Bridging Epigenomics and Patient Data to Detect Enhanceropathies in Cancer
Abstract
The objectives of this proposal are to leverage DNA methylation data and large-scale patient Electronic Health Record (EHR)data to identify and characterize novel, non-coding genetic variants associated with lymphoid and other blood cancers. During the two years of this award, we made substantial progress towards the stated goals of the project, despite the early delays brought on by COVID19. Specifically, we identified new DNA methylation-defined lymphocyte enhancers that regulate key lymphocyte genes and contain non-coding single nucleotide polymorphisms (SNPs) associated with risk for immune disease phenotypes including cancer. We have developed new protocols for functionally analyzing non-coding SNPs and their effects on enhancer function using ATAC-STARR-seq, a massively parallel reporter assay that simultaneously measures chromatin accessibility, transcription factor occupancy and regulatory activity. Integrating these data allowed us to prioritize a high value set of lymphocyte enhancers for further mechanistic studies. Finally, we demonstrate how DNA methylation data can be combined with genotype-phenotype data to understand the function of gene regulatory elements and the genes they target. Our work provides a roadmap for using epigenetic data to bridge the genome-phenome knowledge gap in cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2023
- Accession Number
- AD1203894
Entities
People
- Emily C. Hodges
Organizations
- Vanderbilt University