@article{ff7dd2ab6ea2406d98514907a238021b,
title = "Integrative annotation of variants from 1092 humans: Application to cancer genomics",
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.",
author = "E. Khurana and Y. Fu and V. Colonna and Mu, {X. J.} and Kang, {H. M.} and T. Lappalainen and A. Sboner and L. Lochovsky and J. Chen and A. Harmanci and J. Das and A. Abyzov and S. Balasubramanian and K. Beal and D. Chakravarty and D. Challis and Y. Chen and D. Clarke and L. Clarke and F. Cunningham and Evani, {U. S.} and P. Flicek and R. Fragoza and E. Garrison and Gibbs, {R. A.} and G{\"u}m{\"u}{\c s}, {Z. H.} and J. Herrero and N. Kitabayashi and Y. Kong and K. Lage and V. Liluashvili and Lipkin, {S. M.} and MacArthur, {D. G.} and G. Marth and D. Muzny and Pers, {T. H.} and GRS Ritchie and Rosenfeld, {J. A.} and C. Sisu and X. Wei and M. Wilson and Y. Xue and F. Yu and Dermitzakis, {E. T.} and H. Yu and Rubin, {M. A.} and C. Tyler-Smith and M. Gerstein and Altshuler, {D. M.} and Durbin, {R. M.} and Abecasis, {G. R.} and Bentley, {D. R.} and A. Chakravarti and Clark, {A. G.} and P. Donnelly and Eichler, {E. E.} and Gabriel, {S. B.} and Green, {E. D.} and Hurles, {M. E.} and Knoppers, {B. M.} and Korbel, {J. O.} and Lander, {E. S.} and C. Lee and H. Lehrach and Mardis, {E. R.} and McVean, {G. A.} and Nickerson, {D. A.} and Schmidt, {J. P.} and Sherry, {S. T.} and J. Wang and Wilson, {R. K.} and H. Dinh and C. Kovar and S. Lee and L. Lewis and J. Reid and M. Wang and X. Fang and X. Guo and M. Jian and H. Jiang and X. Jin and G. Li and J. Li and Y. Li and Z. Li and X. Liu and Y. Lu and X. Ma and Z. Su and S. Tai and M. Tang and B. Wang and G. Wang and H. Wu and R. Wu and Y. Yin and W. Zhang and J. Zhao and M. Zhao and X. Zheng and Y. Zhou and N. Gupta and R. Leinonen and Smith, {R. E.} and X. Zheng-Bradley and R. Grocock and S. Humphray and T. James and Z. Kingsbury and R. Sudbrak and Albrecht, {M. W.} and Amstislavskiy, {V. S.} and Borodina, {T. A.} and M. Lienhard and F. Mertes and M. Sultan and B. Timmermann and Yaspo, {M. L.} and L. Fulton and R. Fulton and Weinstock, {G. M.} and S. Balasubramaniam and J. Burton and P. Danecek and Keane, {T. M.} and A. Kolb-Kokocinski and S. McCarthy and J. Stalker and M. Quail and Davies, {C. J.} and J. Gollub and T. Webster and B. Wong and Y. Zhan and A. Auton and M. Bainbridge and J. Lu and U. Nagaswamy and A. Sabo and Y. Wang and J. Yu and Coin, {L. J.} and L. Fang and Q. Li and H. Lin and B. Liu and R. Luo and N. Qin and H. Shao and Y. Xie and C. Ye and C. Yu and F. Zhang and H. Zheng and H. Zhu and Garrison, {E. P.} and D. Kural and Lee, {W. P.} and Leong, {W. F.} and Ward, {A. N.} and J. Wu and M. Zhang and L. Griffin and Hsieh, {C. H.} and Mills, {R. E.} and X. Shi and {von Grotthuss}, M. and C. Zhang and Daly, {M. J.} and DePristo, {M. A.} and E. Banks and G. Bhatia and Carneiro, {M. O.} and {del Angel}, G. and G. Genovese and Handsaker, {R. E.} and C. Hartl and McCarroll, {S. A.} and Nemesh, {J. C.} and Poplin, {R. E.} and Schaffner, {S. F.} and K. Shakir and Yoon, {S. C.} and J. Lihm and V. Makarov and H. Jin and W. Kim and Kim, {K. C.} and T. Rausch and McLaren, {W. M.} and Ritchie, {G. R.} and S. Gottipati and A. Keinan and Rodriguez-Flores, {J. L.} and Sabeti, {P. C.} and Grossman, {S. R.} and S. Tabrizi and R. Tariyal and Cooper, {D. N.} and Ball, {E. V.} and Stenson, {P. D.} and B. Barnes and M. Bauer and R. Cheetham and T. Cox and M. Eberle and S. Kahn and L. Murray and J. Peden and R. Shaw and K. Ye and Batzer, {M. A.} and Konkel, {M. K.} and Walker, {J. A.} and M. Lek and R. Herwig and Shriver, {M. D.} and Bustamante, {C. D.} and Byrnes, {J. K.} and {De La Vega}, M. and S. Gravel and Kenny, {E. E.} and Kidd, {J. M.} and P. Lacroute and Maples, {B. K.} and A. Moreno-Estrada and F. Zakharia and E. Halperin and Y. Baran and Craig, {D. W.} and A. Christoforides and N. Homer and T. Izatt and Kurdoglu, {A. A.} and Sinari, {S. A.} and K. Squire and C. Xiao and J. Sebat and V. Bafna and Burchard, {E. G.} and Hernandez, {R. D.} and Gignoux, {C. R.} and D. Haussler and Katzman, {S. J.} and W. Kent and B. Howie and A. Ruiz-Linares and Devine, {S. E.} and Q. Ayub and {The 1000 Genomes Project Consortium}",
year = "2013",
month = oct,
day = "4",
doi = "10.1126/science.1235587",
language = "English",
volume = "342",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science (AAAS)",
number = "6154",
}
