Determining epitope specificity of T cell receptors with TCRGP

Abstract

T cell receptors (TCRs) can recognize various pathogens and consequently start immune responses. TCRs can be sequenced from individuals and methods analyzing the specificity of the TCRs can help us better understand individuals’ immune status in different diseases. We have developed TCRGP, a novel Gaussian process method to predict if TCRs recognize certain epitopes. This method can utilize CDR sequences from TCRα and TCRβ chains and learn which CDRs are important in recognizing different epitopes. We have experimented with with epitope-specific data against 29 epitopes and performed a comprehensive evaluation with existing prediction methods. On this data, TCRGP outperforms other state-of-the-art methods in epitope-specificity predictions. We also propose a novel analysis approach for combined single-cell RNA and TCRαβ (scRNA+TCRαβ) sequencing data by quantifying epitope-specific TCRs with TCRGP in phenotypes identified from scRNA-seq data. With this approach, we find HBV-epitope specific T cells and their transcriptomic states in hepatocellular carcinoma patients.