Long-read landscapes of DNA methylation in liver pathophysiology
About Chloé Goldsmith
Chloé Goldsmith received her Ph.D. at the University of Newcastle and is a post-doctoral researcher at the French Institute for Health and Medical Research, and the Lyon Cancer Research Center. Her work aims to better understand and exploit the unique characteristics of the methylome during cell transformation and established malignancies, with a goal to develop DNA methylation protocols useful for clinical translation.
The robust detection of differential DNA methylation requires high coverage, particularly in the case of viruses that exhibit high sequence variability, including Hepatitis B Virus (HBV). Moreover, the simultaneous study of DNA methylation in both a host genome and viral pathogen remains difficult. We explore the potential of the CRISPR/Cas9 system for the targeted capture of genomic loci and pathogenic DNA in chronic HBV infected patients; teamed with available data mining tools, we were able to reproduce expected genomic patterns of DNA methylation and identify known differences between cellular subtypes. Moreover, enriching in entire HBV DNA reads allowed the identification of epigenetic heterogeneity in infected patients. The CRISPR/Cas9 enrichment approach, coupled with nanopore sequencing, is a valuable technique for enrichment that allows native quantification of DNA base modifications.