Bioinformatics Core

项目摘要/摘要 对于这个项目，我们将建立一个生物信息学核心来处理和分析大量的数据 这将由其四个项目产生。我们建议对基因组维护和它的 与人类衰老有关的分子和细胞终点。虽然我们过去的工作得出了这样的结论 基因组维护系统中的缺陷具有有害的分子、细胞和生理影响 与正常衰老相似，涉及的最相关的途径及其相对功能尚不确定 重要性，尤其是对人类老龄化而言。缺乏这些信息是一个重要的问题，因为如果没有这些信息， 知识，获得在整个生物体水平上调节衰老的能力是非常不可能的。我们的长期合作 目标是了解决定长寿的机制。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，即与每个项目合作处理 并整合来自所有项目的数据，以实现方案项目赠款的目标 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损伤造成的分子和细胞后果，包括基因组不稳定、转录 压力，以及细胞命运的改变，进而推动癌症和衰老的发生。这一假设 是在本PPG产生的大量数据的基础上制定的。一项专门的 生物信息学的核心是需要一个整合的设施来从整体上管理大量数据 基因组水平由该计划项目的四个高度集成的项目中的每个项目生成。这一生物信息学 将建立核心，以实现三个具体目标：1)开发数据仓库和共享数据的网络门户 由四个项目生成；2)通过处理和分析项目生成的数据来促进项目； 3)在系统一级整合项目数据，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，因为它的建立是为了迎接挑战 由需要生成的大量数据构成，由各种不同的 方法，集成以开发寿命控制模型，并在项目调查人员和 科学界作为一个整体。

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.