Alternative Isoform Regulation in Human Tissue Transcriptomes
Eric T. Wang,Rickard Sandberg,Rickard Sandberg,Shujun Luo,Irina Khrebtukova,Lu Zhang,Christine Mayr,Stephen F. Kingsmore,Gary P. Schroth,Christopher B. Burge +9 more
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TLDR
An in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments yielding a digital inventory of gene and mRNA isoform expression suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.Abstract:
Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon-exon junctions indicated that 92-94% of human genes undergo alternative splicing, 86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or 'switch-like' regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 3' untranslated regions suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.read more
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References
More filters
Journal ArticleDOI
Initial sequencing and analysis of the human genome.
Eric S. Lander,Lauren Linton,Bruce W. Birren,Chad Nusbaum,Michael C. Zody,Jennifer Baldwin,Keri Devon,Ken Dewar,Michael Doyle,William Fitzhugh,Roel Funke,Diane Gage,Katrina Harris,Andrew Heaford,John Howland,Lisa Kann,Jessica A. Lehoczky,Rosie Levine,Paul A. McEwan,Kevin McKernan,James Meldrim,Jill P. Mesirov,Cher Miranda,William Morris,Jerome Naylor,Christina Raymond,Mark Rosetti,Ralph Santos,Andrew Sheridan,Carrie Sougnez,Nicole Stange-Thomann,Nikola Stojanovic,Aravind Subramanian,Dudley Wyman,Jane Rogers,John Sulston,R Ainscough,Stephan Beck,David Bentley,John Burton,C M Clee,Nigel P. Carter,Alan Coulson,Rebecca Deadman,Panos Deloukas,Andrew Dunham,Ian Dunham,Richard Durbin,Lisa French,Darren Grafham,Simon G. Gregory,Tim Hubbard,Sean Humphray,Adrienne Hunt,Matthew Jones,Christine Lloyd,Amanda McMurray,Lucy Matthews,Simon Mercer,Sarah Milne,James C. Mullikin,Andrew J. Mungall,Robert W. Plumb,Mark T. Ross,Ratna Shownkeen,Sarah Sims,Robert H. Waterston,Richard K. Wilson,LaDeana W. Hillier,John Douglas Mcpherson,Marco A. Marra,Elaine R. Mardis,Lucinda Fulton,Asif T. Chinwalla,Kymberlie H. Pepin,Warren Gish,Stephanie L. Chissoe,Michael C. Wendl,Kim D. Delehaunty,Tracie L. Miner,Andrew Delehaunty,Jason B. Kramer,Lisa Cook,Robert S. Fulton,Douglas L. Johnson,Patrick Minx,Sandra W. Clifton,Trevor Hawkins,Elbert Branscomb,Paul Predki,Paul G. Richardson,Sarah Wenning,Tom Slezak,Norman A. Doggett,Jan Fang Cheng,Anne S. Olsen,Susan Lucas,Christopher J. Elkin,Edward Uberbacher,Marvin Frazier,Richard A. Gibbs,Donna M. Muzny,Steven E. Scherer,John Bouck,Erica Sodergren,Kim C. Worley,Catherine M. Rives,James H. Gorrell,Michael L. Metzker,Susan L. Naylor,Raju Kucherlapati,David L. Nelson,George M. Weinstock,Yoshiyuki Sakaki,Asao Fujiyama,Masahira Hattori,Tetsushi Yada,Atsushi Toyoda,Takehiko Itoh,Chiharu Kawagoe,Hidemi Watanabe,Yasushi Totoki,Todd D. Taylor,Jean Weissenbach,Roland Heilig,William Saurin,François Artiguenave,Philippe Brottier,Thomas Brüls,Eric Pelletier,Catherine Robert,Patrick Wincker,André Rosenthal,Matthias Platzer,Gerald Nyakatura,Stefan Taudien,Andreas Rump,Douglas R. Smith,Lynn Doucette-Stamm,Marc Rubenfield,Keith Weinstock,Mei Lee Hong,Joann Dubois,Huanming Yang,Jun Yu,Jian Wang,Guyang Huang,Jun Gu,Leroy Hood,Lee Rowen,Anup Madan,Shizen Qin,Ronald W. Davis,Nancy A. Federspiel,A. Pia Abola,Michael Proctor,Bruce A. Roe,Feng Chen,Huaqin Pan,Juliane Ramser,Hans Lehrach,Richard Reinhardt,W. Richard McCombie,Melissa De La Bastide,Neilay Dedhia,H. Blöcker,K. Hornischer,Gabriele Nordsiek,Richa Agarwala,L. Aravind,Jeffrey A. Bailey,Alex Bateman,Serafim Batzoglou,Ewan Birney,Peer Bork,Daniel G. Brown,Christopher B. Burge,Lorenzo Cerutti,Hsiu Chuan Chen,Deanna M. Church,Michele Clamp,Richard R. Copley,Tobias Doerks,Sean R. Eddy,Evan E. Eichler,Terrence S. Furey,James E. Galagan,James G. R. Gilbert,Cyrus L. Harmon,Yoshihide Hayashizaki,David Haussler,Henning Hermjakob,Karsten Hokamp,Wonhee Jang,L. Steven Johnson,Thomas A. Jones,Simon Kasif,Arek Kaspryzk,Scot Kennedy,W. James Kent,Paul Kitts,Eugene V. Koonin,Ian F Korf,David Kulp,Doron Lancet,Todd M. Lowe,Aoife McLysaght,Tarjei S. Mikkelsen,John V. Moran,Nicola Mulder,Victor J. Pollara,Chris P. Ponting,Greg Schuler,Jörg Schultz,Guy Slater,Arian F.A. Smit,Elia Stupka,Joseph Szustakowki,Danielle Thierry-Mieg,Jean Thierry-Mieg,Lukas Wagner,John W. Wallis,Raymond Wheeler,Alan Williams,Yuri I. Wolf,Kenneth H. Wolfe,Shiaw Pyng Yang,Ru Fang Yeh,Francis S. Collins,Mark S. Guyer,Jane Peterson,Adam Felsenfeld,Kris A. Wetterstrand,Richard M. Myers,Jeremy Schmutz,Mark Dickson,Jane Grimwood,David R. Cox,Maynard V. Olson,Rajinder Kaul,Christopher K. Raymond,Nobuyoshi Shimizu,Kazuhiko Kawasaki,Shinsei Minoshima,Glen A. Evans,Maria Athanasiou,Roger A. Schultz,Aristides Patrinos,Michael J. Morgan +248 more
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
Mapping and quantifying mammalian transcriptomes by RNA-Seq.
