Functional Interpretation of Genome-Wide Association Studies
The Hazelett Laboratory has been involved in functional studies to interpret and extend the findings of genome-wide association studies (GWAS), particularly for cancer. This includes functional annotation of variants and enrichment analysis to identify the cell of origin for disease, design and analysis of follow-up experiments using chromatin conformation capture (3C)-based chromatin assays, allele-specific binding in chromatin immunoprecipitation assays, luciferase assays and other approaches.
Mutations in Cancer
As an extension of work on germline variants in cancer, the Hazelett Lab is investigating the functional significance of noncoding mutations that have accumulated in high-grade serous ovarian cancer and post-treatment recurrences. The team is working to discover how predictable the post-treatment selection process is, and whether/how it might be addressed in the clinic. The Hazelett Laboratory is partnered with the Cedars-Sinai Women’s Cancer Program for this work.
As a critical component of their work, the Hazelett Laboratory is continuously developing bioinformatics tools based on collaborations to service unmet needs in the fields of regulatory genomics and variant annotation. Following is a list of Bioconductor packages generated by members of the Hazelett Lab:
- StatePaintR (under review)
- HiCAGE (in prep)
One of our goals is to understand the rules underlying intrachromosomal looping interactions discovered from 3C-based methods, using epigenomics and machine learning techniques. These studies will lead to mechanistic insight into the link between variation in noncoding DNA and disease.