Yanwen Huang

Yanwen Huang, Lok Ming Lui, Gary P. T. Choi

Many imaging problems require computing spatial transformations induced by spatially varying intensity, feature, or density fields. Canonical examples include distortion correction, deformable image registration, atlas-based segmentation, and deformation-driven image analysis. These tasks can be formulated as geometric mapping problems in which the transformation is constrained to preserve local structure, control boundary behavior, or regulate angular distortion. Such formulations typically lead to variational models, diffusion processes, or elliptic partial differential equations. However, repeatedly solving high-resolution systems becomes computationally expensive when the underlying parameter fields vary across instances. In this work, we propose a resolution-free neural surrogate for geometric parameterization and mapping problems. Given a spatially varying parameter field $p:Ω\to\mathbb{R}^m$ and query locations $\{x_i\}_{i=1}^N\subsetΩ$, the model predicts mapped locations $\{u(x_i)\}_{i=1}^N$ on arbitrary structured or unstructured point sets. To avoid dependence on a fixed grid, we use a multi-resolution geometric encoding strategy that conditions the network on coordinate-augmented samples of the parameter field. The model is trained without labeled solution data by enforcing geometry-aware constraints derived from variational energies, diffusion-based density equalization, and quasi-conformal theory. Experimental results on quasi-conformal mapping and density-equalizing mapping problems are presented to demonstrate the effectiveness of our proposed method.

Shikun Feng, Lixin Yang, Yanwen Huang et al.

Molecular representation learning is fundamental for many drug related applications. Most existing molecular pre-training models are limited in using single molecular modality, either SMILES or graph representation. To effectively leverage both modalities, we argue that it is critical to capture the fine-grained 'semantics' between SMILES and graph, because subtle sequence/graph differences may lead to contrary molecular properties. In this paper, we propose a universal SMILE-graph representation learning model, namely UniMAP. Firstly, an embedding layer is employed to obtain the token and node/edge representation in SMILES and graph, respectively. A multi-layer Transformer is then utilized to conduct deep cross-modality fusion. Specially, four kinds of pre-training tasks are designed for UniMAP, including Multi-Level Cross-Modality Masking (CMM), SMILES-Graph Matching (SGM), Fragment-Level Alignment (FLA), and Domain Knowledge Learning (DKL). In this way, both global (i.e. SGM and DKL) and local (i.e. CMM and FLA) alignments are integrated to achieve comprehensive cross-modality fusion. We evaluate UniMAP on various downstream tasks, i.e. molecular property prediction, drug-target affinity prediction and drug-drug interaction. Experimental results show that UniMAP outperforms current state-of-the-art pre-training methods.We also visualize the learned representations to demonstrate the effect of multi-modality integration.

Yong Zhang, Yanwen Huang, Ning Cheng et al.

Retrieval-augmented generation (RAG) enhances large language models (LLMs) with external context, but retrieved passages are often lengthy, noisy, or exceed input limits. Existing compression methods typically require supervised training of dedicated compression models, increasing cost and reducing portability. We propose Sentinel, a lightweight sentence-level compression framework that reframes context filtering as an attention-based understanding task. Rather than training a compression model, Sentinel probes decoder attention from an off-the-shelf 0.5B proxy LLM using a lightweight classifier to identify sentence relevance. Empirically, we find that query-context relevance estimation is consistent across model scales, with 0.5B proxies closely matching the behaviors of larger models. On the LongBench benchmark, Sentinel achieves up to 5$\times$ compression while matching the QA performance of 7B-scale compression systems. Our results suggest that probing native attention signals enables fast, effective, and question-aware context compression. Code available at: https://github.com/yzhangchuck/Sentinel.

Shikun Feng, Yuyan Ni, Minghao Li et al.

