ArticleScience (New York, N.Y.)2013
Integrative annotation of variants from 1092 humans: application to cancer genomics.
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In one paragraph
Article in Science (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 234 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
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234citing papers in PubMed, 3 pooled it
27.5field-weighted citation impact, top 1% of its field
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Who cites it
234 citing papers in PubMed, 3 syntheses or guidelines pooled it, 402 citations in OpenAlex.
- Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.International journal of cancer · 2025Pooled it
- Identification and Evolutionary Analysis of Potential Candidate Genes in a Human Eating Disorder.BioMed research international · 2016Pooled it
- The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2015Pooled it
- Increased chromatin accessibility following 1α,25-dihydroxyvitamin DToxicology and applied pharmacology · 2026Article
- Mapping the landscape of allele-specific expression in porcine genomes.Genome biology · 2026Article
- Unsupervised Deep Representation Learning and Probabilistic Clustering for the Systems-Level Discovery of Germline Mutation Signatures in Pediatric Cancers.Biomedicines · 2026Article
- Altered benzo[a]pyrene adduct formation in nucleosomes establishes distinct mutational patterns in lung cancer.The Journal of biological chemistry · 2026Article
- The ChickenGTEx portal: a pan-tissue catalogue of regulatory variants shaping transcriptomic and phenotypic diversity.Nucleic acids research · 2026Article
- Nanotechnology-Driven Therapeutic Potential of Raloxifene in Osteoporosis and Cancer: A Recent Review.Current pharmaceutical design · 2026Review
- Comparison of missing data handling methods for variant pathogenicity predictors.NAR genomics and bioinformatics · 2025Article
- Mapping transcription factor binding sites by learning UV damage fingerprints.Nucleic acids research · 2025Article
- Long Non-Coding RNAs and RNA-Binding Proteins in Pancreatic Cancer Development and Progression.Cancers · 2025Review
- Noncoding variation near UBE2E2 orchestrates cardiometabolic pathophenotypes through polygenic effectors.JCI insight · 2024Article
- Oncogenic Enhancers in Leukemia.Blood cancer discovery · 2024Review
- Allele-specific binding (ASB) analyzer for annotation of allele-specific binding SNPs.BMC bioinformatics · 2023Article
- Identifying functional regulatory mutation blocks by integrating genome sequencing and transcriptome data.iScience · 2023Article
- Two germline mutations can serve as genetic susceptibility screening makers for a lung adenocarcinoma family.Journal of cancer research and clinical oncology · 2023Article
- Unified views on variant impact across many diseases.Trends in genetics : TIG · 2023Review
- Identification of Driver Epistatic Gene Pairs Combining Germline and Somatic Mutations in Cancer.International journal of molecular sciences · 2023Article
- Article
174 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
49 authors at 13 institutions in 4 countries.
Ekta Khurana *Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Yao Fu *Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Vincenza Colonna *Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
Xinmeng Jasmine Mu *Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Hyun Min KangCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
Tuuli LappalainenDepartment of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
Andrea SbonerInstitute for Precision Medicine and the Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
Lucas LochovskyProgram in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Jieming ChenProgram in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Arif HarmanciProgram in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Jishnu DasDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA.
Alexej AbyzovProgram in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Suganthi BalasubramanianProgram in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Kathryn BealEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Dimple ChakravartyInstitute for Precision Medicine and the Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
Daniel ChallisBaylor College of Medicine, Human Genome Sequencing Center, Houston, TX 77030, USA.
Yuan ChenWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
Declan ClarkeDepartment of Chemistry, Yale University, New Haven, CT 06520, USA.
Laura ClarkeEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Fiona CunninghamEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Uday S EvaniBaylor College of Medicine, Human Genome Sequencing Center, Houston, TX 77030, USA.
Paul FlicekEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Robert FragozaWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
Erik GarrisonDepartment of Biology, Boston College, Chestnut Hill, MA 02467, USA.
Richard GibbsBaylor College of Medicine, Human Genome Sequencing Center, Houston, TX 77030, USA.
Zeynep H GümüşThe HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10021, USA.
Javier HerreroEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Naoki KitabayashiInstitute for Precision Medicine and the Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
Yong KongDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Kasper LagePediatric Surgical Research Laboratories, MassGeneral Hospital for Children, Massachusetts General Hospital, Boston, MA 02114, USA.
Vaja LiluashviliThe HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10021, USA.
Steven M LipkinDepartment of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Daniel G MacArthurAnalytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Gabor MarthDepartment of Biology, Boston College, Chestnut Hill, MA 02467, USA.
Donna MuznyBaylor College of Medicine, Human Genome Sequencing Center, Houston, TX 77030, USA.
Tune H PersCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
Graham R S RitchieEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
Jeffrey A RosenfeldDepartment of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07101, USA.
Cristina SisuProgram in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Xiaomu WeiWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
Michael WilsonProgram in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Yali XueWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
Fuli YuBaylor College of Medicine, Human Genome Sequencing Center, Houston, TX 77030, USA.
1000 Genomes Project Consortium
Emmanouil T DermitzakisDepartment of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
Haiyuan YuDepartment of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA.
