Poster #86: Mingyao Pan

Antigen-aware TCR embeddings reveal conserved immune patterns for personalized immune monitoring

Mingyao Pan1,2, Jing Hu2, Yizhou Tracy Wang2,3, Yuhao Tan2,3, Hailong Hu2, Ziqi Yang1,2, Julia Fleming1,2, Yuanyuan Pang2, Wang Tong2, Bo Li*2,3 Affiliations 1Department of Bioengineering, School of Engineering, University of Pennsylvania, Philadelphia, PA, USA 2Center for Computational and Genomic Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA. 3Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. *Corresponding author. Email: lib3@chop.edu

T cell receptor (TCR) repertoires are highly individualized, while sampling and technical variation further complicate comparisons across individuals and cohorts. Here, we present TCRmeta, an antigen-aware framework that integrates population-scale repertoire relationships with experimentally defined antigen specificity to establish a shared biological space for repertoire analysis. TCRmeta captured antigen-related relationships and predicted mutation-induced changes in TCR specificity. Despite extensive sequence diversity, TCRmeta revealed a conserved repertoire landscape, enabling construction of a healthy reference for quantifying repertoire dispersal. Across cohorts, aging was associated with conserved V-gene changes and progressive dispersal, with greater dispersal in CMV-positive individuals. Longitudinal analysis showed that repertoires progressively shifted toward the healthy reference landscape during immune recovery following hematopoietic stem cell transplantation or antiretroviral therapy. To directly compare repertoires in TCRmeta space, we developed Energy Shift, a pairwise measure robust to sequencing depth, technical variation, and HLA background while remaining sensitive to biological differences. Together, TCRmeta enables quantitative cross-individual and longitudinal immune monitoring.