The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
ProGen2: Exploring the boundaries of protein language models
Open accessAbstract
Attention-based models trained on protein sequences have demonstrated incredible success at classification and generation tasks relevant for artificial-intelligence-driven protein design. However, we lack a sufficient understanding of how very large-scale models and data play a role in effective protein model development. We introduce a suite of protein language models, named ProGen2, that are scaled up to 6.4B parameters and trained on different sequence datasets drawn from over a billion proteins from genomic, metagenomic, and immune repertoire databases. ProGen2 models show state-of-the-art performance in capturing the distribution of observed evolutionary sequences, generating novel viable sequences, and predicting protein fitness without additional fine-tuning. As large model sizes and raw numbers of protein sequences continue to become more widely accessible, our results suggest that a growing emphasis needs to be placed on the data distribution provided to a protein sequence model. Our models and code are open sourced for widespread adoption in protein engineering. A record of this paper's Transparent Peer Review process is included in the supplemental information.
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.
Integrity signals
Registry
Cites
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Evo also reaches competitive performance with leading protein-specific language models (41, 46–48) (Fig. 2B).”
From Sequence modeling and design from molecular to genome scale with Evo (2024) · cites this paper as [48]
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
Vaswani, A., Shazeer, N., Parmar, N., Uszkoreit, J., Jones, L., Gomez, A. N., Kaiser, L., & Polosukhin, I. (2017) · arXiv · doi:10.48550/arxiv.1706.03762 · Cited by 120,404
Adam: A Method for Stochastic Optimization
Kingma, D. P., & Ba, J. (2014) · arXiv · doi:10.48550/arxiv.1412.6980 · Cited by 98,946
Jakubův, J., Chvalovský, K., Goertzel, Z., et al. (2023) · DROPS (Schloss Dagstuhl – Leibniz Center for Informatics) · doi:10.4230/lipics.itp.2023.19 · Cited by 76,648
Berman, H. M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.235 · Cited by 40,196
Language Models are Few-Shot Learners
Brown, T. B., Mann, B., Ryder, N., Subbiah, M., Kaplan, J., Dhariwal, P., Neelakantan, A., Shyam, P., Sastry, G., Askell, A., et al. (2020) · arXiv · doi:10.48550/arxiv.2005.14165 · Cited by 23,372
Neural Machine Translation by Jointly Learning to Align and Translate
Bahdanau, D., Cho, K., & Bengio, Y. (2014) · arXiv · doi:10.48550/arxiv.1409.0473 · Cited by 16,213
Scaling Laws for Neural Language Models
Kaplan, J., McCandlish, S., Henighan, T., Brown, T. B., Chess, B., Child, R., Gray, S., Radford, A., Wu, J., & Amodei, D. (2020) · arXiv · doi:10.48550/arxiv.2001.08361 · Cited by 9,550
UniProt: a worldwide hub of protein knowledge
The UniProt Consortium (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1049 · Cited by 7,698
Evolutionary-scale prediction of atomic level protein structure with a language model
Lin, Z., Akin, H., Rao, R., Hie, B., Zhu, Z., Lu, W., Smetanin, N., Verkuil, R., Kabeli, O., Shmueli, Y., et al. (2022) · doi:10.1101/2022.07.20.500902 · Cited by 5,990
MMseqs2 enables sensitive protein sequence searching for the analysis of massive data sets
Steinegger, M., & Söding, J. (2017) · Nature Biotechnology · doi:10.1038/nbt.3988 · Cited by 4,840
Cited by
Sorted by citations
Evolutionary-scale prediction of atomic level protein structure with a language model
Lin, Z., Akin, H., Rao, R., Hie, B., Zhu, Z., Lu, W., Smetanin, N., Verkuil, R., Kabeli, O., Shmueli, Y., et al. (2022) · doi:10.1101/2022.07.20.500902 · Cited by 5,990
Simulating 500 million years of evolution with a language model
Hayes, T., Rao, R., Akin, H., Sofroniew, N. J., Oktay, D., Lin, Z., Verkuil, R., Tran, V. Q., Deaton, J., Wiggert, M., et al. (2025) · Science · doi:10.1126/science.ads0018 · Cited by 937
ProtGPT2 is a deep unsupervised language model for protein design
Ferruz, N., Schmidt, S., & Höcker, B. (2022) · Nature Communications · doi:10.1038/s41467-022-32007-7 · Cited by 795
Sequence modeling and design from molecular to genome scale with Evo
Nguyen, E., Poli, M., Durrant, M. G., Kang, B., Katrekar, D., Li, D. B., Bartie, L. J., Thomas, A. W., King, S. H., Brixi, G., et al. (2024) · Science · doi:10.1126/science.ado9336 · Cited by 580
Genome-wide prediction of disease variant effects with a deep protein language model
Brandes, N., Goldman, G., Wang, C. H., Ye, C., & Ntranos, V. (2023) · Nature Genetics · doi:10.1038/s41588-023-01465-0 · Cited by 489
Metadata
- Authors
- Nijkamp, E., Ruffolo, J. A., Weinstein, E. N., Naik, N., & Madani, A.
- Affiliations
- Salesforce (United States) (US)
- Johns Hopkins University (US)
- Columbia University (US)
- Corresponding author
- Madani, Ali
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2023-11
- Volume
- 14
- Issue
- 11
- Pages
- 968-978.e3
- ISSN
- 2405-4712 (ISSN-L)
- OpenAlex
- W4388024559
- Cited by
- 480
- References
- 57
- Citations by year
- 2026: 150 · 2025: 169 · 2024: 112 · 2023: 39
- FWCI
- 42.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 380 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Systems (publishedVersion)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- arXiv (Cornell University) (cc-by)
- 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 › RNA and protein synthesis mechanisms
- Keywords
- protein language models, protein sequence generation, protein fitness prediction, protein design, model scaling, data distribution, immune repertoire, attention-based models
- MeSH terms
- Amino Acid Sequence, Artificial Intelligence, Language, Proteins, Databases, Factual
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
