The challenge of identifying cis-regulatory modules (CRMs) is an important milestone for the ultimate goal of understanding transcriptional regulation in eukaryotic cells. It has been approached, among others, by motif-finding algorithms that identify overrepresented motifs in regulatory sequences. These methods succeed in finding single, well-conserved motifs, but fail to identify combinations of degenerate binding sites, like the ones often found in CRMs. We have developed a method that combines the abilities of existing motif finding with the discriminative power of a machine learning technique to model the regulation of genes (Schultheiss et al. (2009) Bioinformatics 25, 2126–2133). Our software is called kirmes, which stands for kernel-based identification of regulatory modules in eukaryotic sequences. Starting from a set of genes thought to be co-regulated, kirmes can identify the key CRMs responsible for this behavior and can be used to determine for any other gene not included on that list if it is also regulated by the same mechanism. Such gene sets can be derived from microarrays, chromatin immunoprecipitation experiments combined with next-generation sequencing or promoter/whole genome microarrays. The use of an established machine learning method makes the approach fast to use and robust with respect to noise. By providing easily understood visualizations for the results returned, they become interpretable and serve as a starting point for further analysis. Even for complex regulatory relationships, kirmes can be a helpful tool in directing the design of biological experiments.
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