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Lead optimization in drug discovery requires efficiently navigating vast chemical space through iterative cycles to enhance molecular properties while preserving structural similarity to the original lead compound. Despite recent advances,…

Machine Learning · Computer Science 2025-09-29 Ziqing Wang , Yibo Wen , William Pattie , Xiao Luo , Weimin Wu , Jerry Yao-Chieh Hu , Abhishek Pandey , Han Liu , Kaize Ding

Feature-based knowledge distillation has been applied to compress modern recommendation models, usually with projectors that align student (small) recommendation models' dimensions with teacher dimensions. However, existing studies have…

Information Retrieval · Computer Science 2025-01-14 Zhangchi Zhu , Wei Zhang

Aligning large language models to human preferences is inherently multidimensional, yet most pipelines collapse heterogeneous signals into a single optimizeable objective. We seek to answer what it would take to simultaneously align a model…

Machine Learning · Computer Science 2025-10-02 Yiran Shen , Yu Xia , Jonathan Chang , Prithviraj Ammanabrolu

This paper introduces diffusion protein language model (DPLM), a versatile protein language model that demonstrates strong generative and predictive capabilities for protein sequences. We first pre-train scalable DPLMs from…

Machine Learning · Computer Science 2024-10-17 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

Post-training alignment of large language models (LLMs) is a critical challenge, as not all tokens contribute equally to model performance. This paper introduces a selective alignment strategy that prioritizes high-impact tokens within…

Computation and Language · Computer Science 2025-07-11 Zhijin Dong

Preference alignment has become a crucial component in enhancing the performance of Large Language Models (LLMs), yet its impact in Multimodal Large Language Models (MLLMs) remains comparatively underexplored. Similar to language models,…

Computer Vision and Pattern Recognition · Computer Science 2024-07-03 Elmira Amirloo , Jean-Philippe Fauconnier , Christoph Roesmann , Christian Kerl , Rinu Boney , Yusu Qian , Zirui Wang , Afshin Dehghan , Yinfei Yang , Zhe Gan , Peter Grasch

Preference alignment has emerged as an effective strategy to enhance the performance of Multimodal Large Language Models (MLLMs) following supervised fine-tuning. While existing preference alignment methods predominantly target…

Computer Vision and Pattern Recognition · Computer Science 2025-09-08 Zitian Wang , Yue Liao , Kang Rong , Fengyun Rao , Yibo Yang , Si Liu

While knowledge distillation has seen widespread use in pre-training and instruction tuning, its application to aligning language models with human preferences remains underexplored, particularly in the more realistic cross-tokenizer…

Computation and Language · Computer Science 2026-01-21 Truong Nguyen , Phi Van Dat , Ngan Nguyen , Linh Ngo Van , Trung Le , Thanh Hong Nguyen

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

Contrastive learning models have demonstrated impressive abilities to capture semantic similarities by aligning representations in the embedding space. However, their performance can be limited by the quality of the training data and its…

Computer Vision and Pattern Recognition · Computer Science 2025-03-27 Amirabbas Afzali , Borna Khodabandeh , Ali Rasekh , Mahyar JafariNodeh , Sepehr kazemi , Simon Gottschalk

For aligning large language models (LLMs), prior work has leveraged reinforcement learning via human feedback (RLHF) or variations of direct preference optimization (DPO). While DPO offers a simpler framework based on maximum likelihood…

Artificial Intelligence · Computer Science 2025-05-27 Anirudhan Badrinath , Prabhat Agarwal , Jiajing Xu

Multi-objective reinforcement learning (MORL) approaches have emerged to tackle many real-world problems with multiple conflicting objectives by maximizing a joint objective function weighted by a preference vector. These approaches find…

Machine Learning · Computer Science 2023-05-31 Toygun Basaklar , Suat Gumussoy , Umit Y. Ogras

Protein fitness optimization involves finding a protein sequence that maximizes desired quantitative properties in a combinatorially large design space of possible sequences. Recent advances in steering protein generative models (e.g.,…

Biomolecules · Quantitative Biology 2025-10-22 Jason Yang , Wenda Chu , Daniel Khalil , Raul Astudillo , Bruce J. Wittmann , Frances H. Arnold , Yisong Yue

Large language models are often post-trained with sparse verifier rewards, which indicate whether a sampled trajectory succeeds but provide limited guidance about where reasoning succeeds or fails. On-policy distillation (OPD) offers denser…

Machine Learning · Computer Science 2026-05-14 Weichen Yu , Xiaomin Li , Yizhou Zhao , Xiaoze Liu , Ruowang Zhang , Haixin Wang , Yinyi Luo , Chen Henry Wu , Gaurav Mittal , Matt Fredrikson , Yu Hu

Designing protein-binding proteins with high affinity is critical in biomedical research and biotechnology. Despite recent advancements targeting specific proteins, the ability to create high-affinity binders for arbitrary protein targets…

Machine Learning · Computer Science 2025-11-03 Zhenqiao Song , Tiaoxiao Li , Lei Li , Martin Renqiang Min

For protein sequence datasets, unlabeled data has greatly outpaced labeled data due to the high cost of wet-lab characterization. Recent deep-learning approaches to protein prediction have shown that pre-training on unlabeled data can yield…

Machine Learning · Computer Science 2020-12-02 Pascal Sturmfels , Jesse Vig , Ali Madani , Nazneen Fatema Rajani

We introduce ORPO-Distill, a general-purpose method for cross-architecture LLM distillation that formulates the problem as a preference optimization task. Unlike standard CoT distillation, the approach transfers knowledge through diverse…

Machine Learning · Computer Science 2025-09-30 Aasheesh Singh , Vishal Vaddina , Dagnachew Birru

On-policy distillation (OPD) has become a popular training paradigm in the LLM community. This paradigm selects a larger model as the teacher to provide dense, fine-grained signals for each sampled trajectory, in contrast to reinforcement…

Machine Learning · Computer Science 2026-04-09 Chenxu Yang , Chuanyu Qin , Qingyi Si , Minghui Chen , Naibin Gu , Dingyu Yao , Zheng Lin , Weiping Wang , Jiaqi Wang , Nan Duan

Modern Protein Language Models (PLMs) apply transformer-based model architectures from natural language processing to biological sequences, predicting a variety of protein functions and properties. However, protein language has key…

Machine Learning · Computer Science 2026-02-25 Anna Hart , Chi Han , Jeonghwan Kim , Huimin Zhao , Heng Ji

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