TL;DR: Although >90% of uniquely mapped reads fell within known exons, the remaining data suggest new and revised gene models, including changed or additional promoters, exons and 3′ untranscribed regions, as well as new candidate microRNA precursors.
Journal ArticleDOI
Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets
TL;DR: In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of the gene set.
Journal ArticleDOI
Mechanisms of Alternative Pre-Messenger RNA Splicing
TL;DR: This review describes what is currently known of the molecular mechanisms that control changes in splice site choice and starts with the best-characterized systems from the Drosophila sex determination pathway, and then describes the regulators of other systems about whose mechanisms there is some data.
Journal ArticleDOI
The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements
Leming Shi,Laura H. Reid,Wendell D. Jones,Richard Shippy,Janet A. Warrington,Shawn C. Baker,Patrick J. Collins,Francoise de Longueville,Ernest S. Kawasaki,Kathleen Y. Lee,Yuling Luo,Yongming Andrew Sun,James C. Willey,Robert Setterquist,Gavin M. Fischer,Weida Tong,Yvonne P. Dragan,David J. Dix,Felix W. Frueh,Federico Goodsaid,Damir Herman,Roderick V. Jensen,Charles D. Johnson,Edward K. Lobenhofer,Raj K. Puri,Uwe Scherf,Jean Thierry-Mieg,Charles Wang,Michael A Wilson,Paul K. Wolber,Lu Zhang,William Slikker,Shashi Amur,Wenjun Bao,Catalin Barbacioru,Anne Bergstrom Lucas,Vincent Bertholet,Cecilie Boysen,Bud Bromley,Donna Brown,Alan Brunner,Roger D. Canales,Xiaoxi Megan Cao,Thomas A. Cebula,James J. Chen,Jing Cheng,Tzu Ming Chu,Eugene Chudin,John F. Corson,J. Christopher Corton,Lisa J. Croner,Christopher Davies,Timothy Davison,Glenda C. Delenstarr,Xutao Deng,David Dorris,Aron Charles Eklund,Xiaohui Fan,Hong Fang,Stephanie Fulmer-Smentek,James C. Fuscoe,Kathryn Gallagher,Weigong Ge,Lei Guo,Xu Guo,Janet Hager,Paul K. Haje,Jing Han,Tao Han,Heather Harbottle,Stephen C. Harris,Eli Hatchwell,Craig A. Hauser,Susan D. Hester,Huixiao Hong,Patrick Hurban,Scott A. Jackson,Hanlee P. Ji,Charles R. Knight,Winston Patrick Kuo,J. Eugene LeClerc,Shawn Levy,Quan Zhen Li,Chunmei Liu,Ying Liu,Michael Lombardi,Yunqing Ma,Scott R. Magnuson,Botoul Maqsodi,Timothy K. McDaniel,Nan Mei,Ola Myklebost,Baitang Ning,Natalia Novoradovskaya,Michael S. Orr,Terry Osborn,Adam Papallo,Tucker A. Patterson,Roger Perkins,Elizabeth Herness Peters,Ron L. Peterson,Kenneth L. Philips,P. Scott Pine,Lajos Pusztai,Feng Qian,Hongzu Ren,Mitch Rosen,Barry A. Rosenzweig,Raymond R. Samaha,Mark Schena,Gary P. Schroth,Svetlana Shchegrova,Dave D. Smith,Frank Staedtler,Zhenqiang Su,Hongmei Sun,Zoltan Szallasi,Zivana Tezak,Danielle Thierry-Mieg,Karol L. Thompson,Irina Tikhonova,Yaron Turpaz,Beena Vallanat,Christophe Van,Stephen J. Walker,Sue Jane Wang,Yonghong Wang,Russell D. Wolfinger,Alexander Wong,Jie Wu,Chunlin Xiao,Qian Xie,Jun Xu,Wen Yang,Liang Zhang,Sheng Zhong,Yaping Zong +136 more
TL;DR: This study describes the experimental design and probe mapping efforts behind the MicroArray Quality Control project and shows intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed.