Zhixiang Ren

Pengfei Liu, Yiming Ren, Jun Tao et al.

Large language models have made significant strides in natural language processing, enabling innovative applications in molecular science by processing textual representations of molecules. However, most existing language models cannot capture the rich information with complex molecular structures or images. In this paper, we introduce GIT-Mol, a multi-modal large language model that integrates the Graph, Image, and Text information. To facilitate the integration of multi-modal molecular data, we propose GIT-Former, a novel architecture that is capable of aligning all modalities into a unified latent space. We achieve a 5%-10% accuracy increase in properties prediction and a 20.2% boost in molecule generation validity compared to the baselines. With the any-to-language molecular translation strategy, our model has the potential to perform more downstream tasks, such as compound name recognition and chemical reaction prediction.

Marlin B. Schäfer, Ondřej Zelenka, Alexander H. Nitz et al.

We present the results of the first Machine Learning Gravitational-Wave Search Mock Data Challenge (MLGWSC-1). For this challenge, participating groups had to identify gravitational-wave signals from binary black hole mergers of increasing complexity and duration embedded in progressively more realistic noise. The final of the 4 provided datasets contained real noise from the O3a observing run and signals up to a duration of 20 seconds with the inclusion of precession effects and higher order modes. We present the average sensitivity distance and runtime for the 6 entered algorithms derived from 1 month of test data unknown to the participants prior to submission. Of these, 4 are machine learning algorithms. We find that the best machine learning based algorithms are able to achieve up to 95% of the sensitive distance of matched-filtering based production analyses for simulated Gaussian noise at a false-alarm rate (FAR) of one per month. In contrast, for real noise, the leading machine learning search achieved 70%. For higher FARs the differences in sensitive distance shrink to the point where select machine learning submissions outperform traditional search algorithms at FARs $\geq 200$ per month on some datasets. Our results show that current machine learning search algorithms may already be sensitive enough in limited parameter regions to be useful for some production settings. To improve the state-of-the-art, machine learning algorithms need to reduce the false-alarm rates at which they are capable of detecting signals and extend their validity to regions of parameter space where modeled searches are computationally expensive to run. Based on our findings we compile a list of research areas that we believe are the most important to elevate machine learning searches to an invaluable tool in gravitational-wave signal detection.

Tianyu Zhao, Ruoxi Lyu, He Wang et al.

Space-based gravitational wave (GW) detectors will be able to observe signals from sources that are otherwise nearly impossible from current ground-based detection. Consequently, the well established signal detection method, matched filtering, will require a complex template bank, leading to a computational cost that is too expensive in practice. Here, we develop a high-accuracy GW signal detection and extraction method for all space-based GW sources. As a proof of concept, we show that a science-driven and uniform multi-stage self-attention-based deep neural network can identify synthetic signals that are submerged in Gaussian noise. Our method exhibits a detection rate exceeding 99% in identifying signals from various sources, with the signal-to-noise ratio at 50, at a false alarm rate of 1%. while obtaining at least 95% similarity compared with target signals. We further demonstrate the interpretability and strong generalization behavior for several extended scenarios.

Tianyu Zhao, Yue Zhou, Ruijun Shi et al.

The detection of Extreme Mass Ratio Inspirals (EMRIs) is intricate due to their complex waveforms, extended duration, and low signal-to-noise ratio (SNR), making them more challenging to be identified compared to compact binary coalescences. While matched filtering-based techniques are known for their computational demands, existing deep learning-based methods primarily handle time-domain data and are often constrained by data duration and SNR. In addition, most existing work ignores time-delay interferometry (TDI) and applies the long-wavelength approximation in detector response calculations, thus limiting their ability to handle laser frequency noise. In this study, we introduce DECODE, an end-to-end model focusing on EMRI signal detection by sequence modeling in the frequency domain. Centered around a dilated causal convolutional neural network, trained on synthetic data considering TDI-1.5 detector response, DECODE can efficiently process a year's worth of multichannel TDI data with an SNR of around 50. We evaluate our model on 1-year data with accumulated SNR ranging from 50 to 120 and achieve a true positive rate of 96.3% at a false positive rate of 1%, keeping an inference time of less than 0.01 seconds. With the visualization of three showcased EMRI signals for interpretability and generalization, DECODE exhibits strong potential for future space-based gravitational wave data analyses.

