A Data Analysis Center for integration of fly and worm modENCODE datasets

描述(申请人提供)：ENCODE(DNA元素百科全书)和modENCODE(模式生物ENCODE)项目的目标是应用高通量、低成本的方法来生成人类、蠕虫和苍蝇基因组中的功能元件目录，这将作为生物医学研究进展的基础。由于它们较小的基因组规模、强大的遗传学和易于实验，它们可以帮助指导人类基因组中功能元件的研究，揭示全球基因调控和胚胎发育的新见解，并使哺乳动物系统中无法获得的基因功能和调控的实验研究成为可能。这项建议旨在通过创建一个数据分析中心(DAC)来支持、促进和增强对苍蝇和蠕虫的modENCODE联盟的综合分析，以实现对其所有功能元素的高分辨率注释，并揭示包括人类在内的动物基因组的生物学和基因调控的新见解，从而提高这些数据集的价值。我们预见了发改会的四个核心角色，并围绕它们组织了我们的目标。目标1：我们将为Fly和WORM中的数据处理提供通用的计算指南，Fly和WORM是通用的计算基础设施和管道，用于常见的分析和统计任务。目标2：我们将促进和执行特定于元素的综合分析，以基于来自多个组的相关数据集的组合来识别不同类别的功能元素。这包括(A)增强子、启动子、绝缘体和其他调控重要区域，(B)蛋白质编码和非编码基因，(C)转录因子和microRNA靶向的调控网络，以及(D)预测不同类别功能元件的序列特征。目标3：我们将在不同的数据类型上进行探索性数据分析，以发现与不同类别的元素相关的潜在的新的相关性和见解。特别是，我们将应用降维技术来处理基于坐标的全基因组和表观基因组数据集，我们将应用聚类和双向聚类方法来识别功能相关的基因和模块集，我们将分析所发现的网络的结构和动态属性。目标4：我们将对这两种模式生物进行比较分析，并与酵母和人类进行比较分析。我们将提供物种之间的同源基因资源，比较同源细胞系和发育点的调控关系和动力学，并在模式生物和人类之间传播生物学知识。为了实现这四个目标，我们将与该联盟的成员、由所有主要调查人员和分析小组组成的modENCODE分析工作组(AWG)和数据协调中心(DCC)密切合作，该中心负责在该联盟内以及与更大的蠕虫和苍蝇群落共享所有数据。 与公共卫生相关：ENCODE(DNA元素百科全书)和modENCODE(模式生物ENCODE)项目的目标是应用高通量、低成本的方法来生成人类、蠕虫和苍蝇基因组中的功能元件目录，这将作为生物医学研究进展的基础。由于它们较小的基因组规模、强大的遗传学和易于实验，它们可以帮助指导人类基因组中功能元件的研究，揭示全球基因调控和胚胎发育的新见解，并使哺乳动物系统中无法获得的基因功能和调控的实验研究成为可能。这项建议旨在通过创建一个数据分析中心(DAC)来支持、促进和增强对苍蝇和蠕虫的modENCODE联盟的综合分析，以实现对其所有功能元素的高分辨率注释，并揭示包括人类在内的动物基因组的生物学和基因调控的新见解，从而提高这些数据集的价值。

DESCRIPTION (provided by applicant): The aims of the ENCODE (Encyclopedia of DNA Elements) and modENCODE (model organism ENCODE) projects are to apply high-throughput, cost-efficient approaches to generate a catalog of functional elements in the human, worm, and fly genomes, which will serve as the basis for biomedical research advances. By their smaller genome size, powerful genetics, and ease of experimentation, D. melanogaster and C. elegans can help guide the study of functional elements in the human genome, reveal new insights into global gene regulation and embryo development, and enable experimental studies of gene function and regulation which are not accessible in mammalian systems. This proposal aims to enhance the value of these datasets by creating a Data Analysis Center (DAC) to support, facilitate, and enhance integrative analyses of the modENCODE consortium in fly and worm, to achieve a high-resolution annotation of all their functional elements, and to reveal new insights into the biology and gene regulation of animal genomes including the human. We foresee four central roles for the DAC, and have organized our aims around them. Aim 1: We will provide common computational guidelines for data processing in fly and worm, a common computational infrastructure and pipeline for common analysis and statistical tasks. Aim 2: We will facilitate and carry out element-specific integrative analyses to identify diverse classes of functional elements based on combinations of relevant datasets coming from multiple groups. This includes (a) enhancers, promoters, insulators, and other regions of regulatory importance, (b) protein-coding and non-coding genes, (c) regulatory networks of transcription factor and microRNA targeting, and (d) sequence features predictive of diverse classes of functional elements. Aim 3: We will carry out exploratory data analyses across different data types to discover potentially novel correlations and insights relating diverse classes of elements. In particular we will apply dimensionality reduction techniques to coordinate-based genome-wide genomic and epigenomic datasets, we will apply clustering and bi-clustering methods to identify functionally related sets of genes and modules, and we will analyze structural and dynamic properties of discovered networks. Aim 4: We will carry out comparative analyses across the two model organisms, and also with yeast and human. We will provide an ortholog resource between the species, compare regulatory relationships and dynamics for orthologous cell lines and developmental points, and carry over biological knowledge across model organisms and human. To achieve these four aims, we will work closely with members of the consortium, the modENCODE Analysis Working Group (AWG), consisting of all Principal Investigators and analysis groups, and the Data Coordination Center (DCC), responsible for all data sharing within the consortium and with the larger worm and fly communities. PUBLIC HEALTH RELEVANCE: The aims of the ENCODE (Encyclopedia of DNA Elements) and modENCODE (model organism ENCODE) projects are to apply high-throughput, cost-efficient approaches to generate a catalog of functional elements in the human, worm, and fly genomes, which will serve as the basis for biomedical research advances. By their smaller genome size, powerful genetics, and ease of experimentation, D. melanogaster and C. elegans can help guide the study of functional elements in the human genome, reveal new insights into global gene regulation and embryo development, and enable experimental studies of gene function and regulation which are not accessible in mammalian systems. This proposal aims to enhance the value of these datasets by creating a Data Analysis Center (DAC) to support, facilitate, and enhance integrative analyses of the modENCODE consortium in fly and worm, to achieve a high-resolution annotation of all their functional elements, and to reveal new insights into the biology and gene regulation of animal genomes including the human.