当前期刊: Nature Genetics Go to current issue    加入关注   
显示样式:        排序: IF: - GO 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Author Correction: Exploring the coronavirus pandemic with the WashU Virus Genome Browser
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-16
    Jennifer A. Flynn; Deepak Purushotham; Mayank N. K. Choudhary; Xiaoyu Zhuo; Changxu Fan; Gavriel Matt; Daofeng Li; Ting Wang

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-16
  • Treating medical data as a durable asset
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-14
    Amalio Telenti; Xiaoqian Jiang

    Access to medical data is central for conducting research on genomics. However, to tap these metadata (observable traits and phenotypes, diagnoses and medication, and labels), researchers must grapple with the complex and sensitive nature of the information. In this Perspective, we argue that, at this exciting time for genomics and artificial intelligence, several critical aspects of data generation

    更新日期:2020-09-14
  • Complex genetic signatures in immune cells underlie autoimmunity and inform therapy
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-14
    Valeria Orrù; Maristella Steri; Carlo Sidore; Michele Marongiu; Valentina Serra; Stefania Olla; Gabriella Sole; Sandra Lai; Mariano Dei; Antonella Mulas; Francesca Virdis; Maria Grazia Piras; Monia Lobina; Mara Marongiu; Maristella Pitzalis; Francesca Deidda; Annalisa Loizedda; Stefano Onano; Magdalena Zoledziewska; Stephen Sawcer; Marcella Devoto; Myriam Gorospe; Gonçalo R. Abecasis; Matteo Floris;

    We report on the influence of ~22 million variants on 731 immune cell traits in a cohort of 3,757 Sardinians. We detected 122 significant (P < 1.28 × 10−11) independent association signals for 459 cell traits at 69 loci (52 of them novel) identifying several molecules and mechanisms involved in cell regulation. Furthermore, 53 signals at 36 loci overlapped with previously reported disease-associated

    更新日期:2020-09-14
  • NSD1-deposited H3K36me2 directs de novo methylation in the mouse male germline and counteracts Polycomb-associated silencing
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-14
    Kenjiro Shirane; Fumihito Miura; Takashi Ito; Matthew C. Lorincz

    De novo DNA methylation (DNAme) in mammalian germ cells is dependent on DNMT3A and DNMT3L. However, oocytes and spermatozoa show distinct patterns of DNAme. In mouse oocytes, de novo DNAme requires the lysine methyltransferase (KMTase) SETD2, which deposits H3K36me3. We show here that SETD2 is dispensable for de novo DNAme in the male germline. Instead, the lysine methyltransferase NSD1, which broadly

    更新日期:2020-09-14
  • Evolutionary dynamics of neoantigens in growing tumors
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-14
    Eszter Lakatos; Marc J. Williams; Ryan O. Schenck; William C. H. Cross; Jacob Househam; Luis Zapata; Benjamin Werner; Chandler Gatenbee; Mark Robertson-Tessi; Chris P. Barnes; Alexander R. A. Anderson; Andrea Sottoriva; Trevor A. Graham

    Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune response, and consequently undergo evolutionary selection. Here we establish how negative selection shapes the clonality of neoantigens in a growing cancer by constructing a mathematical model of neoantigen evolution. The model predicts that, without immune escape, tumor neoantigens are either clonal or at low

    更新日期:2020-09-14
  • Author Correction: PGBD5 promotes site-specific oncogenic mutations in human tumors
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-11
    Anton G. Henssen; Richard Koche; Jiali Zhuang; Eileen Jiang; Casie Reed; Amy Eisenberg; Eric Still; Ian C. MacArthur; Elias Rodríguez-Fos; Santiago Gonzalez; Montserrat Puiggròs; Andrew N. Blackford; Christopher E. Mason; Elisa de Stanchina; Mithat Gönen; Anne-Katrin Emde; Minita Shah; Kanika Arora; Catherine Reeves; Nicholas D. Socci; Elizabeth Perlman; Cristina R. Antonescu; Charles W. M. Roberts;

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-12
  • Exploring the coronavirus pandemic with the WashU Virus Genome Browser
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-09
    Jennifer A. Flynn; Deepak Purushotham; Mayank N. K. Choudhary; Xiaoyu Zhou; Changxu Fan; Gavriel Matt; Daofeng Li; Ting Wang

    The WashU Virus Genome Browser is a web-based portal for efficient visualization of viral ‘omics’ data in the context of a variety of annotation tracks and host infection responses. The browser features both a phylogenetic-tree-based view and a genomic-coordinate, track-based view in which users can analyze the sequence features of viral genomes, sequence diversity among viral strains, genomic sites

    更新日期:2020-09-10
  • Exploring the structural distribution of genetic variation in SARS-CoV-2 with the COVID-3D online resource
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-09
    Stephanie Portelli; Moshe Olshansky; Carlos H. M. Rodrigues; Elston N. D’Souza; Yoochan Myung; Michael Silk; Azadeh Alavi; Douglas E. V. Pires; David B. Ascher

