Functional genomics articles within Nature Communications

Featured

  • Article
    | Open Access

    eIF5A is critical for protein synthesis but has not yet been associated with congenital human disease. Here, the authors show that EIF5A variants cause a Mendelian disorder via reduced eIF5A-ribosome interactions and this phenotype is partially corrected by spermidine supplementation in yeast and zebrafish.

    • Víctor Faundes
    • , Martin D. Jennings
    •  & Siddharth Banka

  • Article
    | Open Access

    Statistical colocalisation is a method to identify causal genes and shared genetic aetiology across traits. Here, the authors describe HyPrColoc, an efficient Bayesian divisive clustering algorithm which integrates summary statistics from genome-wide association studies to detect clusters of colocalised traits from large numbers of traits.

    • Christopher N. Foley
    • , James R. Staley
    •  & Joanna M. M. Howson

  • Article
    | Open Access

    Genetic elements that control inflammatory gene expression are not fully elucidated. Here the authors conduct a multi-species analysis of chromatin landscape and NF-κB binding in response to the proinflammatory cytokine TNFα, finding that conserved NF-κB bound regions are linked to enhancer activity and disease.

    • Azad Alizada
    • , Nadiya Khyzha
    •  & Michael D. Wilson

  • Article
    | Open Access

    The white pupae (wp) phenotype has been used for decades to selectively remove females of tephritid species in genetic sexing, but the determining gene is unknown. Here, the authors show that wp phenotype is produced by parallel mutations in a Major Facilitator Superfamily domain containing gene across multiple species.

    • Christopher M. Ward
    • , Roswitha A. Aumann
    •  & Marc F. Schetelig

  • Comment
    | Open Access

    Rapidly advancing genomic technologies and cross-disciplinary partnerships are accelerating the biological and clinical interpretation of genome-wide association studies, with some therapies developed based on these findings already being tested in clinical trials. The next decade promises further progress in understanding the function of genetic variants.

    • Florence Lichou
    •  & Gosia Trynka

  • Article
    | Open Access

    Pathogenicity scores are instrumental in prioritizing variants for Mendelian disease, yet their application to common disease is largely unexplored. Here, the authors assess the utility of pathogenicity scores for 41 complex traits and develop a framework to improve their informativeness for common disease.

    • Samuel S. Kim
    • , Kushal K. Dey
    •  & Alkes L. Price

  • Article
    | Open Access

    The bacterium Neisseria meningitidis causes life-threatening meningitis and sepsis. Here, Muir et al. construct a complete collection of defined mutants in protein-coding genes of this organism, which they use to identify its essential genome and to shed light on the functions of multiple genes.

    • Alastair Muir
    • , Ishwori Gurung
    •  & Vladimir Pelicic

  • Article
    | Open Access

    This study presents and validates a novel approach to reliably identify structural variations (SVs) in non-model genomes using whole genome sequencing, which was used to detect 15,483 SVs in 492 Atlantic salmon, shedding light on their roles in genome evolution and the genetic architecture of domestication.

    • Alicia C. Bertolotti
    • , Ryan M. Layer
    •  & Daniel J. Macqueen

  • Article
    | Open Access

    Deep learning models have shown great promise in predicting regulatory effects from DNA sequence. Here the authors evaluate sequence-based epigenomic deep learning models and conclude that these models are not yet ready to inform our knowledge of human disease.

    • Kushal K. Dey
    • , Bryce van de Geijn
    •  & Alkes L. Price

  • Article
    | Open Access

    Mutations in RAS-MAPK pathway genes are implicated in Noonan-spectrum, yet up to 20% of cases have unknown cause. Here, the authors identify RREB1 underlying a 6p microdeletion RASopathy-like syndrome and show that RREB1, SIN3A and KDM1A form a transcriptional repressive complex to control methylation of MAPK pathway genes.

    • Oliver A. Kent
    • , Manipa Saha
    •  & Robert Rottapel

  • Article
    | Open Access

    Although genome-wide association studies have identified genetic variation contributing to disease risk, assigning causal genes is challenging. Here, the authors generate ATAC-seq, Hi-C, Capture Hi-C and RNA-seq data in stimulated CD4+ T cells to identify functional enhancers and demonstrate interactions of expression quantitative trait loci with target genes in rheumatoid arthritis.

    • Jing Yang
    • , Amanda McGovern
    •  & Stephen Eyre

  • Article
    | Open Access

    Mongolia has the highest incidence of—and mortality from—hepatocellular carcinoma (HCC) in the world. Here, the authors examine the genomic and transcriptomic landscape of Mongolian HCC, uncover novel driver mutations, and suggest distinct disease etiologies.

    • Julián Candia
    • , Enkhjargal Bayarsaikhan
    •  & Xin Wei Wang

  • Article
    | Open Access

    Energy metabolism and ATP levels are controlled by an interlocking network of pathways. Here, the authors apply a genome-wide CRISPR screen to define genes that increase or decrease ATP levels to define the “ATPome”, a map of pathways that contribute to cellular ATP regulation.

    • Neal K. Bennett
    • , Mai K. Nguyen
    •  & Ken Nakamura

  • Article
    | Open Access

    Large-scale screens of chemical and genetic vulnerabilities in cancer are typically limited to simple readouts of cell viability. Here, the authors develop a method for profiling post-perturbation transcriptional responses across large pools of cancer cell lines, enabling deep characterization of shared and context-specific responses.

    • James M. McFarland
    • , Brenton R. Paolella
    •  & Aviad Tsherniak

  • Article
    | Open Access

    T cells are a major cell type involved in systemic lupus erythematosus (SLE). Here, the authors use promoter capture-C and ATAC-seq in human follicular T helper cells to identify SLE genes distant from GWAS loci (via 3D interaction) and validate the function of key regulatory elements and genes in vitro.

    • Chun Su
    • , Matthew E. Johnson
    •  & Andrew D. Wells

  • Article
    | Open Access

    Evidence that somatic mutation rates in introns exceed those in exons challenges the molecular evolution tenet that mutation rate and sequence function are independent. Here, authors analyze germline de novo mutations and reveal no evidence for mutation rate differences between exons and introns.

    • Miguel Rodriguez-Galindo
    • , Sònia Casillas
    •  & Antonio Barbadilla

  • Article
    | Open Access

    BRCA1 mutation carriers have higher chances of developing triple-negative breast cancer (TNBC). Here, the authors use the Sleeping Beauty mutagenesis system in Brca1 deficient mice and identify 169 putative driver genes, of which NOTCH1 accelerates TNBC formation through promoting epithelial-mesenchymal transition and cell cycle progression.

    • Kai Miao
    • , Josh Haipeng Lei
    •  & Chu-Xia Deng

  • Article
    | Open Access

    Genetic variants at the RSPO3 locus are associated with waist-to-hip ratio (adjusted for BMI). Here, Loh et al. describe two independent RSPO3 signals that associate with body fat distribution, perform fine-mapping and explore the function of RSPO3 in human adipocyte biology and body fat distribution in zebrafish

    • Nellie Y. Loh
    • , James E. N. Minchin
    •  & Constantinos Christodoulides

  • Article
    | Open Access

    Here the authors perform a gain-of-function screen and identify CDKN2C as a host factor for HBV replication, inducing cell cycle arrest and expression of HBV transcription enhancers. CDKN2C expression correlates with disease progression suggesting a potential role in HBV-induced liver disease.

    • Carla Eller
    • , Laura Heydmann
    •  & Thomas F. Baumert

  • Article
    | Open Access

    Genomic studies of paleopteran insects, such as mayflies, are needed to reconstruct early insect evolution. Here, Almudi and colleagues present the genome of the mayfly Cloeon dipterum and use transcriptomics to characterize its adaptations to distinct habitats and the origin of insect wings.

    • Isabel Almudi
    • , Joel Vizueta
    •  & Fernando Casares

  • Article
    | Open Access

    The MOF acetyltransferase-containing Non-Specific Lethal (NSL) complex is a broad transcription regulator and haploinsufficiency of its KANSL1 subunit results in the Koolen-de Vries syndrome in humans. Here, the authors identify the BET protein BRD4 as evolutionary conserved co-factor of the NSL complex and provide evidence that NSL-deposited histone acetylation induces BRD4 recruitment for transcription of constitutively active genes.

    • Aline Gaub
    • , Bilal N. Sheikh
    •  & Asifa Akhtar

  • Article
    | Open Access

    Genetic variants in the FAM13A locus have been associated with anthropometric and glycemic traits. Here, using fine-mapping, in vitro knockdown studies in pre-adipocytes and in vivo knockout in mice, the authors show that FAM13A is involved in regulating fat distribution and metabolic traits.

    • Mohsen Fathzadeh
    • , Jiehan Li
    •  & Joshua W. Knowles

  • Article
    | Open Access

    Genetic variation in natural populations could represent gene drive resistant alleles, preventing successful application for population management. Here the authors survey 1280 genomes from three mosquito species and concludes natural variation will not be detrimental to deploying gene drive technology.

    • Hanno Schmidt
    • , Travis C. Collier
    •  & Gregory C. Lanzaro

  • Article
    | Open Access

    While genome-wide association studies have yielded thousands of trait-associated loci, identifying causal variants remains challenging. Here, the authors perform seven genomics assays in various cell types to prioritize genetic variants in the TNFAIP3 locus, and report high-priority variants within disease-associated haplotypes.

    • John P. Ray
    • , Carl G. de Boer
    •  & Nir Hacohen

  • Article
    | Open Access

    Heart failure has a heterogeneous etiology and the genetic underpinnings are not well understood. Here, Arvanitis et al. perform GWAS meta-analysis including 10,976 heart failure cases and 437,573 controls, identify new loci near ABO and ACTN2 and show that deletion of a ACTN2 enhancer leads to reduced ACTN2 expression in differentiating cardiomyocytes.

