A Bayesian framework for high-throughput T cell receptor pairing

Abstract

Motivation: The study of T cell receptor (TCR) repertoires has generated new insights into immune system recognition. However, the ability to robustly characterize these populations has been limited by technical barriers and an inability to reliably infer heterodimeric chain pairings for TCRs. Results: Here, we describe a novel analytical approach to an emerging immune repertoire sequencing method, improving the resolving power of this low-cost technology. This method relies upon the distribution of a T cell population across a 96-well plate, followed by barcoding and sequencing of the relevant transcripts from each T cell. Multicell Analytical Deconvolution for High Yield Paired-chain Evaluation (MAD-HYPE) uses Bayesian inference to more accurately extract TCR information, improving our ability to study and characterize T cell populations for immunology and immunotherapy applications. Availability and implementation: The MAD-HYPE algorithm is released as an open-source project under the Apache License and is available from https://github.com/birnbaumlab/MAD-HYPE.