    The emergence of the COVID-19 pandemic has spurred a global rush to uncover basic biological mechanisms to inform effective vaccine and drug development. Despite the novelty of the virus, global sequencing efforts have already identified genomic variation across isolates. To enable easy exploration and spatial visualization of the potential implications of SARS-CoV-2 mutations in infection, host immunity

    更新日期:2020-09-10
  • The UCSC SARS-CoV-2 Genome Browser
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-09
    Jason D. Fernandes; Angie S. Hinrichs; Hiram Clawson; Jairo Navarro Gonzalez; Brian T. Lee; Luis R. Nassar; Brian J. Raney; Kate R. Rosenbloom; Santrupti Nerli; Arjun A. Rao; Daniel Schmelter; Alastair Fyfe; Nathan Maulding; Ann S. Zweig; Todd M. Lowe; Manuel Ares; Russ Corbet-Detig; W. James Kent; David Haussler; Maximilian Haeussler

    The UCSC SARS-CoV-2 Genome Browser (https://genome.ucsc.edu/covid19.html) is an adaptation of our popular genome-browser visualization tool for this virus, containing many annotation tracks and new features, including conservation with similar viruses, immune epitopes, RT–PCR and sequencing primers and CRISPR guides. We invite all investigators to contribute to this resource to accelerate research

    更新日期:2020-09-10
  • Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-07
    Jie Zheng; Valeriia Haberland; Denis Baird; Venexia Walker; Philip C. Haycock; Mark R. Hurle; Alex Gutteridge; Pau Erola; Yi Liu; Shan Luo; Jamie Robinson; Tom G. Richardson; James R. Staley; Benjamin Elsworth; Stephen Burgess; Benjamin B. Sun; John Danesh; Heiko Runz; Joseph C. Maranville; Hannah M. Martin; James Yarmolinsky; Charles Laurin; Michael V. Holmes; Jimmy Z. Liu; Karol Estrada; Rita Santos;

    The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma protein levels. Here we estimated the effects of 1,002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 associations supported by evidence from MR, 130

    更新日期:2020-09-08
  • Author Correction: A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer.
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-03
    Andrea Lunardi,Ugo Ala,Mirjam T Epping,Leonardo Salmena,John G Clohessy,Kaitlyn A Webster,Guocan Wang,Roberta Mazzucchelli,Maristella Bianconi,Edward C Stack,Rosina Lis,Akash Patnaik,Lewis C Cantley,Glenn Bubley,Carlos Cordon-Cardo,William L Gerald,Rodolfo Montironi,Sabina Signoretti,Massimo Loda,Caterina Nardella,Pier Paolo Pandolfi

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-03
  • RNA post-transcriptional modification speaks to chromatin.
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-02
    Dalen Chan,Pedro J Batista

    The role of N6-methyladenosine (m6A) is still not fully understood. Two new studies advance understanding of this RNA modification. One shows that m6A modification of nascent messenger RNA promotes transcription by recruiting the histone H3 K9 demethylase KDM3B. Another study identifies genetic variants that affect m6A deposition and human disease.

    更新日期:2020-09-02
  • RNA closing the Polycomb circle.
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-02
    Ivano Mocavini,Luciano Di Croce

    Binding of RNA to the gene expression regulator Polycomb repressive complex 2 (PRC2) has been proposed to antagonize PRC2’s chromatin recruitment. A new study now shows that RNA is in fact critical for correct recruitment of PRC2 at its target genes in human pluripotent stem cells and suggests that interplay of PRC2 and RNA can fine-tune PRC2’s regulatory role.

    更新日期:2020-09-02
  • Crop genomes and beyond.
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-02

    Increasing amounts of crop genomic resources, along with new technical achievements in genome analysis, can facilitate basic and translational research in agriculture, and expand the ability to meet the global challenge of food production and security.

    更新日期:2020-09-02
  • Subclonal reconstruction of tumors by using machine learning and population genetics.
    Nat. Genet. (IF 27.603) Pub Date : 2020-09-02
    Giulio Caravagna,Timon Heide,Marc J Williams,Luis Zapata,Daniel Nichol,Ketevan Chkhaidze,William Cross,George D Cresswell,Benjamin Werner,Ahmet Acar,Louis Chesler,Chris P Barnes,Guido Sanguinetti,Trevor A Graham,Andrea Sottoriva

    Most cancer genomic data are generated from bulk samples composed of mixtures of cancer subpopulations, as well as normal cells. Subclonal reconstruction methods based on machine learning aim to separate those subpopulations in a sample and infer their evolutionary history. However, current approaches are entirely data driven and agnostic to evolutionary theory. We demonstrate that systematic errors

    更新日期:2020-09-02
  • Alteration of genome folding via contact domain boundary insertion.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-31
    Di Zhang,Peng Huang,Malini Sharma,Cheryl A Keller,Belinda Giardine,Haoyue Zhang,Thomas G Gilgenast,Jennifer E Phillips-Cremins,Ross C Hardison,Gerd A Blobel

