Practical computational methods for regulatory genomics: a cisGRN-Lexicon and cisGRN-browser for gene regulatory networks.

The CYRENE Project focuses on the study of cis-regulatory genomics and gene regulatory networks (GRN) and has three components: a cisGRN-Lexicon, a cisGRN-Browser, and the Virtual Sea Urchin software system. The project has been done in collaboration with Eric Davidson and is deeply inspired by his experimental work in genomic regulatory systems and gene regulatory networks. The current CYRENE cisGRN-Lexicon contains the regulatory architecture of 200 transcription factors encoding genes and 100 other regulatory genes in eight species: human, mouse, fruit fly, sea urchin, nematode, rat, chicken, and zebrafish, with higher priority on the first five species. The only regulatory genes included in the cisGRN-Lexicon (CYRENE genes) are those whose regulatory architecture is validated by what we call the Davidson Criterion: they contain functionally authenticated sites by site-specific mutagenesis, conducted in vivo, and followed by gene transfer and functional test. This is recognized as the most stringent experimental validation criterion to date for such a genomic regulatory architecture. The CYRENE cisGRN-Browser is a full genome browser tailored for cis-regulatory annotation and investigation. It began as a branch of the Celera Genome Browser (available as open source at http://sourceforge.net/projects/celeragb /) and has been transformed to a genome browser fully devoted to regulatory genomics. Its access paradigm for genomic data is zoom-to-the-DNA-base in real time. A more recent component of the CYRENE project is the Virtual Sea Urchin system (VSU), an interactive visualization tool that provides a four-dimensional (spatial and temporal) map of the gene regulatory networks of the sea urchin embryo.