Bioinformatics Core

项目总结/摘要 本计画将建立一个生物资讯学核心，以处理及分析大量的资料 这四个项目将产生的。我们提出了一个比较研究的基因组维护及其 分子和细胞终点与人类衰老的关系。虽然我们过去的工作已经得出结论 基因组维持系统中的缺陷具有有害的分子、细胞和生理效应， 模拟正常衰老，涉及的最相关的途径及其相对功能尚不确定。 重要性，特别是对人类衰老。缺乏这些信息是一个重要的问题，因为，没有这些信息， 知识，获得在整个有机体水平上调节衰老的能力是极不可能的。我们的长期 我们的目标是了解决定寿命的机制。生物信息学核心的总体目标 是为项目调查人员提供计算支持和服务，即，与每个项目一起处理 其中产生的数据，并整合所有项目的数据，以实现计划项目赠款的目标 作为一个整体。该计划的中心假设是，基因组维护的缺陷会导致有害的 未修复的DNA损伤引起的分子和细胞结果，包括基因组不稳定性，转录 压力和细胞命运的变化，这反过来又推动了癌症和衰老的发病机制。这一假设 已根据本PPG中产生的大量数据制定。一个专门的 生物信息学的核心是需要一个统一的设施来管理大量的数据 基因组水平产生的四个高度整合的项目，这个计划项目。这种生物信息学 将建立一个核心，以实现三个具体目标：1）开发一个门户网站，以存储和共享数据 2）通过处理和分析项目产生的数据来促进项目; 3)在系统水平整合项目数据，并确定衰老过程中基因组维持的遗传网络 和长寿。生物信息学核心的作用是重要的，因为它将被建立以迎接挑战 需要生成大量数据，并由各种 方法，综合开发寿命控制模型，并在项目调查人员之间共享， 整个科学界。

PROJECT SUMMARY/ABSTRACT For this program project, we will establish a bioinformatics core to process and analyze the large amount of data that will be generated by its four projects. We propose a comparative study of genome maintenance and its molecular and cellular end points in relation to human aging. While our work in the past has led to the conclusion that defects in genome maintenance systems have detrimental molecular, cellular and physiological effects that mimic normal aging, there is uncertainty about the most relevant pathways involved and their relative functional importance, especially for human aging. Lack of this information is an important problem, because, without this knowledge, acquiring the ability to modulate aging on the whole organism level is highly unlikely. Our long-term goal is to understand the mechanisms that determine longevity. The overall objective of the bioinformatics core is to provide computational support and service to the project investigators, i.e., work with each project to handle data generated therein and to integrate data from all projects to achieve the aims of the program project grant as a whole. The central hypothesis of this Program is that defects in genome maintenance result in deleterious molecular and cellular outcomes caused by unrepaired DNA damage, including genome instability, transcription stress, and cell fate changes, which in turn drive the pathogenesis of both cancer and aging. This hypothesis has been formulated on the basis of a large body of data produced in this PPG. The rationale for a dedicated bioinformatics core is that a consolidated facility is needed to manage the large amount of data on the whole genome level generated by each of four highly integrated projects of this program project. This bioinformatics core will be established to achieve three specific aims: 1) To develop a web portal to warehouse and share data generated by the four projects; 2) To facilitate projects by processing and analyzing the data that they generate; 3) To integrate project data at the systems level and identify a genetic network of genome maintenance in aging and longevity. The function of the bioinformatics core is significant, because it will be set up to meet the challenge posed by the high volume of data that need to be generated, examined at multiple levels by a variety of approaches, integrated to develop the models of lifespan control, and shared among project investigators and the scientific community as a whole.