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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) 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…

Protein sequence design, determined by amino acid sequences, are essential to protein engineering problems in drug discovery. Prior approaches have resorted to evolutionary strategies or Monte-Carlo methods for protein design, but often…

In recent years, there has been a surge in the development of 3D structure-based pre-trained protein models, representing a significant advancement over pre-trained protein language models in various downstream tasks. However, most existing…

Machine Learning · Computer Science 2024-06-04 Jiale Zhao , Wanru Zhuang , Jia Song , Yaqi Li , Shuqi Lu

Protein language models (PLMs) have advanced computational protein science through large-scale pretraining and scalable architectures. In parallel, reinforcement learning (RL) has broadened exploration and enabled precise multi-objective…

Protein Language Models (PLMs), pre-trained on extensive evolutionary data from natural proteins, have emerged as indispensable tools for protein design. While powerful, PLMs often struggle to produce proteins with precisely specified…

Biomolecules · Quantitative Biology 2025-09-15 Long-Kai Huang , Rongyi Zhu , Bing He , Jianhua Yao

Large, pre-trained representation models trained using self-supervised learning have gained popularity in various fields of machine learning because they are able to extract high-quality salient features from input data. As such, they have…

Audio and Speech Processing · Electrical Eng. & Systems 2023-06-16 Hejung Yang , Hong-Goo Kang

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

Bridging the exponentially growing gap between the numbers of unlabeled and labeled protein sequences, several studies adopted semi-supervised learning for protein sequence modeling. In these studies, models were pre-trained with a…

Biomolecules · Quantitative Biology 2021-09-20 Seonwoo Min , Seunghyun Park , Siwon Kim , Hyun-Soo Choi , Byunghan Lee , Sungroh Yoon

Large Language Models (LLMs) have demonstrated exceptional abilities across a broad range of language-related tasks, including generating solutions to complex reasoning problems. An effective technique to enhance LLM performance is…

Computation and Language · Computer Science 2024-12-25 Shuzhang Cai , Twumasi Mensah-Boateng , Xander Kuksov , Jing Yuan , Shaojie Tang

Recent advancements in specialized large-scale architectures for training image and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT4…

Biomolecules · Quantitative Biology 2023-05-04 Sergio Romero-Romero , Sebastian Lindner , Noelia Ferruz

Directed evolution is an iterative laboratory process of designing proteins with improved function by iteratively synthesizing new protein variants and evaluating their desired property with expensive and time-consuming biochemical…

Machine Learning · Computer Science 2025-09-08 Matouš Soldát , Jiří Kléma

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

Representation learning for proteins has primarily focused on the global understanding of protein sequences regardless of their length. However, shorter proteins (known as peptides) take on distinct structures and functions compared to…

Quantitative Methods · Quantitative Biology 2022-11-15 Gil Sadeh , Zichen Wang , Jasleen Grewal , Huzefa Rangwala , Layne Price

We explore optimally training protein language models, an area of significant interest in biological research where guidance on best practices is limited. Most models are trained with extensive compute resources until performance gains…

Machine Learning · Computer Science 2024-11-05 Xingyi Cheng , Bo Chen , Pan Li , Jing Gong , Jie Tang , Le Song

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

State-of-the-art supervised NLP models achieve high accuracy but are also susceptible to failures on inputs from low-data regimes, such as domains that are not represented in training data. As an approximation to collecting ground-truth…

Computation and Language · Computer Science 2023-06-29 Parikshit Bansal , Amit Sharma

Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…

Quantitative Methods · Quantitative Biology 2024-11-04 Liang He , Peiran Jin , Yaosen Min , Shufang Xie , Lijun Wu , Tao Qin , Xiaozhuan Liang , Kaiyuan Gao , Yuliang Jiang , Tie-Yan Liu

Large language models have demonstrated remarkable capabilities across various tasks, primarily attributed to the utilization of diversely sourced data. However, the impact of pretraining data composition on model performance remains poorly…

Machine Learning · Computer Science 2025-01-28 Ce Ge , Zhijian Ma , Daoyuan Chen , Yaliang Li , Bolin Ding

Large language models show great potential in generating and optimizing code. Widely used sampling methods such as Nucleus Sampling increase the diversity of generation but often produce repeated samples for low temperatures and incoherent…

Machine Learning · Computer Science 2024-03-01 Dejan Grubisic , Chris Cummins , Volker Seeker , Hugh Leather