The Computational Genomics Core in this Center will perform bioinformatic, statistical and pathway analyses of genome-wide expression assays of multiple animal models and human patients, and develop comprehensive knowledgebase of the genomic, proteomic, and metabolic response to burn injury for subsequent disease modeling and target prediction. The overall objective of Core is to use state-of-the-art mathematical and computational approaches needed to better understand the complex systems biology presented by injury and critical illness, as outlined in the Major Functions ofthe Core: 1. Investigate via computational analyses the genomic mechanism ofthe adaptive and maladaptive physiological responses to thermo injury in studies of the Research Projects, including 1 a. Develop computational tools for using new exon-junction arrays in studying animal models (mouse and Rhesus monkeys), lb. Analyze the genomic effect of activation and/or inhibition of genes important to insulin resistance and mitochondrial dysfunction in animal models, and 1c. Compare cross species the genomic changes between animal models and burn patients, and between LPS and burns. 2. Integrate the genomic, protein activity and metabolic data generated by the Program for rational target identification of gene candidates for intervention, including 2a. Develop a knowledgebase of molecular derangements in skeletal muscle following thermal injury by integrating findings from the Research Projects with molecular information systematically harvested from the literature as well as comprehensive human transcriptome data of burn patients, and 2b. Conduct computational analysis to identify key gene regulators for follow up intervention studies candidate serine-threonine kinases for follow-up inhibition. 3. Establish a web-based portal ofthe data and knowledgebase as central community resource.
The Computational Genomics Core will develop and apply mathematical and computational methods to analyze, integrate, and share the large amount of research data and findings from the Center as well as the research community in order to understand the molecular mechanism of burn injury and subsequently help identify new targets for intervention. The ultimate goal is to search for better treatments of thermo injury.
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