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Bioinformatics Advance Access originally published online on January 29, 2004
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Bioinformatics 20(6) © Oxford University Press 2004; all rights reserved.

Finding coexpressed genes in counts-based data: an improved measure with validation experiments

Morgan N. Price * and Eleanor Rieffel

FX Palo Alto Laboratory, 3400 Hillview Avenue Building 4, Palo Alto, CA 94304, USA

Received on July 29, 2003 ; revised on October 15, 2003 ; accepted on October 16, 2003
Advance Access Publication January 29, 2004

Motivation: Expressed sequence tag (EST) data reflects variation in gene expression, but previous methods for finding coexpressed genes in EST data are subject to bias and vastly overstate the statistical significance of putatively coexpressed genes.

Results: We introduce a new method (LNP) that reports reasonable p-values and also detects more biological relationships in human dbEST than do previous methods. In simulations with human dbEST library sizes, previous methods report p-values as low as 10–30 on 1/1000 uncorrelated pairs, while LNP reports significance correctly. We validate the analysis on real human genes by comparing coexpressed pairs to gene ontology annotations and find that LNP is more sensitive than the three previous methods. We also find a small but statistically significant level of coexpression between interacting proteins relative to randomized controls. The LNP method is based on a log-normal prior on the distribution of expression levels.

Availability: Source code in Java or R is available at http://ests.sourceforge.net/

Supplementary information: http://ests/sourceforge.net/lnp_supplement.pdf

Contact: mprice{at}cs.cmu.edu

* To whom correspondence should be addressed.


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