April 23, 2019

Advancement in nanopore sequencing opens new areas of cancer biology to exploration

Dr. Jared Simpson, OICR Investigator.

OICR’s Dr. Jared Simpson and collaborators at the University of Oxford create a new method that allows researchers to explore the fundamental, but hard-to-study biological process of DNA replication

How DNA replicates in a cancer cell is difficult to understand, in large part due to the limitations of current technologies. Nanopore sequencing – a fast, portable way to read very long molecules of DNA – could allow researchers to detect DNA replication patterns. Experts in DNA replication from Oxford University, led by Drs. Carolin Müller, Michael Boemo and Conrad Nieduszynski, teamed up with OICR’s expert in nanopore sequencing, Dr. Jared Simpson, to tackle this challenge.

Together, they developed D-NAscent, a sophisticated laboratory protocol and computational tool that together allow researchers to detect and study how DNA is replicated. Recently, the group’s techniques were published in Nature Methods.

“Traditional methods of studying DNA replication have limited resolution – how finely we can see these patterns,” says Simpson, an Investigator at OICR, who helped develop the computational methods used in the study. “With our methods, we can now look at DNA replication on individual, long molecules of DNA at high throughput. This gives us the ability to look for biological patterns that we were once unable to see, for example, in repetitive areas of the genome.”

The collaborators built on the methods that were previously developed by Simpson et al. which have allowed the researchers to study epigenetic changes in cancers and track other diseases like Ebola.

In the study published today, the group used their methods to study yeast cells, which have a simpler and smaller genome than human cells. Now, the group will apply D-NAscent to study the DNA replication dynamics of human cancer biology. They’ve released their software freely to allow other researchers to do so as well.

“We’re very excited to apply D-NAscent in human cancer cells,” says Simpson. “The potential of this technology is what excites me. We’ve opened up an entirely new way to look at genomic diseases – one that can potentially turn an unexplored aspect of biology into new cancer research discoveries.”