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ProteinJEPA: Latent prediction complements protein language models

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Protein language models are trained primarily with masked language modeling (MLM), which predicts amino-acid identities at masked positions. We ask whether latent-space prediction can complement these token-level objectives under matched wall-clock budget. Across pretrained and random-init protein sequence encoders at 35--150M parameters, we find that the best protein-JEPA design is not all-position latent prediction but a variant: predicting latent targets only at masked positions, and retaining the MLM cross-entropy. We call this recipe masked-position MLM+JEPA. On a 16-task downstream suite (15 frozen linear probes plus SCOPe-40 zero-shot fold retrieval), under matched wall-clock budgets, this recipe wins more tasks than it loses against MLM-only continuation: 10 wins / 3 losses / 3 ties (hereafter W/L/T) on pretrained ESM2-35M, 11/2/3 on ESM2-150M while results in pretraining from scratch are mixed (6/8/2). Gains are seen for multiple models on 11 of 16 tasks, including stability, \b{eta}\beta \b{eta}-lactamase fitness, variant effect, intrinsic disorder, remote homology, enzyme classification, and SCOPe-40 fold retrieval. Tasks with more losses than wins are Fluorescence (TAPE) and Peptide-HLA Binding. All-position MLM+JEPA matches MLM-only overall but does not reproduce the masked-position gains. JEPA-only (no MLM) collapses in nearly every experiment. We conclude that JEPA, when combined with MLM, is competitive and can outperform pure MLM in pretraining and continued training, even under matched wall-clock budgets.

Dan Ofer, Dafna Shahaf, Michal Linial• 2026

Related benchmarks

TaskDatasetResultRank
RegressionBeta-lactamase PEER
Spearman Correlation0.81
36
Binary ClassificationNeuropeptide (NeuroPID)
AUC0.985
36
Structural retrievalSCOPe-40
Recall@142.7
34
Disorder PredictionCheZoD
Spearman Correlation0.702
32
Fluorescence predictionTAPE
Spearman Correlation0.636
32
Metal ion binding predictionMetal Ion
ROC-AUC82.4
32
Signal peptide predictionSignalP
ROC AUC0.997
32
Subcellular Localization PredictionSubcellular Localization
ROC AUC0.924
32
Variant Effect PredictionVariant Effect
Spearman Correlation0.856
32
Catalytic Activity PredictionEnzyme
Spearman Correlation0.571
32
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