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.
Key WordsTranscription factor binding sites microRNA target sites computational method network-level conservation comparative genomics metazoan genomes.
The authors are grateful to Chang S. Chan and Kellen Olszewski for critical reading of preliminary versions of this document. The authors are also grateful to members of the Tavazoie group for insightful discussions. Saeed Tavazoie is supported by National Institutes of Health, National Science Foundation, and Defense Advanced Research Projects Agency.