Software Speeds Development of Genome-Scale Models for Drug Discovery

Metabolic networks are the complete set of metabolic and physical processes that determine the physiologic and biochemical characteristics of a cell. Genome-scale models are utilized to predict cell growth rate, combinations of chemicals that can support cell growth, and which genes will cause cell death if they are inactivated.

Developed by SRI International (Menlo Park, CA, USA), the new MetaFlux functionality can be used to design drugs against disease-causing bacteria and metabolically modify bacteria to make chemicals and fuels. It may also provide clues into the growth of bacteria that cannot currently be grown in a laboratory.

MetaFlux software combines flux balance analysis (FBA), a mathematical method to analyze metabolism, with pathway databases that contain information about the network of interactions between proteins and small molecules that forms the biochemical factory of a cell.

“Genome-scale models are very time consuming to construct, because they require an exact description of the hundreds of biochemical reactions within a cell--and a single missing reaction can render a model nonfunctional,” said Peter D. Karp, PhD, director, bioinformatics research group, SRI International. “Our goals were to speed up the development of these models and allow a wider community of scientists to build them. SRI’s bioinformatics research group has already developed two different FBA models using MetaFlux, each within one month of effort.”

Based on mixed integer linear programming, MetaFlux uses a multiple gap-filling method to accelerate the development of FBA models. This technique generates the models directly from pathway/genome databases, which can be constructed, queried, and visualized using SRI’s Pathway Tools software. MetaFlux can also suggest additional reactions, nutrients, and secreted metabolites to complete a model.

During model development, MetaFlux will identify the subset of biomass metabolites (end products of biosynthesis) that cannot currently be produced. The software also paints reaction flux rates onto an automatically generated organism-specific metabolic map diagram, which is very similar to how an online road map shows traffic flow rates.

MetaFlux is part of Pathway Tools, available freely to academic users and for a fee to commercial users. An article describing MetaFlux was published in the online and printed editions of the journal Bioinformatics.

SRI International, a nonprofit research and development organization, performs sponsored R&D for governments, businesses, and foundations. SRI brings its innovations to the marketplace through technology licensing, new products, and spin-off ventures.

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