This book constitutes the thoroughly refereed post-proceedings of two joint RECOMB 2005 satellite events - the First Annual Workshop on Systems Biology, RSB 2005, and the Second Annual Workshop on Regulatory Genomics, RRG 2005, held in San Diego, CA, USA in December 2005.

The 21 revised full papers presented were carefully reviewed and selected for inclusion in the book. The papers address a broad variety of topics in systems biology and regulatory genomics including inference of gene regulatory and protein signaling networks, model prediction of drug mechanism, pathway mapping and evolution in protein interaction networks, multi-scale methods which bridge abstract and detailed models, systematic design of genome-scale experiments, modeling and recognition of regulatory elements, identification and modeling of cis-regulatory regions, modeling the structure and function of the regulatory region, and comparative genomics of regulation.

Research in the ?eld of gene regulation is evolving rapidly in an ever-changing s- enti?c environment. Microarray techniques and comparative genomics have enabled more comprehensive studies of regulatory genomics and are proving to be powerful tools of discovery. The application of chromatin immunoprecipitation and microarrays (chIP-on-chip) to directly study the genomic binding locations of transcription factors has enabled more comprehensive modeling of regulatory networks. In addition, c- plete genome sequences and the comparison of numerous related species has dem- strated that conservation in non-coding DNA sequences often provides evidence for cis-regulatory binding sites. That said, much is still to be learned about the regulatory networks of these sequenced genomes. Systematic methods to decipher the regulatory mechanism are also crucial for c- roboratingthese regulatorynetworks.Thecoreof thesemethodsarethe motifdiscovery algorithms that can help predict cis-regulatory elements. These DNA-motif discovery programsarebecomingmoresophisticatedandare beginningto leverageevidencefrom comparative genomics (phylogenetic footprinting) and chIP-on-chip studies. How to use these new sources of evidence is an active area of research.