Recent advances in nucleic acid sequencing methods help researchers analyze long nucleic acid molecules (1,000 nucleotides or more in length), a technique known as long-read sequencing.

One type of long-read sequencing, called nanopore sequencing, involves threading strands of DNA or RNA nucleotides through small pores within a membrane, generating changes in electric currents that are distinct for each type of nucleotide. While the technique has high accuracy for DNA sequencing, directly reading RNA nucleotides has proven to be tricky due to the modifications that exist on RNA molecules.

Aleksei Aksimentiev, Ph.D., a professor at University of Illinois at Urbana-Champaign, leads a group that aims to improve the accuracy of nanopore sequencing using computational approaches.

“We know how nanopore sequencing works, but we don’t know why,” he says. “Why are the currents what they are? There is a fundamental knowledge gap in linking sequences to currents.”

A physicist by training, Dr. Aksimentiev considers this question one of the most interesting (and most physics-intensive) problem in biophysics. Collaborating with Min Chen, Ph.D., a professor at the University of Massachusetts Amherst, Dr. Aksimentiev and colleagues are developing computational technologies that will help researchers custom design nanopores to more accurately detect nucleotides. They hope to take their improvements a step further by helping researchers more accurately detect modifications that exist on RNA molecules, an area of much interest as described by a recent report from the National Academies of Sciences, Engineering and Medicine.

Dr. Aksimentiev and his group are using a method called all-atom-molecular dynamics, a computer simulation technique that analyzes how atoms move and interact. Through this method, the researchers are working towards understanding how the different changes occur at a nanoscale level.

Eventually, they hope to use the results from their research to develop software that better allows researchers to decode DNA or RNA sequence and that can be used to better design nanopores to detect nucleotides more accurately.

“It's our goal to make our technology accessible, transferable and usable to others,” he says.