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Exome sequencing

About: Exome sequencing is a(n) research topic. Over the lifetime, 13173 publication(s) have been published within this topic receiving 430995 citation(s). The topic is also known as: whole exome sequencing & WES.
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Journal ArticleDOI
Adam Auton1, Gonçalo R. Abecasis2, David Altshuler3, Richard Durbin4, David R. Bentley5, Aravinda Chakravarti6, Andrew G. Clark7, Peter Donnelly8, Evan E. Eichler9, Paul Flicek, Stacey Gabriel10, Richard A. Gibbs11, Eric D. Green12, Matthew E. Hurles4, Bartha Maria Knoppers13, Jan O. Korbel, Eric S. Lander10, Charles Lee14, Hans Lehrach15, Elaine R. Mardis16, Gabor T. Marth17, Gil McVean8, Deborah A. Nickerson9, Jeanette Schmidt18, Stephen T. Sherry12, Jun Wang, Richard K. Wilson16, Eric Boerwinkle11, Harsha Doddapaneni11, Yi Han11, Viktoriya Korchina11, Christie Kovar11, Sandra L. Lee11, Donna M. Muzny11, Jeffrey G. Reid11, Yiming Zhu11, Yuqi Chang19, Qiang Feng19, Qiang Feng20, Xiaodong Fang20, Xiaodong Fang19, Xiaosen Guo20, Xiaosen Guo19, Min Jian19, Min Jian20, Hui Jiang19, Hui Jiang20, Xin Jin19, Tianming Lan19, Guoqing Li19, Jingxiang Li19, Yingrui Li19, Shengmao Liu19, Xiao Liu19, Xiao Liu20, Yao Lu19, Xuedi Ma19, Meifang Tang19, Bo Wang19, Guangbiao Wang19, Honglong Wu19, Renhua Wu19, Xun Xu19, Ye Yin19, Dandan Zhang19, Wenwei Zhang19, Jiao Zhao19, Meiru Zhao19, Xiaole Zheng19, Namrata Gupta10, Neda Gharani21, Lorraine Toji21, Norman P. Gerry21, Alissa M. Resch21, Jonathan Barker, Laura Clarke, Laurent Gil, Sarah E. Hunt, Gavin Kelman, Eugene Kulesha, Rasko Leinonen, William M. McLaren, Rajesh Radhakrishnan, Asier Roa, Dmitriy Smirnov, Richard Smith, Ian Streeter, Anja Thormann, Iliana Toneva, Brendan Vaughan, Xiangqun Zheng-Bradley, Russell J. Grocock5, Sean Humphray5, Terena James5, Zoya Kingsbury5, Ralf Sudbrak22, M. Albrecht, Vyacheslav Amstislavskiy15, Tatiana A. Borodina, Matthias Lienhard15, Florian Mertes15, Marc Sultan15, Bernd Timmermann15, Marie-Laure Yaspo15, Lucinda Fulton16, Victor Ananiev12, Zinaida Belaia12, Dimitriy Beloslyudtsev12, Nathan Bouk12, Chao Chen12, Deanna M. Church, Robert M. Cohen12, Charles Cook12, John Garner12, Timothy Hefferon12, Mikhail Kimelman12, Chunlei Liu12, John Lopez12, Peter Meric12, Chris O’Sullivan12, Yuri Ostapchuk12, Lon Phan12, Sergiy Ponomarov12, Valerie A. Schneider12, Eugene Shekhtman12, Karl Sirotkin12, Douglas J. Slotta12, Hua Zhang12, Senduran Balasubramaniam4, John Burton4, Petr Danecek4, Thomas M. Keane4, Anja Kolb-Kokocinski4, Shane A. McCarthy4, James Stalker4, Michael A. Quail4, Christopher Davies18, Jeremy Gollub18, Teresa Webster18, Brant Wong18, Yiping Zhan18, Christopher L. Campbell1, Yu Kong1, Anthony Marcketta1, Fuli Yu11, Lilian Antunes11, Matthew N. Bainbridge11, Aniko Sabo11, Zhuoyi Huang11, Lachlan J. M. Coin19, Lin Fang19, Lin Fang20, Qibin Li19, Zhenyu Li19, Haoxiang Lin19, Binghang Liu19, Ruibang Luo19, Haojing Shao19, Haojing Shao23, Yinlong Xie19, Chen