    Animal chromosomes are partitioned into contact domains. Pathogenic domain disruptions can result from chromosomal rearrangements or perturbation of architectural factors. However, such broad-scale alterations are insufficient to define the minimal requirements for domain formation. Moreover, to what extent domains can be engineered is just beginning to be explored. In an attempt to create contact

    更新日期:2020-08-31
  • Chromatin binding of FOXA1 is promoted by LSD1-mediated demethylation in prostate cancer.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-31
    Shuai Gao,Sujun Chen,Dong Han,Zifeng Wang,Muqing Li,Wanting Han,Anna Besschetnova,Mingyu Liu,Feng Zhou,David Barrett,My Phu Luong,Jude Owiredu,Yi Liang,Musaddeque Ahmed,Jessica Petricca,Susan Patalano,Jill A Macoska,Eva Corey,Sen Chen,Steven P Balk,Housheng Hansen He,Changmeng Cai

    FOXA1 functions as a pioneer transcription factor by facilitating the access to chromatin for steroid hormone receptors, such as androgen receptor and estrogen receptor1,2,3,4, but mechanisms regulating its binding to chromatin remain elusive. LSD1 (KDM1A) acts as a transcriptional repressor by demethylating mono/dimethylated histone H3 lysine 4 (H3K4me1/2)5,6, but also acts as a steroid hormone receptor

    更新日期:2020-08-31
  • Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-24
    Xihao Li,Zilin Li,Hufeng Zhou,Sheila M Gaynor,Yaowu Liu,Han Chen,Ryan Sun,Rounak Dey,Donna K Arnett,Stella Aslibekyan,Christie M Ballantyne,Lawrence F Bielak,John Blangero,Eric Boerwinkle,Donald W Bowden,Jai G Broome,Matthew P Conomos,Adolfo Correa,L Adrienne Cupples,Joanne E Curran,Barry I Freedman,Xiuqing Guo,George Hindy,Marguerite R Irvin,Sharon L R Kardia,Sekar Kathiresan,Alyna T Khan,Charles

    Large-scale whole-genome sequencing studies have enabled the analysis of rare variants (RVs) associated with complex phenotypes. Commonly used RV association tests have limited scope to leverage variant functions. We propose STAAR (variant-set test for association using annotation information), a scalable and powerful RV association test method that effectively incorporates both variant categories

    更新日期:2020-08-24
  • Author Correction: Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-17
    Brett S Carver,Jennifer Tran,Anuradha Gopalan,Zhenbang Chen,Safa Shaikh,Arkaitz Carracedo,Andrea Alimonti,Caterina Nardella,Shohreh Varmeh,Peter T Scardino,Carlos Cordon-Cardo,William Gerald,Pier Paolo Pandolfi

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-08-20
  • Extrachromosomal DNA is associated with oncogene amplification and poor outcome across multiple cancers.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-17
    Hoon Kim,Nam-Phuong Nguyen,Kristen Turner,Sihan Wu,Amit D Gujar,Jens Luebeck,Jihe Liu,Viraj Deshpande,Utkrisht Rajkumar,Sandeep Namburi,Samirkumar B Amin,Eunhee Yi,Francesca Menghi,Johannes H Schulte,Anton G Henssen,Howard Y Chang,Christine R Beck,Paul S Mischel,Vineet Bafna,Roel G W Verhaak

    Extrachromosomal DNA (ecDNA) amplification promotes intratumoral genetic heterogeneity and accelerated tumor evolution1,2,3; however, its frequency and clinical impact are unclear. Using computational analysis of whole-genome sequencing data from 3,212 cancer patients, we show that ecDNA amplification frequently occurs in most cancer types but not in blood or normal tissue. Oncogenes were highly enriched

    更新日期:2020-08-17
  • Single-cell transcriptomics identifies a distinct luminal progenitor cell type in distal prostate invagination tips.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-17
    Wangxin Guo,Lin Li,Juan He,Zhuang Liu,Ming Han,Fei Li,Xinyi Xia,Xiaoyu Zhang,Yao Zhu,Yu Wei,Yunguang Li,Rebiguli Aji,Hao Dai,Hui Wei,Chunfeng Li,Yu Chen,Luonan Chen,Dong Gao

    The identification of prostate stem/progenitor cells and characterization of the prostate epithelial cell lineage hierarchy are critical for understanding prostate cancer initiation. Here, we characterized 35,129 cells from mouse prostates, and identified a unique luminal cell type (termed type C luminal cell (Luminal-C)) marked by Tacstd2, Ck4 and Psca expression. Luminal-C cells located at the distal

    更新日期:2020-08-17
  • N6-Methyladenosine co-transcriptionally directs the demethylation of histone H3K9me2.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-10
    Yuan Li,Linjian Xia,Kaifen Tan,Xidong Ye,Zhixiang Zuo,Minchun Li,Rui Xiao,Zihan Wang,Xiaona Liu,Mingqiang Deng,Jinru Cui,Mengtian Yang,Qizhi Luo,Sun Liu,Xin Cao,Haoran Zhu,Tianqi Liu,Jiaxin Hu,Junfang Shi,Shan Xiao,Laixin Xia

    A dynamic epigenome is critical for appropriate gene expression in development and health1,2,3,4,5. Central to this is the intricate process of transcription6,7,8,9,10,11, which integrates cellular signaling with chromatin changes, transcriptional machinery and modifications to messenger RNA, such as N6-methyladenosine (m6A), which is co-transcriptionally incorporated. The integration of these aspects

    更新日期:2020-08-10
  • Naming human genes.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-03

    Gene nomenclature can be complicated, and the official naming of genes requires rational standards to avoid confusion and to maximize clarity. The HUGO Gene Nomenclature Committee has released updated guidelines for the naming of human genes, and we encourage the community to adopt these recommendations.

