SPECIAL TUESDAY SEMINAR: ENGINEERING SCHOOL DISTINGUISHED COMPUTATIONAL BIOLOGY COLLOQUIUM: The regulatory genome and the computer

Abstract

The regulatory genome and the computer

The definitive feature of the many thousand cis-regulatory control modules in an animal genome is their information processing capability. These modules are “wired” together in large networks that control major processes such as development; they constitute “genomic computers.” Each control module receives multiple inputs in the form of the incident transcription factors which bind to them. The functions they execute upon these inputs can be reduced to basic AND, OR and NOT logic functions, which are also the unit logic functions of electronic computers. Here we consider the operating principles of the genomic computer, the product of evolution, in comparison to those of electronic computers. For example, in the genomic computer intra-machine communication occurs by means of diffusion (of transcription factors), while in electronic computers it occurs by electron transit along pre-organized wires. There follow fundamental differences in design principle in respect to the meaning of time, speed, multiplicity of processors, memory, robustness of computation and hardware and software. The genomic computer controls spatial gene expression in the development of the body plan, and its appearance in remote evolutionary time must be considered to have been a founding requirement for animal grade life.

Sorin Istrail is the Julie Nguyen Brown Professor of Computational and Mathematical Sciences, Professor of Computer Science, and Director of the Center for Computational Molecular Biology at Brown University. Dr. Istrail was previously Senior Director and then Head of the Informatics Research Group of Celera Genomics, and as such was instrumental in the company’s human genome research. At Celera, Dr. Istrail and his team developed powerful computational tools for genome assembly comparison, automatic annotation of genomes, computational analysis of SNPs, haplotype, and genome-wide disease associations, DNA arrays analysis, and proteomics. Since 2003 Dr. Istrail has been a visiting associate in the Division of Biology at California Institute of Technology, and an Adjunct Professor of Biochemistry and Molecular Biology at George Washington School of Medicine and Health Sciences. He was at Celera Genomics and Applied Biosystems from April 2000 through February 2005. In 2003 he joined the ranks of Applied Biosystems Science Fellows (one of the six Science Fellows in a company of 800 scientists). Prior to Celera, he founded and led the Computational Biology Project at Sandia National Laboratories (1992-2000) within the DOE Applied Mathematics Program, started at DOE by John von Neumann. In 1998, his work on Protein Misfolding Simulations was included by Scientific American in its “Best of 1998” list.

In 2001, Dr. Istrail’s work at Sandia on the statistical mechanics of the Three-Dimensional Ising Model was ranked as the top 7th achievement in Advanced Scientific Computing in the Top 100 U.S. Department of Energy Most Important Discoveries in the DOE’s first 25 years. From 1985 until 1992, Dr. Istrail was a visiting scientist at Massachusetts Institute of Technology.

Dr. Istrail’s work has been focused on computational molecular biology – genomic regulatory systems and networks, genetic patterns of inheritance of complex disease, protein folding and misfolding, and comparative and integrative genomics. His research interests also include combinatorial algorithms, mathematical logic, computational complexity, and applications of computer science methods to biology, physics, and chemistry. He is co-editor-in-chief of the Journal of Computational Biology, co-founder of the RECOMB Conference Series, co-editor of the MIT Press Computational Molecular Biology book series, and co-editor of the Springer-Verlag Lecture Notes in Bioinformatics book series.