The Administrative Core is the central administrative body for the PMRN designed to facilitate the management of projects and flow of data and information between the External Advisory Committee, Scientific Cores, Bridging & Pilot Studies, Steering Committee, and Principal Investigators. The Administrative Core’s main objectives are to:
1) Provide functional structure and network support,
2) Enable effective internal and external communication,
3) Plan and organize activities of the network,
4) Track progress and ensure that the network achieves its set goals,
5) Establish links between the network and other NIH funded consortia as well as links to the scientific communities.
Data Governance Core
The Metabolomics initiative along with the phenotypic data from the pharmacogenomics research network yield vast amounts of data that will provide a comprehensive profile of human physiology, pathology as well as comprehensive read of drug effects. The integrative analysis of these data has the potential to for the first time provide a complete picture of the networks associated with normal and abnormal function and networks associated with drug response phenotypes. The accrual, organization, analysis and presentation of these data pose enormous informatics challenges. The objective of the Data Governance Core core will be to provide a state-of-the-art infrastructure that will enable capturing, organizing and disseminating data and analysis of data. The various network cores will interact virtually to provide the state-of-the-art infrastructure and tools for data uploads, queries, analyses and interpretation of metabolic pathways in human health and pathology. The integrated view of the cell encompassing the metabolome, the transcriptome and phenotype data will yield a comprehensive view of the pathways to disease and potential therapeutic intervention strategies.
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 (see Program Summary). 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 Core C. 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.
The primary function of this core is to provide quantitative data for the largest number of identified metabolites ever reported in metabolomic projects, using samples generated by the bridging and translational projects. There is no single analytical platform or research group that can assay comprehensively all relevant biochemicals, but multiple analytical platforms have matured and will provide complementary data. The goal and opportunity of the analytical core is to combine the capabilities of seven leading laboratories in a collaborative effort to extend the detection and quantification of the broadest and deepest coverage of biochemicals currently possible. This group brings together fifteen diverse analytical platforms in lipid and gas chromatography, mass spectrometry, electrochemical array, NMR and stable isotope based techniques. These techniques cover multiple functional signaling and processing aspects of the metabolome, including energetics, primary metabolites, neurotransmitters, lipids, markers of oxidative damage, gut function and others.
These comprehensive data are essential to the network in order to:
1. map pathways implicated in disease and in response to therapy,
2. inform pharmacogenomics researchers of candidate genes that might be implicated in mechanism of variation of response to treatment,
3. enable the integration of pharmacometabolomic data with pharmacogenomic data towards a systems pharmacology approach to predicting individual response to therapy.
Additionally this core will advance the field of metabolomics through (a) Standardizing and integrating existing analytical processes; (b) Adopting and developing emerging metabolomics technologies; (c) Developing a national repository for metabolomics data together with the database core.
Drug Response Core