Mingqing Wang, Zhiwei Nie, Athanasios V. Vasilakos et al.

Proteins encode diverse functions within complex three-dimensional structures, yet most deep learning representations remain highly entangled, obscuring the biophysical signals that underlie function. Here we introduce ProtDiS, a knowledge-guided framework that decomposes pretrained protein micro-environment embeddings into biologically grounded and task-relevant dimensions. Inspired by the information bottleneck principle, ProtDiS learns representations that balance informativeness and compression, yielding structural features that are more specific, independent, and information-efficient, and achieving consistent improvements across twelve downstream tasks, with the largest gains under structure-based splits. Protein- and residue-level analyses further show that ProtDiS differentiates proteins with similar folds but divergent functions and captures fine-grained biophysical signals critical. These findings suggest that knowledge-guided decomposition provides a general and interpretable approach for structuring latent spaces in protein structural modeling. The source code and implementation details are publicly available at https://github.com/AI-HPC-Research-Team/ProtDiS.

Taojie Kuang, Yiming Ren, Zhixiang Ren

Molecular property prediction, crucial for early drug candidate screening and optimization, has seen advancements with deep learning-based methods. While deep learning-based methods have advanced considerably, they often fall short in fully leveraging 3D spatial information. Specifically, current molecular encoding techniques tend to inadequately extract spatial information, leading to ambiguous representations where a single one might represent multiple distinct molecules. Moreover, existing molecular modeling methods focus predominantly on the most stable 3D conformations, neglecting other viable conformations present in reality. To address these issues, we propose 3D-Mol, a novel approach designed for more accurate spatial structure representation. It deconstructs molecules into three hierarchical graphs to better extract geometric information. Additionally, 3D-Mol leverages contrastive learning for pretraining on 20 million unlabeled data, treating their conformations with identical topological structures as weighted positive pairs and contrasting ones as negatives, based on the similarity of their 3D conformation descriptors and fingerprints. We compare 3D-Mol with various state-of-the-art baselines on 7 benchmarks and demonstrate our outstanding performance.

Ruijun Shi, Yue Zhou, Tianyu Zhao et al.

Space-based gravitational wave (GW) detection is one of the most anticipated GW detection projects in the next decade, which promises to detect abundant compact binary systems. At present, deep learning methods have not been widely explored for GW waveform generation and extrapolation. To solve the data processing difficulty and the increasing waveform complexity caused by the detector's response and second-generation time-delay interferometry (TDI 2.0), an interpretable pre-trained large model named CBS-GPT (Compact Binary Systems Waveform Generation with Generative Pre-trained Transformer) is proposed. For compact binary system waveforms, three models were trained to predict the waveforms of massive black hole binaries (MBHB), extreme mass-ratio inspirals (EMRIs), and galactic binaries (GB), achieving prediction accuracies of at most 99%, 91%, and 99%, respectively. The CBS-GPT model exhibits notable generalization and interpretability, with its hidden parameters effectively capturing the intricate information of waveforms, even with the complex instrument response and a wide parameter range. Our research demonstrates the potential of large models in the GW realm, opening up new opportunities and guidance for future researches such as complex waveforms generation, gap completion, and deep learning model design for GW science.

Haomin Wu, Zhiwei Nie, Hongyu Zhang et al.

Accurate prediction of enzyme kinetic parameters is essential for understanding catalytic mechanisms and guiding enzyme engineering.However, existing deep learning-based enzyme-substrate interaction (ESI) predictors often exhibit performance degradation on sequence-divergent, out-of-distribution (OOD) cases, limiting robustness under biologically relevant perturbations.We propose O$^2$DENet, a lightweight, plug-and-play module that enhances OOD generalization via biologically and chemically informed perturbation augmentation and invariant representation learning.O$^2$DENet introduces enzyme-substrate perturbations and enforces consistency between original and augmented enzyme-substrate-pair representations to encourage invariance to distributional shifts.When integrated with representative ESI models, O$^2$DENet consistently improves predictive performance for both $k_{cat}$ and $K_m$ across stringent sequence-identity-based OOD benchmarks, achieving state-of-the-art results among the evaluated methods in terms of accuracy and robustness metrics.Overall, O$^2$DENet provides a general and effective strategy to enhance the stability and deployability of data-driven enzyme kinetics predictors for real-world enzyme engineering applications.

