A second whittling of the list -- this time to the top 500 health-related gene expressions -- exposed two sets of genes whose activity presaged patient outcome within 40 to 80 hours of the injury. MHC-class II genes -- which recognize infection-fighting proteins known as antigens and transport them to the surface of specialized cells that then carry out the immune response -- showed decreased expression as a patient worsened. At the same time, the expression of genes known as p38 MAPK that help trigger inflammation and swelling -- part of the body's immune arsenal -- clearly spiked.
Combined, these observations suggest that trauma patients who eventually die develop an erratic and paradoxical immune response, Storey said.
"Perhaps that's why they die," he said. "The patients in our fifth category had mass inflammation that wreaked havoc on their organs because p38 MAPK was turned up, but the genes that recognize and help fight pathogens, MHC-class II, were turned down."
Using the set of 3,000 gene expressions, the Princeton researchers created a model intended to help doctors correlate genomic activity with health status. The model resembles the methods used to diagnose conditions such as heart attacks by determining the severity of various factors, Storey said. The model is composed of five separate graphs, with each one correlating expression patterns in a specific gene family to the five categories of patient conditions based on likelihood of death that the researchers previously established. The model is set to a timescale of 12 hours to roughly 10 days following injury.
The model shows, for example, that if one family of genes exhibits a jump in expression early on, the patient's condition might be in the deadly fifth category; however, if activity for those same genes diminishes quickly, the patient could experience a good outcome. The same determination is made for each of the
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