Scientists at UT Southwestern are making significant strides towards creating a comprehensive map of the mammalian immune system.
Uncovering Novel Genes Crucial for Immunity: A Groundbreaking Study
In a significant stride forward in immunology, a team led by Bruce Beutler, M.D., director of the Center for the Genetics of Host Defense (CGHD) at the University of Texas Southwestern (UTSW), has identified 101 promising gene candidates likely to be vital for immunity.
The study, published in the Proceedings of the National Academy of Sciences, employs a software tool called Candidate Explorer (CE), developed by lead author Darui Xu, a computational biologist at CGHD. CE uses a machine-learning algorithm to pinpoint chemically induced mutations probably linked to immune-related traits.
The mouse and human genomes share a remarkable similarity, with almost all mouse genes having a human counterpart. Leveraging this, the team used CE to analyze around 87,000 mutation/trait associations, identifying 2,336 mutations in 1,279 genes as potential candidates for trait causation.
CE assigns a score indicating the likelihood that a particular mutation-phenotype association will be confirmed as causal if the mutation is recreated or the gene is knocked out. Over time, the program 'learns' from experiments verifying or excluding causal hypotheses.
The study focused on cellular changes related to immunity, including B cells, T cells, macrophages, and natural killer cells. The majority of identified genes also play a role in human immunity.
The research team included scientists from UTSW, Japan, and China. Key UTSW contributors were Dr. Cheng Cheng 'Alec' Zhang, Professor of Physiology, and Dr. Xing Yang, a postdoctoral researcher in the Zhang Lab.
The work was supported by the National Institutes of Health (grants R01 AI125581 and U19 AI100627). Beutler holds the Raymond and Ellen Willie Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie, Sr.
All mutations are openly accessible to the scientific community via a public repository, and causation data can be viewed within the Candidate Explorer tool on the CGHD website, Mutagenetix. This open-access approach fosters further research and collaboration in the field.
