The Pharmacometabolomic Research Network (PMRN) in conjunction with the well-established pharmacogenetics research network (PGRN) offers a unique and unprecedented opportunity to the biomedical research community to identify integrated metabolite/gene parts lists and linked pathways associated with normal and diseased humans, both prior to and post drug treatment. PMRN will utilize soft tissue samples and immortalized cells isolated from patients with cardiovascular and neuropsychiatric diseases from PGRN to design cell and model animal experiments for metabolomic assays. The resulting measurements have the power to provide extremely detailed insights into mechanisms, pathways and phenotypes in diseased states. Effects of drug treatment and response will also be investigated. The vast amounts of metabolite data from PMRN and the genomic, transcriptomic and phenotypic data from PGRN projects will need to be validated, analyzed and integrated to provide biological knowledge that will further serve as important hypotheses for experimental investigations and provide models for diseases. There is a need to develop significant bioinformatics infrastructure to achieve these goals and this will form the primary focus of the Bioinformatics. Towards this end, we will develop an analysis pipeline that will encompass development and utilization of statistical validation and analysis of data, functional module and pathway reconstruction, and dynamic network modeling. The analysis pipeline will be biologist-friendly and will be made accessible to the PMRN and to the larger biomedical research community. Our strategy is illustrated in a simple cartoon. The specific objectives that are framed by the pipeline developments include the following.
The Bioinformatics team will be directed by Palsson and Subramaniam (UCSD) and other Co-Is include, Zhao-Bang Zeng (NC State) and Peter Karp (SRI). Palsson is a pioneer in metabolic systems biology and has been instrumental in the reconstruction of the most comprehensive metabolic maps and models in E. Coli, Yeast and Human. Subramaniam is a pioneer in Bioinformatics and Systems Biology and is the Director of two Glue Grant Bioinformatics Teams. His laboratory has developed several bioinformatics strategies for transcriptomics, proteomics and metabolomics [Hsiao et al., 2004; Hsiao and Subramaniam, 2008;Gupta et al., 2010; Gupta et al., 2009; Maurya et al., 2007]. His developments in LIPID MAPS project will be essential for the PMRN Informatics. Karp is the pioneer of pathway maps in multiple organisms. He is primary developer of EcoCyc, HumanCyc and MetaCyc and brings an important component of pathway development to PMRN. Zeng is the pioneer in statistical genetics analysis and software development for mapping quantitative trait loci. His team has developed a series of statistical analysis methods for metabolomics data in the last two years and has been instrumental in working with various PMRN Bridge projects in study designs and in metabolomics data
|Bernhard Palsson||Shankar Subramaniam||Zhao-Beng Zeng||Lexin Li|