Rasmussen's team faced the challenge that no single clinical variable, or combination of clinical variables, could accurately warn that a liver transplant patient was heading for trouble. They decided to look at all of the RNA molecules produced in cells from 111 liver biopsy specimens collected over time from 57 hepatitis C infected patients who had undergone liver transplant surgery. Such a set of molecules is called a transcriptome, a collection of works "written" from the DNA code in response to a viral infection. Her team applied leading-edge mathematical modeling systems to cull patterns of gene expression.
"We were able to identify a molecular signature of gene expression for those patients at risk of developing severe fibrosis in their transplanted livers," Rasmussen said. Significantly, her team also discovered that these alterations in gene expression occur before there is evidence in the liver tissue of disease progression.
"That suggested to us that events that occur during the early stages when the transplanted liver is becoming infected with the patient's hepatitis C virus influence the course of the disease," Rasmussen said. Her team also observed a precursor state a set of conditions that foretold problems ahead that was common for different, severe clinical outcomes. Her team went on to describe the probable cellular network that could be the basis for the initial transition to severe liver disease.
They hope the findings open new avenues in research to delay disease progression and extend the survival of transplanted livers.
Both the Rasmussen and the Diamond teams employed systems biology methods to understand the root of post-transplant liver disease recurrence. This approach looks at the complex interactions between pathogens, in this case the hepatitis C virus, and the organism they infect. These interactions are largely studied in their entirety at the scale of
|Contact: Leila Gray|
University of Washington