Tools for annotating mutations in the 3D cancer genome

用于注释 3D 癌症基因组突变的工具

基本信息

批准号：
9899958
负责人：
Kai Tan
金额：
$ 32.15万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-19 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9899958
关键词：
3-Dimensional Affect Architecture Area Benchmarking Cancer Etiology Chromatin Collaborations Communication Communities Computer software Computing Methodologies DNA Data Databases Disease Enhancers Gaussian model Genetic Enhancer Element Genetic Transcription Genome Genomics Goals Informatics Investigation Letters Malignant Neoplasms Methods Modeling Mutation Mutation Analysis Oncogene Deregulation Performance Point Mutation Regulator Genes Research Research Personnel Role Seminal Standardization Structure Structure-Activity Relationship Technology Tissues Transact Untranslated RNA Variant base bioinformatics tool cancer cell cancer genome cancer type causal variant cell type data integration epigenomics genome database genome sequencing innovation insertion/deletion mutation insight programs promoter repository tool transcriptomics tumor tumorigenesis

项目摘要

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.

项目摘要基因组测序揭示了数千种与各种类型相关的突变癌症。绝大多数已确定的变体是不编码的。许多开创性研究表明，非编码突变会破坏3D基因组建筑并引起癌症。加速在这个新兴领域的发现研究，用于突变和3D基因组综合分析的生物信息学工具组织数据至关重要。在这个项目中，我们将开发一套生物信息学工具可预测3D基因组组织的层次结构并使用此类工具信息以解释和识别因果非编码突变。在AIM 1中，我们将开发一种识别破坏染色质域和的突变的方法癌症中的子域边界。在AIM 2中，我们将使用与疾病相关的增强子 - 启动子网络，用于优先考虑破坏增强子功能的突变。在AIM 3中，我们将开发一个3D癌症基因组数据库，用于策展，查询和可视化染色质相互作用数据以及转录组，表观基因组和突变数据。