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Democratizing Protein Language Models with Parameter-Efficient Fine-Tuning
Open accessPreprint — 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.
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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
- ORCID
- 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)
- PMC
- PMC11214071
- 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
- hybrid
- doi.org
- 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
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