Researchers at UT Southwestern are advancing towards the creation of an outline detailing the structure of the mammalian immune system.
In a groundbreaking study published in the Proceedings of the National Academy of Sciences, a team of researchers from UT Southwestern identified over 1,000 gene mutations that may significantly impact immune responses. The study, which received support from the National Institutes of Health, is part of a larger research program led by Nobel Prize laureate Bruce Beutler, Director of the Center for the Genetics of Host Defense (CGHD).
The research team, which includes Leonard Shultz, Bo Li, and other UT Southwestern scientists, used a software tool called Candidate Explorer (CE) developed by Darui Xu, a computational biologist at CGHD. CE is designed to identify gene mutations likely affecting immune responses in mice by using a machine-learning algorithm to evaluate about 87,000 mutation/trait associations.
The study focused on changes in cells related to immunity, such as B cells, T cells, macrophages, and natural killer cells. Using CE, the researchers identified 2,336 mutations in 1,279 genes as good or excellent candidates for causation of traits. Notably, Bruce Beutler has already verified many of these candidates.
The work received support from the National Institutes of Health (grants R01 AI125581 and U19 AI100627). In addition to UT Southwestern researchers, scientists from Japan and China also contributed to the study. All mutations and data supporting causation are made available to the scientific community through a public repository, Mutagenetix, and the Candidate Explorer program on the CGHD website.
Bruce Beutler, who holds the Raymond and Ellen Willie Distinguished Chair in Cancer Research, won the 2011 Nobel Prize in Physiology or Medicine for his discovery of an important family of receptors that allow mammals to quickly sense infection and trigger an inflammatory response. This latest study further solidifies his position as a leading figure in the field of immunology.
Stephen Lyon, Chun Hui Bu, Sara Hildebrand, and many others from UT Southwestern are co-authors on the study. CE provides a score that tells the likelihood that a particular mutation-phenotype association will be verified for cause and effect if the mutation is re-created or the gene is knocked out. This tool could prove invaluable in the ongoing quest to understand the complexities of the immune system and develop new treatments for immune-related diseases.
