Resolving complex genomic structures and regulation patterns in cervical cancer

A vast majority of cervical cancer cases are due to human papillomavirus (HPV) infection. Vanessa Porter and her team sequenced the whole genomes of 59 cervical cancer samples from Uganda (HTMCP) and the USA (TCGA), using the PromethION, to identify the genomic perturbations arising as a consequence of HPV integration. They classified integration events into six categories based on their structure and impact on the human genome. They studied the methylation status of CpGs within and proximal to the HPV genome at individual integration events, inferring epigenetic status of the viral genome within each sample, and found that there were different methylation patterns between integration events. Haplotype-aware DNA methylation indicated allele-specific dysregulation of the human epigenome near HPV integration events. Haplotype-resolved genomes and methylomes have enabled a detailed view of the structure and function of HPV integration events.

What will you lean?

• Understand how to identify and categorise virus-mediated structural rearrangements that are otherwise cryptic to short-read technologies using nanopore sequencing
• Learn how to resolve and visualise complex structural variants with multiple breakpoints
• Learn how to distinguish and separately analyse the methylation of identical viral segments that are distributed across the tumour genome
• Learn how to use regions that are differentially methylated between haplotypes to identify genomic events (e.g., viral integrations) that affect the epigenome

Meet the speaker

Vanessa Porter is a PhD candidate in Dr. Marco Marra’s lab at the Canada’s Michael Smith Genome Sciences Centre in Vancouver. This is Vanessa’s last year in the Doctor of Medical Genetics program at the University of British Columbia. Her project investigates how Human papillomavirus (HPV) in different contexts affects the structure and regulation of cervical cancer genomes using multi-omics analyses.