    更新日期:2020-08-03
  • Guidelines for human gene nomenclature.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-03
    Elspeth A Bruford,Bryony Braschi,Paul Denny,Tamsin E M Jones,Ruth L Seal,Susan Tweedie

    Standardized gene naming is crucial for effective communication about genes, and as genomics becomes increasingly important in health care, the need for a consistent language to refer to human genes becomes ever more essential. Here, we present the current HUGO Gene Nomenclature Committee (HGNC) guidelines for naming not only protein-coding genes but also RNA genes and pseudogenes, and we outline the

    更新日期:2020-08-03
  • TADs without borders.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-03
    Irene Farabella,Marc A Marti-Renom

    Genomes are highly organized in space and time. Compartments, topologically associating domains (TADs) and loops are three dimensional (3D) genome features that have been extensively studied. Among these three levels of organization, TADs have sparked the most debate. New microscopy data shed light on how TADs and their leaky borders contribute to gene regulation.

    更新日期:2020-08-03
  • Analysis of Ugandan cervical carcinomas identifies human papillomavirus clade-specific epigenome and transcriptome landscapes.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-03
    Alessia Gagliardi,Vanessa L Porter,Zusheng Zong,Reanne Bowlby,Emma Titmuss,Constance Namirembe,Nicholas B Griner,Hilary Petrello,Jay Bowen,Simon K Chan,Luka Culibrk,Teresa M Darragh,Mark H Stoler,Thomas C Wright,Patee Gesuwan,Maureen A Dyer,Yussanne Ma,Karen L Mungall,Steven J M Jones,Carolyn Nakisige,Karen Novik,Jackson Orem,Martin Origa,Julie M Gastier-Foster,Robert Yarchoan,Corey Casper,Gordon B

    Cervical cancer is the most common cancer affecting sub-Saharan African women and is prevalent among HIV-positive (HIV+) individuals. No comprehensive profiling of cancer genomes, transcriptomes or epigenomes has been performed in this population thus far. We characterized 118 tumors from Ugandan patients, of whom 72 were HIV+, and performed extended mutation analysis on an additional 89 tumors. We

    更新日期:2020-08-03
  • DNA mismatch repair promotes APOBEC3-mediated diffuse hypermutation in human cancers.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-03
    David Mas-Ponte,Fran Supek

    Certain mutagens, including the APOBEC3 (A3) cytosine deaminase enzymes, can create multiple genetic changes in a single event. Activity of A3s results in striking ‘mutation showers’ occurring near DNA breakpoints; however, less is known about the mechanisms underlying the majority of A3 mutations. We classified the diverse patterns of clustered mutagenesis in tumor genomes, which identified a new

    更新日期:2020-08-03
  • Landscape of G-quadruplex DNA structural regions in breast cancer.
    Nat. Genet. (IF 27.603) Pub Date : 2020-08-03
    Robert Hänsel-Hertsch,Angela Simeone,Abigail Shea,Winnie W I Hui,Katherine G Zyner,Giovanni Marsico,Oscar M Rueda,Alejandra Bruna,Alistair Martin,Xiaoyun Zhang,Santosh Adhikari,David Tannahill,Carlos Caldas,Shankar Balasubramanian

    Response and resistance to anticancer therapies vary due to intertumor and intratumor heterogeneity1. Here, we map differentially enriched G-quadruplex (G4) DNA structure-forming regions (∆G4Rs) in 22 breast cancer patient-derived tumor xenograft (PDTX) models. ∆G4Rs are associated with the promoters of highly amplified genes showing high expression, and with somatic single-nucleotide variants. Differences

    更新日期:2020-08-03
  • European maize genomes highlight intraspecies variation in repeat and gene content.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-27
    Georg Haberer,Nadia Kamal,Eva Bauer,Heidrun Gundlach,Iris Fischer,Michael A Seidel,Manuel Spannagl,Caroline Marcon,Alevtina Ruban,Claude Urbany,Adnane Nemri,Frank Hochholdinger,Milena Ouzunova,Andreas Houben,Chris-Carolin Schön,Klaus F X Mayer

    The diversity of maize (Zea mays) is the backbone of modern heterotic patterns and hybrid breeding. Historically, US farmers exploited this variability to establish today’s highly productive Corn Belt inbred lines from blends of dent and flint germplasm pools. Here, we report de novo genome sequences of four European flint lines assembled to pseudomolecules with scaffold N50 ranging from 6.1 to 10

