Computational biology and bioinformatics articles within Nature Communications

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  • Article
    | Open Access

    Taxonomy classification of amplicon sequences is an important step in investigating microbial communities in microbiome analysis. Here, the authors show incorporating environment-specific taxonomic abundance information can lead to improved species-level classification accuracy across common sample types.

    • Benjamin D. Kaehler
    • , Nicholas A. Bokulich
    •  & Gavin A. Huttley

  • Article
    | Open Access

    There has been a rapid rise in single cell RNA-seq methods and associated pipelines. Here the authors use simulated data to systematically evaluate the performance of 3000 possible pipelines to derive recommendations for data processing and analysis of different types of scRNA-seq experiments.

    • Beate Vieth
    • , Swati Parekh
    •  & Ines Hellmann

  • Article
    | Open Access

    Programmed ribosomal frameshifting (PRF) is an alternative translation strategy that causes controlled slippage of the ribosome along the mRNA, changing the sequence of the synthesized protein. Here the authors provide a thermodynamic framework that explains how mRNA sequence determines the efficiency of frameshifting.

    • Lars V. Bock
    • , Neva Caliskan
    •  & Helmut Grubmüller

  • Article
    | Open Access

    Single-cell ATAC-seq data is challenging to analyse for reasons such as high dimensionality and sparsity. Here, the authors develop SCALE, a deep learning method that leverages latent feature extraction for various tasks of scATACseq data analysis.

    • Lei Xiong
    • , Kui Xu
    •  & Qiangfeng Cliff Zhang

  • Article
    | Open Access

    Deep learning approaches for image preprocessing and analysis offer important advantages, but these are rarely incorporated into user-friendly software. Here the authors present an easy-to-use visual programming toolbox integrating deep-learning and interactive data visualization for image analysis.

    • Primož Godec
    • , Matjaž Pančur
    •  & Blaž Zupan

  • Article
    | Open Access

    Here, using the diatom Phaeodactylum tricornutum as a model organism, the authors combine functional genomics, phylogenetics, and metabolic modeling to describe how diatoms might have functionally integrated nitrogen metabolism during evolution and how metabolic flux is regulated across cellular compartments

    • Sarah R. Smith
    • , Chris L. Dupont
    •  & Andrew E. Allen

  • Article
    | Open Access

    Homologs are paired in Drosophila somatic cells from embryogenesis to adulthood. Using a computational approach for haplotype-resolved Hi-C, the authors reveal highly structured homolog pairing in Drosophila embryos during zygotic genome activation and demonstrate its application to mammalian embryos.

    • Jelena Erceg
    • , Jumana AlHaj Abed
    •  & C.-ting Wu

  • Article
    | Open Access

    Trans-homolog interactions, such as homolog pairing, are highly structured and associated with gene function in Drosophila cells. Here, the authors use haplotype-resolved Hi-C to identify genome-wide trans-homolog interactions in a Drosophila hybrid cell line and investigate their patterns and functional roles.

    • Jumana AlHaj Abed
    • , Jelena Erceg
    •  & C.-ting Wu

  • Article
    | Open Access

    Cellular systems have numerous mechanisms to control gene expression. Here the authors build a Tet-On system with conditional destablising elements to regulate gene expression and protein stability, allowing fine modulation of mESC signalling pathways.

    • Elisa Pedone
    • , Lorena Postiglione
    •  & Lucia Marucci

  • Article
    | Open Access

    The increasing accessibility of single cell RNA sequencing demands tools that enable data visualization and interpretation. Here, the authors introduce Vision, a flexible annotation tool that operates directly on the manifold of cell-cell similarity and aids interpretation of cellular heterogeneity.

    • David DeTomaso
    • , Matthew G. Jones
    •  & Nir Yosef

  • Article
    | Open Access

    Epigenomic data on chromatin accessibility and transcription factor occupancy can reveal enhancer landscapes in cancer. Here, the authors develop a computational strategy called PSIONIC (patient-specific inference of networks informed by chromatin) to model the impact of enhancers on transcriptional programs in gynecologic and basal breast cancers.

    • Hatice U. Osmanbeyoglu
    • , Fumiko Shimizu
    •  & Christina S. Leslie

  • Article
    | Open Access

    Age-related tissue alterations have been associated with a decline in stem cell number and function. Here the authors report a single cell multi-omics study of mouse muscle stem cells, combining single cell transcriptome and DNA methylome profiling and find that aged cells have a global increase of uncoordinated transcriptional heterogeneity biased towards genes regulating cell-niche interactions.

    • Irene Hernando-Herraez
    • , Brendan Evano
    •  & Wolf Reik

  • Article
    | Open Access

    Cardiomyocytes obtained from human induced pluripotent stem cells are increasingly used for drug testing, but they are not always predictive of the heart contractile responses. Here the authors develop a method to measure cytosolic calcium, action potentials and contraction simultaneously, to achieve higher sensitivity for drug screenings.

