December 17, 2020
Dr. Jared Simpson and collaborators develop new nanopore-based methods to investigate two understudied aspects of disease biology
Studying DNA modifications may offer new insights into cancer – and the tools to read these changes are now in our hands.
In a recent publication in Nature Methods, OICR Investigator Dr. Jared Simpson and collaborators at Johns Hopkins University describe a new method to investigate two key aspects of disease biology, methylation and chromatin accessibility, simultaneously. These aspects can help describe how genes are organized and switched on and off in a cell, which may enable future progress in cancer research and discovery.
The group’s new method, coined nanoNOMe-seq, is built for nanopore sequencing – a fast, portable way to read long molecules of DNA. nanoNOMe serves as an additional tool that extends the utility of nanopore sequencing technologies.
“Our collaborators developed the lab protocols and we developed the analysis software to determine where DNA modifications occurred,” says Simpson. “Now, with this method, other researchers can investigate how DNA is modified within a cell to give an extra layer of information that the community can decode into new insights and discoveries.”
Dr. Michael Molnar, Scientific Associate in the Simpson Lab at OICR, led the development of the analysis software behind nanoNOMe.
“At times, it seemed like it might not be possible to develop a statistical model that could make sense of all the data,” says Molnar. “But we were able to persist and develop the nanoNOMe software, which showed a high degree of accuracy. We hope this method will enable others to discover long-range patterns and make new connections in sequencing data.”
nanoNOMe was first released as a preprint, which has already been cited in other scholarly articles including a tool for methylation pattern visualization, an analysis of human chromosome 8, and a published review on long-read sequencing among other publications. Simpson and Molnar’s collaborators plan to further investigate methylation and chromatin accessibility in human cancer cells with nanoNOMe.
“If you’re interested in understanding how methylation relates to open chromatin, then you can use this protocol,” says Simpson. “This is opening a new space for the community to explore interactions between chromatin and DNA methylation.”