DNA microarray technology has transformed genomics — the study of genes and their function — by enabling scientists to monitor the expression of thousands of genes simultaneously. Microarrays are slides patterned with thousands of microscopic spots containing DNA molecules, or probes. Each probe is designed to hybridize uniquely to one DNA sequence, or target. As targets hybridize to probes, the various regions on a chip become fluorescent.
The potential applications of microarray technology to medicine, says Ian Laurenzi, are huge. Unfortunately, no probe sequence binds exclusively to its target; instead, because of overlaps in sequence, any or all DNA target species may bind to the microarray probe. This phenomenon, known as cross-hybridization, undermines the accuracy of the probe.
Laurenzi, assistant professor of chemical engineering, and his students are the first researchers to simulate the performance of microarrays. They have developed algorithms that can characterize the cross-hybridization occurring in any microarray design.
“Using our stochastic computational methodologies,” says Laurenzi, “we are able to quantify the quality of microarray designs for a wide variety of screening applications.
“A microarray is really a complicated network of chemical reactions between all probes and all targets. To evaluate microarrays in the lab can be expensive and time-consuming. But with simulation, we can evaluate all of the chemical reactions simultaneously.”
Laurenzi’s group works in the lab to evaluate the crosshybridization of yeast DNA to probes designed for yeast genes.
“We are currently developing methods of probe design that will reliably relate changes in genetic expression to changes in fluorescence intensity.”
