PreprintCited by 86Machine Learning in BioinformaticsProtein Structure and DynamicsBioinformatics and Genomic Networks

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Democratizing Protein Language Models with Parameter-Efficient Fine-Tuning

Open access

Preprint — published as 10.1073/pnas.2405840121 · Paper page

Abstract

Proteomics has been revolutionized by large pre-trained protein language models, which learn unsupervised representations from large corpora of sequences. The parameters of these models are then fine-tuned in a supervised setting to tailor the model to a specific downstream task. However, as model size increases, the computational and memory footprint of fine-tuning becomes a barrier for many research groups. In the field of natural language processing, which has seen a similar explosion in the size of models, these challenges have been addressed by methods for parameter-efficient fine-tuning (PEFT). In this work, we newly bring parameter-efficient fine-tuning methods to proteomics. Using the parameter-efficient method LoRA, we train new models for two important proteomic tasks: predicting protein-protein interactions (PPI) and predicting the symmetry of homooligomers. We show that for homooligomer symmetry prediction, these approaches achieve performance competitive with traditional fine-tuning while requiring reduced memory and using three orders of magnitude fewer parameters. On the PPI prediction task, we surprisingly find that PEFT models actually outperform traditional fine-tuning while using two orders of magnitude fewer parameters. Here, we go even further to show that freezing the parameters of the language model and training only a classification head also outperforms fine-tuning, using five orders of magnitude fewer parameters, and that both of these models outperform state-of-the-art PPI prediction methods with substantially reduced compute. We also demonstrate that PEFT is robust to variations in training hyper-parameters, and elucidate where best practices for PEFT in proteomics differ from in natural language processing. Thus, we provide a blueprint to democratize the power of protein language model tuning to groups which have limited computational resources.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2023.11.09.566187

