12. NAIR Software: Advancements in Network Analysis of Immune Repertoire for T Cell Receptor Profiling

T cells are essential to adaptive immune responses, particularly in counteracting tumor immunity. This abstract presents an updated version of the Network Analysis of Immune Repertoire (NAIR) software for comprehensive T cell receptor (TCR) sequence analysis. Our enhanced NAIR software constructed network within TCR repertoire based on TCR sequence similarity, enabled by tailored search algorithms. These algorithms effectively identify disease-associated TCR clusters and public TCR clusters shared across multiple samples, facilitating the discovery of potential disease-specific TCR signatures. The other feature of the NAIR software is the ability of quantification of the TCR network by network properties. To manage the complexity of network properties and their correlation with clinical outcomes, we employ group lasso regularization. This novel approach highlights network properties significantly associated with clinical outcomes, thus identifying crucial TCR features.The updated NAIR software can now process single-cell TCR sequencing data. In addition, we've broadened the pipeline to incorporate TCR sequences with single-cell gene expression data, using a Graph deep learning model. This allows for a detailed analysis of TCR diversity and gene expression profiles at a single-cell level, providing deeper insights into T cell functionality. The updated software also introduces an innovative technique to predict the binding peptides by integrating of TCR sequence vectorization, TCR sequence similarity networks, and V/J gene in a deep learning framework. It is refined and validated on TCR dataset that given binding antigen. By merging network analysis, advanced statistical methods, and deep learning, this enhanced NAIR software provides a powerful platform for TCR repertoire data analysis. This tool helps unravel the complex relationship between TCR, disease progression, and clinical outcomes, fostering improved understanding of immune system dynamics and paving the way for immunotherapy and precision medicine advancements.

T cell receptor

network analysis

group lasso

single-cell sequencing

cancer immunotherapy

deep learning