Functional Annotation

After using GWAS to narrow down regions in the genome to investigate, we can carry out a number of assays to functionally annotate the genome in a variety of cancer cell types:

  • determine the levels of gene expression with RNA-seq;

  • identifying active and regulatory regions with the use of ChIP-seq and ATAC-seq;

  • assigning enhancers to genes with 3D chromatin methods including capture HiC and Micro C;

  • assessing the biological consequence of genetic variants with luciferase reporter assays and Massively Parallel Reporter Assays (MPRA);

  • determine if variants have an effect using eQTL, TWAS, MWAS;

  • further integrating different datasets to determine if there is any co-localisation of the functional variants

Further Reading

HE Speedy, R Beekman, V Chapaprieta, G Orlando, PJ Law, ...; 2019; Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics; Nature Communications; 10(1):3615 PMID: 31399598

JB Studd, J Vijayakrishnan, M Yang, G Migliorini, K Paulsson, ...; 2017; Genetic and regulatory mechanism of susceptibility to high-hyperdiploid acute lymphoblastic leukaemia at 10q21. 2; Nature Communications; 8:14616 PMID: 28256501