Ye19, Chang Yu19, Fan Zhang19, Hancheng Zheng19, Zhu Hongmei19, Can Alkan24, Elif Dal24, Fatma Kahveci24, Erik Garrison4, Deniz Kural, Wan-Ping Lee, Wen Fung Leong25, Michael Strömberg5, Alistair Ward17, Jiantao Wu5, Mengyao Zhang26, Mark J. Daly10, Mark A. DePristo, Robert E. Handsaker26, Robert E. Handsaker10, Eric Banks10, Gaurav Bhatia10, Guillermo del Angel10, Giulio Genovese10, Heng Li10, Seva Kashin10, Seva Kashin26, Steven A. McCarroll10, Steven A. McCarroll26, James Nemesh10, Ryan Poplin10, Seungtai Yoon27, Jayon Lihm27, Vladimir Makarov28, Srikanth Gottipati7, Alon Keinan7, Juan L. Rodriguez-Flores7, Tobias Rausch, Markus Hsi-Yang Fritz, Adrian M. Stütz, Kathryn Beal, Avik Datta, Javier Herrero29, Graham R. S. Ritchie, Daniel R. Zerbino, Pardis C. Sabeti10, Pardis C. Sabeti26, Ilya Shlyakhter10, Ilya Shlyakhter26, Stephen F. Schaffner10, Stephen F. Schaffner26, Joseph J. Vitti26, Joseph J. Vitti10, David Neil Cooper30, Edward V. Ball30, Peter D. Stenson30, Bret Barnes5, Markus J. Bauer5, R. Keira Cheetham5, Anthony J. Cox5, Michael A. Eberle5, Scott Kahn5, Lisa Murray5, John F. Peden5, Richard Shaw5, Eimear E. Kenny28, Mark A. Batzer31, Miriam K. Konkel31, Jerilyn A. Walker31, Daniel G. MacArthur26, Monkol Lek26, Ralf Herwig15, Li Ding16, Daniel C. Koboldt16, David E. Larson16, Kai Ye16, Simon Gravel13, Anand Swaroop12, Emily Y. Chew12, Tuuli Lappalainen32, Yaniv Erlich32, Melissa Gymrek10, Melissa Gymrek26, Thomas Willems33, Jared T. Simpson34, Mark D. Shriver35, Jeffrey A. Rosenfeld36, Carlos Bustamante37, Stephen B. Montgomery37, Francisco M. De La Vega37, Jake K. Byrnes, Andrew Carroll, Marianne K. DeGorter37, Phil Lacroute37, Brian K. Maples37, Alicia R. Martin37, Andrés Moreno-Estrada38, Andrés Moreno-Estrada37, Suyash Shringarpure37, Fouad Zakharia37, Eran Halperin39, Eran Halperin40, Yael Baran39, Eliza Cerveira, Jaeho Hwang, Ankit Malhotra, Dariusz Plewczynski, Kamen Radew, Mallory Romanovitch, Chengsheng Zhang, Fiona Hyland18, David Craig41, Alexis Christoforides41, Nils Homer42, Tyler Izatt41, Ahmet Kurdoglu41, Shripad Sinari41, Kevin Squire43, Chunlin Xiao12, Jonathan Sebat44, Danny Antaki44, Madhusudan Gujral44, Amina Noor44, Kenny Ye1, Esteban G. Burchard45, Ryan D. Hernandez45, Christopher R. Gignoux45, David Haussler46, David Haussler47, Sol Katzman47, W. James Kent47, Bryan Howie48, Andres Ruiz-Linares29, Emmanouil T. Dermitzakis49, Emmanouil T. Dermitzakis50, Scott E. Devine51, Hyun Min Kang2, Jeffrey M. Kidd2, Thomas W. Blackwell2, Sean Caron2, Wei Chen52, S. Emery2, Lars G. Fritsche2, Christian Fuchsberger2, Goo Jun53, Goo Jun2, Bingshan Li54, Robert H. Lyons2, Chris Scheller2, Carlo Sidore55, Carlo Sidore2, Carlo Sidore56, Shiya Song2, Elzbieta Sliwerska2, Daniel Taliun2, Adrian Tan2, Ryan P. Welch2, Mary Kate Wing2, Xiaowei Zhan57, Philip Awadalla34, Philip Awadalla58, Alan Hodgkinson58, Yun Li59, Xinghua Shi60, Andrew Quitadamo60, Gerton Lunter8, Jonathan Marchini8, Simon Myers8, Claire Churchhouse8, Olivier Delaneau49, Olivier Delaneau8, Anjali