    更新日期:2020-07-27
  • APOBEC3-dependent kataegis and TREX1-driven chromothripsis during telomere crisis.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-27
    John Maciejowski,Aikaterini Chatzipli,Alexandra Dananberg,Kevan Chu,Eleonore Toufektchan,Leszek J Klimczak,Dmitry A Gordenin,Peter J Campbell,Titia de Lange

    Chromothripsis and kataegis are frequently observed in cancer and may arise from telomere crisis, a period of genome instability during tumorigenesis when depletion of the telomere reserve generates unstable dicentric chromosomes1,2,3,4,5. Here we examine the mechanism underlying chromothripsis and kataegis by using an in vitro telomere crisis model. We show that the cytoplasmic exonuclease TREX1,

    更新日期:2020-07-27
  • Cross-species chromatin interactions drive transcriptional rewiring in Epstein-Barr virus-positive gastric adenocarcinoma.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-27
    Atsushi Okabe,Kie Kyon Huang,Keisuke Matsusaka,Masaki Fukuyo,Manjie Xing,Xuewen Ong,Takayuki Hoshii,Genki Usui,Motoaki Seki,Yasunobu Mano,Bahityar Rahmutulla,Teru Kanda,Takayoshi Suzuki,Sun Young Rha,Tetsuo Ushiku,Masashi Fukayama,Patrick Tan,Atsushi Kaneda

    Epstein–Barr virus (EBV) is associated with several human malignancies including 8–10% of gastric cancers (GCs). Genome-wide analysis of 3D chromatin topologies across GC lines, primary tissue and normal gastric samples revealed chromatin domains specific to EBV-positive GC, exhibiting heterochromatin-to-euchromatin transitions and long-range human–viral interactions with non-integrated EBV episomes

    更新日期:2020-07-27
  • Characterizing the ecological and evolutionary dynamics of cancer.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-27
    Nastaran Zahir,Ruping Sun,Daniel Gallahan,Robert A Gatenby,Christina Curtis

    Tumor initiation and progression are somatic evolutionary processes driven by the accumulation of genetic alterations, some of which confer selective fitness advantages to the host cell. This gene-centric model has shaped the field of cancer biology and advanced understanding of cancer pathophysiology. Importantly, however, each genotype encodes diverse phenotypic traits that permit acclimation to

    更新日期:2020-07-27
  • Prostate cancer reactivates developmental epigenomic programs during metastatic progression.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-20
    Mark M Pomerantz,Xintao Qiu,Yanyun Zhu,David Y Takeda,Wenting Pan,Sylvan C Baca,Alexander Gusev,Keegan D Korthauer,Tesa M Severson,Gavin Ha,Srinivas R Viswanathan,Ji-Heui Seo,Holly M Nguyen,Baohui Zhang,Bogdan Pasaniuc,Claudia Giambartolomei,Sarah A Alaiwi,Connor A Bell,Edward P O'Connor,Matthew S Chabot,David R Stillman,Rosina Lis,Alba Font-Tello,Lewyn Li,Paloma Cejas,Andries M Bergman,Joyce Sanders

    Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions—from normal prostate epithelium to localized PCa to metastases—in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa

    更新日期:2020-07-20
  • Imprecise DNMT1 activity coupled with neighbor-guided correction enables robust yet flexible epigenetic inheritance.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-20
    Qiujun Wang,Guang Yu,Xuan Ming,Weikun Xia,Xiguang Xu,Yu Zhang,Wenhao Zhang,Yuanyuan Li,Chunyi Huang,Hehuang Xie,Bing Zhu,Wei Xie

    The epigenome, including DNA methylation, is stably propagated during mitotic division. However, single-cell clonal expansion produces heterogeneous methylomes, thus raising the question of how the DNA methylome remains stable despite constant epigenetic drift. Here, we report that a clonal population of DNA (cytosine-5)-methyltransferase 1 (DNMT1)-only cells produces a heterogeneous methylome, which

    更新日期:2020-07-20
  • The DNA methylation landscape of advanced prostate cancer.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-13
    Shuang G Zhao,William S Chen,Haolong Li,Adam Foye,Meng Zhang,Martin Sjöström,Rahul Aggarwal,Denise Playdle,Arnold Liao,Joshi J Alumkal,Rajdeep Das,Jonathan Chou,Junjie T Hua,Travis J Barnard,Adina M Bailey,Eric D Chow,Marc D Perry,Ha X Dang,Rendong Yang,Ruhollah Moussavi-Baygi,Li Zhang,Mohammed Alshalalfa,S Laura Chang,Kathleen E Houlahan,Yu-Jia Shiah,Tomasz M Beer,George Thomas,Kim N Chi,Martin Gleave

    Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes that were detectable only with integrated whole-genome

    更新日期:2020-07-13
  • Racism and the status quo.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-06

    When the status quo in science continues to perpetuate ingrained systems of discrimination, inequality and racism, the beneficiaries of these systems must not only reexamine their collective practices but also redress historical injustices through consequential, concrete actions that will lead to change. We cannot focus only on the first steps of listening and learning to build a better, fairer scientific

    更新日期:2020-07-06
  • Navigating the path to distant metastasis.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-06
    Trevor A Graham,Darryl Shibata

    How ‘difficult’ is it for somatic evolution to produce a cell that is capable of leaving the primary tumor and growing in a distant organ? In this issue, Reiter et al. assess genetic diversity across metastatic lesions and identify a tight selective bottleneck preceding distant metastasis.

