Aller directement au contenu principal

Rédiger un PREreview

Protein Language Models Outperform BLAST for Evolutionarily Distant Enzymes: A Systematic Benchmark of EC Number Prediction

Publié
Serveur de preprints
bioRxiv
DOI
10.64898/2026.03.31.715487

Accurate prediction of Enzyme Commission (EC) numbers is foundational to genome annotation, metabolic reconstruction, and enzyme engineering. Protein language models (PLMs) have transformed protein function prediction, yet their systematic evaluation for EC number prediction across architectures, EC hierarchy levels, and sequence identity thresholds is lacking. Here we present a comprehensive benchmark of three PLMs (ESM2-650M, ESM2-3B, ProtT5-XL) combined with nine downstream neural architectures, evaluated across four EC hierarchy levels and four sequence identity thresholds with 1,296 trained models in total. Our results establish that simple MLP classifiers achieve 98.0% accuracy at EC1, 96.9% at EC2, 96.6% at EC3, and 97.0% at EC4, matching or marginally exceeding a train-set-matched BLASTp baseline (±0.7 pp) for in-distribution proteins. Crucially, PLM-based methods dramatically outperform BLAST for evolutionarily distant eukaryotes: gains reach +31.8 pp over a fair 90K-sequence BLAST baseline ( Giardia lamblia ) and +26.4 pp over a full 520K SwissProt database ( Trichomonas vaginalis ). For held-out prokaryotic proteomes, PLMs outperform BLAST by a mean of +16.9 pp at EC4. Our benchmark reveals that (i) MLP architectures are sufficient and consistently superior to CNN/ResNet/Transformer variants, (ii) ESM2-650M is statistically distinguishable from but practically equivalent to the 5× larger ESM2-3B, and (iii) Transformer re-encoding of PLM embeddings fails at a shared learning rate due to convergence instability. All code, models, and benchmark results are available at [ https://github.com/r-mbio/plm_benchmark.git ].

Vous pouvez rédiger un PREreview de Protein Language Models Outperform BLAST for Evolutionarily Distant Enzymes: A Systematic Benchmark of EC Number Prediction. Un PREreview est une évaluation d'un preprint et peut varier de quelques phrases à un rapport détaillé, semblable à un rapport d'évaluation par les pairs organisé par une revue.

Avant de commencer

Nous vous demanderons de vous connecter avec votre identifiant ORCID iD. Si vous n'en avez pas, vous pouvez en créer un.

Qu’est-ce qu’un ORCID iD ?

Un ORCID iD est un identifiant unique qui vous distingue de toute personne ayant le même nom ou nom similaire.

Commencer maintenant