Researchers at University of Illinois showed a new method using nanopores to identify, count and map methylations which may be a cancer signal, with extraordinary resolution.
Jean-Pierre Leburton, a professor of electrical and computer engineering at Illinois University said that single or less methylations is not a problem, however if there are a number of them and they are found close to each other, it is not good. DNA methylation is really a beginning process for cancer. So we have to find how many of them found and how closely they are packed. That can reveal as the stage of cancer.
Limitation in resolution is a major challenge on others efforts to detect methylation with the help of nanopores. Researchers initiate this by making a tiny hole in a flat sheet which has only one molecule or atom thickness. The pore is dipped in a salt solution and an electrical current is applied to force the DNA molecule through the hole. Researchers are aware that a methyl group is threaded through the dips in the current. But when two or three methyl groups are closer to each other, the pore counts it as one signal, Leburton mentioned.
Nanopores To Detect Methylations
The Illinois team tried a little different strategy. Instead of dipping, they applied current directly on the conductive sheet around the pore. In collaboration with Klaus Schulten, a professor of physics at Illinois, Leburton’s team made use of advanced computer simulations to examine applying current to various flat materials, like molybdenum disulfide and graphene, as methylated DNA was passed through.
“Our simulations denote that assessing the current through the membrane instead of just the solution around it is much more precise,” Leburton said. “If you have two methylations close together, even only 10 base pairs away, you continue to see two dips and no overlapping. We also can map where they are on the strand, so we can see how many there are and where they are.”
Leburton’s group is working with collaborators to improve DNA threading, to cut down on noise in the electrical signal and to perform experiments to verify their simulations.
Written by Lax Mariappan Msc