Protein language models (PLMs) have transferred the latest advances from natural language processing to computational biology. These models, trained on large corpora of protein sequence data, are widely used to translate amino acid sequences into latent-space embeddings, ready for use in diverse downstream tasks (DTs).
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
The paper introduces Murmur2Vec, a lightweight, alignment‑free embedding that uses k‑mer counts hashed with MurmurHash to create a compact representation for biological sequences. It provides a full theoretical analysis, including bias/variance formulas, a Johnson–Lindenstrauss‑style concentration bound, and an excess‑risk bound that clarifies the trade‑off between hash‑table size and classifier performance. Empirically, Murmur2Vec matches or surpasses a fine‑tuned 650M‑parameter ESM‑2 protein language model across several classification tasks, including SARS‑CoV‑2 spike lineage and HIV‑1 Env subtype identification.
By Sarwan Ali, Taslim Murad, Imdadullah Khan, Safi Faizullah
The paper introduces a scalable method to interpret sparse autoencoder (SAE) features in the ESM-2 protein language model by leveraging geometrically inspired features of the protein α‑carbon backbone. Across 8M layers of ESM-2, a false discovery rate–controlled analysis shows that local geometry is significantly associated with many SAE features, revealing substructure within known biological labels and enabling annotation of unannotated metagenomic proteins. Ablation experiments demonstrate that removing these geometric features shifts ESM-2’s predicted contact maps toward the descriptor, linking mechanistic interpretability with structural biology.
By Siddharth Setlur, Djordje Mihajlovic, Darrick Lee
MT-ProtBERT is a multi‑task extension of ProtBERT designed for classifying intrinsically disordered proteins (IDPs) in low‑data settings. It combines Dynamic Window Masking, a Multi‑Scale 1D Convolutional classifier, and auxiliary biochemistry‑informed objectives to jointly optimize masked language modeling and domain‑specific tasks. In experiments on phosphorylation site prediction and protein compaction prediction, MT‑ProtBERT outperforms the RNN‑based IDP model PARROT across all limited‑data tasks.
By Jian Sun, Kingshuk Ghosh, Lilianna Houston, Mohammad H. Mahoor
arXiv:2603.18908v5 Announce Type: replace
Abstract: Independently trained language models often learn compatible late-stage representations, despite differences in training objectives, architectures,...
By Matt Gorbett, Suman Jana
arXiv:2604. 26170v2 Announce Type: replace Abstract: Adapting large language models (LLMs) to a targeted task efficiently and effectively remains a fundamental challenge.
By Ting-Wei Li, Sirui Chen, Jiaru Zou, Yingbing Huang, Tianxin Wei, Jingrui He, Hanghang Tong
arXiv:2512. 15133v3 Announce Type: replace-cross Abstract: Proteins inherently possess a consistent sequence-structure duality.
By Yi Zhou, Haohao Qu, Yunqing Liu, Shanru Lin, Le Song, Wenqi Fan
arXiv:2608. 06111v1 Announce Type: cross Abstract: Positional embeddings (PE) in Transformers encode token distance and order but are largely agnostic to \textit{syntactic structure}.
By Haris Riaz, Hyungji Kim, Mihai Surdeanu
arXiv:2609.37675v1 Announce Type: new
Abstract: Protein Language Models (PLMs) have made remarkable progress following scaling laws established in natural language processing across sequence- and str...
By Biswajit Banerjee, Claudia Alvarez Carreno, Anton S. Petrov
arXiv:2505.10202v2 Announce Type: replace
Abstract: Large Language Models (LLMs) have achieved remarkable success but face significant computational and memory challenges, particularly due to their e...
By Jintian Shao, Hongyi Huang, Jiayi Wu, YiMing Cheng, ZhiYu Wu, You Shan, MingKai Zheng
arXiv:2607. 07984v1 Announce Type: new Abstract: Neural architecture search (NAS) methods have grown increasingly efficient, yet they remain bounded by manually engineered search spaces that require substantial domain expertise and must be rebuilt for every new task.
By Seokhoon Jeong, Mijung Kim, Taehwan Kim