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Predicting protein function from amino acid sequence remains a central challenge in data-scarce (low-$N$) regimes, limiting machine learning-guided protein design when only small amounts of assay-labeled sequence-function data are…

Machine Learning · Computer Science 2025-08-27 Darin Tsui , Kunal Talreja , Amirali Aghazadeh

The rapid advancements in transformer-based language models have revolutionized natural language processing, yet understanding the internal mechanisms of these models remains a significant challenge. This paper explores the application of…

Machine Learning · Computer Science 2025-02-14 Edith Natalia Villegas Garcia , Alessio Ansuini

Sparse autoencoders (SAEs) have recently emerged as a powerful tool for interpreting the internal representations of large language models (LLMs), revealing latent latent features with semantical meaning. This interpretability has also…

Other Quantitative Biology · Quantitative Biology 2025-07-11 Haoxiang Guan , Jiyan He , Jie Zhang

Sparse Autoencoder (SAE) has emerged as a powerful tool for mechanistic interpretability of large language models. Recent works apply SAE to protein language models (PLMs), aiming to extract and analyze biologically meaningful features from…

Quantitative Methods · Quantitative Biology 2026-01-21 Xiangyu Liu , Haodi Lei , Yi Liu , Yang Liu , Wei Hu

While the activations of neurons in deep neural networks usually do not have a simple human-understandable interpretation, sparse autoencoders (SAEs) can be used to transform these activations into a higher-dimensional latent space which…

Machine Learning · Computer Science 2025-08-07 Gonçalo Paulo , Alex Mallen , Caden Juang , Nora Belrose

Intermediate layers of large language models (LLMs) best predict human brain responses to language, one of the most robust findings in computational neurolinguistics, yet why remains mechanistically unexplained. We address this gap by…

Computation and Language · Computer Science 2026-05-25 Dongxin Guo , Jikun Wu , Siu Ming Yiu

Large Language Models (LLMs) have transformed natural language processing, yet their internal mechanisms remain largely opaque. Recently, mechanistic interpretability has attracted significant attention from the research community as a…

Machine Learning · Computer Science 2025-09-24 Dong Shu , Xuansheng Wu , Haiyan Zhao , Daking Rai , Ziyu Yao , Ninghao Liu , Mengnan Du

Protein language models (PLMs) have revolutionised computational biology through their ability to generate powerful sequence representations for diverse prediction tasks. However, their black-box nature limits biological interpretation and…

Biomolecules · Quantitative Biology 2025-04-11 Jan van Eck , Dea Gogishvili , Wilson Silva , Sanne Abeln

Understanding the multilingual mechanisms of large language models (LLMs) provides insight into how they process different languages, yet this remains challenging. Existing studies often focus on individual neurons, but their polysemantic…

Current Large Language Models (LLMs) for understanding proteins primarily treats amino acid sequences as a text modality. Meanwhile, Protein Language Models (PLMs), such as ESM-2, have learned massive sequential evolutionary knowledge from…

Machine Learning · Computer Science 2024-12-17 Nuowei Liu , Changzhi Sun , Tao Ji , Junfeng Tian , Jianxin Tang , Yuanbin Wu , Man Lan

Protein language models have revolutionized structure prediction, but their nonlinear nature obscures how sequence representations inform structure prediction. While sparse autoencoders (SAEs) offer a path to interpretability here by…

Biomolecules · Quantitative Biology 2025-03-13 Nithin Parsan , David J. Yang , John J. Yang

Large language models (LLMs) demonstrate exceptional performance on tasks requiring complex linguistic abilities, such as reference disambiguation and metaphor recognition/generation. Although LLMs possess impressive capabilities, their…

Computation and Language · Computer Science 2025-09-16 Yi Jing , Zijun Yao , Hongzhu Guo , Lingxu Ran , Xiaozhi Wang , Lei Hou , Juanzi Li

Vision foundation models (FMs) achieve state-of-the-art performance in medical imaging. However, they encode information in abstract latent representations that clinicians cannot interrogate or verify. The goal of this study is to…

Computer Vision and Pattern Recognition · Computer Science 2026-03-26 Philipp Wesp , Robbie Holland , Vasiliki Sideri-Lampretsa , Sergios Gatidis

Sparse Autoencoders (SAEs) have emerged as a popular tool for interpreting the hidden states of large language models (LLMs). By learning to reconstruct activations from a sparse bottleneck layer, SAEs discover interpretable features from…

Computer Vision and Pattern Recognition · Computer Science 2025-09-19 Matthew Lyle Olson , Musashi Hinck , Neale Ratzlaff , Changbai Li , Phillip Howard , Vasudev Lal , Shao-Yen Tseng

The parallels between protein sequences and natural language in their sequential structures have inspired the application of large language models (LLMs) to protein understanding. Despite the success of LLMs in NLP, their effectiveness in…

Quantitative Methods · Quantitative Biology 2024-07-09 Yiqing Shen , Zan Chen , Michail Mamalakis , Luhan He , Haiyang Xia , Tianbin Li , Yanzhou Su , Junjun He , Yu Guang Wang

Mechanistic interpretability of large language models (LLMs) aims to uncover the internal processes of information propagation and reasoning. Sparse autoencoders (SAEs) have demonstrated promise in this domain by extracting interpretable…

Machine Learning · Computer Science 2025-05-26 Wei Shi , Sihang Li , Tao Liang , Mingyang Wan , Guojun Ma , Xiang Wang , Xiangnan He

Protein sequences are abundant in repeating segments, both as exact copies and as approximate segments with mutations. These repeats are important for protein structure and function, motivating decades of algorithmic work on repeat…

Machine Learning · Computer Science 2026-05-26 Gal Pomerants , Yaniv Nikankin , Anja Reusch , Tomer Tsaban , Ora Schueler-Furman , Yonatan Belinkov

Protein language models (pLMs) pre-trained on vast protein sequence databases excel at various downstream tasks but often lack the structural knowledge essential for some biological applications. To address this, we introduce a method to…

Large Language Models (LLMs) encode factual knowledge within hidden parametric spaces that are difficult to inspect or control. While Sparse Autoencoders (SAEs) can decompose hidden activations into more fine-grained, interpretable…

Machine Learning · Computer Science 2026-01-14 Minglai Yang , Xinyu Guo , Zhengliang Shi , Jinhe Bi , Steven Bethard , Mihai Surdeanu , Liangming Pan

Fine-tuning Pre-trained protein language models (PLMs) has emerged as a prominent strategy for enhancing downstream prediction tasks, often outperforming traditional supervised learning approaches. As a widely applied powerful technique in…

Computation and Language · Computer Science 2024-04-24 Yang Tan , Mingchen Li , Bingxin Zhou , Bozitao Zhong , Lirong Zheng , Pan Tan , Ziyi Zhou , Huiqun Yu , Guisheng Fan , Liang Hong
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