Tools for annotating mutations in the 3D cancer genome

项目摘要 基因组测序揭示了数千种与不同类型相关的突变 癌症的威胁。绝大多数已识别的变体都是非编码的。一批 开创性研究表明，非编码突变可以扰乱3D基因组 建筑和致癌。为了加快在这一新兴领域的发现 用于突变和3D基因组集成分析的调查、生物信息学工具 迫切需要组织数据。在这个项目中，我们将开发一套 生物信息学工具预测3D基因组组织的层次结构并使用 解释和识别因果非编码突变的信息。在目标1中，我们将 开发一种方法来识别破坏染色质结构域和 癌症中的亚域边界。在目标2中，我们将使用与疾病相关的增强剂- 用于区分干扰增强子功能的突变的优先顺序的启动子网络。在目标3中，我们 将开发一个3D癌症基因组数据库，用于管理、查询和可视化 染色质相互作用数据以及转录、表观基因组和突变数据。

Project Summary Genome sequencing has revealed thousands of mutations associated with various types of cancer. The vast majority of the identified variants are noncoding. A number of seminal studies have revealed that noncoding mutations can disrupt 3D genome architecture and cause cancer. To accelerate discovery in this emerging area of investigation, bioinformatics tools for integrative analysis of mutation and 3D genome organization data is critically needed. In this project, we will develop a suite of bioinformatics tools to predict the hierarchy of 3D genome organization and use such information to interpret and identify causal noncoding mutations. In aim 1, we will develop a method for identifying mutations that disrupt chromatin domain and subdomain boundaries in cancers. In aim 2, we will use disease-relevant enhancer- promoter network for prioritizing mutations that disrupt enhancer function. In aim 3, we will develop a 3D cancer genome database for curating, querying and visualizing chromatin interaction data together with transcriptomic, epigenomic, and mutation data.