Combining pattern discovery and discriminant analysis to predict gene co-regulation

Abstract

Motivation: Several pattern discovery methods have been proposed to detect over-represented motifs in upstream sequences of co-regulated genes, and are for example used to predict cis-acting elements from clusters of co-expressed genes. The clusters to be analyzed are often noisy, containing a mixture of co-regulated and non-co-regulated genes. We propose a method to discriminate co-regulated from non-co-regulated genes on the basis of counts of pattern occurrences in their non-coding sequences. Methods: String-based pattern discovery is combined with discriminant analysis to classify genes on the basis of putative regulatory motifs. Results: The approach is evaluated by comparing the significance of patterns detected in annotated regulons (positive control), random gene selections (negative control) and high-throughput regulons (noisy data) from the yeast Saccharomyces cerevisiae. The classification is evaluated on the annotated regulons, and the robustness and rejection power is assessed with mixtures of co-regulated and random genes. © Oxford University Press 2004; all rights reserved.