Recently, a noticeable trend has emerged in developing pre-trained foundation models in the domains of CV and NLP. However, for molecular pre-training, there lacks a universal model capable of effectively applying to various categories of molecular tasks, since existing prevalent pre-training methods exhibit effectiveness for specific types of downstream tasks. Furthermore, the lack of profound understanding of existing pre-training methods, including 2D graph masking, 2D-3D contrastive learning, and 3D denoising, hampers the advancement of molecular foundation models. In this work, we provide a unified comprehension of existing pre-training methods through the lens of contrastive learning. Thus their distinctions lie in clustering different views of molecules, which is shown beneficial to specific downstream tasks. To achieve a complete and general-purpose molecular representation, we propose a novel pre-training framework, named UniCorn, that inherits the merits of the three methods, depicting molecular views in three different levels. SOTA performance across quantum, physicochemical, and biological tasks, along with comprehensive ablation study, validate the universality and effectiveness of UniCorn.

Bowen Gao, Yanwen Huang, Yiqiao Liu et al.

The discovery of novel small molecule drugs remains a critical scientific challenge with far-reaching implications for treating diseases and advancing human health. Traditional drug development--especially for small molecule therapeutics--is a highly complex, resource-intensive, and time-consuming process that requires multidisciplinary collaboration. Recent breakthroughs in artificial intelligence (AI), particularly the rise of large language models (LLMs), present a transformative opportunity to streamline and accelerate this process. In this paper, we introduce PharmAgents, a virtual pharmaceutical ecosystem driven by LLM-based multi-agent collaboration. PharmAgents simulates the full drug discovery workflow--from target discovery to preclinical evaluation--by integrating explainable, LLM-driven agents equipped with specialized machine learning models and computational tools. Through structured knowledge exchange and automated optimization, PharmAgents identifies potential therapeutic targets, discovers promising lead compounds, enhances binding affinity and key molecular properties, and performs in silico analyses of toxicity and synthetic feasibility. Additionally, the system supports interpretability, agent interaction, and self-evolvement, enabling it to refine future drug designs based on prior experience. By showcasing the potential of LLM-powered multi-agent systems in drug discovery, this work establishes a new paradigm for autonomous, explainable, and scalable pharmaceutical research, with future extensions toward comprehensive drug lifecycle management.

Bowen Gao, Minsi Ren, Yuyan Ni et al.

In the field of Structure-based Drug Design (SBDD), deep learning-based generative models have achieved outstanding performance in terms of docking score. However, further study shows that the existing molecular generative methods and docking scores both have lacked consideration in terms of specificity, which means that generated molecules bind to almost every protein pocket with high affinity. To address this, we introduce the Delta Score, a new metric for evaluating the specificity of molecular binding. To further incorporate this insight for generation, we develop an innovative energy-guided approach using contrastive learning, with active compounds as decoys, to direct generative models toward creating molecules with high specificity. Our empirical results show that this method not only enhances the delta score but also maintains or improves traditional docking scores, successfully bridging the gap between SBDD and real-world needs.

Yanwen Huang, Yong Zhang, Ning Cheng et al.

Large language models (LLMs) often exhibit Context Faithfulness Hallucinations, where outputs deviate from retrieved information due to incomplete context integration. Our analysis reveals a strong correlation between token-level uncertainty and hallucinations. We hypothesize that attention mechanisms inherently encode context utilization signals, supported by probing analysis. Based on these insights, we propose Dynamic Attention-Guided Context Decoding (DAGCD), a lightweight framework that leverages attention distributions and uncertainty signals in a single-pass decoding. Experiments on open-book QA datasets demonstrate DAGCD's effectiveness, yielding significant improvements in faithfulness and robustness while preserving computational efficiency.

Junguang Jiang, Yanwen Huang, Bin Liu et al.

In real-world recommender systems, different retrieval objectives are typically addressed using task-specific datasets with carefully designed model architectures. We demonstrate that Large Language Models (LLMs) can function as universal retrievers, capable of handling multiple objectives within a generative retrieval framework. To model complex user-item relationships within generative retrieval, we propose multi-query representation. To address the challenge of extremely large candidate sets in industrial recommender systems, we introduce matrix decomposition to boost model learnability, discriminability, and transferability, and we incorporate probabilistic sampling to reduce computation costs. Finally, our Universal Retrieval Model (URM) can adaptively generate a set from tens of millions of candidates based on arbitrary given objective while keeping the latency within tens of milliseconds. Applied to industrial-scale data, URM outperforms expert models elaborately designed for different retrieval objectives on offline experiments and significantly improves the core metric of online advertising platform by $3\%$.

