Project Grant R01AI195878

The National Institute of Allergy and Infectious Diseases, part of the Department of Health and Human Services National Institutes of Health, awarded Trustees of Dartmouth College $717,139 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop a computational platform identifying clinically effective T-cell receptors (TCRs) for infectious diseases based on receptor sequences provided by users.

The platform identifies TCRs putatively capable of recognizing microbial pathogens and activating T cells to contain infections by analyzing TCR sequences, microbiome composition, and HLA genotype information computationally retrieved from publicly available RNA-seq datasets. In Aim 1, the recipient will create a database of TCRs and corresponding T cell subtype information from single-cell RNA-seq data using TRUST4, a method developed by the research team, to assemble TCR sequences without requiring target-amplified TCR-seq data. The database enables users to search for TCRs recognizing the same antigen as a queried TCR using sequence similarity, motif matching, and deep-learning-based embedding space distance, returning cell subsets and states of T cells bearing user-interested TCRs, with antigen-experienced cell types such as memory CD8 T cells suggesting potential immune activation. In Aim 2, the recipient will create a database associating TCRs with their microbial targets by computationally reconstructing TCR repertoire and microbiome composition information from publicly available bulk RNA-seq data, developing methods to examine co-occurrence and abundance correlation between user-queried TCRs and microbe species across collected samples to predict binding targets.

The award period extends from September 1, 2026, through August 31, 2031. Work is performed in Hanover, New Hampshire.