Gupta-Hinch8, Warren W. Kretzschmar8, Zamin Iqbal8, Iain Mathieson8, Androniki Menelaou61, Androniki Menelaou8, Andy Rimmer49, Dionysia Kiara Xifara8, Taras K. Oleksyk62, Yunxin Fu53, Xiaoming Liu53, Momiao Xiong53, Lynn B. Jorde17, David J. Witherspoon17, Jinchuan Xing36, Brian L. Browning9, Sharon R. Browning9, Fereydoun Hormozdiari9, Peter H. Sudmant9, Ekta Khurana7, Chris Tyler-Smith4, Cornelis A. Albers63, Qasim Ayub4, Yuan Chen4, Vincenza Colonna55, Vincenza Colonna4, Luke Jostins8, Klaudia Walter4, Yali Xue4, Mark Gerstein64, Alexej Abyzov65, Suganthi Balasubramanian64, Jieming Chen64, Declan Clarke64, Yao Fu64, Arif Harmanci64, Mike Jin64, Dong-Hoon Lee64, Jeremy Liu64, Xinmeng Jasmine Mu10, Xinmeng Jasmine Mu64, Jing Zhang64, Yan Zhang64, Christopher Hartl10, Khalid Shakir10, Jeremiah D. Degenhardt7, Sascha Meiers, Benjamin Raeder, Francesco Paolo Casale, Oliver Stegle, Eric-Wubbo Lameijer66, Ira M. Hall16, Vineet Bafna44, Jacob J. Michaelson44, Eugene J. Gardner51, Ryan E. Mills2, Gargi Dayama2, Ken Chen67, Xian Fan67, Zechen Chong67, Tenghui Chen67, Mark Chaisson9, John Huddleston9, Maika Malig9, Bradley J. Nelson9, Nicholas F. Parrish54, Ben Blackburne4, Sarah J. Lindsay4, Zemin Ning4, Yujun Zhang4, Hugo Y. K. Lam, Cristina Sisu64, Danny Challis11, Uday S. Evani11, James T. Lu11, Uma Nagaswamy11, Jin Yu11, Wangshen Li19, Lukas Habegger64, Haiyuan Yu7, Fiona Cunningham, Ian Dunham, Kasper Lage10, Kasper Lage26, Jakob Berg Jespersen10, Jakob Berg Jespersen68, Jakob Berg Jespersen26, Heiko Horn26, Heiko Horn10, Donghoon Kim64, Rob DeSalle69, Apurva Narechania69, Melissa A. Wilson Sayres70, Fernando L. Mendez37, G. David Poznik37, Peter A. Underhill37, David Mittelman71, Ruby Banerjee4, Maria Cerezo4, Thomas W. Fitzgerald4, Sandra Louzada4, Andrea Massaia4, Fengtang Yang4, Divya Kalra11, Walker Hale11, Xu Dan19, Kathleen C. Barnes6, Christine Beiswanger21, Hongyu Cai19, Hongzhi Cao19, Hongzhi Cao20, Brenna M. Henn72, Danielle Jones7, Jane Kaye8, Alastair Kent73, Angeliki Kerasidou8, Rasika A. Mathias6, Pilar N. Ossorio74, Michael Parker8, Charles N. Rotimi12, Charmaine D.M. Royal75, Karla Sandoval37, Yeyang Su19, Zhongming Tian19, Sarah A. Tishkoff76, Marc Via77, Yuhong Wang19, Huanming Yang19, Ling Yang19, Jiayong Zhu19, Walter F. Bodmer8, Gabriel Bedoya78, Zhiming Cai19, Yang Gao79, Jiayou Chu80, Leena Peltonen, Andrés C. García-Montero81, Alberto Orfao81, Julie Dutil82, Juan Carlos Martínez-Cruzado62, R. Mathias6, Anselm Hennis83, Harold Watson83, Colin A. McKenzie83, Firdausi Qadri84, Regina C. LaRocque84, Xiaoyan Deng, Danny Asogun, Onikepe A. Folarin, Christian T. Happi26, Omonwunmi Omoniwa26, Matt Stremlau10, Matt Stremlau26, Ridhi Tariyal10, Ridhi Tariyal26, M Jallow85, M Jallow8, Fatoumatta Sisay Joof8, Fatoumatta Sisay Joof85, Tumani Corrah8, Tumani Corrah85, Kirk A. Rockett8, Kirk A. Rockett85, Dominic P. Kwiatkowski8, Dominic P. Kwiatkowski85, Jaspal S. Kooner86, Tran Tinh Hien8, Sarah J. Dunstan8, Sarah J. Dunstan87, Nguyen ThuyHang8, Richard Fonnie, Robert F. Garry88, Lansana Kanneh, Lina M. Moses88, John S. Schieffelin88, Donald S. Grant88, Carla Gallo89, Giovanni Poletti89, Danish Saleheen76, Asif Rasheed, Lisa D. Brooks12, Adam Felsenfeld12, Jean E. McEwen12, Yekaterina Vaydylevich12, Audrey Duncanson90, Michael Dunn90, Jeffery A. Schloss12 