    更新日期:2020-07-06
  • RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-06
    Yicheng Long,Taeyoung Hwang,Anne R Gooding,Karen J Goodrich,John L Rinn,Thomas R Cech

    Many chromatin-binding proteins and protein complexes that regulate transcription also bind RNA. One of these, Polycomb repressive complex 2 (PRC2), deposits the H3K27me3 mark of facultative heterochromatin and is required for stem cell differentiation. PRC2 binds RNAs broadly in vivo and in vitro. Yet, the biological importance of this RNA binding remains unsettled. Here, we tackle this question in

    更新日期:2020-07-06
  • Discovery of regulatory noncoding variants in individual cancer genomes by using cis-X.
    Nat. Genet. (IF 27.603) Pub Date : 2020-07-06
    Yu Liu,Chunliang Li,Shuhong Shen,Xiaolong Chen,Karol Szlachta,Michael N Edmonson,Ying Shao,Xiaotu Ma,Judith Hyle,Shaela Wright,Bensheng Ju,Michael C Rusch,Yanling Liu,Benshang Li,Michael Macias,Liqing Tian,John Easton,Maoxiang Qian,Jun J Yang,Shaoyan Hu,A Thomas Look,Jinghui Zhang

    We developed cis-X, a computational method for discovering regulatory noncoding variants in cancer by integrating whole-genome and transcriptome sequencing data from a single cancer sample. cis-X first finds aberrantly cis-activated genes that exhibit allele-specific expression accompanied by an elevated outlier expression. It then searches for causal noncoding variants that may introduce aberrant

    更新日期:2020-07-06
  • Pachytene piRNAs as beneficial regulators or a defense system gone rogue.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-29
    Alexei A Aravin

    Pachytene Piwi-interacting RNAs (piRNAs) are abundant small non-coding RNAs expressed in mammalian germ lines. A new study indicates that, among the diverse pool of piRNA sequences, a small number act as highly selective guides that induce cleavage of coding and non-coding transcripts, thus promoting piRNA generation and regulating gene expression.

    更新日期:2020-06-29
  • The evolutionarily conserved piRNA-producing locus pi6 is required for male mouse fertility.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-29
    Pei-Hsuan Wu,Yu Fu,Katharine Cecchini,Deniz M Özata,Amena Arif,Tianxiong Yu,Cansu Colpan,Ildar Gainetdinov,Zhiping Weng,Phillip D Zamore

    Pachytene PIWI-interacting RNAs (piRNAs), which comprise >80% of small RNAs in the adult mouse testis, have been proposed to bind and regulate target RNAs like microRNAs, cleave targets like short interfering RNAs or lack biological function altogether. Although piRNA pathway protein mutants are male sterile, no biological function has been identified for any mammalian piRNA-producing locus. Here,

    更新日期:2020-06-29
  • High-definition likelihood inference of genetic correlations across human complex traits.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-29
    Zheng Ning,Yudi Pawitan,Xia Shen

    Genetic correlation is a central parameter for understanding shared genetic architecture between complex traits. By using summary statistics from genome-wide association studies (GWAS), linkage disequilibrium score regression (LDSC) was developed for unbiased estimation of genetic correlations. Although easy to use, LDSC only partially utilizes LD information. By fully accounting for LD across the

    更新日期:2020-06-29
  • Privacy challenges and research opportunities for genomic data sharing.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-29
    Luca Bonomi,Yingxiang Huang,Lucila Ohno-Machado

    The sharing of genomic data holds great promise in advancing precision medicine and providing personalized treatments and other types of interventions. However, these opportunities come with privacy concerns, and data misuse could potentially lead to privacy infringement for individuals and their blood relatives. With the rapid growth and increased availability of genomic datasets, understanding the

    更新日期:2020-06-29
  • Genetic analyses support the contribution of mRNA N6-methyladenosine (m6A) modification to human disease heritability.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-29
    Zijie Zhang,Kaixuan Luo,Zhongyu Zou,Maguanyun Qiu,Jiakun Tian,Laura Sieh,Hailing Shi,Yuxin Zou,Gao Wang,Jean Morrison,Allen C Zhu,Min Qiao,Zhongshan Li,Matthew Stephens,Xin He,Chuan He

    N6-methyladenosine (m6A) plays important roles in regulating messenger RNA processing. Despite rapid progress in this field, little is known about the genetic determinants of m6A modification and their role in common diseases. In this study, we mapped the quantitative trait loci (QTLs) of m6A peaks in 60 Yoruba (YRI) lymphoblastoid cell lines. We found that m6A QTLs are largely independent of expression

