Inferring Gene Transcription Networks: The Davidson Model
 
Sorin Istrail
Celera Genomics

Joint work with Vladimir Filkov (UC Davis) and Eric Davidson (Caltech)

In 2001 Eric Davidson published his “Genomic Regulatory Systems” book where he reports on 30 years of work, together with his colleagues, on purple sea urchin.  Their work provided a general experimental framework for the study of a gene’s cis-regulatory region (an upstream DNA sequence containing a series of consecutive binding sites). Their approach consisted of systematic, almost exhaustive, series of mutations of individual binding sites, together with the associated measurements of the transcription rates. By quantitative analysis, they were able to infer a complete set of minimal functional units of regulation and their interrelations. They proceeded hierarchically to uncover “modularity” and  “hardwired information processing logic” of a gene’s cis-region. Most of their work was focused on the endo16 gene. Their extraordinary technology and the inference of the underlying “network” for this gene resulted in the most completely understood transcriptional system to date.

It is quite remarkable how combinatorial and robust their approach is. We will present an analysis and a mathematical formalism for the Davidson transcriptional network inference technology. We will also present a glace into our recent work with Eric Davidson towards the identification of the regulatory “programming language.”