Transcription factor and microRNA motif discovery: The Amadeus platform and a compendium of metazoan target sets

We present a threefold contribution to the computational task of motif discovery, a key component in the effort of delineating the regulatory map of a genome: ( 1) We constructed a comprehensive large-scale, publicly-available compendium of transcription factor and microRNA target gene sets derived from diverse high-throughput experiments in several metazoans. We used the compendium as a benchmark for motif discovery tools. ( 2) We developed Amadeus, a highly efficient, user-friendly software platform for genome-scale detection of novel motifs, applicable to a wide range of motif discovery tasks. Amadeus improves upon extant tools in terms of accuracy, running time, output information, and ease of use and is the only program that attained a high success rate on the metazoan compendium. ( 3) We demonstrate that by searching for motifs based on their genome- wide localization or chromosomal distributions ( without using a predefined target set), Amadeus uncovers diverse known phenomena, as well as novel regulatory motifs.