A Web-Based Data Source for Metabolomics Analysis

Case Western Reserve University, Cleveland OH

Investigators

Abstract

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)." Case Western Reserve University has been awarded a grant to build computational tools to facilitate research in metabolic profiles. Metabolites are molecules that are intermediates and products of metabolism. Current blood-labs in most hospitals and health care centers in the country can only measure in a blood sample small numbers of (less than 15) metabolites. However, recent advances in high-energy physics technologies has now made it possible (for researchers for the time being) to measure much larger numbers of metabolites in a blood sample, up to about 300 of them. When these measurements differ from those in a healthy individual (i.e., the control subject), the basic question is: what do they mean? Currently, the above question can only be answered manually by experts in metabolic biochemistry. This project will test the validity of computationally and algorithmically deduced first-cut interpretations of such large sets of metabolite measurements. These interpretations are made available through web-based, database-enabled, easy-to-use, online and reliably correct software systems that are - Scalable to the complete metabolic network, not parts of it and - Grounded by the well-known and accepted metabolic biochemistry principles, instead of being done manually as there are not enough metabolic biochemistry experts around to manually interpret each such lab result. This project develops a web-based resource and its tools to enable the research community to help answer the above-listed question. The tools of the resource include - Observed Metabolite Analysis tool that eliminates those metabolic paths that cannot have caused the observed measurements (i.e., inactive metabolic paths in the metabolic network), and provides a small list of activated metabolic paths that may have caused the observed measurements. Note that no effort is made to return actual flux estimations in the network, simplifying the task at hand, - Metabolomics-Oriented Querying tool, that allows researchers/users to further focus on activated metabolic paths within a subnetwork (by allowing them to formulate queries about activated paths, futile cycles, etc.), and provides users with explanations of its query answers, - Metabolomics-Oriented Visualization tool, which provides visualizations of activated paths within the complete metabolic network or zoomed-in and focused parts of the network, allowing users to visually interpret and analyze the results. The resulting online tools will be an excellent web-based educational tool for educating students in metabolic biochemistry, biology, bioinformatics, and metabolomics--to train them on the use of bioinformatics tools in terms of metabolic network models. Additional information about the project may be found at http://nashua.case.edu/.