Interview: Investigating epigenomic alterations in cancer with nanopore sequencing

Alberto Magi is an Associate Professor of Bioengineering at the Department of Information Engineering at the University of Florence in Italy, where he develops computational tools to analyse nanopore sequencing data in the study of genetic and epigenetic alterations in cancer. Here we talk to Alberto about how nanopore sequencing is impacting the study of epigenetics, and more on how his work aims to understand clonal epigenomic evolution and drug resistance mechanisms in acute myeloid leukemias (AMLs).

You can also watch his recent talk below, where he covers her work in more detail.

What are your current research interests?

My research focuses on computational genomics, and in particular the development of new algorithms for the study of human genetic variation using data from nanopore sequencing, with the aim to develop new solutions in order to understand the molecular mechanisms underlying tumour evolution.

How is nanopore sequencing changing the study of epigenetics? How has it benefitted your work?

Nanopore sequencing is capable of studying epigenomic alterations with unprecedented resolution. This allows the identification of differential methylation in low density CpG regions, drastically outperforming classical bisulfite conversion methods. Thanks to nanopore sequencing, we were able to discover a novel epigenomic mechanism which was the basis of cancer chemoresistance acquisition.

What impact could the ability to identify epigenomic alterations have for our understanding and treatment of cancer?

We propose a model whereby accumulation of hyper- or hypo-methylation in relapsing acute myeloid leukaemia’s (AMLs) at sparse CpGs of gene-bodies is the consequence of selective pressure of chemotherapy on the epigenomic heterogeneity of primary leukemias, as generated by maintenance failures and aberrant expression of DNMT1 (epigenetic-instability at CpG-poor regions). In principle, epigenetic alterations are reversible, thus opening the possibility of pharmacological modulation of epigenetic heterogeneity to prevent the emergence of drug resistance in cancer cells.

What have been the main challenges in your work and how have you approached them?

When we started to explore nanopore data, there were few tools capable of analysing this type of data. To overcome this limitation, we developed several tools to analyse structural variations and epigenetic alterations in cancer.

What’s next for your research?

To use nanopore sequencing to study genomic and epigenomic alterations in solid cancers.

To learn more about other applications of nanopore sequencing in cancer research, click here.