Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics

Ekta Khurana; Yao Fu; Vincenza Colonna; Xinmeng Jasmine Mu; Hyun Min Kang; Tuuli Lappalainen; Andrea Sboner; Lucas Lochovsky; Jieming Chen; Arif Harmanci; Jishnu Das; Alexej Abyzov; Suganthi Balasubramanian; Kathryn Beal; Dimple Chakravarty; Daniel Challis; Yuan Chen; Declan Clarke; Laura Clarke; Fiona Cunningham; Uday S. Evani; Paul Flicek; Robert Fragoza; Erik Garrison; Richard Gibbs; Zeynep H. Gümüş; Javier Herrero; Naoki Kitabayashi; Yong Kong; Kasper Lage; Vaja Liluashvili; Steven M. Lipkin; Daniel G. MacArthur; Gabor Marth; Donna Muzny; Tune Hannes Pers; Graham R. S. Ritchie; Jeffrey A. Rosenfeld; Cristina Sisu; Xiaomu Wei; Michael Wilson; Yali Xue; Fuli Yu; Emmanouil T. Dermitzakis; Haiyuan Yu; Mark A. Rubin; Chris Tyler-Smith; Mark Gerstein

doi:10.1126/science.1235587

Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics

Ekta Khurana, Yao Fu, Vincenza Colonna, Xinmeng Jasmine Mu, Hyun Min Kang, Tuuli Lappalainen, Andrea Sboner, Lucas Lochovsky, Jieming Chen, Arif Harmanci, Jishnu Das, Alexej Abyzov, Suganthi Balasubramanian, Kathryn Beal, Dimple Chakravarty, Daniel Challis, Yuan Chen, Declan Clarke, Laura Clarke, Fiona CunninghamUday S. Evani, Paul Flicek, Robert Fragoza, Erik Garrison, Richard Gibbs, Zeynep H. Gümüş, Javier Herrero, Naoki Kitabayashi, Yong Kong, Kasper Lage, Vaja Liluashvili, Steven M. Lipkin, Daniel G. MacArthur, Gabor Marth, Donna Muzny, Tune Hannes Pers, Graham R. S. Ritchie, Jeffrey A. Rosenfeld, Cristina Sisu, Xiaomu Wei, Michael Wilson, Yali Xue, Fuli Yu, Emmanouil T. Dermitzakis, Haiyuan Yu, Mark A. Rubin, Chris Tyler-Smith, Mark Gerstein

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

Identifying Important Identifiers Each of us has millions of sequence variations in our genomes. Signatures of purifying or negative selection should help identify which of those variations is functionally important. Khurana et al. (1235587) used sequence polymorphisms from 1092 humans across 14 populations to identify patterns of selection, especially in noncoding regulatory regions. Noncoding regions under very strong negative selection included binding sites of some chromatin and general transcription factors (TFs) and core motifs of some important TF families. Positive selection in TF binding sites tended to occur in network hub promoters. Many recurrent somatic cancer variants occurred in noncoding regulatory regions and thus might indicate mutations that drive cancer.

Original language	English
Article number	1235587
Journal	Science
Volume	342
Issue number	6154
Number of pages	9
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.1235587
Publication status	Published - 2013

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Khurana, E., Fu, Y., Colonna, V., Mu, X. J., Kang, H. M., Lappalainen, T., Sboner, A., Lochovsky, L., Chen, J., Harmanci, A., Das, J., Abyzov, A., Balasubramanian, S., Beal, K., Chakravarty, D., Challis, D., Chen, Y., Clarke, D., Clarke, L., ... Gerstein, M. (2013). Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics. Science, 342(6154), Article 1235587. https://doi.org/10.1126/science.1235587

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title = "Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics",

abstract = "Identifying Important Identifiers Each of us has millions of sequence variations in our genomes. Signatures of purifying or negative selection should help identify which of those variations is functionally important. Khurana et al. (1235587) used sequence polymorphisms from 1092 humans across 14 populations to identify patterns of selection, especially in noncoding regulatory regions. Noncoding regions under very strong negative selection included binding sites of some chromatin and general transcription factors (TFs) and core motifs of some important TF families. Positive selection in TF binding sites tended to occur in network hub promoters. Many recurrent somatic cancer variants occurred in noncoding regulatory regions and thus might indicate mutations that drive cancer.",

author = "Ekta Khurana and Yao Fu and Vincenza Colonna and Mu, {Xinmeng Jasmine} and Kang, {Hyun Min} and Tuuli Lappalainen and Andrea Sboner and Lucas Lochovsky and Jieming Chen and Arif Harmanci and Jishnu Das and Alexej Abyzov and Suganthi Balasubramanian and Kathryn Beal and Dimple Chakravarty and Daniel Challis and Yuan Chen and Declan Clarke and Laura Clarke and Fiona Cunningham and Evani, {Uday S.} and Paul Flicek and Robert Fragoza and Erik Garrison and Richard Gibbs and G{\"u}m{\"u}{\c s}, {Zeynep H.} and Javier Herrero and Naoki Kitabayashi and Yong Kong and Kasper Lage and Vaja Liluashvili and Lipkin, {Steven M.} and MacArthur, {Daniel G.} and Gabor Marth and Donna Muzny and Pers, {Tune Hannes} and Ritchie, {Graham R. S.} and Rosenfeld, {Jeffrey A.} and Cristina Sisu and Xiaomu Wei and Michael Wilson and Yali Xue and Fuli Yu and Dermitzakis, {Emmanouil T.} and Haiyuan Yu and Rubin, {Mark A.} and Chris Tyler-Smith and Mark Gerstein",

