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Masked language modeling (MLM) is the standard objective for training protein language models, typically implemented by randomly masking individual residues at a fixed rate (e.g., 15%). This practice implicitly assumes that all sequence…

Machine Learning · Computer Science 2026-05-19 Thomas Walton , Ayan Goel , Amirali Aghazadeh

We introduce Concept Bottleneck Protein Language Models (CB-pLM), a generative masked language model with a layer where each neuron corresponds to an interpretable concept. Our architecture offers three key benefits: i) Control: We can…

A plethora of protein language models have been released in recent years. Yet comparatively little work has addressed how to best sample from them to optimize desired biological properties. We fill this gap by proposing a flexible,…

Machine Learning · Computer Science 2026-05-08 Calvin McCarter , Nick Bhattacharya , Sebastian W. Ober , Hunter Elliott

Deciphering the function of unseen protein sequences is a fundamental challenge with broad scientific impact, yet most existing methods depend on task-specific adapters or large-scale supervised fine-tuning. We introduce the…

Machine Learning · Computer Science 2025-10-14 Xinhui Chen , Zuchao Li , Mengqi Gao , Yufeng Zhang , Chak Tou Leong , Haoyang Li , Jiaqi Chen

Predicting the biophysical and functional properties of proteins is essential for in silico protein design. Machine learning has emerged as a promising technique for such prediction tasks. However, the relative scarcity of in vitro…

Machine Learning · Computer Science 2025-07-17 Jacob Beck , Shikha Surana , Manus McAuliffe , Oliver Bent , Thomas D. Barrett , Juan Jose Garau Luis , Paul Duckworth

Language Models (LMs) excel in understanding textual descriptions of proteins, as evident in biomedical question-answering tasks. However, their capability falters with raw protein data, such as amino acid sequences, due to a deficit in…

Quantitative Methods · Quantitative Biology 2024-05-22 Zhiyuan Liu , An Zhang , Hao Fei , Enzhi Zhang , Xiang Wang , Kenji Kawaguchi , Tat-Seng Chua

Performance prediction is a method to estimate the performance of Language Models (LMs) on various Natural Language Processing (NLP) tasks, mitigating computational costs associated with model capacity and data for fine-tuning. Our paper…

Computation and Language · Computer Science 2024-12-17 David Anugraha , Genta Indra Winata , Chenyue Li , Patrick Amadeus Irawan , En-Shiun Annie Lee

In contrast to their remarkable performance on general knowledge QA, the true abilities of Large Language Models (LLMs) in tasks demanding deep, specialized reasoning, such as in protein biology, have yet to be thoroughly investigated.…

Quantitative Methods · Quantitative Biology 2025-12-30 Dingyi Rong , Zijian Chen , Qi Jia , Kaiwei Zhang , Haotian Lu , Guangtao Zhai , Ning Liu

How can we extend a pre-trained model to many language understanding tasks, without labeled or additional unlabeled data? Pre-trained language models (PLMs) have been effective for a wide range of NLP tasks. However, existing approaches…

Computation and Language · Computer Science 2023-05-29 Xuandong Zhao , Siqi Ouyang , Zhiguo Yu , Ming Wu , Lei Li

There is considerable interest in predicting the pathogenicity of protein variants in human genes. Due to the sparsity of high quality labels, recent approaches turn to \textit{unsupervised} learning, using Multiple Sequence Alignments…

Machine Learning · Computer Science 2022-12-09 Allan Zhou , Nicholas C. Landolfi , Daniel C. O'Neill

Large-scale Protein Language Models (PLMs) have improved performance in protein prediction tasks, ranging from 3D structure prediction to various function predictions. In particular, AlphaFold, a ground-breaking AI system, could potentially…

Quantitative Methods · Quantitative Biology 2022-10-18 Mingyang Hu , Fajie Yuan , Kevin K. Yang , Fusong Ju , Jin Su , Hui Wang , Fei Yang , Qiuyang Ding

Molecular generative models, often employing GPT-style language modeling on molecular string representations, have shown promising capabilities when scaled to large datasets and model sizes. However, it remains unclear and subject to debate…

Machine Learning · Computer Science 2026-02-02 Dong Xu , Qihua Pan , Sisi Yuan , Jianqiang Li , Zexuan Zhu , Junkai Ji

Protein language models (PLMs) have shown promise in improving the understanding of protein sequences, contributing to advances in areas such as function prediction and protein engineering. However, training these models from scratch…

Machine Learning · Computer Science 2024-12-19 Shivasankaran Vanaja Pandi , Bharath Ramsundar

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…

Pre-trained multilingual language models such as mBERT have shown immense gains for several natural language processing (NLP) tasks, especially in the zero-shot cross-lingual setting. Most, if not all, of these pre-trained models rely on…

Computation and Language · Computer Science 2020-10-26 Aditi Chaudhary , Karthik Raman , Krishna Srinivasan , Jiecao Chen

Rapid identification of candidate materials with target properties has become a key task in materials science. Machine learning has emerged as an alternative to physics-based simulation, offering a faster and cheaper way to filter materials…

Artificial Intelligence · Computer Science 2026-05-19 Claire Schlesinger , Circe Hsu , Peter Schindler , Robin Walters

Protein Language Models (PLMs) have emerged as performant and scalable tools for predicting the functional impact and clinical significance of protein-coding variants, but they still lag experimental accuracy. Here, we present a novel…

Genes, proteins and other biological entities influence one another via causal molecular networks. Causal relationships in such networks are mediated by complex and diverse mechanisms, through latent variables, and are often specific to…

Machine Learning · Computer Science 2025-03-07 Izzy Newsham , Luka Kovačević , Richard Moulange , Nan Rosemary Ke , Sach Mukherjee

Understanding the relationships between protein sequence, structure and function is a long-standing biological challenge with manifold implications from drug design to our understanding of evolution. Recently, protein language models have…

Quantitative Methods · Quantitative Biology 2024-01-29 Dexiong Chen , Philip Hartout , Paolo Pellizzoni , Carlos Oliver , Karsten Borgwardt

Generative modeling for protein engineering is key to solving fundamental problems in synthetic biology, medicine, and material science. We pose protein engineering as an unsupervised sequence generation problem in order to leverage the…