Shuang Ge, Shuqing Sun, Huan Xu et al.

The development of single-cell and spatial transcriptomics has revolutionized our capacity to investigate cellular properties, functions, and interactions in both cellular and spatial contexts. However, the analysis of single-cell and spatial omics data remains challenging. First, single-cell sequencing data are high-dimensional and sparse, often contaminated by noise and uncertainty, obscuring the underlying biological signals. Second, these data often encompass multiple modalities, including gene expression, epigenetic modifications, and spatial locations. Integrating these diverse data modalities is crucial for enhancing prediction accuracy and biological interpretability. Third, while the scale of single-cell sequencing has expanded to millions of cells, high-quality annotated datasets are still limited. Fourth, the complex correlations of biological tissues make it difficult to accurately reconstruct cellular states and spatial contexts. Traditional feature engineering-based analysis methods struggle to deal with the various challenges presented by intricate biological networks. Deep learning has emerged as a powerful tool capable of handling high-dimensional complex data and automatically identifying meaningful patterns, offering significant promise in addressing these challenges. This review systematically analyzes these challenges and discusses related deep learning approaches. Moreover, we have curated 21 datasets from 9 benchmarks, encompassing 58 computational methods, and evaluated their performance on the respective modeling tasks. Finally, we highlight three areas for future development from a technical, dataset, and application perspective. This work will serve as a valuable resource for understanding how deep learning can be effectively utilized in single-cell and spatial transcriptomics analyses, while inspiring novel approaches to address emerging challenges.

Yaxin Xu, Yue Zhou, Tianyu Zhao et al.

The modeling of bio-molecular system across molecular scales remains a central challenge in scientific research. Large language models (LLMs) are increasingly applied to bio-molecular discovery, yet systematic evaluation across multi-scale biological problems and rigorous assessment of their tool-augmented capabilities remain limited. We reveal a systematic gap between LLM performance and mechanistic understanding through the proposed cross-scale bio-molecular benchmark: BioMol-LLM-Bench, a unified framework comprising 26 downstream tasks that covers 4 distinct difficulty levels, and computational tools are integrated for a more comprehensive evaluation. Evaluation on 13 representative models reveals 4 main findings: chain-of-thought data provides limited benefit and may even reduce performance on biological tasks; hybrid mamba-attention architectures are more effective for long bio-molecular sequences; supervised fine-tuning improves specialization at the cost of generalization; and current LLMs perform well on classification tasks but remain weak on challenging regression tasks. Together, these findings provide practical guidance for future LLM-based modeling of molecular systems.

Pengfei Liu, Jun Tao, Zhixiang Ren

Deep learning has significantly advanced molecular modeling and design, enabling efficient understanding and discovery of novel molecules. In particular, large language models (LLMs) introduce a fresh research paradigm to tackle scientific problems from a natural language processing (NLP) perspective. LLMs significantly enhance our understanding and generation of molecules, often surpassing existing methods with their capabilities to decode and synthesize complex molecular patterns. However, two key issues remain: how to quantify the match between model and data modalities and how to identify the knowledge-learning preferences of models. To address these challenges, we propose a multi-modal benchmark, named ChEBI-20-MM, and perform 1263 experiments to assess the model's compatibility with data modalities and knowledge acquisition. Through the modal transition probability matrix, we provide insights into the most suitable modalities for tasks. Furthermore, we introduce a statistically interpretable approach to discover context-specific knowledge mapping by localized feature filtering. Our analysis offers an exploration of the learning mechanism and paves the way for advancing LLMs in molecular science.

