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Publication Date:
January 2011
ISSN:
1544-6115
DOI:
10.2202/1544-6115.1565

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Editor-in-Chief: Stumpf, Michael P.H.

Editorial Board Member: Beaumont, Mark / Binder, Harald / Gupta, Mayetri / Hubbard, Alan E. / Husmeier, Dirk / Ji, Hongkai / Keles, Sunduz / Kerr, Kathleen / Lazzeroni, Laura / Lin, Shili / Ma, Ping / Marjoram, Paul / Mertens, Bart / Nerman, Olle / G. Petretto, Enrico / Plagnol, Vincent / Purdom, Elizabeth / Robin, Stéphane / Rzhetsky, Andrey / Sanguinetti, Guido / van der Laan, Mark J. / von Haeseler, Arndt / Weeks, Daniel E. / Wiuf, Carsten / Zhao, Hongyu

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IMPACT FACTOR 2011: 1.517
5-year IMPACT FACTOR: 1.704
Rank 27 out of 116 in category Statistics & Probability in the 2011 Thomson Reuters Journal Citation Report/Science Edition

A Three Component Latent Class Model for Robust Semiparametric Gene Discovery

Marco Alfo' / Alessio Farcomeni / Luca Tardella

1Sapienza - Università di Roma

1Sapienza - Università di Roma

1Sapienza - Università di Roma

Citation Information: Statistical Applications in Genetics and Molecular Biology. Volume 10, Issue 1, Pages 1–19, ISSN (Online) 1544-6115, DOI: 10.2202/1544-6115.1565, January 2011

Publication History:
Published Online:
2011-01-21

We propose a robust model for discovering differentially expressed genes which directly incorporates biological significance, i.e., effect dimension. Using the so-called c-fold rule, we transform the expressions into a nominal observed random variable with three categories: below a fixed lower threshold, above a fixed upper threshold or within the two thresholds. Gene expression data is then transformed into a nominal variable with three levels possibly originated by three different distributions corresponding to under expressed, not differential, and over expressed genes. This leads to a statistical model for a 3-component mixture of trinomial distributions with suitable constraints on the parameter space. In order to obtain the MLE estimates, we show how to implement a constrained EM algorithm with a latent label for the corresponding component of each gene. Different strategies for a statistically significant gene discovery are discussed and compared. We illustrate the method on a little simulation study and a real dataset on multiple sclerosis.

Keywords: differentially expressed genes; effect size; microarray data; mixture model

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