Yining Huang

Yuanqi Du, Yingheng Wang, Yining Huang et al.

We introduce M$^2$Hub, a toolkit for advancing machine learning in materials discovery. Machine learning has achieved remarkable progress in modeling molecular structures, especially biomolecules for drug discovery. However, the development of machine learning approaches for modeling materials structures lag behind, which is partly due to the lack of an integrated platform that enables access to diverse tasks for materials discovery. To bridge this gap, M$^2$Hub will enable easy access to materials discovery tasks, datasets, machine learning methods, evaluations, and benchmark results that cover the entire workflow. Specifically, the first release of M$^2$Hub focuses on three key stages in materials discovery: virtual screening, inverse design, and molecular simulation, including 9 datasets that covers 6 types of materials with 56 tasks across 8 types of material properties. We further provide 2 synthetic datasets for the purpose of generative tasks on materials. In addition to random data splits, we also provide 3 additional data partitions to reflect the real-world materials discovery scenarios. State-of-the-art machine learning methods (including those are suitable for materials structures but never compared in the literature) are benchmarked on representative tasks. Our codes and library are publicly available at https://github.com/yuanqidu/M2Hub.

Zaixi Zhang, Jiaxian Yan, Yining Huang et al.

Structure-based drug design (SBDD) leverages the three-dimensional geometry of proteins to identify potential drug candidates. Traditional approaches, rooted in physicochemical modeling and domain expertise, are often resource-intensive. Recent advancements in geometric deep learning, which effectively integrate and process 3D geometric data, alongside breakthroughs in accurate protein structure predictions from tools like AlphaFold, have significantly propelled the field forward. This paper systematically reviews the state-of-the-art in geometric deep learning for SBDD. We begin by outlining foundational tasks in SBDD, discussing prevalent 3D protein representations, and highlighting representative predictive and generative models. Next, we provide an in-depth review of key tasks, including binding site prediction, binding pose generation, de novo molecule generation, linker design, protein pocket generation, and binding affinity prediction. For each task, we present formal problem definitions, key methods, datasets, evaluation metrics, and performance benchmarks. Lastly, we explore current challenges and future opportunities in SBDD. Challenges include oversimplified problem formulations, limited out-of-distribution generalization, biosecurity concerns related to the misuse of structural data, insufficient evaluation metrics and large-scale benchmarks, and the need for experimental validation and enhanced model interpretability. Opportunities lie in leveraging multimodal datasets, integrating domain knowledge, developing comprehensive benchmarks, establishing criteria aligned with clinical outcomes, and designing foundation models to expand the scope of design tasks. We also curate \url{https://github.com/zaixizhang/Awesome-SBDD}, reflecting ongoing contributions and new datasets in SBDD.

Zhihao Xu, Shengjie Gong, Jiapeng Tang et al.

We present a novel approach for synthesizing 3D facial motions from audio sequences using key motion embeddings. Despite recent advancements in data-driven techniques, accurately mapping between audio signals and 3D facial meshes remains challenging. Direct regression of the entire sequence often leads to over-smoothed results due to the ill-posed nature of the problem. To this end, we propose a progressive learning mechanism that generates 3D facial animations by introducing key motion capture to decrease cross-modal mapping uncertainty and learning complexity. Concretely, our method integrates linguistic and data-driven priors through two modules: the linguistic-based key motion acquisition and the cross-modal motion completion. The former identifies key motions and learns the associated 3D facial expressions, ensuring accurate lip-speech synchronization. The latter extends key motions into a full sequence of 3D talking faces guided by audio features, improving temporal coherence and audio-visual consistency. Extensive experimental comparisons against existing state-of-the-art methods demonstrate the superiority of our approach in generating more vivid and consistent talking face animations. Consistent enhancements in results through the integration of our proposed learning scheme with existing methods underscore the efficacy of our approach. Our code and weights will be at the project website: \url{https://github.com/ffxzh/KMTalk}.

Natalie Maus, Yimeng Zeng, Haydn Thomas Jones et al.

