Researchers at UT Southwestern are nearing completion of a spatial layout for the mammalian immune system.
In a groundbreaking study, a team led by Dr. Bruce Beutler, Regental Professor and professor of immunology and internal medicine at UT Southwestern, has identified 101 novel gene candidates with a high likelihood of being essential for immunity. The research, published in the Proceedings of the National Academy of Sciences, is part of a larger research program aimed at identifying every mutation that may affect the mouse animal cell system.
Dr. Beutler, who 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, directed the study. The current research focused on changes in cells known to be tied to immunity, specifically B cells, T cells, macrophages, and natural killer cells.
A key tool in this study was Candidate Explorer (CE), a software written by Darui Xu, a computational biologist at CGHD. CE uses a machine-learning algorithm to identify chemically induced mutations likely to cause traits related to immunity. Over time, CE learns from experiments in which researchers re-create the mutation and verify or exclude the hypothesis of causation. The software 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.
The team used CE to evaluate approximately 87,000 mutation/trait associations and identified 2,336 mutations in 1,279 genes as good or excellent candidates for causation of traits. All these mutations are now available to the scientific community through a public repository, and the data supporting causation are viewable within the Candidate Explorer program on the CGHD website, Mutagenetix.
This joint study with UT Southwestern investigators pursuing the identification of gene mutations related to the immune system in mice also included researchers from Japan and China. The work received support from the National Institutes of Health (grants R01 AI125581 and U19 AI100627).
Dr. Beutler, who also holds the Raymond and Ellen Willie Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie, Sr., expressed his satisfaction with the findings, stating, "This research provides a valuable resource for the scientific community, helping us to better understand the complexities of the immune system and potentially leading to new treatments for immune-related diseases."
