MotifCombinator: a web-based tool to search for combinations of cis-regulatory motifs

We here introduced MotifCombinator, an online tool with a user-friendly interface, to systematically search for combinations composed of any number of motifs based on regression methods. The tool utilizes well-known regression methods (the multivariate linear regression, the multivariate adaptive regression spline or MARS, and the multivariate logistic regression method) for this purpose, and uses the genetic algorithm to search for combinations composed of any desired number of motifs. The visualization systems in this tool help users to intuitively grasp the process of the combination search, and the backup system allows users to easily stop and restart calculations that are expected to require large computational time. This tool also provides preparatory steps needed for systematic combination search – i.e., selecting single motifs to constitute combinations and cutting out redundant similar motifs based on clustering analysis.MotifCombinator helps users to systematically search for motif combinations that play an important role in gene expression as measured by microarrays.Gene expression in eukaryotes is controlled by combinatorial regulation of transcription factors and cis-regulatory elements. Many types of transcription factors are bound to their respective regulatory DNA elements, and the interactions between the factors and elements control the gene expression. Molecular experiments can identify several binding sites for selected transcription factors, but they are too laborious and time-consuming to be applied to large-scale studies. Computational methods are thus required for processing genomic data to reveal the combinatorial regulation on a genomic scale.Recently, some computational methods have been developed to detect combinations of patterns (motifs) of cis-regulatory elements. They process data of upstream sequences selected from genomic sequences, as well as data of either expression levels measured by DNA microarrays or binding information given