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Transformer models have advanced the state of the art in many Natural Language Processing (NLP) tasks. In this paper, we present a new Transformer architecture, Extended Transformer Construction (ETC), that addresses two key challenges of…

Multimodal protein language models deliver strong performance on mutation-effect prediction, but training such models from scratch demands substantial computational resources. In this paper, we propose a fine-tuning framework called…

Quantitative Methods · Quantitative Biology 2026-02-02 Junde Xu , Yapin Shi , Lijun Lang , Taoyong Cui , Zhiming Zhang , Guangyong Chen , Jiezhong Qiu , Pheng-Ann Heng

Large protein language models are adept at capturing the underlying evolutionary information in primary structures, offering significant practical value for protein engineering. Compared to natural language models, protein amino acid…

Computation and Language · Computer Science 2023-10-27 Yang Tan , Mingchen Li , Pan Tan , Ziyi Zhou , Huiqun Yu , Guisheng Fan , Liang Hong

This paper demonstrates that language models are strong structure-based protein designers. We present LM-Design, a generic approach to reprogramming sequence-based protein language models (pLMs), that have learned massive sequential…

Machine Learning · Computer Science 2023-02-10 Zaixiang Zheng , Yifan Deng , Dongyu Xue , Yi Zhou , Fei YE , Quanquan Gu

Protein language models leverage evolutionary information to perform state-of-the-art 3D structure and zero-shot variant prediction. Yet, extracting and explaining all the mutational interactions that govern model predictions remains…

Biomolecules · Quantitative Biology 2024-05-14 Darin Tsui , Amirali Aghazadeh

Most end-to-end (E2E) speech recognition models are composed of encoder and decoder blocks that perform acoustic and language modeling functions. Pretrained large language models (LLMs) have the potential to improve the performance of E2E…

Audio and Speech Processing · Electrical Eng. & Systems 2023-08-04 Shaoshi Ling , Yuxuan Hu , Shuangbei Qian , Guoli Ye , Yao Qian , Yifan Gong , Ed Lin , Michael Zeng

The 21st century is presenting humankind with unprecedented environmental and medical challenges. The ability to design novel proteins tailored for specific purposes could transform our ability to respond timely to these issues. Recent…

Biomolecules · Quantitative Biology 2022-08-24 Noelia Ferruz , Birte Höcker

Protein language models (PLMs) have demonstrated remarkable success in protein modeling and design, yet their internal mechanisms for predicting structure and function remain poorly understood. Here we present a systematic approach to…

Biomolecules · Quantitative Biology 2024-12-18 Elana Simon , James Zou

Protein is linked to almost every life process. Therefore, analyzing the biological structure and property of protein sequences is critical to the exploration of life, as well as disease detection and drug discovery. Traditional protein…

Machine Learning · Computer Science 2021-12-08 Yijia Xiao , Jiezhong Qiu , Ziang Li , Chang-Yu Hsieh , Jie Tang

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

Deep neural-network-based language models (LMs) are increasingly applied to large-scale protein sequence data to predict protein function. However, being largely black-box models and thus challenging to interpret, current protein LM…

Quantitative Methods · Quantitative Biology 2024-08-06 Mai Ha Vu , Rahmad Akbar , Philippe A. Robert , Bartlomiej Swiatczak , Victor Greiff , Geir Kjetil Sandve , Dag Trygve Truslew Haug

With the exponential increase of the protein sequence databases over time, multiple-sequence alignment (MSA) methods, like PSI-BLAST, perform exhaustive and time-consuming database search to retrieve evolutionary information. The resulting…

Quantitative Methods · Quantitative Biology 2023-08-21 Issar Arab

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

Energy-based language models (ELMs) parameterize an unnormalized distribution for natural sentences and are radically different from popular autoregressive language models (ALMs). As an important application, ELMs have been successfully…

Computation and Language · Computer Science 2023-05-30 Hong Liu , Zhaobiao Lv , Zhijian Ou , Wenbo Zhao , Qing Xiao

Language models for biological and chemical sequences enable crucial applications such as drug discovery, protein engineering, and precision medicine. Currently, these language models are predominantly based on Transformer architectures.…

Large language models (LLMs) face the challenges in fine-tuning and deployment due to their high memory demands and computational costs. While parameter-efficient fine-tuning (PEFT) methods aim to reduce the memory usage of the optimizer…

Machine Learning · Computer Science 2023-10-31 Jeonghoon Kim , Jung Hyun Lee , Sungdong Kim , Joonsuk Park , Kang Min Yoo , Se Jung Kwon , Dongsoo Lee

Processing long contexts is increasingly important for Large Language Models (LLMs) in tasks like multi-turn dialogues, code generation, and document summarization. This paper addresses the challenges of achieving high long-context…

Computation and Language · Computer Science 2026-04-15 Zihan Liao , Jun Wang , Hang Yu , Lingxiao Wei , Jianguo Li , Jun Wang , Wei Zhang

Machine learning and the use of neural networks has increased precipitously over the past few years primarily due to the ever-increasing accessibility to data and the growth of computation power. It has become increasingly easy to harness…

Machine Learning · Computer Science 2020-08-05 Aaron Hein , Casey Cole , Homayoun Valafar

We consider the protein sequence engineering problem, which aims to find protein sequences with high fitness levels, starting from a given wild-type sequence. Directed evolution has been a dominating paradigm in this field which has an…

Machine Learning · Computer Science 2025-01-20 Yinkai Wang , Jiaxing He , Yuanqi Du , Xiaohui Chen , Jianan Canal Li , Li-Ping Liu , Xiaolin Xu , Soha Hassoun

The impact of Transformer-based language models has been unprecedented in Natural Language Processing (NLP). The success of such models has also led to their adoption in other fields including bioinformatics. Taking this into account, this…

Machine Learning · Computer Science 2025-07-21 Nimisha Ghosh , Daniele Santoni , Debaleena Nawn , Eleonora Ottaviani , Giovanni Felici