SRI International Uses Groundbreaking Computational Approach to Analyze Bacterium

MENLO PARK, Calif. – February 23, 2005 – SRI International, an independent nonprofit research and development organization, today announced it has performed a series of important computational analyses ­ in a collaborative project with an international team of researchers ­ to report the complete genome sequence of Francisella tularensis, a bacterium that causes tularemia, or "rabbit fever" in animals and humans. An article about the findings is published in the February 2005 issue of Nature Genetics and appeared online January 9, 2005.  The research findings increase the understanding of how highly virulent human pathogens evolve and could expedite strategies to combat them.  In addition, the study will specifically support work on improved countermeasures against tularemia.

"Enzymes in metabolic pathways are the most frequent type of anti-microbial drug target.  The first phase of our work involved predicting the metabolic pathways of Francisella tularensis," said Peter Karp, Ph.D., director of SRI International's Bioinformatics Research Group. "We found an unexpectedly high proportion of pathways that had been disrupted by pseudogenes, explaining the fastidious nutritional requirements of the bacterium. In the second pathway analysis, we identified 74 candidate genes that filled holes in the predicted pathways, thus increasing the completeness of the genome annotation."

Pathway holes are biochemical steps in metabolic pathways for which no enzyme has been identified in the organism's genome.  Classical genome analysis typically fails to identify the functions of up to half the genes in a bacterial genome.   SRI's pathway hole filling algorithm, developed jointly by Drs. Peter Karp and Michelle Green of SRI, found high probability candidates for 74 of the 390 pathway holes in Francisella tularensis, and lower probability candidates for many others.  

The predicted metabolic pathways of Francisella , as well as its genome and predicted operons, are available through the FrantCyc database on the SRI Web site at URL BioCyc.org.  The BioCyc database collection includes pathway and genome databases for virtually all category A, B, and C agents, including Bacillus anthracis (anthrax), Rickettsia prowazekii (typhus), and Vibrio cholerae (cholera).  Each database includes the genome annotated with predicted metabolic pathways and operons of the organism.   This collection constitutes a unique resource for biodefense research because of the important role of metabolic enzymes in drug discovery.  

SRI researchers collaborated with a large, interdisciplinary team on the Francisella tularensis project. The team included researchers from the Swedish Defense Research Agency, Umeå, Sweden; the Defence Science and Technology Laboratory in Salisbury, U.K.; and the Lawrence Livermore National Laboratory in Livermore, Calif.

About SRI International
Silicon Valley-based SRI International ( www.sri.com ) is one of the world's leading independent research and technology development organizations. Founded as Stanford Research Institute in 1946, SRI has been meeting the strategic needs of clients for almost 60 years. The nonprofit research institute performs client-sponsored research and development for government agencies, commercial businesses and private foundations. In addition to conducting contract R&D, SRI licenses its technologies, forms strategic partnerships and creates spin-off companies.

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