    更新日期:2020-06-29
  • Single-cell analysis of clonal maintenance of transcriptional and epigenetic states in cancer cells.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-29
    Zohar Meir,Zohar Mukamel,Elad Chomsky,Aviezer Lifshitz,Amos Tanay

    Propagation of clonal regulatory programs contributes to cancer development. It is poorly understood how epigenetic mechanisms interact with genetic drivers to shape this process. Here, we combine single-cell analysis of transcription and DNA methylation with a Luria–Delbrück experimental design to demonstrate the existence of clonally stable epigenetic memory in multiple types of cancer cells. Longitudinal

    更新日期:2020-06-29
  • Genomic analyses implicate noncoding de novo variants in congenital heart disease.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-29
    Felix Richter,Sarah U Morton,Seong Won Kim,Alexander Kitaygorodsky,Lauren K Wasson,Kathleen M Chen,Jian Zhou,Hongjian Qi,Nihir Patel,Steven R DePalma,Michael Parfenov,Jason Homsy,Joshua M Gorham,Kathryn B Manheimer,Matthew Velinder,Andrew Farrell,Gabor Marth,Eric E Schadt,Jonathan R Kaltman,Jane W Newburger,Alessandro Giardini,Elizabeth Goldmuntz,Martina Brueckner,Richard Kim,George A Porter,Daniel

    A genetic etiology is identified for one-third of patients with congenital heart disease (CHD), with 8% of cases attributable to coding de novo variants (DNVs). To assess the contribution of noncoding DNVs to CHD, we compared genome sequences from 749 CHD probands and their parents with those from 1,611 unaffected trios. Neural network prediction of noncoding DNV transcriptional impact identified a

    更新日期:2020-06-29
  • Author Correction: Cas9 activates the p53 pathway and selects for p53-inactivating mutations.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-25
    Oana M Enache,Veronica Rendo,Mai Abdusamad,Daniel Lam,Desiree Davison,Sangita Pal,Naomi Currimjee,Julian Hess,Sasha Pantel,Anwesha Nag,Aaron R Thorner,John G Doench,Francisca Vazquez,Rameen Beroukhim,Todd R Golub,Uri Ben-David

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-06-25
  • Cohesin promotes stochastic domain intermingling to ensure proper regulation of boundary-proximal genes.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-22
    Jennifer M Luppino,Daniel S Park,Son C Nguyen,Yemin Lan,Zhuxuan Xu,Rebecca Yunker,Eric F Joyce

    The human genome can be segmented into topologically associating domains (TADs), which have been proposed to spatially sequester genes and regulatory elements through chromatin looping. Interactions between TADs have also been suggested, presumably because of variable boundary positions across individual cells. However, the nature, extent and consequence of these dynamic boundaries remain unclear.

    更新日期:2020-06-23
  • Author Correction: A transcriptomic analysis of the phylum Nematoda.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-15
    John Parkinson,Makedonka Mitreva,Claire Whitton,Marian Thomson,Jennifer Daub,John Martin,Ralf Schmid,Neil Hall,Bart Barrell,Robert H Waterston,James P McCarter,Mark L Blaxter

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-06-15
  • Recurrent inversion toggling and great ape genome evolution.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-15
    David Porubsky,Ashley D Sanders,Wolfram Höps,PingHsun Hsieh,Arvis Sulovari,Ruiyang Li,Ludovica Mercuri,Melanie Sorensen,Shwetha C Murali,David Gordon,Stuart Cantsilieris,Alex A Pollen,Mario Ventura,Francesca Antonacci,Tobias Marschall,Jan O Korbel,Evan E Eichler

    Inversions play an important role in disease and evolution but are difficult to characterize because their breakpoints map to large repeats. We increased by sixfold the number (n = 1,069) of previously reported great ape inversions by using single-cell DNA template strand and long-read sequencing. We find that the X chromosome is most enriched (2.5-fold) for inversions, on the basis of its size and

    更新日期:2020-06-15
  • Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-15
    Marijana Vujkovic,Jacob M Keaton,Julie A Lynch,Donald R Miller,Jin Zhou,Catherine Tcheandjieu,Jennifer E Huffman,Themistocles L Assimes,Kimberly Lorenz,Xiang Zhu,Austin T Hilliard,Renae L Judy,Jie Huang,Kyung M Lee,Derek Klarin,Saiju Pyarajan,John Danesh,Olle Melander,Asif Rasheed,Nadeem H Mallick,Shahid Hameed,Irshad H Qureshi,Muhammad Naeem Afzal,Uzma Malik,Anjum Jalal,Shahid Abbas,Xin Sheng,Long

    We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis

    更新日期:2020-06-15
  • TETs compete with DNMT3 activity in pluripotent cells at thousands of methylated somatic enhancers.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-08
    Jocelyn Charlton,Eunmi J Jung,Alexandra L Mattei,Nina Bailly,Jing Liao,Eric J Martin,Pay Giesselmann,Björn Brändl,Elena K Stamenova,Franz-Josef Müller,Evangelos Kiskinis,Andreas Gnirke,Zachary D Smith,Alexander Meissner

