Fig. 2. MODIFY achieves accurate and robust zero-shot protein fitness prediction.

The ensemble ML model of MODIFY was compared with five state-of-the-art unsupervised protein fitness predictors (ESM-1v, ESM-2, EVmutation, EVE, and MSA Transformer) for zero-shot protein fitness predictions. a Comparison on the ProteinGym benchmark, which contains 87 Deep Mutational Scanning (DMS) assays across diverse protein families, using Spearman correlation as the evaluation metric. b The counts of each method achieving the best performance (including ties) on the 87 DMS datasets. c The average performances of all methods on proteins with low, medium, and high MSA depths.