Many key challenges in biological design-such as small-molecule drug discovery, antimicrobial peptide development, and protein engineering-can be framed as black-box optimization over vast, complex structured spaces. Existing methods rely mainly on raw structural data and struggle to exploit the rich scientific literature. While large language models (LLMs) have been added to these pipelines, they have been confined to narrow roles within structure-centered optimizers. We instead cast biological black-box optimization as a fully agentic, language-based reasoning process. We introduce Purely Agentic BLack-box Optimization (PABLO), a hierarchical agentic system that uses scientific LLMs pretrained on chemistry and biology literature to generate and iteratively refine biological candidates. On both the standard GuacaMol molecular design and antimicrobial peptide optimization tasks, PABLO achieves state-of-the-art performance, substantially improving sample efficiency and final objective values over established baselines. Compared to prior optimization methods that incorporate LLMs, PABLO achieves competitive token usage per run despite relying on LLMs throughout the optimization loop. Beyond raw performance, the agentic formulation offers key advantages for realistic design: it naturally incorporates semantic task descriptions, retrieval-augmented domain knowledge, and complex constraints. In follow-up in vitro validation, PABLO-optimized peptides showed strong activity against drug-resistant pathogens, underscoring the practical potential of PABLO for therapeutic discovery.

Haydn Jones, Yimeng Zeng, Alden Rose et al.

Manually curated biomedical repositories -- spanning bioactivity, genomics, and chemistry -- are expensive to maintain, lag behind primary literature, and discard experimental context, obscuring nuances needed to assess data correctness and coverage. We show that PubMed itself can be autonomously and cost-effectively turned into structured datasets that are larger, more nuanced, and more accurate than the curated databases they replace. We present three coupled contributions: (1) an LLM-based entity-tagging pipeline, grounded in nine biomedical ontologies, that tags 4.5B entities across 19 categories in a 22.5M-paper, 2.5T-token PubMed corpus; (2) hybrid sparse-dense retrieval supporting entity-filtered semantic queries over the tagged corpus; and (3) Starling, a multi-agent deep research system that, given only a natural-language task description, designs precision- and recall-targeted retrieval filters, induces an extraction schema, and emits structured records with nuance-rich fields and supporting passages. Across six tasks -- blood-brain barrier permeability, oral bioavailability, acute toxicity (LD50), gene-disease associations, protein subcellular localization, and chemical reactions -- Starling produces ~6.3M records (91K-3M per task); several are, to our knowledge, the largest public datasets for their property. Frontier-model rejection of our extractions is 0.6-7.7% across tasks, far below error rates we measure on widely used curated counterparts (e.g., 16.5% on BBB_Martins, 7.3% on Bioavailability_Ma). Beyond scale and accuracy, the supporting passages carry nuance tabular databases discard -- e.g., oral bioavailability may depend on fed vs. fasted state. Together, the corpus, retrieval, and agent establish a foundation for AI-driven therapeutic design. Code and datasets: https://github.com/starling-labs/starling.

Gang Dai, Yining Huang, Yiming Xia et al.

The efficient Test-Time Scaling (TTS) paradigm offers a promising perspective for enhancing the generation performance of diffusion models. However, current solutions are limited to a static, pre-defined noise pool and suffer from inflexible noise exploration across the denoising trajectory. To bridge this gap, we propose RTS, a novel Reward-guided Trajectory Scaling method to fully unlock the generative potential of diffusion models. Unlike existing methods, RTS facilitates the synthesis of refined, high-fidelity images via two core innovations: 1) a reward-guided noise optimization strategy to actively direct the search towards promising regions; and 2) a sparse test-time scaling framework together with a PCA-driven curvature analysis scheme to prioritize key intermediate steps in the entire denoising space, effectively compressing the search space. Experiments show our approach outperforms baselines by 15.6% across GenEval Score, and a 60.4% enhancement in ImageReward score, setting a new SOTA while providing a practical guideline for more effective test-time scaling across diffusion-specific architectures.

Zuobai Zhang, Pascal Notin, Yining Huang et al.

