MOTIVATION: Next-generation (NextGen) sequencing is becoming increasingly popular as an alternative for transcriptional profiling, as is the case for micro RNAs (miRNA) profiling and classification. miRNAs are a new class of molecules that are regulated in response to differentiation, tumorigenesis or infection. Our primary motivating application is to identify different viral infections based on the induced change in the host miRNA profile. Statistical challenges are encountered because of special features of NextGen sequencing data: the data are read counts that are extremely skewed and non-negative; the total number of reads varies dramatically across samples that require appropriate normalization. Statistical tools developed for microarray expression data, such as principal component analysis, are sub-optimal for analyzing NextGen sequencing data. RESULTS: We propose a family of Poisson factor models that explicitly takes into account the count nature of sequencing data and automatically incorporates sample normalization through the use of offsets. We develop an efficient algorithm for estimating the Poisson factor model, entitled Poisson Singular Value Decomposition with Offset (PSVDOS). The method is shown to outperform several other normalization and dimension reduction methods in a simulation study. Through analysis of an miRNA profiling experiment, we further illustrate that our model achieves insightful dimension reduction of the miRNA profiles of 18 samples: the extracted factors lead to more accurate and meaningful clustering of the cell lines. AVAILABILITY: The PSVDOS software is available on request.
MOTIVATION: Next-generation (NextGen) sequencing is becoming increasingly popular as an alternative for transcriptional profiling, as is the case for micro RNAs (miRNA) profiling and classification. miRNAs are a new class of molecules that are regulated in response to differentiation, tumorigenesis or infection. Our primary motivating application is to identify different viral infections based on the induced change in the host miRNA profile. Statistical challenges are encountered because of special features of NextGen sequencing data: the data are read counts that are extremely skewed and non-negative; the total number of reads varies dramatically across samples that require appropriate normalization. Statistical tools developed for microarray expression data, such as principal component analysis, are sub-optimal for analyzing NextGen sequencing data. RESULTS: We propose a family of Poisson factor models that explicitly takes into account the count nature of sequencing data and automatically incorporates sample normalization through the use of offsets. We develop an efficient algorithm for estimating the Poisson factor model, entitled Poisson Singular Value Decomposition with Offset (PSVDOS). The method is shown to outperform several other normalization and dimension reduction methods in a simulation study. Through analysis of an miRNA profiling experiment, we further illustrate that our model achieves insightful dimension reduction of the miRNA profiles of 18 samples: the extracted factors lead to more accurate and meaningful clustering of the cell lines. AVAILABILITY: The PSVDOS software is available on request.
Authors: Alkes L Price; Nick J Patterson; Robert M Plenge; Michael E Weinblatt; Nancy A Shadick; David Reich Journal: Nat Genet Date: 2006-07-23 Impact factor: 38.330
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Robert Penny; Miguel A Piris; Rajiv Sarin; Aldo Scarpa; Tatsuhiro Shibata; Marc van de Vijver; P Andrew Futreal; Hiroyuki Aburatani; Mónica Bayés; David D L Botwell; Peter J Campbell; Xavier Estivill; Daniela S Gerhard; Sean M Grimmond; Ivo Gut; Martin Hirst; Carlos López-Otín; Partha Majumder; Marco Marra; John D McPherson; Hidewaki Nakagawa; Zemin Ning; Xose S Puente; Yijun Ruan; Tatsuhiro Shibata; Michael R Stratton; Hendrik G Stunnenberg; Harold Swerdlow; Victor E Velculescu; Richard K Wilson; Hong H Xue; Liu Yang; Paul T Spellman; Gary D Bader; Paul C Boutros; Peter J Campbell; Paul Flicek; Gad Getz; Roderic Guigó; Guangwu Guo; David Haussler; Simon Heath; Tim J Hubbard; Tao Jiang; Steven M Jones; Qibin Li; Nuria López-Bigas; Ruibang Luo; Lakshmi Muthuswamy; B F Francis Ouellette; John V Pearson; Xose S Puente; Victor Quesada; Benjamin J Raphael; Chris Sander; Tatsuhiro Shibata; Terence P Speed; Lincoln D Stein; Joshua M Stuart; Jon W Teague; Yasushi Totoki; Tatsuhiko Tsunoda; Alfonso Valencia; 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Yusuke Nakamura; Hidewaki Nakagawa; Jun Kusada; Tatsuhiko Tsunoda; Satoru Miyano; Hiroyuki Aburatani; Kazuto Kato; Akihiro Fujimoto; Teruhiko Yoshida; Elias Campo; Carlos López-Otín; Xavier Estivill; Roderic Guigó; Silvia de Sanjosé; Miguel A Piris; Emili Montserrat; Marcos González-Díaz; Xose S Puente; Pedro Jares; Alfonso Valencia; Heinz Himmelbauer; Heinz Himmelbaue; Victor Quesada; Silvia Bea; Michael R Stratton; P Andrew Futreal; Peter J Campbell; Anne Vincent-Salomon; Andrea L Richardson; Jorge S Reis-Filho; Marc van de Vijver; Gilles Thomas; Jocelyne D Masson-Jacquemier; Samuel Aparicio; Ake Borg; Anne-Lise Børresen-Dale; Carlos Caldas; John A Foekens; Hendrik G Stunnenberg; Laura van't Veer; Douglas F Easton; Paul T Spellman; Sancha Martin; Anna D Barker; Lynda Chin; Francis S Collins; Carolyn C Compton; Martin L Ferguson; Daniela S Gerhard; Gad Getz; Chris Gunter; Alan Guttmacher; Mark Guyer; D Neil Hayes; Eric S Lander; Brad Ozenberger; Robert Penny; Jane Peterson; Chris Sander; Kenna M Shaw; Terence P Speed; Paul T Spellman; Joseph G Vockley; David A Wheeler; Richard K Wilson; Thomas J Hudson; Lynda Chin; Bartha M Knoppers; Eric S Lander; Peter Lichter; Lincoln D Stein; Michael R Stratton; Warwick Anderson; Anna D Barker; Cindy Bell; Martin Bobrow; Wylie Burke; Francis S Collins; Carolyn C Compton; Ronald A DePinho; Douglas F Easton; P Andrew Futreal; Daniela S Gerhard; Anthony R Green; Mark Guyer; Stanley R Hamilton; Tim J Hubbard; Olli P Kallioniemi; Karen L Kennedy; Timothy J Ley; Edison T Liu; Youyong Lu; Partha Majumder; Marco Marra; Brad Ozenberger; Jane Peterson; Alan J Schafer; Paul T Spellman; Hendrik G Stunnenberg; Brandon J Wainwright; Richard K Wilson; Huanming Yang Journal: Nature Date: 2010-04-15 Impact factor: 49.962
Authors: Isaac B Hilton; Jeremy M Simon; Jason D Lieb; Ian J Davis; Blossom Damania; Dirk P Dittmer Journal: J Virol Date: 2013-08-28 Impact factor: 5.103