    • Marios Arvanitis
    • , Emmanouil Tampakakis
    •  & Alexis Battle

  • Article
    | Open Access

    In Drosophila, transcription is thought to be required for TAD formation, while the role of architectural proteins remains controversial. Here, the authors find that deletion of domain boundaries at the fly Notch locus results in TAD fusion and long-range topological defects, loss of architectural protein and RNA Pol II chromatin binding, and transcription defects.

    • Rodrigo G. Arzate-Mejía
    • , Angel Josué Cerecedo-Castillo
    •  & Félix Recillas-Targa

  • Article
    | Open Access

    Studying the genetic effects on early stages of human development is challenging due to a scarcity of biological material. Here, the authors utilise induced pluripotent stem cells from 125 donors to track gene expression changes and expression quantitative trait loci at single cell resolution during in vitro endoderm differentiation.

    • Anna S. E. Cuomo
    • , Daniel D. Seaton
    •  & Oliver Stegle

  • Article
    | Open Access

    There is increasing evidence that protein-coding genes can emerge de novo from noncoding genomic regions. Vakirlis et al. propose that sequences encoding transmembrane polypeptides can emerge de novo in thymine-rich genomic regions and provide organisms with fitness benefits.

    • Nikolaos Vakirlis
    • , Omer Acar
    •  & Anne-Ruxandra Carvunis

  • Article
    | Open Access

    Pre-malignant cells harbouring oncogenic mutations can populate and spread throughout a tissue. Here, using a rainbow mouse system, the authors explore how clonal expansion in the mouse intestine might explain high levels of intra-tumoural heterogeneity observed in the disease.

    • Peter G. Boone
    • , Lauren K. Rochelle
    •  & Joshua C. Snyder

  • Article
    | Open Access

    Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that affects the connective tissue. Here, López-Isac et al. identify 13 new risk loci for SSc as well as loci specific for limited cutaneous and diffuse SSc and, defining credible sets and performing functional annotation, highlight key pathways and cell types for SSc.

    • Elena López-Isac
    • , Marialbert Acosta-Herrera
    •  & Javier Martin

  • 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

    In plants, 3′ Pol II pausing helps prevent transcriptional interference. Here the authors provide evidence that BORDER proteins are enriched in intergenic regions and inhibit transcriptional interference between closely spaced genes by preventing RNA polymerase from intruding into the promoters of nearby downstream genes.

    • Xuhong Yu
    • , Pascal G. P. Martin
    •  & Scott D. Michaels

  • 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

    Although many neuropsychiatric risk genes are known to contribute to epigenetic regulation of gene expression, very little is known about specific chromatin-associated mechanisms that govern the formation and maintenance of neuronal connectivity. Here, the authors report that transcallosal connectivity is critically dependent on C11orf46/ARL14EP, a nuclear protein encoded in the chromosome 11p13 WAGR risk locus, and that RNA-guided epigenetic editing of hyperexpressed Sema6a gene promoters in C11orf46-knockdown neurons resulted in normalization of expression and rescue of transcallosal dysconnectivity via repressive chromatin remodeling.

    • Cyril J. Peter
    • , Atsushi Saito
    •  & Atsushi Kamiya

  • Article
    | Open Access

    Off-target effects in CRISPR screens for essential regulatory elements have not been systematically evaluated. Here the authors find Cas9 nuclease, CRISPRi/a each have distinct off-target effects, and that these can be accurately identified and removed using the GuideScan sgRNA specificity score.

    • Josh Tycko
    • , Michael Wainberg
    •  & Michael C. Bassik

  • Article
    | Open Access

    Interpreting genetic variation in the noncoding genome remains challenging, with functional effects difficult to predict. Here, the authors perform saturation mutagenesis combined with massively parallel reporter assays for 20 disease-associated regulatory elements, quantifying the effects of over 30,000 variants.

    • Martin Kircher
    • , Chenling Xiong
    •  & Nadav Ahituv

  • Article
    | Open Access

    Functional variants have been proposed to alter transcription factor binding. Here, the authors provide direct evidence that functional variants within the TBC1D4 gene, encoding an NFκB binding site, can alter transcription factor binding, and use CRISPR-Cas9 to reveal localization of the transcription factor to be the regulator of chromatin accessibility and p65 binding and ultimately TBC1D4 expression.

    • Andrew D. Johnston
    • , Claudia A. Simões-Pires
    •  & John M. Greally

  • Article
    | Open Access

    The position, shape and number of transcription start sites (TSS) regulate gene expression. Here authors present MAPCap, a method for high-resolution detection and differential expression analysis of TSS, and apply MAPCap to early fly development, detecting stage and sex-specific promoter and enhancer activity.

    • Vivek Bhardwaj
    • , Giuseppe Semplicio
    •  & Asifa Akhtar

Browse broader subjects

Browse narrower subjects

Browse Functional genomics across other nature.com journals