

  • Article
    | Open Access

    MHCII proteins bind and present both foreign and self-antigens to potentially activate CD4+ T cells via cognate T cell receptors (TCRs) during the adaptive immune response. Here, the authors combine NMR-detected H/D exchange with Markov modelling analysis to shed light on the dynamics of MHCII peptide exchange.

    • Marek Wieczorek
    • , Jana Sticht
    •  & Christian Freund

  • Article
    | Open Access

    Multi-layered neural architectures that implement learning require elaborate mechanisms for symmetric backpropagation of errors that are biologically implausible. Here the authors propose a simple resolution to this problem of blame assignment that works even with feedback using random synaptic weights.

    • Timothy P. Lillicrap
    • , Daniel Cownden
    •  & Colin J. Akerman

  • Article
    | Open Access

    Accurate estimations of the frequency distribution of rare variants are needed to quantify the discovery power and guide large-scale human sequencing projects. This study describes an algorithm called UnseenEst to estimate the distribution of genetic variations using tens of thousands of exomes.

    • James Zou
    • , Gregory Valiant
    •  & Daniel G. MacArthur

  • Article
    | Open Access

    Early vestibular pathways are thought to code sensory inputs regarding self-motion via changes in firing rate. Here, the authors record from both regular and irregular afferents in macaques, and find both irregular afferents and central neurons also represent self-motion via temporally precise spike timing.

    • Mohsen Jamali
    • , Maurice J. Chacron
    •  & Kathleen E. Cullen

  • Article
    | Open Access

    Absolute concentration robustness (ACR), independence of the steady-state concentration of a molecule from the environment, is difficult to predict. Here, the authors derive a network structure-based necessary condition for ACR, and suggest that metabolites satisfying the condition are prevalent.

    • Jeanne M. O. Eloundou-Mbebi
    • , Anika Küken
    •  & Zoran Nikoloski

  • Article
    | Open Access

    Cancer cells reprogramme their metabolism with unclear clinical implications. Here, the authors analyse the expression of metabolic genes across 20 types of solid cancers and find that clinical aggressiveness, poor survival and metastasis are associated with the deregulation of mitochondrial metabolism.

    • Edoardo Gaude
    •  & Christian Frezza

  • Article
    | Open Access

    Expression of TEM β-lactamase is a predominant mechanism underlying antibiotic resistance in pathogenic Gram-negative bacteria. Here, the authors use Markov state models to reveal and experimentally confirm hidden conformations that determine TEM substrate specificity.

    • Kathryn M. Hart
    • , Chris M. W. Ho
    •  & Gregory R. Bowman

  • Article
    | Open Access

    Retinitis pigmentosa is often caused by mutations that affect the activity or transport of rhodopsin, but some mutations cause disease even though an apparently functional protein is produced. Here the authors show that three such enigmatic mutants retain scramblase activity but are unable to dimerize.

    • Birgit Ploier
    • , Lydia N. Caro
    •  & Anant K. Menon

  • Article
    | Open Access

    Many drugs are small molecule inhibitors of cell signalling. Through single cell analysis and mathematical modelling here the authors show that cell-to-cell variability diversifies inhibition response into digital and analogue, and that the two translate into distinct long-term functional responses.

    • Robert M. Vogel
    • , Amir Erez
    •  & Grégoire Altan-Bonnet

  • Article
    | Open Access

    Building multi-component enzymatic processes in one pot is challenged by the inherent complexity of each biochemical system. Here, the authors use online mass spectroscopy and engineering systems theory to achieve forward design of a ten-membered reaction cascade.

    • Christoph Hold
    • , Sonja Billerbeck
    •  & Sven Panke

  • Article
    | Open Access

    A wealth of gene expression data is publicly available, yet is little use without additional human curation. Ma’ayan and colleagues report a crowdsourcing project involving over 70 participants to annotate and analyse thousands of human disease-related gene expression datasets.

    • Zichen Wang
    • , Caroline D. Monteiro
    •  & Avi Ma’ayan

  • Article
    | Open Access

    Plasticity and clonal population structure in bacterial genomes can hinder traditional SNP-based genetic association studies. Here, Corander and colleagues present a method to identify variable-length sequence elements enriched in a phenotype of interest, and demonstrate its use in human pathogens.

    • John A. Lees
    • , Minna Vehkala
    •  & Jukka Corander

  • Article
    | Open Access

    Genome interpretation and analysis of allelic activity requires appropriate haplotype phasing. Here the authors present phASER, a fast and accurate method for variant phrasing from RNA-seq and genome sequencing data.

    • Stephane E. Castel
    • , Pejman Mohammadi
    •  & Tuuli Lappalainen

  • Article
    | Open Access

    To modulate gene expression, the glucocorticoid receptor binds to response elements (RE) that vary in sequence. Here, the authors show that RE sequences can modulate glucocorticoid receptor structure and activity, which might provide regulatory specificity towards individual target genes.

    • Stefanie Schöne
    • , Marcel Jurk
    •  & Sebastiaan H. Meijsing

  • Article
    | Open Access

    Clonal haematopoiesis has been thought to occur in less than 10% of individuals younger than 70 years old. Here, the authors use an error corrected next-generation sequencing method to find clonal haematopoiesis in the peripheral blood of 19 of 20 healthy 50–70 year old individuals.

    • Andrew L. Young
    • , Grant A. Challen
    •  & Todd E. Druley

  • Article
    | Open Access

    Long non-coding RNAs are increasingly recognised to be important factors in regulating cellular processes and comprise a large faction of the transcriptome, however most are uncharacterised. Here the authors present RACE-Seq, a tool to improve and extend the annotation of low-expression transcripts.

    • Julien Lagarde
    • , Barbara Uszczynska-Ratajczak
    •  & Jennifer Harrow

  • Article
    | Open Access

    Despite their complexity, ecological networks appear robust to species loss. Here, Strona and Lafferty use artificial life simulations and real-world data to show that such robustness applies to stable conditions, but can collapse when the environment changes.

    • Giovanni Strona
    •  & Kevin D. Lafferty

  • Article
    | Open Access

    The cornea is formed of cells that originate from the outer circle of stem cells and that move towards its centre. Here, the authors show that the movement pattern is self-organised, requiring no cues, and that stem cell leakage may account for the presence of stem cells at the centre of the cornea.

    • Erwin P. Lobo
    • , Naomi C. Delic
    •  & J. Guy Lyons

  • Article
    | Open Access

    It is difficult to image haematopoietic stem cells (HSC) in their niche. Here, the authors present a new high-throughput computational approach to visualise HSCs in vivoat a high spatial and temporal resolution and also use a Msi2-reporter to label endogenous HSCs and progenitors, enabling cell tracking

    • Claire S. Koechlein
    • , Jeffrey R. Harris
    •  & Tannishtha Reya

  • Article
    | Open Access

    Chromosomal aberrations can be detected by global gene expression analysis. Here, the authors report eSNP-Karyotyping, a new method that can detect chromosomal aberrations by measuring the ratio of expression between the two alleles without comparison to a matched diploid sample.

    • Uri Weissbein
    • , Maya Schachter
    •  & Nissim Benvenisty

  • Article
    | Open Access

    Here, Libertini and colleagues devise a computation tool that can analyze whole-genome bisulfite sequencing (WGBS) data to recover of ∼30% of the lost differential methylation position information. They use COMETgazer and COMETvintage to analyze 13 diffferent methylome data to demonstrate their performance.

    • Emanuele Libertini
    • , Simon C. Heath
    •  & Stephan Beck

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