Current Bioinformatics Seminar
Time: 11AM Tuesdays.
Venue: Teams
28 June 2022
Differential analysis of genome organization in the immune system
Hannah CoughlanWEHI Bioinformatics
The immune system is comprised of defined cell types, each with a critical role in maintaining health. It is now known that immune cells possess distinct genomic organization but what is the relationship between structure and function in immune cell types? How does the chromatin structure effect gene regulation? High throughput chromatin conformation capture (HiC) can examine three-dimensional chromatin structure such as interactions of genes and regulatory elements or large-scale chromosome structure at a range of length scales. By measuring the frequency of long-range interactions, cell type specific chromatin structure can be identified. We used the statistically robust R package diffHic to incorporate biological replicate variability in identifying significant changes in chromatin interaction frequency between immune cells under different conditions. Instead of identifying either the presence or absence of structure, diffHic uses the edgeR framework to identify strengthening and weakening chromatin structure. Here I will present two projects that utilised differential analysis of the genome to gain insight into the function of immune cells. Naïve B lymphocytes undergo proliferation and differentiation upon activation with a pathogen. How is chromatin structure maintained and established through changes from a quiescent to a rapidly expanding state and then finally an into antibody secreting plasmablast? We examined chromatin structure and gene expression in B cells prior to, during and after activation. Second, I will demonstrate the impact of heterochromatin loss on transcription and genome organization in thymocytes, a precursor to T cells.