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 34

  1. Aghajanyan, A. , Zettlemoyer, L. , Gupta, S. : Intrinsic dimensionality explains the effectiveness of language model fine-tuning. arXiv preprint arXiv:2012.13255 (2020) · DOI
  2. 2019, Unified rational protein engineering with sequence-based deep representation learning, Nature Methods, 16, 1315, 10.1038/s41592-019-0598-1 · DOI · Paper page
  3. Avraham, O. , Tsaban, T. , Ben-Aharon, Z. , Tsaban, L. , Schueler-Furman, O. : Protein language models can capture protein quaternary state. bioRxiv pp. 2023–03 (2023) · DOI
  4. 10.1126/science.abj8754 · DOI · Paper page
  5. Bepler, T. , Berger, B. : Learning protein sequence embeddings using information from structure. International Conference on Learning Representations (2019)
  6. 2021, Learning the protein language: Evolution, structure, and function, Cell Systems, 12, 654, 10.1016/j.cels.2021.05.017 · DOI · Paper page
  7. 10.1093/nar/28.1.235 · DOI · Paper page
  8. Bernett, J. , Blumenthal, D.B. , List, M. : Cracking the black box of deep sequence-based protein-protein interaction prediction. bioRxiv pp. 2023–01 (2023) · DOI
  9. 2023, Towards a structurally resolved human protein interaction network, Nature Structural & Molecular Biology, 30, 216, 10.1038/s41594-022-00910-8 · DOI · Paper page
  10. 10.1093/bioinformatics/btz328 · DOI
  11. Chithrananda, S. , Grand, G. , Ramsundar, B. : ChemBERTa: large-scale self-supervised pretraining for molecular property prediction. arXiv preprint arXiv:2010.09885 (2020) · arXiv
  12. Cui, H. , Wang, C. , Maan, H. , Pang, K. , Luo, F. , Wang, B. : scGPT: Towards building a foundation model for single-cell multi-omics using generative ai. bioRxiv pp. 2023–04 (2023) · DOI · Paper page
  13. 2021, ProtTrans: Toward understanding the language of life through self-supervised learning, IEEE transactions on pattern analysis and machine intelligence, 44, 7112
  14. Evans, R. , O’Neill, M. , Pritzel, A. , Antropova, N. , Senior, A. , Green, T. , Žídek, A. , Bates, R. , Blackwell, S. , Yim, J. , et al.: Protein complex prediction with AlphaFold-Multimer. biorxiv pp. 2021–10 (2021) · DOI · Paper page
  15. Fang, Y. , Liang, X. , Zhang, N. , Liu, K. , Huang, R. , Chen, Z. , Fan, X. , Chen, H. : Mol-instructions: A large-scale biomolecular instruction dataset for large language models. arXiv preprint arXiv:2306.08018 (2023) · arXiv
  16. Houlsby, N. , Giurgiu, A. , Jastrzebski, S. , Morrone, B. , De Laroussilhe, Q. , Gesmundo, A. , Attariyan, M. , Gelly, S. : Parameter-efficient transfer learning for NLP. In: International Conference on Machine Learning. pp. 2790–2799. PMLR (2019)
  17. Hu, E.J. , Shen, Y. , Wallis, P. , Allen-Zhu, Z. , Li, Y. , Wang, S. , Wang, L. , Chen, W. : LoRA: Low-rank adaptation of large language models. arXiv preprint arXiv:2106.09685 (2021) · arXiv
  18. 2006, 3DComplex: a structural classification of protein complexes, PLoS Computational Biology, 2, e155, 10.1371/journal.pcbi.0020155 · DOI
  19. 10.1126/science.ade2574 · DOI · Paper page
  20. 10.1038/s41586-020-2188-x · DOI · Paper page
  21. Nijkamp, E. , Ruffolo, J.A. , Weinstein, E.N. , Naik, N. , Madani, A. : Progen2: exploring the boundaries of protein language models. Cell Systems (2022) · DOI · Paper page
  22. 2012, Flaws in evaluation schemes for pair-input computational predictions, Nature Methods, 9, 1134, 10.1038/nmeth.2259 · DOI
  23. 10.1073/pnas.2016239118 · DOI · Paper page
  24. Ross, J. , Belgodere, B. , Chenthamarakshan, V. , Padhi, I. , Mroueh, Y. , Das, P. : Large-scale chemical language representations capture molecular structure and properties. arXiv preprint arXiv:2106.09553 (2021) · DOI
  25. Schweke, H. , Levin, T. , Pacesa, M. , Goverde, C.A. , Kumar, P. , Duhoo, Y. , Dornfeld, L.J. , Dubreuil, B. , Georgeon, S. , Ovchinnikov, S. , et al.: An atlas of protein homo-oligomerization across domains of life. bioRxiv pp. 2023–06 (2023) · DOI · Paper page
  26. 10.1093/bioinformatics/btac258 · DOI
  27. Singhal, K. , Azizi, S. , Tu, T. , Mahdavi, S.S. , Wei, J. , Chung, H.W. , Scales, N. , Tanwani, A. , Cole-Lewis, H. , Pfohl, S. , et al.: Large language models encode clinical knowledge. Nature pp. 1–9 (2023)
  28. Sivarajkumar, S. , Kelley, M. , Samolyk-Mazzanti, A. , Visweswaran, S. , Wang, Y. : An empirical evaluation of prompting strategies for large language models in zero-shot clinical natural language processing. arXiv preprint arXiv:2309.08008 (2023) · DOI
  29. Sledzieski, S. , Devkota, K. , Singh, R. , Cowen, L. , Berger, B. : TT3D: Leveraging pre-computed protein 3D sequence models to predict protein-protein interactions. Bioinformatics p. btad663 (2023) · DOI
  30. 2021, D-SCRIPT translates genome to phenome with sequence-based, structure-aware, genome-scale predictions of protein-protein interactions, Cell Systems, 12, 969, 10.1016/j.cels.2021.08.010 · DOI
  31. 10.1038/nbt.3988 · DOI · Paper page
  32. 10.1093/bioinformatics/btac429 · DOI · Paper page
  33. Wu, R. , Ding, F. , Wang, R. , Shen, R. , Zhang, X. , Luo, S. , Su, C. , Wu, Z. , Xie, Q. , Berger, B. , et al.: High-resolution de novo structure prediction from primary sequence. bioRxiv pp. 2022–07 (2022) · DOI · Paper page
  34. 2023, Evaluation of AlphaFold-Multimer prediction on multi-chain protein complexes, Bioinformatics, 39, btad424, 10.1093/bioinformatics/btad424 · DOI · Paper page

Metadata

Authors
Sledzieski, S., Kshirsagar, M., Baek, M., Berger, B., Dodhia, R., & Ferres, J. L.
Affiliations
  • Microsoft (United States) (US)
  • Seoul National University (KR)
  • MIT Computer Science and Artificial Intelligence Laboratory (US)
Corresponding author
  • Berger, Bonnie
  • Ferres, Juan Lavista
Venue
Proceedings of the National Academy of Sciences
Publisher
openRxiv
Published
2023-11-10
Volume
121
Issue
26
Pages
e2405840121-e2405840121
ISSN
0027-8424 (ISSN-L)
OpenAlex
W4399849668
Cited by
86
References
1
Citations by year
2026: 35 · 2025: 41 · 2024: 10
FWCI
11.71
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • National Science Foundation (2141064)
  • Microsoft
  • National Institutes of Health
  • National Institute of General Medical Sciences (R35GM141861)
  • National Science Foundation Graduate Research Fellowship Program (2141064)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
protein language models, parameter-efficient fine-tuning, LoRa, protein-protein interaction prediction, computational resource constraints, hyperparameter robustness, protein sequence representation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review