Back to all publications...

Tranception: protein fitness prediction with autoregressive transformers and inference-time retrieval

The ability to accurately model the fitness landscape of protein sequences is critical to a wide range of applications, from quantifying the effects of human variants on disease likelihood, to predicting immune-escape mutations in viruses and designing novel biotherapeutic proteins. Deep generative models of protein sequences trained on multiple sequence alignments have been the most successful approaches so far to address these tasks. The performance of these methods is however contingent on the availability of sufficiently deep and diverse alignments for reliable training. Their potential scope is thus limited by the fact many protein families are hard, if not impossible, to align. Large language models trained on massive quantities of non-aligned protein sequences from diverse families address these problems and show potential to eventually bridge the performance gap. We introduce Tranception, a novel transformer architecture leveraging autoregressive predictions and retrieval of homologous sequences at inference to achieve state-of-the-art fitness prediction performance. Given its markedly higher performance on multiple mutants, robustness to shallow alignments and ability to score indels, our approach offers significant gain of scope over existing approaches. To enable more rigorous model testing across a broader range of protein families, we develop ProteinGym – an extensive set of multiplexed assays of variant effects, substantially increasing both the number and diversity of assays compared to existing benchmarks.

Pascal Notin, Mafalda Dias, Jonathan Frazer, Javier Marchena-Hurtado, Aidan Gomez, Debora Marks, Yarin Gal
ICML, 2022
[Preprint] [BibTex] [Code]

Are you looking to do a PhD in machine learning? Did you do a PhD in another field and want to do a postdoc in machine learning? Would you like to visit the group?

How to apply


We are located at
Department of Computer Science, University of Oxford
Wolfson Building
Parks Road
Twitter: @OATML_Oxford
Github: OATML