Developing Informatics Technologies to Model Cancer Gene Regulation

项目总结 反式作用因子如何调控癌症中全基因组的基因表达尚不清楚，这促使了一种 越来越多的Chip-seq、DNase-seq和atac-seq(简写为“cistrome”)实验要映射 全基因组转录因子结合位点和染色质状态。重大的生物学见解是 通过对循环数据的计算分析获得的，特别是在与其他已发表的 Cstrome和基因表达数据集。然而，大多数癌症生物学家发现计算数据分析和 细胞周期和表观基因组数据的整合成为其癌症基因中最具限制性的单一瓶颈 监管研究，因为缺乏信息学专门知识和与 海量的公开数据。我们之前已经开发了Cistrome分析管道(AP) 和Cistrome数据浏览器(DB)来克服这一挑战。这项提议的目标是扩大 Cistrome AP和DB的功能，以改进收集、管理、分析、集成、 Cstrome及相关数据类型的可视化和传播。灵活、直观的用户 经验将使实验癌症生物学家能够创建更有洞察力的转录和 癌症研究中的表观遗传基因调控。 具体地说，我们建议改进和扩展我们现有的Cistrome分析管道(http://cistrome.org/ap) 和Cistrome数据浏览器(通过开发信息学来开发http://cistrome.org/db)基础设施和接口 解决Cystrome数据分析的四个关键方面的技术。首先，我们将设计、开发和 通过用户友好的界面部署软件，以改进自动化数据收集、处理和 注释。这将使未发布的和公开的历史数据能够被联合分析并转换为 可用于综合分析的格式和统计表达式。第二，我们将制定方法 使用所有可用的cstrome数据来归因于未公开表示的Tf结合/细胞类型组合 储存库。第三，我们将开发系统，允许基因表达数据与蛋白质组数据相结合 阐明调控机制。第四，我们将开发基于Web的交互式工具，用于可视化 数百个不同分辨率的电子显微镜样本。最后，我们将开展外展活动，以提高 改进Cistrome功能、用户界面、与其他工具的互操作性，促进Cistrome数据的使用 在癌症研究方面。

PROJECT SUMMARY How trans-acting factors regulate genome-wide gene expression in cancer is poorly understood, motivating an increasing number of ChIP-seq, DNase-seq, and ATAC-seq (simplified as “cistrome”) experiments to map genome-wide transcription factor binding sites and chromatin status. Significant biological insights have been gained through the computational analysis of cistrome data, especially when integrated with other published cistrome and gene expression data sets. However, most cancer biologists find computational data analysis and integration of cistrome and epigenome data to be the single most limiting bottleneck in their cancer gene regulation studies due to the lack of informatics expertise and computational infrastructure relative to the extraordinary volume of publicly available data. We have previously developed Cistrome Analysis Pipeline (AP) and Cistrome Data Browser (DB) to overcome this challenge. The objective of this proposal is to expand the functionality of Cistrome AP and DB to improve the collection, management, analysis, integration, visualization, and dissemination of cistrome and related data types. A flexible and intuitive user experience will empower experimental cancer biologists to create more insightful models of transcriptional and epigenetic gene regulation in cancer research. Specifically, we propose to improve and extend our existing Cistrome Analysis Pipeline (http://cistrome.org/ap) and Cistrome Data Browser (http://cistrome.org/db) infrastructure and interface by developing informatics technologies that address four critical aspects of cistrome data analysis. First, we will design, develop, and deploy software through a user-friendly interface to improve automated data collection, processing, and annotation. This will enable unpublished and public cistrome data to be jointly analyzed and converted into formats and statistical expressions that can be used for integrative analysis. Second, we will develop methods to use all available cistrome data to impute TF binding/cell-type combinations that are not represented in public repositories. Third, we will develop systems to allow gene expression data to be integrated with cistrome data to elucidate regulatory mechanisms. Fourth, we will develop interactive web based tools for the visualization of hundreds of cistrome samples at multiple resolutions. Finally, we will engage in outreach activities to improve improve Cistrome functions, user interface, interoperability with other tools, and promote the Cistrome data use in cancer research.