Mark A RubinInstitute for Precision Medicine and the Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
Chris Tyler-SmithWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
Mark GersteinProgram in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Yale University · USCornell University · USBaylor College of Medicine · USWellcome Sanger Institute · GBEuropean Bioinformatics Institute · GBWellcome Trust · GBBoston College · USUniversity of Geneva · CHAmerican Museum of Natural History · USBaylor Genetics · USBroad Institute · USHarvard University · USMassachusetts General Hospital · US
Funding
Large Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7MClinical and Translational Science CenterUL1TR000457 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI IMPERATO-MCGINLEY, JULIANNE L · 2012 to 2016
$46.0MVIRAL SEQUENCES IN PEDIATRIC HIV INFECTION IN PRG12RR003050 · NCRR · PONCE SCHOOL OF MEDICINE · PI ARMSTRONG, RAUL A · 1985 to 2011
$28.1MVIRAL SEQUENCES IN PEDIATRIC HIV INFECTION IN PRG12MD007579 · NIMHD · PONCE SCHOOL OF MEDICINE · PI TORRES-RUIZ, JOSE A · 2012 to 2018
$15.9MEDAC: ENCODE Data Analysis CenterU41HG007000 · NHGRI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WENG, ZHIPING · 2012 to 2016
$9.8MEpitomic Biomarkers of Prostate CancerU01CA111275 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M, RUBIN, MARK A. · 2004 to 2015
$6.8MUnderstanding Obesity In Relation to the Built EnvironmentP20MD006899 · NIMHD · JACKSON STATE UNIVERSITY · PI ANTOINE-LAVIGNE, DONNA A · 2012 to 2016
$5.3MRobust Software Tools for Variant Identification and Functional AssessmentU01HG006513 · NHGRI · UNIVERSITY OF UTAH · PI ABECASIS, GONCALO, MARTH, GABOR T · 2012 to 2015
$4.2MNatural Genetic Variation in the Human GenomeR01HG002898 · NHGRI · UNIVERSITY OF MARYLAND BALTIMORE · PI DEVINE, SCOTT E · 2004 to 2019
$3.7MSoftware Tools for Next-Generation Sequencer DataR01HG004719 · NHGRI · BOSTON COLLEGE · PI MARTH, GABOR T · 2008 to 2011
$2.5MWhole Genome Sequencing to Discover Familial Myeloma Risk GenesR01CA167824 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LIPKIN, STEVEN M, OFFIT, KENNETH · 2012 to 2016
$1.9MComprehensive Prostate Cancer Characterization by Genomic and Transcriptomic ProfR01CA152057 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI RUBIN, MARK A. · 2011 to 2013
$1.8MNCATS NIH HHS UL1 TR000457NCI NIH HHS CA167824NCI NIH HHS R01 CA152057NCI NIH HHS R01CA152057NCI NIH HHS R01 CA166661NCI NIH HHS R01 CA167824NCI NIH HHS U01 CA111275NCRR NIH HHS G12 RR003050NHGRI NIH HHS HG005718NHGRI NIH HHS HG007000NHGRI NIH HHS R01 HG002898NHGRI NIH HHS R01 HG004719NHGRI NIH HHS R01HG4719NHGRI NIH HHS U01 HG005718NHGRI NIH HHS U01 HG006513NHGRI NIH HHS U01HG6513NHGRI NIH HHS U41 HG007000NHGRI NIH HHS U54 HG003079NIGMS NIH HHS GM104424NIGMS NIH HHS R01 GM097358NIGMS NIH HHS R01 GM104424NIMHD NIH HHS G12 MD007579NIMHD NIH HHS P20 MD006899Wellcome Trust 085532Wellcome Trust 090532Wellcome Trust 095908Wellcome Trust 098051Wellcome Trust WT085532Wellcome Trust WT090532Wellcome Trust WT095908Wellcome Trust WT098051
Abstract
Interpreting variants, especially noncoding ones, in the increasing number of personal genomes is challenging. We used patterns of polymorphisms in functionally annotated regions in 1092 humans to identify deleterious variants; then we experimentally validated candidates. We analyzed both coding and noncoding regions, with the former corroborating the latter. We found regions particularly sensitive to mutations ("ultrasensitive") and variants that are disruptive because of mechanistic effects on transcription-factor binding (that is, "motif-breakers"). We also found variants in regions with higher network centrality tend to be deleterious. Insertions and deletions followed a similar pattern to single-nucleotide variants, with some notable exceptions (e.g., certain deletions and enhancers). On the basis of these patterns, we developed a computational tool (FunSeq), whose application to ~90 cancer genomes reveals nearly a hundred candidate noncoding drivers.
Indexed as
Genetic VariationBinding SitesGenome, HumanGenomicsHumansKruppel-Like Transcription FactorsMolecular Sequence AnnotationMutationNeoplasmsPolymorphism, Single NucleotidePopulationRNA, UntranslatedSelection, GeneticKruppel-Like Transcription FactorsRNA, UntranslatedZNF274 protein, human
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.