Designing novel functional proteins crucially depends on accurately modeling their fitness landscape. Given the limited availability of functional annotations from wet-lab experiments, previous methods have primarily relied on self-supervised models trained on vast, unlabeled protein sequence or structure datasets. While initial protein representation learning studies solely focused on either sequence or structural features, recent hybrid architectures have sought to merge these modalities to harness their respective strengths. However, these sequence-structure models have so far achieved only incremental improvements when compared to the leading sequence-only approaches, highlighting unresolved challenges effectively leveraging these modalities together. Moreover, the function of certain proteins is highly dependent on the granular aspects of their surface topology, which have been overlooked by prior models. To address these limitations, we introduce the Sequence-Structure-Surface Fitness (S3F) model - a novel multimodal representation learning framework that integrates protein features across several scales. Our approach combines sequence representations from a protein language model with Geometric Vector Perceptron networks encoding protein backbone and detailed surface topology. The proposed method achieves state-of-the-art fitness prediction on the ProteinGym benchmark encompassing 217 substitution deep mutational scanning assays, and provides insights into the determinants of protein function. Our code is at https://github.com/DeepGraphLearning/S3F.

Felix Teufel, Aaron W. Kollasch, Yining Huang et al.

Accurately predicting protein fitness with minimal experimental data is a persistent challenge in protein engineering. We introduce PRIMO (PRotein In-context Mutation Oracle), a transformer-based framework that leverages in-context learning and test-time training to adapt rapidly to new proteins and assays without large task-specific datasets. By encoding sequence information, auxiliary zero-shot predictions, and sparse experimental labels from many assays as a unified token set in a pre-training masked-language modeling paradigm, PRIMO learns to prioritize promising variants through a preference-based loss function. Across diverse protein families and properties-including both substitution and indel mutations-PRIMO outperforms zero-shot and fully supervised baselines. This work underscores the power of combining large-scale pre-training with efficient test-time adaptation to tackle challenging protein design tasks where data collection is expensive and label availability is limited.

Guanghao Wei, Yining Huang, Chenru Duan et al.

Recent progress of deep generative models in the vision and language domain has stimulated significant interest in more structured data generation such as molecules. However, beyond generating new random molecules, efficient exploration and a comprehensive understanding of the vast chemical space are of great importance to molecular science and applications in drug design and materials discovery. In this paper, we propose a new framework, ChemFlow, to traverse chemical space through navigating the latent space learned by molecule generative models through flows. We introduce a dynamical system perspective that formulates the problem as learning a vector field that transports the mass of the molecular distribution to the region with desired molecular properties or structure diversity. Under this framework, we unify previous approaches on molecule latent space traversal and optimization and propose alternative competing methods incorporating different physical priors. We validate the efficacy of ChemFlow on molecule manipulation and single- and multi-objective molecule optimization tasks under both supervised and unsupervised molecular discovery settings. Codes and demos are publicly available on GitHub at https://github.com/garywei944/ChemFlow.

Yining Huang, Keke Tang, Meilian Chen et al.

Since the inception of the Transformer architecture in 2017, Large Language Models (LLMs) such as GPT and BERT have evolved significantly, impacting various industries with their advanced capabilities in language understanding and generation. These models have shown potential to transform the medical field, highlighting the necessity for specialized evaluation frameworks to ensure their effective and ethical deployment. This comprehensive survey delineates the extensive application and requisite evaluation of LLMs within healthcare, emphasizing the critical need for empirical validation to fully exploit their capabilities in enhancing healthcare outcomes. Our survey is structured to provide an in-depth analysis of LLM applications across clinical settings, medical text data processing, research, education, and public health awareness. We begin by exploring the roles of LLMs in various medical applications, detailing their evaluation based on performance in tasks such as clinical diagnosis, medical text data processing, information retrieval, data analysis, and educational content generation. The subsequent sections offer a comprehensive discussion on the evaluation methods and metrics employed, including models, evaluators, and comparative experiments. We further examine the benchmarks and datasets utilized in these evaluations, providing a categorized description of benchmarks for tasks like question answering, summarization, information extraction, bioinformatics, information retrieval and general comprehensive benchmarks. This structure ensures a thorough understanding of how LLMs are assessed for their effectiveness, accuracy, usability, and ethical alignment in the medical domain. ...