Yeshiva University1, University of Michigan2, Vertex Pharmaceuticals3, Wellcome Trust Sanger Institute4, Illumina5, Johns Hopkins University6, Cornell University7, University of Oxford8, University of Washington9, Broad Institute10, Baylor College of Medicine11, National Institutes of Health12, McGill University13, Ewha Womans University14, Max Planck Society15, Washington University in St. Louis16, University of Utah17, Thermo Fisher Scientific18, Beijing Institute of Genomics19, University of Copenhagen20, Coriell Institute For Medical Research21, Maastricht University22, University of Queensland23, Bilkent University24, Kansas State University25, Harvard University26, Cold Spring Harbor Laboratory27, Icahn School of Medicine at Mount Sinai28, University College London29, Cardiff University30, Louisiana State University31, Columbia University32, Massachusetts Institute of Technology33, Ontario Institute for Cancer Research34, Pennsylvania State University35, Rutgers University36, Stanford University37, CINVESTAV38, Tel Aviv University39, University of California, Berkeley40, Translational Genomics Research Institute41, Life Technologies42, University of California, Los Angeles43, University of California, San Diego44, University of California, San Francisco45, Howard Hughes Medical Institute46, University of California, Santa Cruz47, University of Chicago48, University of Geneva49, Swiss Institute of Bioinformatics50, University of Maryland, Baltimore51, University of Pittsburgh52, University of Texas Health Science Center at Houston53, Vanderbilt University54, National Research Council55, University of Sassari56, University of Texas Southwestern Medical Center57, Université de Montréal58, University of North Carolina at Chapel Hill59, University of North Carolina at Charlotte60, Utrecht University61, University of Puerto Rico at Mayagüez62, Radboud University Nijmegen63, Yale University64, Mayo Clinic65, Leiden University66, University of Texas MD Anderson Cancer Center67, Technical University of Denmark68, American Museum of Natural History69, Arizona State University70, Virginia Tech71, Stony Brook University72, Genetic Alliance73, University of Wisconsin-Madison74, Duke University75, University of Pennsylvania76, University of Barcelona77, University of Antioquia78, Peking University79, Peking Union Medical College80, University of Salamanca81, Ponce Health Sciences University82, University of the West Indies83, International Centre for Diarrhoeal Disease Research, Bangladesh84, Medical Research Council85, Hammersmith Hospital86, University of Melbourne87, Tulane University88, Cayetano Heredia University89, Wellcome Trust90
01 Oct 2015-Nature
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

