Functional genomics articles within Nature

Featured

  • Article |

    Variant-to-gene-to-program is a new approach to building maps of genome function to link risk variants to disease genes and to convergent signalling pathways in an unbiased manner; its strength is demonstrated in coronary artery disease.

    • Gavin R. Schnitzler
    • , Helen Kang
    •  & Jesse M. Engreitz

  • Article
    | Open Access

    Using single-cell and spatial transcriptomics, human embryonic limb development across space and time and the diversification and cross-species conservation of cells are demonstrated.

    • Bao Zhang
    • , Peng He
    •  & Sarah A. Teichmann

  • Article |

    Integration of multiomics data with functional analysis of pancreatic tissues from individuals with early-stage type 2 diabetes indicates that the genetic risk converges on RFX6, which regulates chromatin architecture at multiple risk loci.

    • John T. Walker
    • , Diane C. Saunders
    •  & Marcela Brissova

  • Perspective |

    Technical developments and large collaborative research networks in neurogenomics promise rapid progress in neuroscience, but translation of results from model systems to human brains is limited by sample availability, technical challenges and ethical issues.

    • Genevieve Konopka
    •  & Aparna Bhaduri

  • Perspective |

    Although the catalogue of human protein-coding genes is nearing completion, the number of non-coding RNA genes remains highly uncertain, and for all genes much work remains to be done to understand their functions.

    • Paulo Amaral
    • , Silvia Carbonell-Sala
    •  & Steven L. Salzberg

  • Article
    | Open Access

    An in vivo single-cell CRISPR screening method identifies transcriptional phenotypes of 22q11.2 deletion syndrome associated with a broad dysregulation of a class of disease susceptibility genes that are important for RNA processing and synaptic function.

    • Antonio J. Santinha
    • , Esther Klingler
    •  & Randall J. Platt

  • Article
    | Open Access

    Triacylglycerols are an energy source produced in humans by DGAT1 and DGAT2, but disrupting these enzymes reveals a noncanonical pathway involving the protein DIESL (formerly TMEM68) and its regulator TMX1, which is important during lipid scarcity.

    • Gian-Luca McLelland
    • , Marta Lopez-Osias
    •  & Thijn R. Brummelkamp

  • Article |

    A machine learning approach is used to analyse multi-omics (proteomics, metabolomics and transcriptomics) data, producing genetic scores for more than 17,000 biomolecular traits in human blood, and identifying possible associations with disease.

    • Yu Xu
    • , Scott C. Ritchie
    •  & Michael Inouye

  • Article
    | Open Access

    The authors present two technologies for spatially resolved, genome-wide, joint profiling of the epigenome and transcriptome by cosequencing chromatin accessibility and gene expression, or histone modifications and gene expression on the same tissue section at near-single-cell resolution.

    • Di Zhang
    • , Yanxiang Deng
    •  & Rong Fan

  • Article
    | Open Access

    Evolutionary analyses of single-nucleus transcriptome data for testes from 11 species are reported, illuminating the molecular evolution of spermatogenesis and associated forces, and providing a resource for investigating the testis across mammals.

    • Florent Murat
    • , Noe Mbengue
    •  & Henrik Kaessmann

  • Article
    | Open Access

    Single-cell transcriptomic profiling and functional assays are used to identify subpopulations of eosinophils that are present in the mouse gastrointestinal tract and provide insight into the role of these cells in inflammatory bowel diseases in humans.

    • Alessandra Gurtner
    • , Costanza Borrelli
    •  & Isabelle C. Arnold

  • Article |

    Klunk and colleagues identify signatures of natural selection imposed by Yersinia pestis and demonstrate their effect on genetic diversity and susceptibility to certain diseases in the present day.

    • Jennifer Klunk
    • , Tauras P. Vilgalys
    •  & Luis B. Barreiro

  • Article
    | Open Access

    Live-seq, a single-cell transcriptome profiling approach that preserves cell viability during RNA extraction using fluidic force microscopy, can address a range of biological questions by transforming scRNA-seq from an end-point to a temporal analysis approach.

    • Wanze Chen
    • , Orane Guillaume-Gentil
    •  & Bart Deplancke

  • Article |

    To understand the contribution of variants to transcript expression regulation, long-read transcriptome data are generated from the GTEx resource, and a new software package to perform allele-specific analysis is developed.

    • Dafni A. Glinos
    • , Garrett Garborcauskas
    •  & Beryl B. Cummings

  • Article |

    The systematic categorization of human enhancers by their cofactor dependencies provides a conceptual framework to understand the sequence and chromatin diversity of enhancers and their roles in different gene-regulatory programmes.

    • Christoph Neumayr
    • , Vanja Haberle
    •  & Alexander Stark

  • Article |

    A new high-throughput assay applied to 1,000 enhancers and 1,000 promoters in human cells reveals how different classes of enhancers and promoters control RNA expression.

