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December 2, 2005

Center of Excellence in Computational Biology Formed

Nicole Hemsoth

SRI International, an independent nonprofit research and development organization, has announced the formation of its Center of Excellence in Computational Biology. The Center's mission is to conduct collaborative research in symbolic systems biology, synthetic biology and bioinformatics to advance scientific understanding of biological systems and accelerate drug discovery and development.

The Center already is attracting new projects and funding as it engages researchers, biologists and computer scientists at numerous R&D organizations. It will extend SRI's efforts to find new and better ways to combat diseases such as cancer and problems associated with aging and sleep disorders.

SRI expects to accelerate biomedical discovery by encouraging collaboration and aligning the research goals of related but disparate disciplines. While the goal of systems biology is to model life by understanding how it naturally emerges from biological components such as genes, the goal of synthetic biology is to create logic machines by integrating components into higher-order genetic networks using mathematical modeling. Symbolic systems biology seeks to understand how the pathways of cell biology can be modeled with the same tools used to model computer circuits.

“Because the Center will make the first strides to formally synthesize three of the most revolutionary disciplines of early 21st century biology, it is poised to break new ground and improve the quality and reach of biomedical research,” said Patrick Lincoln, Ph.D. Lincoln has served as the Director of SRI's Computer Science Laboratory for seven years. He will also serve as the Director of the new Center of Excellence in Computational Biology.

The Center recently was awarded continuation of an important grant from the National Institute of General Medical Sciences (NIGMS, a unit of the National Institutes of Health) to model complex mammalian signaling networks based on signaling of the epidermal growth factor receptor (EGFR). Several other important interdisciplinary projects include:

– BioSPICE (Biological Simulation Program for Intra-Cellular Evaluation): SRI provides an open-source, DARPA-funded computing environment that biologists can extend, modify and control based on their individual needs. Research areas include integrated system design and modeling tools, biological data warehousing, biological process ontologies, and database and tool interoperability.

– Pathway Logic: Pathway Logic is SRI's unique approach to modeling biological entities and processes based on a simple but powerful logic. Pathway Logic software allows a rich set of logical operators to define relationships among the components of complex biological systems. It is being used to develop a new science of symbolic systems biology. For example, SRI researchers are using Pathway Logic tools to model cellular networks for breast cancer research and to help predict response to cancer therapies.

– BioCyc Collection of Pathway/Genome Databases: SRI has developed the BioCyc collection of databases, which combine information about genomes and biochemical pathways. Understanding these pathways is critical in the development of pharmaceuticals, which mostly operate by blocking or enhancing interactions in particular pathways. In July 2005, SRI significantly expanded the collection to include databases for 160 organisms, including the HumanCyc database of human metabolic pathways.

– Pathway Tools Software: Pathway Tools is a bioinformatics software system for pathway analysis of genomes, and for creating Pathway/Genome databases. It can infer the metabolic pathways, pathway hole fillers and operons of an organism from its sequenced genome. Operons are gene clusters that encode proteins to perform coordinated functions. The software allows scientists to interactively refine Pathway/Genome databases to model the evolving knowledge of an organism's genome and biochemical networks. Pathway Tools also supports analysis of omics datasets using cellular pathway maps. Omics refers to genome-based systems biology.

– HumanCyc Bioinformatics Database: SRI created this database by performing a computational analysis of the human genome to predict metabolic pathways and to predict new gene functions within the human genome. Using SRI's PathoLogic pathway prediction software, part of SRI's Pathway Tools suite, the analysis assigned 622 human enzymes to roles in 135 predicted metabolic pathways.

– Hybrid Qualitative/Quantitative Modeling: SRI's approach for analyzing complex biological systems is based on modeling both continuous and discrete behaviors of the system simultaneously in the HybridSAL language. The HybridSAL framework is used to build models of genetic and metabolic regulatory networks in cells, as well as pharmacokinetic/pharmacodynamic compartmental models of the whole organism, such as that for blood glucose metabolism. Such models are abstracted from a complex hybrid system into a simpler tractable system, which enables deep analysis of subtle properties and aids human understanding of important facets of disease and health.