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Codon language embeddings provide strong signals for protein engineering

View ORCID ProfileCarlos Outeiral, View ORCID ProfileCharlotte M. Deane
doi: https://doi.org/10.1101/2022.12.15.519894
Carlos Outeiral
1Department of Statistics, University of Oxford, 24-29 St Giles’, Oxford, OX1 3LB, Oxfordshire, United Kingdom
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  • ORCID record for Carlos Outeiral
  • For correspondence: carlos@outeiral.net deane@stats.ox.ac.uk
Charlotte M. Deane
1Department of Statistics, University of Oxford, 24-29 St Giles’, Oxford, OX1 3LB, Oxfordshire, United Kingdom
2Division of Biologics, Exscientia, Ltd., Oxford Science Park, The Schrödinger Building, Oxford, OX4 4GE, Oxfordshire, United Kingdom
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  • For correspondence: carlos@outeiral.net deane@stats.ox.ac.uk
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Abstract

Protein representations from deep language models have yielded state-of-the-art performance across many tasks in computational protein engineering. In recent years, progress has primarily focused on parameter count, with recent models’ capacities surpassing the size of the very datasets they were trained on. Here, we propose an alternative direction. We show that large language models trained on codons, instead of amino acid sequences, provide high-quality representations that outperform comparable state-of-the-art models across a variety of tasks. In some tasks, like species recognition, prediction of protein and transcript abundance, or melting point estimation, we show that a language model trained on codons outperforms every other published protein language model, including some that contain over 50 times more parameters. These results suggest that, in addition to commonly studied scale and model complexity, the information content of biological data provides an orthogonal direction to improve the power of machine learning in biology.

  • language models
  • protein representations
  • deep learning
  • protein engineering

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 19, 2022.
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Codon language embeddings provide strong signals for protein engineering
Carlos Outeiral, Charlotte M. Deane
bioRxiv 2022.12.15.519894; doi: https://doi.org/10.1101/2022.12.15.519894
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Codon language embeddings provide strong signals for protein engineering
Carlos Outeiral, Charlotte M. Deane
bioRxiv 2022.12.15.519894; doi: https://doi.org/10.1101/2022.12.15.519894

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