Fastcompare: A Nonalignment Approach for Genome-Scale Discovery of DNA and mRNA Regulatory Elements Using Network-Level Conservation

Here, we describe the usage of Fastcompare, a simple and efficient comparative approach for finding short noncoding DNA (e.g., transcription factor binding sites) and mRNA (e.g., microRNA target sites) sequences that are globally conserved between two genomes. Fastcompare is based on the network-level conservation principle, according to which the connectivity of transcriptional regulatory networks should be largely conserved between two closely related genomes. We describe here the procedure for applying Fastcompare to large genomes (with an emphasis on metazoan genomes), including scoring of exhaustive motif lists, determination of conservation threshold using sequence randomizations, and discovery of interactions between regulatory elements.