9,821 citations


Journal ArticleDOI
TL;DR: The ANNOVAR tool to annotate single nucleotide variants and insertions/deletions, such as examining their functional consequence on genes, inferring cytogenetic bands, reporting functional importance scores, finding variants in conserved regions, or identifying variants reported in the 1000 Genomes Project and dbSNP is developed.
Abstract: High-throughput sequencing platforms are generating massive amounts of genetic variation data for diverse genomes, but it remains a challenge to pinpoint a small subset of functionally important variants. To fill these unmet needs, we developed the ANNOVAR tool to annotate single nucleotide variants (SNVs) and insertions/deletions, such as examining their functional consequence on genes, inferring cytogenetic bands, reporting functional importance scores, finding variants in conserved regions, or identifying variants reported in the 1000 Genomes Project and dbSNP. ANNOVAR can utilize annotation databases from the UCSC Genome Browser or any annotation data set conforming to Generic Feature Format version 3 (GFF3). We also illustrate a 'variants reduction' protocol on 4.7 million SNVs and indels from a human genome, including two causal mutations for Miller syndrome, a rare recessive disease. Through a stepwise procedure, we excluded variants that are unlikely to be causal, and identified 20 candidate genes including the causal gene. Using a desktop computer, ANNOVAR requires ∼4 min to perform gene-based annotation and ∼15 min to perform variants reduction on 4.7 million variants, making it practical to handle hundreds of human genomes in a day. ANNOVAR is freely available at http://www.openbioinformatics.org/annovar/.

