Rule-based Clustering for Gene Promoter Structure Discovery

Background: The genetic cellular response to internal and external changes is determined by the sequence and structure of gene-regulatory promoter regions. Objectives: Using data on gene-regulatory elements (i.e., either putative or known transcription factor binding sites) and data on gene expression profiles we can discover structural elements in promoter regions and infer the underlying programs of gene regulation. Such hypotheses obtained in silico can greatly assist us in experiment planning. The principal obstacle for such approaches is the combinatorial explosion in different combinations of promoter elements to be examined. Methods: Stemming from several state-of-the-art machine learning approaches we here propose a heuristic, rule-based clustering method that uses gene expression similarity to guide the search for informative structures in promoters, thus exploring only the most promising parts of the vast and expressively rich rule-space. Results: We present the utility of the method in the analysis of gene expression data on budding yeast S. cerevisiae where cells were induced to proliferate peroxisomes. Conclusions: We demonstrate that the proposed approach is able to infer informative relations uncovering relatively complex structures in gene promoter regions that regulate gene expression.