Bioinformatics articles within Nature Communications

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  • Article
    | Open Access

    When the antibiotic erythromycin is bound to the ribosomal exit tunnel, ErmBL peptide translation stalls and allows translation of the downstream methyltransferase ErmB. Here the authors combine cryo-EM and molecular dynamics simulations to identify the underlying basis for the inhibition of peptide bond formation that results in ribosome stalling.

    • Stefan Arenz
    • , Lars V. Bock
    •  & Daniel N. Wilson

  • Article
    | Open Access

    Current methods for mapping RNA-RNA interactions have to rely on an ‘anchor’ protein or RNA. Here, the authors report the MARIO (Mapping RNA interactome in vivo) technology that can massively reveal RNA-RNA interactions and RNA structure from unperturbed cells.

    • Tri C. Nguyen
    • , Xiaoyi Cao
    •  & Sheng Zhong

  • Article
    | Open Access

    Diversity of an organism’s B- and T-cell repertoires is clinically important, but difficult to estimate due to uncertainty in the number of clones in a sample, sampling bias and experimental noise. Here Kaplinsky and Arnaout present Recon, a method that reconstructs the distribution of the overall repertoire from sample measurements.

    • Joseph Kaplinsky
    •  & Ramy Arnaout

  • Article
    | Open Access

    Mutations in proteins that localize to primary cilia cause devastating diseases, yet the primary cilium is a poorly understood organelle. Here the authors use interaction proteomics to identify a network of human ciliary proteins that provides new insights into several biological processes and diseases.

    • Karsten Boldt
    • , Jeroen van Reeuwijk
    •  & Kathy Williamson

  • Article
    | Open Access

    Genotype–phenotype landscapes are an important characteristic for understanding the evolution of traits. Here the authors construct the local landscape for the alternative splicing of FAS/CD95 exon 6, revealing the regulation of splicing and the evolution of regulatory information between species.

    • Philippe Julien
    • , Belén Miñana
    •  & Ben Lehner

  • Article
    | Open Access

    DNA N6-methyladenine is prevalent in prokaryotes, and is recently also detected in eukaryotes such as roundworm and fly. Here, Luo et al. report a DpnI-assisted base resolution method that detects 6mA genome-wide with nanograms of input DNA and lower sequencing depth than the previous restriction enzyme-based approach.

    • Guan-Zheng Luo
    • , Fang Wang
    •  & Chuan He

  • Article
    | Open Access

    Read mapping and alignment tools are critical for many applications based on MinION sequencers. Here, the authors present GraphMap, a mapping algorithm designed to analyze nanopore sequencing reads, that progressively refines candidate alignments to handle potentially high error rates to align long reads.

    • Ivan Sović
    • , Mile Šikić
    •  & Niranjan Nagarajan

  • Article
    | Open Access

    Mutations in aggregation prone regions of recombinant proteins often improve their solubility, although they might cause negative effects on their structure and function. Here, the authors identify proteins hot spots that can be exploited to optimize solubility without compromising stability.

    • Ashok Ganesan
    • , Aleksandra Siekierska
    •  & Joost Schymkowitz

  • Article
    | Open Access

    Attempts to predict novel use for existing drugs rarely consider information on the impact on the genes perturbed in a given disease. Here, the authors present a novel network-based drug-disease proximity measure that provides insight on gene specific therapeutic effect of drugs and may facilitate drug repurposing.

    • Emre Guney
    • , Jörg Menche
    •  & Albert-László Barábasi

  • Article
    | Open Access

    This study examines ancient genomes of individuals from the late Iron Age to the middle Anglo-Saxon period in the East of England. Using a newly devised analytic algorithm, the author also estimate the relative ancestry of East English genome derived from Anglo-Saxon migrations and to the rest of Europe.

    • Stephan Schiffels
    • , Wolfgang Haak
    •  & Richard Durbin

  • Article
    | Open Access

    Imaging flow cytometry enables high-throughput acquisition of fluorescence, brightfield and darkfield images of biological cells. Here, Blasi et al.demonstrate that applying machine learning algorithms on brightfield and darkfield images can detect cellular phenotypes without the need for fluorescent stains, enabling label-free assays.

    • Thomas Blasi
    • , Holger Hennig
    •  & Paul Rees

  • Article
    | Open Access

    Colorectal cancer subtypes can be distinguished by their different biological and molecular properties. Here the authors present microRNA Master Regulator Analysis, a tool to identify microRNAs driving subtype-specific gene expression and cancer variation.