Yanwen Huang, Lok Ming Lui, Gary P. T. Choi

Density-equalizing map (DEM) serves as a powerful technique for creating shape deformations with the area changes reflecting an underlying density function. In recent decades, DEM has found widespread applications in fields such as data visualization, geometry processing, and medical imaging. Traditional approaches to DEM primarily rely on iterative numerical solvers for diffusion equations or optimization-based methods that minimize handcrafted energy functionals. However, these conventional techniques often face several challenges: they may suffer from limited accuracy, produce overlapping artifacts in extreme cases, and require substantial algorithmic redesign when extended from 2D to 3D, due to the derivative-dependent nature of their energy formulations. In this work, we propose a novel learning-based density-equalizing mapping framework (LDEM) using deep neural networks. Specifically, we introduce a loss function that enforces density uniformity and geometric regularity, and utilize a hierarchical approach to predict the transformations at both the coarse and dense levels. Our method demonstrates superior density-equalizing and bijectivity properties compared to prior methods for a wide range of simple and complex density distributions, and can be easily applied to surface remeshing with different effects. Also, it generalizes seamlessly from 2D to 3D domains without structural changes to the model architecture or loss formulation. Altogether, our work opens up new possibilities for scalable and robust computation of density-equalizing maps for practical applications.

Bowen Gao, Haichuan Tan, Yanwen Huang et al.

Recent advancements in structure-based drug design (SBDD) have significantly enhanced the efficiency and precision of drug discovery by generating molecules tailored to bind specific protein pockets. Despite these technological strides, their practical application in real-world drug development remains challenging due to the complexities of synthesizing and testing these molecules. The reliability of the Vina docking score, the current standard for assessing binding abilities, is increasingly questioned due to its susceptibility to overfitting. To address these limitations, we propose a comprehensive evaluation framework that includes assessing the similarity of generated molecules to known active compounds, introducing a virtual screening-based metric for practical deployment capabilities, and re-evaluating binding affinity more rigorously. Our experiments reveal that while current SBDD models achieve high Vina scores, they fall short in practical usability metrics, highlighting a significant gap between theoretical predictions and real-world applicability. Our proposed metrics and dataset aim to bridge this gap, enhancing the practical applicability of future SBDD models and aligning them more closely with the needs of pharmaceutical research and development.

Yanwen Huang, Bowen Gao, Yinjun Jia et al.

Small molecules play a pivotal role in modern medicine, and scrutinizing their interactions with protein targets is essential for the discovery and development of novel, life-saving therapeutics. The term "bioactivity" encompasses various biological effects resulting from these interactions, including both binding and functional responses. The magnitude of bioactivity dictates the therapeutic or toxic pharmacological outcomes of small molecules, rendering accurate bioactivity prediction crucial for the development of safe and effective drugs. However, existing structural datasets of small molecule-protein interactions are often limited in scale and lack systematically organized bioactivity labels, thereby impeding our understanding of these interactions and precise bioactivity prediction. In this study, we introduce a comprehensive dataset of small molecule-protein interactions, consisting of over a million binding structures, each annotated with real biological activity labels. This dataset is designed to facilitate unbiased bioactivity prediction. We evaluated several classical models on this dataset, and the results demonstrate that the task of unbiased bioactivity prediction is challenging yet essential.

Shikun Feng, Jiaxin Zheng, Yinjun Jia et al.

Molecular representation learning is pivotal for various molecular property prediction tasks related to drug discovery. Robust and accurate benchmarks are essential for refining and validating current methods. Existing molecular property benchmarks derived from wet experiments, however, face limitations such as data volume constraints, unbalanced label distribution, and noisy labels. To address these issues, we construct a large-scale and precise molecular representation dataset of approximately 140,000 small molecules, meticulously designed to capture an extensive array of chemical, physical, and biological properties, derived through a robust computational ligand-target binding analysis pipeline. We conduct extensive experiments on various deep learning models, demonstrating that our dataset offers significant physicochemical interpretability to guide model development and design. Notably, the dataset's properties are linked to binding affinity metrics, providing additional insights into model performance in drug-target interaction tasks. We believe this dataset will serve as a more accurate and reliable benchmark for molecular representation learning, thereby expediting progress in the field of artificial intelligence-driven drug discovery.