    • Drew T. Bergman
    • , Thouis R. Jones
    •  & Jesse M. Engreitz

  • Article |

    Analyses of single-cell whole-genome sequencing data show that somatic mutations are increased in the brain of individuals with Alzheimer’s disease compared to neurotypical individuals, with a pattern of genomic damage distinct from that of normal ageing.

    • Michael B. Miller
    • , August Yue Huang
    •  & Christopher A. Walsh

  • Article |

    A genome-scale gain-of-function screen using overexpression of nearly 12,000 open reading frames (ORFs) identifies positive regulators of human T cell function and suggests that ORF-based screens could be applied clinically to improve T cell therapies.

    • Mateusz Legut
    • , Zoran Gajic
    •  & Neville E. Sanjana

  • Article
    | Open Access

    Analyses of circulating cell-free RNA (cfRNA) in blood samples from pregnant mothers identify changes in gene expression that could be used in liquid biopsy tests to identify and monitor individuals who are at risk of preeclampsia.

    • Mira N. Moufarrej
    • , Sevahn K. Vorperian
    •  & Stephen R. Quake

  • Article |

    In mouse models of pancreatic cancer, a cooperative interaction between tissue damage and Kras gene mutation rapidly induces cancer-associated chromatin states in pre-malignant tissue, leading to gene dysregulation and neoplastic transformation.

    • Direna Alonso-Curbelo
    • , Yu-Jui Ho
    •  & Scott W. Lowe

  • Article |

    An ultra-high-throughput multiplex protein–DNA binding assay is used to assess binding of 270 human transcription factors to 95,886 noncoding variants in the human genome, providing data to improve prediction of the effects of noncoding variants on transcription factor binding and thereby increase understanding of molecular pathways involved in diverse human traits and genetic diseases.

    • Jian Yan
    • , Yunjiang Qiu
    •  & Bing Ren

  • Article |

    Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

    • Alexander G. Bick
    • , Joshua S. Weinstock
    •  & Pradeep Natarajan

  • Article |

    Haploid genetic screening of cells under different types of mitochondrial perturbation shows that a pathway involving OMA1, DELE1 and the eIF2α kinase HRI communicates mitochondrial stress to the cytosol to trigger the integrated stress response.

    • Evelyn Fessler
    • , Eva-Maria Eckl
    •  & Lucas T. Jae

  • Review Article |

    This Review examines inflammatory bowel disease in the context of human genetics studies that help to identify pathways that regulate homeostasis of the mucosal immune system and discusses future prospects for disease-subtype classification and therapeutic intervention.

    • Daniel B. Graham
    •  & Ramnik J. Xavier

  • Review Article |

    This Review describes progress in the study of human genetics, in which rapid advances in technology, foundational genomic resources and analytical tools have contributed to the understanding of the mechanisms responsible for many rare and common diseases and to preventative and therapeutic strategies for many of these conditions.

    • Melina Claussnitzer
    • , Judy H. Cho
    •  & Mark I. McCarthy

  • Letter |

    CRISPR–Cas9 engineering of the Drosophila Atpα gene (encoding the α-subunit of the sodium pump) is used to study the ability of mutations that evolved independently in several insect orders to confer resistance to keystone plant toxins.

    • Marianthi Karageorgi
    • , Simon C. Groen
    •  & Noah K. Whiteman

  • Article |

    The transcriptomes of seven major organs across developmental stages from several mammalian species are used for comparative analyses of gene expression and evolution across organ development.

    • Margarida Cardoso-Moreira
    • , Jean Halbert
    •  & Henrik Kaessmann

  • Letter |

    A screen of 23 transcriptional cofactors for their ability to activate 72,000 candidate core promoters in Drosophila melanogaster identified distinct compatibility groups, providing insight into mechanisms that underlie the selective activation of transcriptional programs.

    • Vanja Haberle
    • , Cosmas D. Arnold
    •  & Alexander Stark

  • Article |

    In a screen of 324 human cancer cell lines and utilising a systematic target prioritization framework, the Werner syndrome ATP-dependent helicase is shown to be a synthetic lethal target in tumours from multiple cancer types with microsatellite instability, providing a new target for cancer drug development.

    • Fiona M. Behan
    • , Francesco Iorio
    •  & Mathew J. Garnett

  • Article |

    Germline BRCA1 loss-of-function variants are associated with predisposition to early-onset breast and ovarian cancer; here the authors use CRISPR/Cas9 genome editing to functionally assess thousands of BRCA1 variants in order to facilitate the clinical interpretation of these variants.

    • Gregory M. Findlay
    • , Riza M. Daza
    •  & Jay Shendure

  • Letter
    | Open Access

    The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

    • Xin Li
    • , Yungil Kim
    •  & Stephen B. Montgomery

  • Article |

    The authors describe a two-cell-type CRISPR screen to identify tumour-intrinsic genes that regulate the sensitivity of cancer cells to effector T cell function.

    • Shashank J. Patel
    • , Neville E. Sanjana
    •  & Nicholas P. Restifo

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