    • Berend J. van Meer
    • , Ana Krotenberg
    •  & Christine L. Mummery

  • Article
    | Open Access

    Variation of recombination rates within genomes has important implications in genetics and evolution. Here, the authors develop a method for building genome-wide recombination maps from single individuals using linked-read sequencing data, and report its application in mouse and stickleback fish.

    • Andreea Dréau
    • , Vrinda Venu
    •  & Felicity C. Jones

  • Article
    | Open Access

    Meiotic crossovers (COs) generate genetic variation and ensure proper chromosome segregation. Here, the authors develop a method for identifying COs at kilobase resolution in pooled recombinants using linked-read sequencing data, and apply it to investigate genome-wide CO landscapes of Arabidopsis thaliana.

    • Hequan Sun
    • , Beth A. Rowan
    •  & Korbinian Schneeberger

  • Article
    | Open Access

    Sexual dimorphism is observed frequently in immune disorders, but the underlying insights are still unclear. Here the authors analyze transcriptome and epigenome changes induced by interferon in various mouse immune cell types, and find only a restricted set of sexual dimorphism genes in innate immunity and macrophages.

    • Shani Talia Gal-Oz
    • , Barbara Maier
    •  & Tal Shay

  • Article
    | Open Access

    Nanoparticles are a promising approach to increase immunogenicity of protein antigens for vaccines. Here, Brouwer et al. design self-assembling, two-component protein NPs that present native-like SOSIP trimers of HIV envelope protein and determine immunogenicity in a small animal model.

    • Philip J. M. Brouwer
    • , Aleksandar Antanasijevic
    •  & Rogier W. Sanders

  • Article
    | Open Access

    Invasive non-typhoidal Salmonella (iNTS) infections are dominated by antibiotic resistant isolates of the sequence type (ST) 313. Here, the authors identify the ST313 sublineage II.1 in the Democratic Republic of the Congo exhibiting extensive drug resistance and genetic signatures potentially associated with host adaptation.

    • Sandra Van Puyvelde
    • , Derek Pickard
    •  & Stijn Deborggraeve

  • Article
    | Open Access

    HiChIP/PLAC-seq assay is popular for profiling 3D genome interactions among regulatory elements at kilobase resolution. Here the authors describe FitHiChIP an empirical null-based, flexible computational method for statistical significance estimation and loop calling from HiChIP data.

    • Sourya Bhattacharyya
    • , Vivek Chandra
    •  & Ferhat Ay

  • Article
    | Open Access

    Epistasis underlies the complexity of genotype-phenotype maps. Here, the authors analyze 8,192 mutants that link two phenotypically distinct variants of the Entacmaea quadricolor fluorescent protein, and show the existence, but also the sparsity, of high-order epistatic interactions.

    • Frank J. Poelwijk
    • , Michael Socolich
    •  & Rama Ranganathan

  • Article
    | Open Access

    TDP43 aggregates are a hallmark of amyotrophic lateral sclerosis. By using deep mutagenesis to measure the toxicity of more than 50,000 mutations in the prion domain of TDP43, the authors conclude that mutations that increase toxicity promote formation of liquid-like condensates, while aggregation of TDP43 is protective for the cell.

    • Benedetta Bolognesi
    • , Andre J. Faure
    •  & Ben Lehner

  • Article
    | Open Access

    UPF1 mediates the decay of target mRNA in a 3′ untranslated region (UTR)-length-dependent manner. Here the authors reveal that the 3′UTR-length-dependent regulation of UPF1-dependent mRNA decay occurs through EJC-independent but miRNA-dependent regulation.

    • Jungyun Park
    • , Jwa-Won Seo
    •  & Jin-Wu Nam

  • Article
    | Open Access

    Recent studies have identified a large, phylogenetically distinct clade of bacteria, the candidate phyla radiation (CPR). Here, Méheust and colleagues analyze almost 3600 genomes to characterize the protein family content of CPR versus other bacteria and archaea.

    • Raphaël Méheust
    • , David Burstein
    •  & Jillian F. Banfield

  • Article
    | Open Access

    Identifying ligands which activate the specific effectors driving particular in vivo drug effects remains challenging. Here, the authors apply unsupervised clustering of pharmacodynamic parameters to classify GPCR ligands into different categories with similar signaling profiles and shared frequency of report of side effects.

    • Besma Benredjem
    • , Jonathan Gallion
    •  & Graciela Pineyro

  • Article
    | Open Access

    We currently lack generic methods to map RNA modifications across the entire transcriptome. Here, the authors demonstrate that m6A RNA modifications can be detected with high accuracy using nanopore direct RNA sequencing.