8,141 citations


Journal ArticleDOI
Daniel C. Koboldt1, Robert S. Fulton1, Michael D. McLellan1, Heather Schmidt1, Joelle Kalicki-Veizer1, Joshua F. McMichael1, Lucinda Fulton1, David J. Dooling1, Li Ding1, Elaine R. Mardis1, Richard K. Wilson1, Adrian Ally2, Miruna Balasundaram2, Yaron S.N. Butterfield2, Rebecca Carlsen2, Candace Carter2, Andy Chu2, Eric Chuah2, Hye Jung E. Chun2, Robin J.N. Coope2, Noreen Dhalla2, Ranabir Guin2, Carrie Hirst2, Martin Hirst2, Robert A. Holt2, Darlene Lee2, Haiyan I. Li2, Michael Mayo2, Richard A. Moore2, Andrew J. Mungall2, Erin Pleasance2, A. Gordon Robertson2, Jacqueline E. Schein2, Arash Shafiei2, Payal Sipahimalani2, Jared R. Slobodan2, Dominik Stoll2, Angela Tam2, Nina Thiessen2, Richard Varhol2, Natasja Wye2, Thomas Zeng2, Yongjun Zhao2, Inanc Birol2, Steven J.M. Jones2, Marco A. Marra2, Andrew D. Cherniack3, Gordon Saksena3, Gordon Saksena4, Robert C. Onofrio3, Nam H. Pho3, Scott L. Carter3, Steven E. Schumacher3, Steven E. Schumacher4, Barbara Tabak4, Barbara Tabak3, Bryan Hernandez3, Jeff Gentry3, Huy Nguyen3, Andrew Crenshaw3, Kristin G. Ardlie3, Rameen Beroukhim4, Rameen Beroukhim3, Wendy Winckler3, Gad Getz4, Gad Getz3, Stacey Gabriel3, Matthew Meyerson3, Matthew Meyerson4, Lynda Chin4, Lynda Chin5, Raju Kucherlapati4, Katherine A. Hoadley6, J. Todd Auman6, Cheng Fan6, Yidi J. Turman6, Yan Shi6, Ling Li6, Michael D. Topal6, Xiaping He6, Hann Hsiang Chao6, Aleix Prat6, Grace O. Silva6, Michael D. Iglesia6, Wei Zhao6, Jerry Usary6, Jonathan S. Berg6, Michael C. Adams6, Jessica K. Booker6, Junyuan Wu6, Anisha Gulabani6, Tom Bodenheimer6, Alan P. Hoyle6, Janae V. Simons6, Matthew G. Soloway6, Lisle E. Mose6, Stuart R. Jefferys6, Saianand Balu6, Joel S. Parker6, D. Neil Hayes6, Charles M. Perou6, Simeen Malik7, Swapna Mahurkar7, Hui Shen7, Daniel J. Weisenberger7, Timothy J. Triche7, Phillip H. Lai7, Moiz S. Bootwalla7, Dennis T. Maglinte7, Benjamin P. Berman7, David Van Den Berg7, Stephen B. Baylin8, Peter W. Laird7, Chad J. Creighton9, Lawrence A. Donehower9, Michael S. Noble4, Doug Voet4, Nils Gehlenborg4, Daniel Di Cara4, Juinhua Zhang5, Hailei Zhang4, Chang-Jiun Wu5, Spring Yingchun Liu4, Michael S. Lawrence4, Lihua Zou4, Andrey Sivachenko4, Pei Lin4, Petar Stojanov4, Rui Jing4, Juok Cho4, Raktim Sinha4, Richard W. Park4, Marc Danie Nazaire4, James A. Robinson4, Helga Thorvaldsdottir4, Jill P. Mesirov4, Peter J. Park4, Sheila Reynolds10, Richard Kreisberg10, Brady Bernard10, Ryan Bressler10, Timo Erkkilä11, Jake Lin10, Vesteinn Thorsson10, Wei Zhang5, Ilya Shmulevich10, Giovanni Ciriello12, Nils Weinhold12, Nikolaus Schultz12, Jianjiong Gao12, Ethan Cerami12, Benjamin Gross12, Anders Jacobsen12, Rileen Sinha12, B. Arman Aksoy12, Yevgeniy Antipin12, Boris Reva12, Ronglai Shen12, Barry S. Taylor12, Marc Ladanyi12, Chris Sander12, Pavana Anur13, Paul T. Spellman13, Yiling Lu5, Wenbin Liu5, Roel R.G. Verhaak5, Gordon B. Mills5, Gordon B. Mills14, Rehan Akbani5, Nianxiang Zhang5, Bradley M. Broom5, Tod D. Casasent5, Chris Wakefield5, Anna K. Unruh5, Keith A. Baggerly5, Kevin R. Coombes5, John N. Weinstein5, David Haussler15, Christopher C. Benz16, Joshua M. Stuart15, Stephen C. Benz15, Jingchun Zhu15, Christopher Szeto15, Gary K. Scott16, Christina Yau16, Evan O. Paull15, Daniel E. Carlin15, Christopher K. Wong15, Artem Sokolov15, Janita Thusberg16, Sean D. Mooney16, Sam Ng15, Theodore C. Goldstein15, Kyle Ellrott15, Mia Grifford15, Christopher Wilks15, Singer Ma15, Brian Craft15, Chunhua Yan17, Ying Hu17, Daoud Meerzaman17, Julie M. Gastier-Foster18, Julie M. Gastier-Foster19, Jay Bowen19, Nilsa C. Ramirez19, Nilsa