    • Laura Cantini
    • , Claudio Isella
    •  & Enzo Medico

  • Article
    | Open Access

    In chromatin endogenous cleavage (ChEC), micrococcal nuclease (MNase) is fused to a protein of interest and its cleavage is thus targeted to specific genomic loci in vivo. Here, the authors show that time-resolved ChEC-seq (high-throughput sequencing after ChEC) can detect DNA shape patterns regardless of motif strength.

    • Gabriel E. Zentner
    • , Sivakanthan Kasinathan
    •  & Steven Henikoff

  • Article
    | Open Access

    Ageing increases the risk of many diseases. Here the authors compare blood cell transcriptomes of over 14,000 individuals and identify a set of about 1,500 genes that are differently expressed with age, shedding light on transcriptional programs linked to the ageing process and age-associated diseases.

    • Marjolein J. Peters
    • , Roby Joehanes
    •  & Andrew D. Johnson

  • Article
    | Open Access

    Culturing new microorganisms requires a great deal of experience, and trial and error. Here, the authors build a database of >3,300 culturing media recipes and >18,000 microbial species that allows the prediction of appropriate media recipes for the growth of new microbes based on their 16S rDNA sequences.

    • Matthew A. Oberhardt
    • , Raphy Zarecki
    •  & Eytan Ruppin

  • Article
    | Open Access

    Lactobacillus is a lactic acid bacteria and has a wide range of application from use in probiotic food production to biotherapeutics. Here, the authors sequence and compare the genomes of 213 different Lactobacillusstrains and related genera, and provide new insight into phylogenomic organization and adaptive immunity elements in this bacteria family.

    • Zhihong Sun
    • , Hugh M. B. Harris
    •  & Paul W. O’Toole

  • Article
    | Open Access

    This paper described a new and efficient method for de novoassembly of multiple DNA sequence information from mutagenized clone libraries. Using codon-barcoded libraries and calling the method JigsawSeq, the authors overcome limitations of short-read sequencing assembly from next-generation sequencing.

    • Namjin Cho
    • , Byungjin Hwang
    •  & Duhee Bang

  • Article
    | Open Access

    Members of the PUF family of RNA-binding proteins bind multiple mRNAs in vivo. Here the authors show that the S. cerevisiaePuf5p binds targets of varying lengths that correlate with biological functions. The RNA-binding sites adopt different structures to adapt to a fixed protein scaffold.

    • Daniel Wilinski
    • , Chen Qiu
    •  & Marvin Wickens

  • Article
    | Open Access

    Phosphoproteomics can offer significant insight into cell signalling and how signalling is modified in response to perturbations. Here the authors develop a new tool for the analysis of high-content phosphoproteomics in the context of kinase/phosphatase-substrate knowledge, which is used to train logic models.

    • Camille D. A. Terfve
    • , Edmund H. Wilkes
    •  & Julio Saez-Rodriguez

  • Article
    | Open Access

    Mathematical models are used to predict malaria burden to inform disease control efforts. Here, Cameron et al. use Bayesian statistics to calibrate previous models against a data set of age-structured prevalence and incidence, generating stratified forecasts of the prevalence–incidence relationship.

    • Ewan Cameron
    • , Katherine E. Battle
    •  & Peter W. Gething

  • Article
    | Open Access

    With the rapid increase in the volume of publically available RNA-seq data, quality control is an increasingly important consideration. Here Feng et al. develop mRIN, a method to directly assess mRNA integrity, and show that RNA degradation in post-mortem samples has a strong impact on global expression profiles.

    • Huijuan Feng
    • , Xuegong Zhang
    •  & Chaolin Zhang

  • Article
    | Open Access

    Changes in protein–protein interactions result in changes to cellular phenotype. Here the authors use crosslinking mass spectrometry to derive a quantitative protein interaction network in drug-sensitive and -resistant HeLa cells, and uncover a chemoresistant ‘edgotype’.

    • Juan D. Chavez
    • , Devin K. Schweppe
    •  & James E. Bruce

  • Article |

    Although many heteromeric protein complexes exhibit 1:1 ratios between their components, a significant number feature uneven stoichiometry. Marsh et al. perform a global analysis of uneven stoichiometry, identifying structural mechanisms by which it is achieved, and explaining its differential conservation.

    • Joseph A. Marsh
    • , Holly A. Rees
    •  & Sarah A. Teichmann

  • Article
    | Open Access

    Efficacy of anticancer treatments vary across patients, imposing a need for personalized approaches. Here the authors show that responsiveness to chemotherapy can be predicted using tumour explant cultures in a patient-matched microenvironment, coupled with a machine-learning algorithm.

