BIOSTATISTICS AND EVOLUTIONARY ANALYSIS

核心C负责将生物统计学和克隆进化分析应用于巴雷特食管 研究计划P01数据，包括数据分析，数据管理和数据传播到所有 项目和核心。核心C参与了从最初的项目到整个项目实验的所有阶段。 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，对所得数据进行分析。因为Core 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相互作用方面发挥了关键作用 和核心。在本供资期内，核心C对核心B和 项目已经导致了许多研究产品的生产，如一组生物标志物， 预测未来癌症的高灵敏度和特异性;更好地了解癌症的演变 推动癌症进展的动力学，以及非甾体抗炎药（NSAID）的使用， 与Barrett食管患者癌症发病率的显著降低相关， 进展为癌症的高风险标志物。我们建议在下一个 资助期表观遗传改变和扩大小组的遗传病变，在我们的大巴雷特的 队列。在Barrett食管中驱动肿瘤进展的克隆进化呈现出独特的 研究设计和分析的机遇和挑战。肿瘤是否进展到 恶性肿瘤取决于已经发展的突变，环境的选择压力， 通过DMadamage和表观遗传改变产生新的克隆和异质性，以及如何 克隆竞争随着时间的推移而发生。核心C有机会和专业知识， 帮助计划项目理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.