Can I read Conditional generation of real antigen-specific T cell receptor sequences on EtoBox?

Conditional generation of real antigen-specific T cell receptor sequences by Dhuvarakesh Karthikeyan & Sarah N. Bennett & Amy G. Reynolds & Benjamin G. Vincent & Alex Rubinsteyn is a book available to read on EtoBox.

What is Conditional generation of real antigen-specific T cell receptor sequences about?

Nature Machine Intelligence, doi:10.1038/s42256-025-01096-6Despite recent advances in T cell receptor (TCR) engineering, designing functional TCRs against arbitrary targets remains challenging due to complex rules governing cross-reactivity and limited paired data. Here we present TCR-TRANSLATE, a sequence-to-sequence framework that adapts low-resource machine translation techniques to generate antigen-specifc TCR sequences against unseen epitopes. By evaluating 12 model variants of the BART and T5 model architectures, we identifed key factors afecting performance and utility, revealing discordances between these objectives. Our fagship model, TCRT5, outperforms existing approaches on computational benchmarks, prioritizing functionally relevant sequences at higher ranks. Most signifcantly, we experimentally validated a computationally designed TCR against Wilms’ tumour antigen, a therapeutically relevant target in leukaemia, excluded from our training and validation sets. Although the identifed TCR shows cross-reactivity with pathogen-derived peptides, highlighting limitations in specifcity, our work represents the successful computational design of a functional TCR construct again

Author

Dhuvarakesh Karthikeyan & Sarah N. Bennett & Amy G. Reynolds & Benjamin G. Vincent & Alex Rubinsteyn

Publisher

x

Published

2025

Language

EN