Taojie Kuang, Pengfei Liu, Zhixiang Ren

The precise prediction of molecular properties is essential for advancements in drug development, particularly in virtual screening and compound optimization. The recent introduction of numerous deep learning-based methods has shown remarkable potential in enhancing molecular property prediction (MPP), especially improving accuracy and insights into molecular structures. Yet, two critical questions arise: does the integration of domain knowledge augment the accuracy of molecular property prediction and does employing multi-modal data fusion yield more precise results than unique data source methods? To explore these matters, we comprehensively review and quantitatively analyze recent deep learning methods based on various benchmarks. We discover that integrating molecular information significantly improves molecular property prediction (MPP) for both regression and classification tasks. Specifically, regression improvements, measured by reductions in root mean square error (RMSE), are up to 4.0%, while classification enhancements, measured by the area under the receiver operating characteristic curve (ROC-AUC), are up to 1.7%. We also discover that enriching 2D graphs with 1D SMILES boosts multi-modal learning performance for regression tasks by up to 9.1%, and augmenting 2D graphs with 3D information increases performance for classification tasks by up to 13.2%, with both enhancements measured using ROC-AUC. The two consolidated insights offer crucial guidance for future advancements in drug discovery.

Pengfei Liu, Shuang Ge, Jun Tao et al.

Advancements in artificial intelligence for molecular science are necessitating a paradigm shift from purely data-driven predictions to knowledge-guided computational reasoning. Existing molecular models are predominantly proprietary, lacking general molecular intelligence and generalizability. This underscores the necessity for computational methods that can effectively integrate scientific logic with deep learning architectures. Here we introduce a multi-task large reasoning model designed to emulate the cognitive processes of molecular scientists through structured reasoning and reflection. Our approach incorporates multi-specialist modules to provide versatile molecular expertise and a chain-of-thought (CoT) framework enhanced by reinforcement learning infused with molecular knowledge, enabling structured and reflective reasoning. Systematic evaluations across 10 molecular tasks and 47 metrics demonstrate that our model achieves an average 50.3% improvement over the base architecture, outperforming over 20 state-of-the-art baselines, including ultra-large-parameter foundation models, despite using significantly fewer training data and computational resources. This validates that embedding explicit reasoning mechanisms enables high-efficiency learning, allowing smaller-scale models to surpass massive counterparts in both efficacy and interpretability. The practical utility of this computational framework was validated through a case study on the design of central nervous system (CNS) drug candidates, illustrating its capacity to bridge data-driven and knowledge-integrated approaches for intelligent molecular design.

Pengfei Liu, Jun Tao, Zhixiang Ren

Drug-drug interaction event (DDIE) prediction is crucial for preventing adverse reactions and ensuring optimal therapeutic outcomes. However, existing methods often face challenges with imbalanced datasets, complex interaction mechanisms, and poor generalization to unknown drug combinations. To address these challenges, we propose a knowledge augmentation framework that adaptively infuses prior drug knowledge into a large language model (LLM). This framework utilizes reinforcement learning techniques to facilitate adaptive knowledge extraction and synthesis, thereby efficiently optimizing the strategy space to enhance the accuracy of LLMs for DDIE predictions. As a result of few-shot learning, we achieved a notable improvement compared to the baseline. This approach establishes an effective framework for scientific knowledge learning for DDIE predictions.

Zhiwei Nie, Hongyu Zhang, Hao Jiang et al.

