Deep generative selection models of T and B cell receptor repertoires with soNNia

Isacchini, Giulio; Walczak, Aleksandra M.; Mora, Thierry; Nourmohammad, Armita

Subclasses of lymphocytes carry different functional roles to work together and produce an immune response and lasting immunity. Additionally to these functional roles, T and B cell lymphocytes rely on the diversity of their receptor chains to recognize different pathogens. The lymphocyte subclasses emerge from common ancestors generated with the same diversity of receptors during selection processes. Here, we leverage biophysical models of receptor generation with machine learning models of selection to identify specific sequence features characteristic of functional lymphocyte repertoires and subrepertoires. Specifically, using only repertoire-level sequence information, we classify CD4(+) and CD8(+) T cells, find correlations between receptor chains arising during selection, and identify T cell subsets that are targets of pathogenic epitopes. We also show examples of when simple linear classifiers do as well as more complex machine learning methods.