    • Huanle Liu
    • , Oguzhan Begik
    •  & Eva Maria Novoa

  • Article
    | Open Access

    While many pleiotropic genetic loci have been identified, how they contribute to phenotypes across traits and diseases is unclear. Here, the authors propose decomposition of genetic associations (DeGAs), which uses singular value decomposition, to characterize the underlying latent structure of genetic associations of 2,138 phenotypes.

    • Yosuke Tanigawa
    • , Jiehan Li
    •  & Manuel A. Rivas

  • Article
    | Open Access

    HIV-1 usually targets active genes and integrates near the nuclear pore compartment. Here the authors show that recurrently targeted genes are proximal to super-enhancer genomic elements, which cluster in specific spatial compartments of the T cell nucleus, suggesting a role for nuclear organisation in viral infection.

    • Bojana Lucic
    • , Heng-Chang Chen
    •  & Marina Lusic

  • Article
    | Open Access

    Light intensity on the retina can fluctuate rapidly during natural vision, posing a challenge for encoding visual information. Here, the authors report that mechanisms of sensitization/facilitation maintain the sensitivity of the numerically dominant neural pathway in the primate retina during dynamic vision.

    • Todd R. Appleby
    •  & Michael B. Manookin

  • Article
    | Open Access

    Archaea and bacteria often have gene pairs with overlapping stop and start codons, suggesting translational coupling. Here, Huber et al. analyse overlapping gene pairs from 720 genomes, and validate translational coupling via termination-reinitiation for 14 gene pairs in Haloferax volcanii and Escherichia coli.

    • Madeleine Huber
    • , Guilhem Faure
    •  & Jörg Soppa

  • Article
    | Open Access

    Prediction of protein structures on the scale of genomes remains a challenge. Here the authors introduce a protein structure prediction method that uses deep learning to predict inter-atomic distances, torsion angles and hydrogen bonds, and apply it to predict the structures of 1475 Pfam domains.

    • Joe G. Greener
    • , Shaun M. Kandathil
    •  & David T. Jones

  • Comment
    | Open Access

    Forecasting is beginning to be integrated into decision-making processes for infectious disease outbreak response. We discuss how technologies could accelerate the adoption of forecasting among public health practitioners, improve epidemic management, save lives, and reduce the economic impact of outbreaks.

    • Dylan B. George
    • , Wendy Taylor
    •  & Nicholas G. Reich

  • Article
    | Open Access

    The effect of spontaneous variations in prestimulus neural activity on subsequent perception is incompletely understood. Here, using MEG, the authors identify two distinct neural processes that can influence object recognition in different ways.

    • Ella Podvalny
    • , Matthew W. Flounders
    •  & Biyu J. He

  • Article
    | Open Access

    Non-additive genetic interactions are plastic and can complicate genetic prediction. Here, using deep mutagenesis of the lambda repressor, Li et al. reveal that changes in gene expression can alter the strength and direction of genetic interactions between mutations in many genes and develop mathematical models for predicting them.

    • Xianghua Li
    • , Jasna Lalić
    •  & Ben Lehner

  • Article
    | Open Access

    PrediXcan is a widely used gene expression imputation method that links genetic variants to gene expression. Here, the authors develop EpiXcan which leverages epigenetic annotations to inform transcriptomic imputation and further use the obtained gene-trait associations for computational drug repurposing.

    • Wen Zhang
    • , Georgios Voloudakis
    •  & Panos Roussos

  • Article
    | Open Access

    Multi-omic profiling is a powerful approach to dissecting molecular mechanisms in disease. Here the authors generate whole proteome, phosphoproteome and transcriptome profiles from two mouse models of high-grade glioma driven by different oncogenes, and validate identified master regulators with a CRISPR screen.

    • Hong Wang
    • , Alexander K. Diaz
    •  & Junmin Peng

  • Article
    | Open Access

    The advent of single-cell RNA sequencing has revealed significant transcriptional heterogeneity in cancer, but its relationship to genomic heterogeneity remains unclear. Focusing on acute myeloid leukemia samples, the authors describe a general approach for linking mutation-containing cells to their transcriptional phenotypes using single-cell RNA sequencing data.

    • Allegra A. Petti
    • , Stephen R. Williams
    •  & Timothy J. Ley

  • Article
    | Open Access

    Gene activation requires an increase of successful initiation events. Here, by employing a genome-wide kinetic analysis of transcription, the authors showed that gene activation generally requires a decrease in RNA Polymerase II (Pol II) promoter-proximal pausing while transcription of enhancer elements is not limited by Pol II pausing.

    • Saskia Gressel
    • , Björn Schwalb
    •  & Patrick Cramer

  • Article
    | Open Access

    Efficient sampling of rare events in all-atom molecular dynamics simulations remains a challenge. Here, the authors adapt the Predictive Information Bottleneck framework to sample biomolecular structure and dynamics through iterative rounds of biased simulations and deep learning.

    • Yihang Wang
    • , João Marcelo Lamim Ribeiro
    •  & Pratyush Tiwary

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