BIOSTATISTICS AND EVOLUTIONARY ANALYSIS

核心C负责对Barrett‘s食道进行生物统计学和克隆进化分析 研究方案P01数据，包括数据分析、数据管理和向所有人传播数据 项目和核心。核心C从最初开始就参与了项目的所有阶段的实验 实验设计，开发用于质量控制和自动基因分型的生物信息学软件 在实验过程中，对结果数据进行分析。因为核心C集成了数据和实验 在所有项目和核心中，它在促进项目之间的互动方面发挥了关键作用 和核心。在本供资期间，核心C对核心B和核心C产生的数据进行分析 项目已经导致了一些研究产品的生产，例如一组具有 预测未来癌症的高度敏感性和特异性；更好地理解进化 推动癌症进展的动力和非类固醇抗炎药(NSAID)的使用是 与Barrett‘s食道癌发病率显著降低相关的分子药物 高危进展到癌症的标志物。我们建议在下一次扩展这些分析 我们的大巴雷特病的表观遗传改变和扩大的遗传损害小组的资助期 一群人。推动Barrett‘s食道肿瘤进展的克隆进化呈现独特 研究设计和分析的机遇和挑战。无论肿瘤是否进展到 恶性依赖于已经形成的突变，环境的选择压力， 通过DMAdamage和表观遗传改变产生新克隆和异质性，以及如何 随着时间的推移，克隆竞争会上演。核心C有机会和专业知识使重要的 帮助计划项目了解这些过程并实现其特定目标。

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.