Rational drug discovery: what can we learn from regulatory networks?

Abstract To enable the list of genes and proteins contained within genomic databases to be useful for drug discovery, we need to understand how the genome maps into the phenome. An essential, but not explicitly listed ingredient of the genome is the regulatory interactions between genes and proteins that form a genome-wide network. How can the concept of regulatory networks increase our understanding of living systems? Networks are more than just static ‘wiring diagrams’. Gene interactions impose dynamic constraints, which, although obvious in emergent phenotypic properties, are not captured by traditional one-gene-one trait approaches. Understanding the nature of these constraints in gene-activation state space will pave the way to a holistic yet formal and genomics-based approach to rational drug development.