BIOSTATISTICS AND EVOLUTIONARY ANALYSIS

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Core C is responsible for applying biostatistical and clonal evolutionary analyses to the Barrett's Esophagus Research Program P01 data, including data analysis, data management and data dissemination to all Projects and Cores. Core C is involved in all stages of experiments across the Projects from the initial experimental design, to developing bioinformatics software for quality control and automated genotyping during experiments, to analyses of the resulting data. Because Core C integrates data and experiments across all projects and cores, it has played a critical role in facilitating the interactions between the Projects and Cores. During the current funding period, Core C analysis of the data produced by Core B and the Projects has led to the production of a number of research products such as a panel of biomarkers with a high sensitivity and specificity for the prediction of future cancer; better understanding of the evolutionary dynamics that are driving progression to cancer and that non-steroidal anti-inflammatory drug (NSAID) use is associated with a significant decrease in cancer incidence in Barrett's esophagus patients with molecular markers of high risk of progression to cancer. We are proposing to extend these analysesduring the next funding period to epigenetic alterations and an expanded panel of genetic lesions in our large Barrett's cohort. The clonal evolution that drives neoplastic progression in Barrett's esophagus presents unique opportunities and challenges for study design and analysis. Whether or not a neoplasm progresses to malignancy depends upon the mutations that have developed, the selective pressures of the environment, the generation of new clones and heterogeneity through DMAdamage and epigenetic alterations, and how clonal competition plays out over time. Core C has the opportunity and expertise to make significant contributions to assisting the Program Project to understand these processes and fulfill its specific aims.