Sampling Sequence Space? It's EMPIRIC

Date Posted: 2011-04-20

Bolon New
A new study by the Bolon Lab, published in the Proceedings of the National Academy of Sciences, describes a novel technique to produce all potential individual mutations and, using deep sequencing technology, simultaneously analyze each change’s impact on the cell.

Using sequencing technology inspired by the human genome project, Dan Bolon and colleagues have developed a method called EMPIRIC to analyze hundreds of different mutations in a single test tube. Ordinarily used to read a DNA sequence over an entire genome this Band-aid-sized sequencing chip was utilized by the Bolon Lab to accurately count and record the abundance of hundreds of distinct cells in a test tube that differ by individual mutations. Simply put, mutations that are beneficial will grow rapidly and increase in abundance, while mutations that are harmful will decrease in relative abundance.

Their findings were consistent with current models of molecular evolution that show a large number of mutations are harmful, but the great majority of mutations have little to no effect on the cell’s function. With this approach, scientists can gain new insights into a host of biological questions including how environmental pressures influence evolutionary processes on a genetic level, what mutations are likely to cause genetic disease and how to screen viruses for mutations that might lead to drug resistance.

“One of the truly exciting aspects about this approach is that it’s so general,” said Dr. Bolon. “While our experiments were carried out on yeast cells, it can be applied to any fast growing cell that can be genetically manipulated such as cancer cells, viruses or bacteria.”

The full UMass Medical School Communications can be found here.