Author name cluster

Ming Qin

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

4 papers

2 author rows

NeurIPS Conference 2024 Conference Paper

DePLM: Denoising Protein Language Models for Property Optimization

Zeyuan Wang
Keyan Ding
Ming Qin
Xiaotong Li
Xiang Zhuang
Yu Zhao
Jianhua Yao
Qiang Zhang

Protein optimization is a fundamental biological task aimed at enhancing theperformance of proteins by modifying their sequences. Computational methodsprimarily rely on evolutionary information (EI) encoded by protein languagemodels (PLMs) to predict fitness landscape for optimization. However, thesemethods suffer from a few limitations. (1) Evolutionary processes involve thesimultaneous consideration of multiple functional properties, often overshadowingthe specific property of interest. (2) Measurements of these properties tend to betailored to experimental conditions, leading to reduced generalizability of trainedmodels to novel proteins. To address these limitations, we introduce DenoisingProtein Language Models (DePLM), a novel approach that refines the evolutionaryinformation embodied in PLMs for improved protein optimization. Specifically, weconceptualize EI as comprising both property-relevant and irrelevant information, with the latter acting as “noise” for the optimization task at hand. Our approachinvolves denoising this EI in PLMs through a diffusion process conducted in therank space of property values, thereby enhancing model generalization and ensuringdataset-agnostic learning. Extensive experimental results have demonstrated thatDePLM not only surpasses the state-of-the-art in mutation effect prediction butalso exhibits strong generalization capabilities for novel proteins.

PDF Details DOI

ICML Conference 2024 Conference Paper

Knowledge-aware Reinforced Language Models for Protein Directed Evolution

Yuhao Wang
Qiang Zhang 0026
Ming Qin
Xiang Zhuang
Xiaotong Li
Zhichen Gong
Zeyuan Wang
Yu Zhao 0009

Directed evolution, a cornerstone of protein optimization, is to harness natural mutational processes to enhance protein functionality. Existing Machine Learning-assisted Directed Evolution (MLDE) methodologies typically rely on data-driven strategies and often overlook the profound domain knowledge in biochemical fields. In this paper, we introduce a novel Knowledge-aware Reinforced Language Model (KnowRLM) for MLDE. An Amino Acid Knowledge Graph (AAKG) is constructed to represent the intricate biochemical relationships among amino acids. We further propose a Protein Language Model (PLM)-based policy network that iteratively samples mutants through preferential random walks on the AAKG using a dynamic sliding window mechanism. The novel mutants are actively sampled to fine-tune a fitness predictor as the reward model, providing feedback to the knowledge-aware policy. Finally, we optimize the whole system in an active learning approach that mimics biological settings in practice. KnowRLM stands out for its ability to utilize contextual amino acid information from knowledge graphs, thus attaining advantages from both statistical patterns of protein sequences and biochemical properties of amino acids. Extensive experiments demonstrate the superior performance of KnowRLM in more efficiently identifying high-fitness mutants compared to existing methods.

Details

ECAI Conference 2023 Conference Paper

Active Finetuning Protein Language Model: A Budget-Friendly Method for Directed Evolution

Ming Qin
Keyan Ding
Bin Wu 0025
Zhenping Li
Haihong Yang
Zeyuan Wang
Hongbin Ye
Haoran Yu

Directed evolution is a widely-used strategy of protein engineering to improve protein function via mimicking natural mutation and selection. Machine learning-assisted directed evolution (MLDE) approaches aim to learn a fitness predictor, thereby efficiently searching for optimal mutants within the vast combinatorial mutation space. Since annotating mutants is both costly and labor-intensive, how to efficiently sample and utilize informative protein mutants to train the predictor is a critical problem in MLDE. Previous MLDE works just simply utilized pre-trained protein language models (PPLMs) for sampling without tailoring to the specific target protein of interest, which has not fully exploited the potential of PPLMs. In this work, we propose a novel method, the Actively-Finetuned Protein language model for Directed Evolution(AFP-DE), which leverages PPLMs to actively sample and fine-tune themselves, continuously improving the model’s sampling and overall performance through iterations, to achieve efficient directed protein evolution. Extensive experiments have shown the effectiveness of our method in generating optimal mutants with minimal annotation effort, outperforming previous works even with fewer annotated mutants, making it budget-friendly for biological experiments.

Details

AAAI Conference 2022 Conference Paper

Molecular Contrastive Learning with Chemical Element Knowledge Graph

Yin Fang
Qiang Zhang
Haihong Yang
Xiang Zhuang
Shumin Deng
Wen Zhang
Ming Qin
Zhuo Chen

Molecular representation learning contributes to multiple downstream tasks such as molecular property prediction and drug design. To properly represent molecules, graph contrastive learning is a promising paradigm as it utilizes selfsupervision signals and has no requirements for human annotations. However, prior works fail to incorporate fundamental domain knowledge into graph semantics and thus ignore the correlations between atoms that have common attributes but are not directly connected by bonds. To address these issues, we construct a Chemical Element Knowledge Graph (KG) to summarize microscopic associations between elements and propose a novel Knowledge-enhanced Contrastive Learning (KCL) framework for molecular representation learning. KCL framework consists of three modules. The first module, knowledge-guided graph augmentation, augments the original molecular graph based on the Chemical Element KG. The second module, knowledge-aware graph representation, extracts molecular representations with a common graph encoder for the original molecular graph and a Knowledgeaware Message Passing Neural Network (KMPNN) to encode complex information in the augmented molecular graph. The final module is a contrastive objective, where we maximize agreement between these two views of molecular graphs. Extensive experiments demonstrated that KCL obtained superior performances against state-of-the-art baselines on eight molecular datasets. Visualization experiments properly interpret what KCL has learned from atoms and attributes in the augmented molecular graphs.

PDF Details