    • Biswanath Majumder
    • , Ulaganathan Baraneedharan
    •  & Pradip K. Majumder

  • Article
    | Open Access

    The standardization of clinical sequencing data generation and analysis is of critical importance. Here, the authors develop the Genome Comparison and Analytic Testing platform to facilitate the development of performance metrics and comparisons of analysis tools for clinical sequencing studies.

    • Gareth Highnam
    • , Jason J. Wang
    •  & David Mittelman

  • Article |

    Strand-specific RNA-seq (ssRNA-seq) data often lack information on 5′ and 3′ ends of transcripts. Here the authors present a novel method for ssRNA-seq that enables the simultaneous profiling of gene expression, TSSs and polyadenylation sites at near-base resolution with a single library.

    • Saurabh Agarwal
    • , Todd S. Macfarlan
    •  & Shigeki Iwase

  • Article
    | Open Access

    RNA sequencing has enabled the global analysis of both gene expression levels and splicing events. Here, the authors develop a multivariate approach that is able to identify SNPs that influence splicing, and investigate the overlap of these with functional domains across the genome, including previously identified GWAS signals.

    • Jean Monlong
    • , Miquel Calvo
    •  & Roderic Guigó

  • Article
    | Open Access

    Feeding is an important behaviour, but its quantification remains challenging, particularly in small animal models like Drosophila melanogaster. Here the authors describe a method which uses capacitive sensing for automated high-resolution measuring of feeding behaviour in individual flies.

    • Pavel M. Itskov
    • , José-Maria Moreira
    •  & Carlos Ribeiro

  • Article |

    Immunosequencing enables cost-effective sequencing of repertoires of immune cells, but it often suffers from amplification biases when attempting cell quantification. Here, the authors present a powerful multiplex PCR assay that allows for quantitative and unbiased analysis of frequency of different T cell receptors.

    • Christopher S. Carlson
    • , Ryan O. Emerson
    •  & Harlan Robins

  • Article
    | Open Access

    Tumour biopsies contain contaminating normal cells and these can influence the analysis of tumour samples. In this study, Yoshihara et al.develop an algorithm based on gene expression profiles from The Cancer Genome Atlas to estimate the number of contaminating normal cells in tumour samples.

    • Kosuke Yoshihara
    • , Maria Shahmoradgoli
    •  & Roel G.W. Verhaak

  • Article
    | Open Access

    Semi-automated imaging systems help with the task of classifying large numbers of biological images. This study presents a novel framework—CARTA—with an active learning algorithm combined with a genetic algorithm, whose applications include the classification of magnetic resonance imaging of cancer cells.

    • Natsumaro Kutsuna
    • , Takumi Higaki
    •  & Seiichiro Hasezawa

  • Article |

    The detection of subclonal variants in heterogeneous cancer specimens is a challenge due to errors that occur during sequencing. In this study, a statistical algorithm and a sequencing strategy are reported that circumvent this issue and can accurately detect variants at a frequency as low as 1/10,000.

    • Moritz Gerstung
    • , Christian Beisel
    •  & Niko Beerenwinkel

  • Article
    | Open Access

    Understanding the genetics and physiology of domesticated species is important for crop improvement. By studying natural variation and the phenotypic traits of 413 diverse accessions of rice, Zhao et al. identify many common genetic variants that influence quantitative traits such as seed size and flowering time.

    • Keyan Zhao
    • , Chih-Wei Tung
    •  & Susan R. McCouch

  • Article
    | Open Access

    The appearance of a new intron that splits an exon without disrupting the corresponding peptide sequence is a rare event in vertebrate genomes. Hellstenet al.demonstrate that, under certain circumstances, a functional intron can be produced in a single step by segmental genomic duplication.

    • Uffe Hellsten
    • , Julie L. Aspden
    •  & Daniel S. Rokhsar

  • Article
    | Open Access

    Recent developments in sequencing technologies have provided the opportunity to investigate the biodiversity of ecosystems. Such a metagenomic approach, combined with taxon clustering, is used here to demonstrate that the species richness of a marine community in Scotland is much greater than anticipated.

    • Vera G. Fonseca
    • , Gary R. Carvalho
    •  & Simon Creer

  • Article
    | Open Access

    There has been great interest in attempting to identify gene expression signatures that predict cancer survival. In this study a new algorithm is developed to analyse gene expression datasets that accurately classify both ER+ and ER− breast cancers into low- and high-risk groups.

    • Jie Li
    • , Anne E.G. Lenferink
    •  & Edwin Wang

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