    Mammalian cells stably maintain high levels of DNA methylation despite expressing both positive (DNMT3A/B) and negative (TET1-3) regulators. Here, we analyzed the independent and combined effects of these regulators on the DNA methylation landscape using a panel of knockout human embryonic stem cell (ESC) lines. The greatest impact on global methylation levels was observed in DNMT3-deficient cells

    更新日期:2020-06-08
  • Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-08
    Kazuyoshi Ishigaki,Masato Akiyama,Masahiro Kanai,Atsushi Takahashi,Eiryo Kawakami,Hiroki Sugishita,Saori Sakaue,Nana Matoba,Siew-Kee Low,Yukinori Okada,Chikashi Terao,Tiffany Amariuta,Steven Gazal,Yuta Kochi,Momoko Horikoshi,Ken Suzuki,Kaoru Ito,Satoshi Koyama,Kouichi Ozaki,Shumpei Niida,Yasushi Sakata,Yasuhiko Sakata,Takashi Kohno,Kouya Shiraishi,Yukihide Momozawa,Makoto Hirata,Koichi Matsuda,Masashi

    The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.58 × 10−9). East Asian–specific missense variants

    更新日期:2020-06-08
  • CTCF is dispensable for immune cell transdifferentiation but facilitates an acute inflammatory response.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-08
    Grégoire Stik,Enrique Vidal,Mercedes Barrero,Sergi Cuartero,Maria Vila-Casadesús,Julen Mendieta-Esteban,Tian V Tian,Jinmi Choi,Clara Berenguer,Amaya Abad,Beatrice Borsari,François le Dily,Patrick Cramer,Marc A Marti-Renom,Ralph Stadhouders,Thomas Graf

    Three-dimensional organization of the genome is important for transcriptional regulation1,2,3,4,5,6,7. In mammals, CTCF and the cohesin complex create submegabase structures with elevated internal chromatin contact frequencies, called topologically associating domains (TADs)8,9,10,11,12. Although TADs can contribute to transcriptional regulation, ablation of TAD organization by disrupting CTCF or the

    更新日期:2020-06-08
  • DNMT3A and TET2 mutations reshape hematopoiesis in opposing ways.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-05
    Isaac F López-Moyado,Anjana Rao

    TET2 and DNMT3A mutations lead to similar long-term outcomes in blood cancers despite the antagonistic biochemical functions of their encoded proteins. A new study highlights the opposing effects of TET2 and DNMT3A mutations in shaping the early erythroid or myeloid bias of hematopoietic progenitors.

    更新日期:2020-06-05
  • Going virtual.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-05

    One of the many consequences of the global COVID-19 pandemic is the need for the scientific community to adapt to the cancellation of conferences and events because of travel restrictions and social-distancing guidelines. We have seen a very swift conversion to online meetings, which have allowed for this established form of science communication to continue and opened new avenues for innovation in

    更新日期:2020-06-05
  • Exploring and visualizing large-scale genetic associations by using PheWeb.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-01
    Sarah A Gagliano Taliun,Peter VandeHaar,Andrew P Boughton,Ryan P Welch,Daniel Taliun,Ellen M Schmidt,Wei Zhou,Jonas B Nielsen,Cristen J Willer,Seunggeun Lee,Lars G Fritsche,Michael Boehnke,Gonçalo R Abecasis

    更新日期:2020-06-01
  • Selective Mediator dependence of cell-type-specifying transcription.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-01
    Martin G Jaeger,Björn Schwalb,Sebastian D Mackowiak,Taras Velychko,Alexander Hanzl,Hana Imrichova,Matthias Brand,Benedikt Agerer,Someth Chorn,Behnam Nabet,Fleur M Ferguson,André C Müller,Andreas Bergthaler,Nathanael S Gray,James E Bradner,Christoph Bock,Denes Hnisz,Patrick Cramer,Georg E Winter

    The Mediator complex directs signals from DNA-binding transcription factors to RNA polymerase II (Pol II). Despite this pivotal position, mechanistic understanding of Mediator in human cells remains incomplete. Here we quantified Mediator-controlled Pol II kinetics by coupling rapid subunit degradation with orthogonal experimental readouts. In agreement with a model of condensate-driven transcription

    更新日期:2020-06-01
  • Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy.
    Nat. Genet. (IF 27.603) Pub Date : 2020-06-01
    Alejandro Jiménez-Sánchez,Paulina Cybulska,Katherine LaVigne Mager,Simon Koplev,Oliver Cast,Dominique-Laurent Couturier,Danish Memon,Pier Selenica,Ines Nikolovski,Yousef Mazaheri,Yonina Bykov,Felipe C Geyer,Geoff Macintyre,Lena Morrill Gavarró,Ruben M Drews,Michael B Gill,Anastasios D Papanastasiou,Ramon E Sosa,Robert A Soslow,Tyler Walther,Ronglai Shen,Dennis S Chi,Kay J Park,Travis Hollmann,Jorge

    In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor–immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy

    更新日期:2020-06-01