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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

Protein language models (pLMs) produce per-residue representations that capture evolutionary and structural information, yet their mean-pooled sequence embeddings are not explicitly trained to reflect functional, evolutionary or structural…

Machine Learning · Computer Science 2026-05-11 Dan Ofer , Oriel Perets , Michal Linial , Nadav Rappoport

Protein language models (pLMs) have recently gained significant attention for their ability to uncover relationships between sequence, structure, and function from evolutionary statistics, thereby accelerating therapeutic drug discovery.…

Machine Learning · Computer Science 2026-03-04 Darshan Patil , Pranshu Malviya , Mathieu Reymond , Quentin Fournier , Sarath Chandar

Protein language models (PLMs) have emerged as powerful tools to detect complex patterns of protein sequences. However, the capability of PLMs to fully capture information on protein sequences might be limited by focusing on single…

Machine Learning · Computer Science 2025-05-27 Hazem Alsamkary , Mohamed Elshaffei , Mohamed Elkerdawy , Ahmed Elnaggar

Protein language models have shown remarkable success in learning biological information from protein sequences. However, most existing models are limited by either autoencoding or autoregressive pre-training objectives, which makes them…

Quantitative Methods · Quantitative Biology 2024-12-10 Bo Chen , Xingyi Cheng , Pan Li , Yangli-ao Geng , Jing Gong , Shen Li , Zhilei Bei , Xu Tan , Boyan Wang , Xin Zeng , Chiming Liu , Aohan Zeng , Yuxiao Dong , Jie Tang , Le Song

Large Language Models (LLMs) stand at the forefront of a number of Natural Language Processing (NLP) tasks. Despite the widespread adoption of LLMs in NLP, much of their potential in broader fields remains largely unexplored, and…

Machine Learning · Computer Science 2024-03-11 Zhiqiang Zhong , Kuangyu Zhou , Davide Mottin

Several machine learning methods aim to learn or reason about complex physical systems. A common first-step towards reasoning is to infer system parameters from observations of its behavior. In this paper, we investigate the performance of…

Computation and Language · Computer Science 2024-02-07 Sean Memery , Mirella Lapata , Kartic Subr

Pre-trained LLMs have demonstrated substantial capabilities across a range of conventional natural language processing (NLP) tasks, such as summarization and entity recognition. In this paper, we explore the application of LLMs in the…

Quantitative Methods · Quantitative Biology 2024-08-14 Kamyar Zeinalipour , Neda Jamshidi , Monica Bianchini , Marco Maggini , Marco Gori

Instruction-tuned Large Language Models (LLMs) can perform a wide range of tasks given natural language instructions to do so, but they are sensitive to how such instructions are phrased. This issue is especially concerning in healthcare,…

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) encode rich biological information, yet their internal neuron representations are poorly understood. We introduce the first automated framework for labeling every neuron in a PLM with biologically grounded…

Machine Learning · Computer Science 2025-07-10 Arjun Banerjee , David Martinez , Camille Dang , Ethan Tam

Attention-based models trained on protein sequences have demonstrated incredible success at classification and generation tasks relevant for artificial intelligence-driven protein design. However, we lack a sufficient understanding of how…

Machine Learning · Computer Science 2022-06-29 Erik Nijkamp , Jeffrey Ruffolo , Eli N. Weinstein , Nikhil Naik , Ali Madani

Antibodies are vital proteins offering robust protection for the human body from pathogens. The development of general protein and antibody-specific pre-trained language models both facilitate antibody prediction tasks. However, there have…

Computation and Language · Computer Science 2023-03-03 Danqing Wang , Fei Ye , Hao Zhou

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

Despite being self-supervised, protein language models have shown remarkable performance in fundamental biological tasks such as predicting impact of genetic variation on protein structure and function. The effectiveness of these models on…

Machine Learning · Computer Science 2022-11-21 Onuralp Soylemez , Pablo Cordero

Current protein language models (PLMs) learn protein representations mainly based on their sequences, thereby well capturing co-evolutionary information, but they are unable to explicitly acquire protein functions, which is the end goal of…

Biomolecules · Quantitative Biology 2023-07-06 Minghao Xu , Xinyu Yuan , Santiago Miret , Jian Tang

Recent developments in Natural Language Processing (NLP) demonstrate that large-scale, self-supervised pre-training can be extremely beneficial for downstream tasks. These ideas have been adapted to other domains, including the analysis of…

Computation and Language · Computer Science 2021-02-02 Matthew B. A. McDermott , Brendan Yap , Harry Hsu , Di Jin , Peter Szolovits

Pre-trained language models (PLMs) have been the de facto paradigm for most natural language processing (NLP) tasks. This also benefits biomedical domain: researchers from informatics, medicine, and computer science (CS) communities propose…

Computation and Language · Computer Science 2023-07-18 Benyou Wang , Qianqian Xie , Jiahuan Pei , Zhihong Chen , Prayag Tiwari , Zhao Li , Jie fu

Language is essentially a complex, intricate system of human expressions governed by grammatical rules. It poses a significant challenge to develop capable AI algorithms for comprehending and grasping a language. As a major approach,…

Large language models (LLMs) have been applied to tasks in healthcare, ranging from medical exam questions to responding to patient questions. With increasing institutional partnerships between companies producing LLMs and healthcare…

Computation and Language · Computer Science 2024-04-10 Jesutofunmi A. Omiye , Haiwen Gui , Shawheen J. Rezaei , James Zou , Roxana Daneshjou