Researchers will analyze genetic mutations in pediatric liver transplant patients to predict who is more likely to reject a donor organ.

The project, led by Dr. Rakesh Sindhi, co-director of Children's Hospital's Hillman Center for Pediatric Transplantation, could eventually lead to tailored antirejection strategies that minimize medications and reduce expensive hospital stays.

"We are absolutely at the cutting edge," Dr. Sindhi said. The study was awarded a four-year, $1.1 million grant from the National Institutes of Health.

Dr. Sindhi said the project could lead to strategies that reduce rejection rates in pediatric liver transplant patients from about 50 percent to 20 percent.

Researchers will use commercially available DNA chips to look for up to 500,000 mutations in the genetic code of the participants prior to their liver transplantations. Everyone carries millions of these alterations, called nucleotide polymorphisms, but only a fraction of them might cause cellular dysfunction, Dr. Sindhi said.

The idea is to see whether the patients who reject the donor organ have what he calls "a unique genomic fingerprint" that distinguishes them from those who develop transplant tolerance.

Also, the researchers will collect blood samples before transplant surgery and one, four to six, and 12 months after the operation to look at the activity of all cataloged genes, some 50,000 of them, that make measurable proteins. Again, they will look for patterns that might predict whether a patient is likely to reject the donor liver.

When the immune system interacts with foreign tissue, it might react by eliminating cells that would attack it, which would lead to tolerance, or it might target the tissue, leading to rejection. It could also take a middle ground in which certain cells behave like antirejection drugs, Dr. Sindhi said.

Identifying key genes in white blood cells and learning what they are doing in each of those situations could help doctors decide when to increase the dose of antirejection drugs and when it's safe to taper them, he said.

Traditionally, doctors run blood tests to see whether the organ is working properly, and usually give more antirejection drugs if it isn't.

But "by that time the liver is already dysfunctioning, so it's kind of late," Dr. Sindhi said. "The whole idea is to come up with ways where we don't really wait for children to develop rejection or to develop a good outcome."

The data-crunching needs of the research are astounding, he said. "We are crashing computers like you wouldn't believe," he said. "Just the storage alone is crazy."