Understanding and modeling enzyme-substrate interactions is crucial for catalytic mechanism research, enzyme engineering, and metabolic engineering. Although a large number of predictive methods have emerged, they do not incorporate prior knowledge of enzyme catalysis to rationally modulate general protein-molecule features that are misaligned with catalytic patterns. To address this issue, we introduce a two-stage progressive framework, OmniESI, for enzyme-substrate interaction prediction through conditional deep learning. By decomposing the modeling of enzyme-substrate interactions into a two-stage progressive process, OmniESI incorporates two conditional networks that respectively emphasize enzymatic reaction specificity and crucial catalysis-related interactions, facilitating a gradual feature modulation in the latent space from general protein-molecule domain to catalysis-aware domain. On top of this unified architecture, OmniESI can adapt to a variety of downstream tasks, including enzyme kinetic parameter prediction, enzyme-substrate pairing prediction, enzyme mutational effect prediction, and enzymatic active site annotation. Under the multi-perspective performance evaluation of in-distribution and out-of-distribution settings, OmniESI consistently delivered superior performance than state-of-the-art specialized methods across seven benchmarks. More importantly, the proposed conditional networks were shown to internalize the fundamental patterns of catalytic efficiency while significantly improving prediction performance, with only negligible parameter increases (0.16%), as demonstrated by ablation studies on key components. Overall, OmniESI represents a unified predictive approach for enzyme-substrate interactions, providing an effective tool for catalytic mechanism cracking and enzyme engineering with strong generalization and broad applicability.

Taojie Kuang, Qianli Ma, Athanasios V. Vasilakos et al.

In recent years, deep learning techniques have made significant strides in molecular generation for specific targets, driving advancements in drug discovery. However, existing molecular generation methods present significant limitations: those operating at the atomic level often lack synthetic feasibility, drug-likeness, and interpretability, while fragment-based approaches frequently overlook comprehensive factors that influence protein-molecule interactions. To address these challenges, we propose a novel fragment-based molecular generation framework tailored for specific proteins. Our method begins by constructing a protein subpocket and molecular arm concept-based neural network, which systematically integrates interaction force information and geometric complementarity to sample molecular arms for specific protein subpockets. Subsequently, we introduce a diffusion model to generate molecular backbones that connect these arms, ensuring structural integrity and chemical diversity. Our approach significantly improves synthetic feasibility and binding affinity, with a 4% increase in drug-likeness and a 6% improvement in synthetic feasibility. Furthermore, by integrating explicit interaction data through a concept-based model, our framework enhances interpretability, offering valuable insights into the molecular design process.

Pengfei Liu, Jun Tao, Zhixiang Ren

The task of chemical reaction predictions (CRPs) plays a pivotal role in advancing drug discovery and material science. However, its effectiveness is constrained by the vast and uncertain chemical reaction space and challenges in capturing reaction selectivity, particularly due to existing methods' limitations in exploiting the data's inherent knowledge. To address these challenges, we introduce a data-curated self-feedback knowledge elicitation approach. This method starts from iterative optimization of molecular representations and facilitates the extraction of knowledge on chemical reaction types (RTs). Then, we employ adaptive prompt learning to infuse the prior knowledge into the large language model (LLM). As a result, we achieve significant enhancements: a 14.2% increase in retrosynthesis prediction accuracy, a 74.2% rise in reagent prediction accuracy, and an expansion in the model's capability for handling multi-task chemical reactions. This research offers a novel paradigm for knowledge elicitation in scientific research and showcases the untapped potential of LLMs in CRPs.

Zhixiang Ren, Yongheng Liu, Tianhui Shi et al.

The plethora of complex artificial intelligence (AI) algorithms and available high performance computing (HPC) power stimulates the expeditious development of AI components with heterogeneous designs. Consequently, the need for cross-stack performance benchmarking of AI-HPC systems emerges rapidly. The de facto HPC benchmark LINPACK can not reflect AI computing power and I/O performance without representative workload. The current popular AI benchmarks like MLPerf have fixed problem size therefore limited scalability. To address these issues, we propose an end-to-end benchmark suite utilizing automated machine learning (AutoML), which not only represents real AI scenarios, but also is auto-adaptively scalable to various scales of machines. We implement the algorithms in a highly parallel and flexible way to ensure the efficiency and optimization potential on diverse systems with customizable configurations. We utilize operations per second (OPS), which is measured in an analytical and systematic approach, as the major metric to quantify the AI performance. We perform evaluations on various systems to ensure the benchmark's stability and scalability, from 4 nodes with 32 NVIDIA Tesla T4 (56.1 Tera-OPS measured), up to 512 nodes with 4096 Huawei Ascend 910 (194.53 Peta-OPS measured), and the results show near-linear weak scalability. With flexible workload and single metric, our benchmark can scale and rank AI-HPC easily.