The pattern analysis and computational biology core (core B) will provide computational and statistical support to this program project grant. The core will also provide web resources for storing and sharing data and information and a tissue database developed for a Gl-spore grant for pancreatic tissues. The major goal is to discover patterns of genetic/expression/amplification change in pancreaticcancer cells and tissues that are predictive for therapeutic choice or clinical outcome. By storing data in descriptive object formats and using novel computational tools, patterns that will be most useful for clinical applications will be identified and carefully validated. Through additional bioinformatics support and genome analysis,these results will be used to discover potential drug targets. In project 1, statistical support for the analysis of immunohistochemical measurements designed to explore redox control in pancreatic cancer tissues will be provided. In project 2, studies of the effects of large numbers of agents on mutant cell lines will be supported by providing suitable data storage, additional information about the drugs and chemicals, and prediction of the cellular functions and pathways that might be affected by the presence of the tumor suppressor mutations. In project 3, in addition to data storage, support will be provided for the identification of changes in gene number and expression and the effect of these changes on biochemical pathways and drug sensitivities. Interactive maps of the human genome will be prepared for displaying the principal genetic, gene amplification/loss, expression data, and mutationalchanges in pancreatic cells that are being discovered in this project and others will be developed. Data objects will be developed to model all project data in order to facilitate pattern searching that will facilitate identifying new drug targets. Through additionalbioinformatics support and genome analysis, we will help to rationalize the kinds of alterations in nucleotide and DNA metabolism that influence the effects of gemcitabineand any other new drugs discovered on this program project grant on pancreatic cancer cells.
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