English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Integrative annotation of variants from 1092 humans: application to cancer genomics

Khurana, E., Fu, Y., Colonna, V., Mu, X. J., Kang, H. M., Lappalainen, T., et al. (2013). Integrative annotation of variants from 1092 humans: application to cancer genomics. Science, 342(6154), 1235587-1235587. doi:10.1126/science.1235587.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-02F5-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-B2D1-C
Genre: Journal Article

Files

show Files
hide Files
:
Khurana.pdf (Publisher version), 3MB
Name:
Khurana.pdf
Description:
Science. Author manuscript; available in PMC 2014 March 09.
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
2013
Copyright Info:
2013 by the American Association for the Advancement of Science; all rights reserved
License:
-

Locators

show

Creators

show
hide
 Creators:
Khurana, E., Author
Fu, Y., Author
Colonna, V., Author
Mu, X. J., Author
Kang, H. M., Author
Lappalainen, T., Author
Sboner, A., Author
Lochovsky, L., Author
Chen, J., Author
Harmanci, A., Author
Das, J., Author
Abyzov, A., Author
Balasubramanian, S., Author
Beal, K., Author
Chakravarty, D., Author
Challis, D., Author
Chen, Y., Author
Clarke, D., Author
Clarke, L., Author
Cunningham, F., Author
Evani, U. S., AuthorFlicek, P., AuthorFragoza, R., AuthorGarrison, E., AuthorGibbs, R., AuthorGumus, Z. H., AuthorHerrero, J., AuthorKitabayashi, N., AuthorKong, Y., AuthorLage, K., AuthorLiluashvili, V., AuthorLipkin, S. M., AuthorMacArthur, D. G., AuthorMarth, G., AuthorMuzny, D., AuthorPers, T. H., AuthorRitchie, G. R., AuthorRosenfeld, J. A., AuthorSisu, C., AuthorWei, X., AuthorWilson, M., AuthorXue, Y., AuthorYu, F., Author1000 Genomes Project, Consortium1, AuthorLehrach, H.1, 2, Author              Sudbrak, R.1, 2, Author              Albrecht, M. W.1, AuthorAmstislavskiy, V.3, Author              Borodina, T. A., AuthorLienhard, M.4, Author              Mertes, F.2, Author              Sultan, M.3, Author              Timmermann, B.5, Author              Yaspo, M. L.6, Author              Dermitzakis, E. T., AuthorYu, H., AuthorRubin, M. A., AuthorTyler-Smith, C., AuthorGerstein, M., Author more..
Affiliations:
11000 Genomes Project Consortium, ou_persistent22              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
3Human Chromosome 21 (Marie-Laure Yaspo), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479652              
4Bioinformatics (Ralf Herwig), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479648              
5Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              
6Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117287              

Content

show
hide
Free keywords: Binding Sites/genetics *Genetic Variation Genome, Human Genomics Humans Kruppel-Like Transcription Factors/metabolism Molecular Sequence Annotation/*methods Mutation Neoplasms/*genetics Polymorphism, Single Nucleotide Population/genetics RNA, Untranslated/genetics Selection, Genetic
 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.

Details

show
hide
Language(s): eng - English
 Dates: 2013-10-04
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1126/science.1235587
ISSN: 1095-9203 (Electronic)0036-8075 (Print)
 Degree: -

Event

show

Legal Case

show

Project information

show hide
Project name : 1000 Genomes Project
Grant ID : 01GS08201
Funding program : -
Funding organization : BMBF

Source 1

show
hide
Title: Science
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Washington, D.C. : American Association for the Advancement of Science
Pages: - Volume / Issue: 342 (6154) Sequence Number: - Start / End Page: 1235587 - 1235587 Identifier: ISSN: 0036-8075
CoNE: https://pure.mpg.de/cone/journals/resource/991042748276600_1