year = "2013",

doi = "10.1126/science.1235587",

language = "English",

volume = "342",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6154",

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Khurana, E, Fu, Y, Colonna, V, Mu, XJ, Kang, HM, Lappalainen, T, Sboner, A, Lochovsky, L, Chen, J, Harmanci, A, Das, J, Abyzov, A, Balasubramanian, S, Beal, K, Chakravarty, D, Challis, D, Chen, Y, Clarke, D, Clarke, L, Cunningham, F, Evani, US, Flicek, P, Fragoza, R, Garrison, E, Gibbs, R, Gümüş, ZH, Herrero, J, Kitabayashi, N, Kong, Y, Lage, K, Liluashvili, V, Lipkin, SM, MacArthur, DG, Marth, G, Muzny, D, Pers, TH, Ritchie, GRS, Rosenfeld, JA, Sisu, C, Wei, X, Wilson, M, Xue, Y, Yu, F, Dermitzakis, ET, Yu, H, Rubin, MA, Tyler-Smith, C & Gerstein, M 2013, 'Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics', Science, vol. 342, no. 6154, 1235587. https://doi.org/10.1126/science.1235587

TY - JOUR

T1 - Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics

AU - Khurana, Ekta

AU - Fu, Yao

AU - Colonna, Vincenza

AU - Mu, Xinmeng Jasmine

AU - Kang, Hyun Min

AU - Lappalainen, Tuuli

AU - Sboner, Andrea

AU - Lochovsky, Lucas

AU - Chen, Jieming

AU - Harmanci, Arif

AU - Das, Jishnu

AU - Abyzov, Alexej

AU - Balasubramanian, Suganthi

AU - Beal, Kathryn

AU - Chakravarty, Dimple

AU - Challis, Daniel

AU - Chen, Yuan

AU - Clarke, Declan

AU - Clarke, Laura

AU - Cunningham, Fiona

AU - Evani, Uday S.

AU - Flicek, Paul

AU - Fragoza, Robert

AU - Garrison, Erik

AU - Gibbs, Richard

AU - Gümüş, Zeynep H.

AU - Herrero, Javier

AU - Kitabayashi, Naoki

AU - Kong, Yong

AU - Lage, Kasper

AU - Liluashvili, Vaja

AU - Lipkin, Steven M.

AU - MacArthur, Daniel G.

AU - Marth, Gabor

AU - Muzny, Donna

AU - Pers, Tune Hannes

AU - Ritchie, Graham R. S.

AU - Rosenfeld, Jeffrey A.

AU - Sisu, Cristina

AU - Wei, Xiaomu

AU - Wilson, Michael

AU - Xue, Yali

AU - Yu, Fuli

AU - Dermitzakis, Emmanouil T.

AU - Yu, Haiyuan

AU - Rubin, Mark A.

AU - Tyler-Smith, Chris

AU - Gerstein, Mark

PY - 2013

Y1 - 2013

N2 - Identifying Important Identifiers Each of us has millions of sequence variations in our genomes. Signatures of purifying or negative selection should help identify which of those variations is functionally important. Khurana et al. (1235587) used sequence polymorphisms from 1092 humans across 14 populations to identify patterns of selection, especially in noncoding regulatory regions. Noncoding regions under very strong negative selection included binding sites of some chromatin and general transcription factors (TFs) and core motifs of some important TF families. Positive selection in TF binding sites tended to occur in network hub promoters. Many recurrent somatic cancer variants occurred in noncoding regulatory regions and thus might indicate mutations that drive cancer.

AB - Identifying Important Identifiers Each of us has millions of sequence variations in our genomes. Signatures of purifying or negative selection should help identify which of those variations is functionally important. Khurana et al. (1235587) used sequence polymorphisms from 1092 humans across 14 populations to identify patterns of selection, especially in noncoding regulatory regions. Noncoding regions under very strong negative selection included binding sites of some chromatin and general transcription factors (TFs) and core motifs of some important TF families. Positive selection in TF binding sites tended to occur in network hub promoters. Many recurrent somatic cancer variants occurred in noncoding regulatory regions and thus might indicate mutations that drive cancer.

U2 - 10.1126/science.1235587

DO - 10.1126/science.1235587

M3 - Journal article

C2 - 24092746

SN - 0036-8075

VL - 342

JO - Science

JF - Science

IS - 6154

M1 - 1235587

ER -

Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics

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