C. Ramirez18, Aaron D. Black19, Robert E. Pyatt18, Robert E. Pyatt19, Peter White18, Peter White19, Erik Zmuda19, Jessica Frick19, Tara M. Lichtenberg19, Robin Brookens19, Myra M. George19, Mark Gerken19, Hollie A. Harper19, Kristen M. Leraas19, Lisa Wise19, Teresa R. Tabler19, Cynthia McAllister19, Thomas Barr19, Melissa Hart-Kothari19, Katie Tarvin, Charles Saller, George E. Sandusky20, Colleen Mitchell21, Mary Iacocca22, Jennifer Brown22, Brenda Rabeno22, Christine Czerwinski22, Nicholas J. Petrelli22, Oleg Dolzhansky, Mikhail Abramov23, Olga Voronina, Olga Potapova, Jeffrey R. Marks24, Wiktoria Maria Suchorska, Dawid Murawa, Witold Kycler, Matthew Ibbs, Konstanty Korski, Arkadiusz Spychała, Pawel Murawa, Jacek J. Brzeziński, Hanna Perz, Radoslaw Łaźniak, M. Teresiak, Honorata Tatka, Ewa Leporowska, Marta Bogusz-Czerniewicz, Julian Malicki, Andrzej Mackiewicz, Maciej Wiznerowicz, Xuan Van Le, Bernard Kohl, Nguyen Viet Tien, Richard Thorp, Nguyen Van Bang, Howard H. Sussman25, Bui Duc Phu, Richard A. Hajek14, Nguyen Phi Hung17, Huynh Quyet Thang, Khurram Z. Khan, Robert Penny, David Mallery, Erin Curley, Candace Shelton, Peggy Yena, James N. Ingle26, Fergus J. Couch26, Wilma L. Lingle26, Tari A. King12, Ana M. Gonzalez-Angulo5, Ana M. Gonzalez-Angulo14, Mary D. Dyer14, Shuying Liu14, Xiaolong Meng14, Modesto Patangan14, Frederic Waldman27, Frederic Waldman28, Hubert Stoppler27, W. Kimryn Rathmell6, Leigh B. Thorne6, Mei Huang6, Lori Boice6, Ashley Hill6, Carl Morrison29, Carmelo Gaudioso29, Wiam Bshara29, Kelly Daily30, Sophie C. Egea30, Mark D. Pegram30, Carmen Gomez-Fernandez30, Rajiv Dhir31, Rohit Bhargava31, Adam Brufsky31, Craig D. Shriver32, Jeffrey A. Hooke32, Jamie Leigh Campbell32, Richard J. Mural33, Hai Hu33, Stella Somiari33, Caroline Larson33, Brenda Deyarmin33, Leonid Kvecher33, Albert J. Kovatich, Matthew J. Ellis1, Thomas Stricker34, Kevin P. White34, Olufunmilayo I. Olopade34, Chunqing Luo33, Yaqin Chen33, Ron Bose1, Li-Wei Chang1, Andrew H. Beck4, Todd Pihl35, Mark A. Jensen35, Robert Sfeir35, Ari B. Kahn35, Anna Chu35, Prachi Kothiyal35, Zhining Wang35, Eric E. Snyder35, Joan Pontius35, Brenda Ayala35, Mark Backus35, Jessica Walton35, Julien Baboud35, Dominique L. Berton35, Matthew C. Nicholls35, Deepak Srinivasan35, Rohini Raman35, Stanley Girshik35, Peter A. Kigonya35, Shelley Alonso35, Rashmi N. Sanbhadti35, Sean P. Barletta35, David Pot35, Margi Sheth17, John A. Demchok17, Kenna R. Mills Shaw17, Liming Yang17, Greg Eley, Martin L. Ferguson, Roy Tarnuzzer17, Jiashan Zhang17, Laura A.L. Dillon17, Kenneth H. Buetow17, Peter Fielding17, Bradley A. Ozenberger17, Mark S. Guyer17, Heidi J. Sofia17, Jacqueline D. Palchik17 
04 Oct 2012-Nature
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Abstract: We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.

8,025 citations


Journal ArticleDOI
01 Nov 2012-Nature
TL;DR: It is shown that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites.
Abstract: By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.

7,236 citations


Journal ArticleDOI
28 Oct 2010-Nature
Abstract: The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.

7,174 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20227
20211,756
20201,594
20191,522
20181,381
20171,441

Top Attributes

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Topic's top 5 most impactful authors

Richard A. Gibbs

130 papers, 29.7K citations

James R. Lupski

102 papers, 6.1K citations

Donna M. Muzny

92 papers, 20.8K citations

Fowzan S. Alkuraya

71 papers, 3.5K citations

Naomichi Matsumoto

68 papers, 3K citations