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.

Public Health Relevance

Disruption of the three-dimensional genome is an emerging hallmark of many tumor types. Computational methods are critical for discovering mutations that affect three- dimensional genome and cause cancer. ! !

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01CA226187-01
Application #
9507112
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Li, Jerry
Project Start
2018-04-19
Project End
2021-03-31
Budget Start
2018-04-19
Budget End
2019-03-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104