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Bioinformatics Advance Access originally published online on September 19, 2007
Bioinformatics 2007 23(21):2881-2887; doi:10.1093/bioinformatics/btm453
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Moderated statistical tests for assessing differences in tag abundance

Mark D. Robinson 1,2 and Gordon K. Smyth 2,*

1Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010 and 2Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

*To whom correspondence should be addressed.


  Abstract

Motivation: Digital gene expression (DGE) technologies measure gene expression by counting sequence tags. They are sensitive technologies for measuring gene expression on a genomic scale, without the need for prior knowledge of the genome sequence. As the cost of sequencing DNA decreases, the number of DGE datasets is expected to grow dramatically.

Various tests of differential expression have been proposed for replicated DGE data using binomial, Poisson, negative binomial or pseudo-likelihood (PL) models for the counts, but none of the these are usable when the number of replicates is very small.

Results: We develop tests using the negative binomial distribution to model overdispersion relative to the Poisson, and use conditional weighted likelihood to moderate the level of overdispersion across genes. Not only is our strategy applicable even with the smallest number of libraries, but it also proves to be more powerful than previous strategies when more libraries are available. The methodology is equally applicable to other counting technologies, such as proteomic spectral counts.

Availability: An R package can be accessed from http://bioinf.wehi.edu.au/resources/

Contact: smyth{at}wehi.edu.au

Supplementary information: http://bioinf.wehi.edu.au/resources/

Associate Editor: David Rocke

Received on June 18, 2007; revised on July 16, 2007; accepted on August 27, 2007

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