Your browser doesn't support javascript.
loading
Integrative annotation of variants from 1092 humans: application to cancer genomics.
Khurana, Ekta; Fu, Yao; Colonna, Vincenza; Mu, Xinmeng Jasmine; Kang, Hyun Min; Lappalainen, Tuuli; Sboner, Andrea; Lochovsky, Lucas; Chen, Jieming; Harmanci, Arif; Das, Jishnu; Abyzov, Alexej; Balasubramanian, Suganthi; Beal, Kathryn; Chakravarty, Dimple; Challis, Daniel; Chen, Yuan; Clarke, Declan; Clarke, Laura; Cunningham, Fiona; Evani, Uday S; Flicek, Paul; Fragoza, Robert; Garrison, Erik; Gibbs, Richard; Gümüs, Zeynep H; Herrero, Javier; Kitabayashi, Naoki; Kong, Yong; Lage, Kasper; Liluashvili, Vaja; Lipkin, Steven M; MacArthur, Daniel G; Marth, Gabor; Muzny, Donna; Pers, Tune H; Ritchie, Graham R S; Rosenfeld, Jeffrey A; Sisu, Cristina; Wei, Xiaomu; Wilson, Michael; Xue, Yali; Yu, Fuli; Dermitzakis, Emmanouil T; Yu, Haiyuan; Rubin, Mark A; Tyler-Smith, Chris; Gerstein, Mark.
Afiliação
  • Khurana E; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
  • Fu Y; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
  • Colonna V; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
  • Mu XJ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
  • Kang HM; Institute of Genetics and Biophysics, National Research Council (CNR), 80131 Naples, Italy.
  • Lappalainen T; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
  • Sboner A; Center for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Lochovsky L; Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.
  • Chen J; Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, 1211 Geneva, Switzerland.
  • Harmanci A; Swiss Institute of Bioinformatics, 1211 Geneva, Switzerland.
  • Das J; Institute 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.
  • Abyzov A; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10021, USA.
  • Balasubramanian S; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
  • Beal K; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
  • Chakravarty D; Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, CT 06520, USA.
  • Challis D; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
  • Chen Y; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
  • Clarke D; Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA.
  • Clarke L; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
  • Cunningham F; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
  • Evani US; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
  • Flicek P; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
  • Fragoza R; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
  • Garrison E; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Gibbs R; Institute 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.
  • Gümüs ZH; Baylor College of Medicine, Human Genome Sequencing Center, Houston, TX 77030, USA.
  • Herrero J; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
  • Kitabayashi N; Department of Chemistry, Yale University, New Haven, CT 06520, USA.
  • Kong Y; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Lage K; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Liluashvili V; Baylor College of Medicine, Human Genome Sequencing Center, Houston, TX 77030, USA.
  • Lipkin SM; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • MacArthur DG; Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
  • Marth G; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
  • Muzny D; Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.
  • Pers TH; Baylor College of Medicine, Human Genome Sequencing Center, Houston, TX 77030, USA.
  • Ritchie GRS; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10021, USA.
  • Rosenfeld JA; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, 10065, USA.
  • Sisu C; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Wei X; Institute 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.
  • Wilson M; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
  • Xue Y; Keck Biotechnology Resource Laboratory, Yale University, New Haven, CT 06511, USA.
  • Yu F; Pediatric Surgical Research Laboratories, MassGeneral Hospital for Children, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Dermitzakis ET; Harvard Medical School, Boston, MA 02115, USA.
  • Yu H; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
  • Rubin MA; Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
  • Tyler-Smith C; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10021, USA.
  • Gerstein M; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, 10065, USA.
Science ; 342(6154): 1235587, 2013 Oct 04.
Article em En | MEDLINE | ID: mdl-24092746
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.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Anotação de Sequência Molecular / Neoplasias Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2013 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Anotação de Sequência Molecular / Neoplasias Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2013 Tipo de documento: Article