arXiv Machine Learning
Aug 27

Interpreting Protein Language Model Embeddings via Orthogonal Projection for Protein Fitness Prediction

The paper introduces a method that uses orthogonal projection to remove the influence of known biochemical features from protein language model (PLM) embeddings, allowing the authors to assess how much these features contribute to protein fitness predictions. By applying this technique to high‑order and interaction effects, they demonstrate that eliminating these interpretable features reduces downstream classifier performance, indicating that PLM embeddings encode patterns correlated with biochemical properties. The authors also show that these biochemical features explain a substantial portion of the variance in the classifier’s predictions, suggesting that PLM embeddings capture biologically relevant information.

By Paulo Yanez Sarmiento, Pia Francesca Rissom, Manuel Pfeuffer, Marco Simnacher, Jordan F. Safer, Sumaiya Iqbal, Henrike O. Heyne, Nadja Klein, Bernhard Y. Renard
arXiv AI
Sep 7

ProtLingo: Efficient Protein Language Modeling via Conditional Memory and Expert Routing

ProtLingo is a protein language modeling framework that enhances a pretrained single‑sequence Transformer backbone with conditional local memory and sparse expert routing. It maps residue representations into discrete codes, composes local windows into latent N‑gram addresses, and retrieves reusable residual signals for recurring sequence contexts. The model also converts selected feed‑forward blocks into sparse Mixture‑of‑Experts layers, allowing residue‑dependent computation while activating only a subset of parameters, achieving competitive performance on protein fitness prediction, FLIP benchmarks, and supervised contact prediction with a 150M‑parameter backbone.

By Mingrui Li, Sixian Shen, Minzhang Li, Ruiyi Zhang, Kexin Zhang, Jiakai Zhang, Jingyi Yu