Yining Huang, Keke Tang, Meilian Chen

Emerging Large Language Models (LLMs) like GPT-4 have revolutionized Natural Language Processing (NLP), showing potential in traditional tasks such as Named Entity Recognition (NER). Our study explores a three-phase training strategy that harnesses GPT-4's capabilities to enhance the BERT model's performance on NER. Initially, GPT-4 annotates a subset of the CONLL2003 and additional BBC dataset without fine-tuning. We then train BERT using a mix of original and LLM-annotated data, analyzing the efficacy of LLM annotations against traditional methods. The second phase involves comparative experiments with different training regimens, assessing the synergy between distilled and original data. We observe that sequential strategies, particularly a simple mix of training first with distilled data followed by original data, significantly boost performance. In the third phase, we investigate various data blending techniques, including sigmoid and power decay functions, to optimize the training process further. Our results indicate that a strategic mix of distilled and original data markedly elevates the NER capabilities of BERT. Our approach presents a scalable methodology that reduces manual annotation costs and increases efficiency, making it especially pertinent in resource-limited and closed-network environments. The study concludes that while the 'Simple Mix' strategy yields the best results, understanding its underlying mechanisms requires further research. Future work will also focus on refining prompt designs and enhancing annotation selection processes, aiming to extend our methodology to diverse NLP tasks.

Yining Huang, Bin Li, Keke Tang et al.

Large-scale generative models like DeepSeek-R1 and OpenAI-O1 benefit substantially from chain-of-thought (CoT) reasoning, yet pushing their performance typically requires vast data, large model sizes, and full-parameter fine-tuning. While parameter-efficient fine-tuning (PEFT) helps reduce cost, most existing approaches primarily address domain adaptation or layer-wise allocation rather than explicitly tailoring data and parameters to different response demands. Inspired by "Thinking, Fast and Slow," which characterizes two distinct modes of thought-System 1 (fast, intuitive, often automatic) and System 2 (slower, more deliberative and analytic)-we draw an analogy that different "subregions" of an LLM's parameters might similarly specialize for tasks that demand quick, intuitive responses versus those requiring multi-step logical reasoning. Therefore, we propose LoRA-PAR, a dual-system LoRA framework that partitions both data and parameters by System 1 or System 2 demands, using fewer yet more focused parameters for each task. Specifically, we classify task data via multi-model role-playing and voting, and partition parameters based on importance scoring, then adopt a two-stage fine-tuning strategy of training System 1 tasks with supervised fine-tuning (SFT) to enhance knowledge and intuition and refine System 2 tasks with reinforcement learning (RL) to reinforce deeper logical deliberation next. Extensive experiments show that the two-stage fine-tuning strategy, SFT and RL, lowers active parameter usage while matching or surpassing SOTA PEFT baselines.

Yining Huang, Shaoze Lin, Yijun Wei et al.

We propose a knowledge engine called Sinoledge mainly for doctors, physicians, and researchers in medical field to organize thoughts, manage reasoning process, test and deploy to production environments effortlessly. Our proposal can be related to rule engine usually used in business or medical fields. More importantly, our proposal provides a user-friendly interface, an easy-maintain way of organizing knowledge, an understandable testing functionality and a highly available and efficient back-end architecture.

Yining Huang, Meilian Chen, Keke Tang

We introduce a framework for AI-based medical consultation system with knowledge graph embedding and reinforcement learning components and its implement. Our implement of this framework leverages knowledge organized as a graph to have diagnosis according to evidence collected from patients recurrently and dynamically. According to experiment we designed for evaluating its performance, it archives a good result. More importantly, for getting better performance, researchers can implement it on this framework based on their innovative ideas, well designed experiments and even clinical trials.