arXiv subjects

Zhixiang Ren

Publications and source records attributed to Zhixiang Ren.

At least 19 recordsLinked to original sources

arXiv2026

A Multitask Large Reasoning Model for Molecular Science

Artificial intelligence in molecular science must move beyond pattern recognition toward chemically valid and interpretable reasoning. We present a task-adaptive large reasoning model that integrates chemical knowledge through a synergistic multispecialist architecture, chain-of-thought supervision, and molecule-informed reinforcement learning. Task-conditioned routing coordinates prediction and inference specialists across 10 molecular tasks spanning molecular description and generation, nomenclature translation, property prediction, and reaction prediction. The model outperforms more than 20 general-purpose and molecular large language models, improves aggregate performance over the base model by 50.3%, and surpasses the leading molecular multitask baseline on most tasks. Analyses of specialist representations and reasoning pathways reveal task-specific adaptation while retaining interpretable chemical inference. A case study further demonstrates an integrated workflow for central nervous system candidate generation, property screening, molecular interpretation, and retrosynthetic planning. These results demonstrate a versatile multi-task framework for knowledge-guided molecular reasoning and design, with the potential to serve as a core task engine for future molecular science agents.

cs.LG↗

arXiv2026

Learning Protein Structure-Function Relationships through Knowledge-guided Representation Decomposition

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.

q-bio.BM↗

arXiv2026

The limits of bio-molecular modeling with large language models : a cross-scale evaluation

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.

cs.LG↗

arXiv2026

Enhanced Drug-drug Interaction Prediction Using Adaptive Knowledge Integration

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.

cs.LG↗

arXiv2026

Pseudodata-guided Invariant Representation Learning Boosts the Out-of-Distribution Generalization in Enzymatic Kinetic Parameter Prediction

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.

cs.LG↗

arXiv2025

OmniESI: A unified framework for enzyme-substrate interaction prediction with progressive conditional deep learning

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.

q-bio.BM↗

arXiv2025

Compact Binary Coalescence Gravitational Wave Signals Counting and Separation

As next-generation gravitational-wave (GW) observatories approach unprecedented sensitivities, the need for robust methods to analyze increasingly complex, overlapping signals becomes ever more pressing. Existing matched-filtering approaches and deep-learning techniques can typically handle only one or two concurrent signals, offering limited adaptability to more varied and intricate superimposed waveforms. To overcome these constraints, we present the UnMixFormer, an attention-based architecture that not only identifies the unknown number of concurrent compact binary coalescence GW events but also disentangles their individual waveforms through a multi-decoder architecture, even when confronted with five overlapping signals. Our UnMixFormer is capable of capturing both short- and long-range dependencies by modeling them in a dual-path manner, while also enhancing periodic feature representation by incorporating Fourier Analysis Networks. Our approach adeptly processes binary black hole, binary neutron star, and neutron star-black hole systems over extended time series data (16,384 samples). When evaluating on synthetic data with signal-to-noise ratios (SNR) ranging from 10 to 50, our method achieves 99.89% counting accuracy, a mean overlap of 0.9831 between separated waveforms and templates, and robust generalization ability to waveforms with spin precession, orbital eccentricity, and higher modes, marking a substantial advance in the precision and versatility of GW data analysis.

gr-qc↗

arXiv2025

GWAI: Artificial Intelligence Platform for Enhanced Gravitational Wave Data Analysis

Gravitational wave (GW) astronomy has opened new frontiers in understanding the cosmos, while the integration of artificial intelligence (AI) in science promises to revolutionize data analysis methodologies. However, a significant gap exists, as there is currently no dedicated platform that enables scientists to develop, test, and evaluate AI algorithms efficiently for GW data analysis. To address this gap, we introduce GWAI, a pioneering AI-centered software platform designed for GW data analysis. GWAI contains a three-layered architecture that emphasizes simplicity, modularity, and flexibility, covering the entire analysis pipeline. GWAI aims to accelerate scientific discoveries, bridging the gap between advanced AI techniques and astrophysical research.

gr-qc↗

arXiv2025

Dawning of a New Era in Gravitational Wave Data Analysis: Unveiling Cosmic Mysteries via Artificial Intelligence -- A Systematic Review

Gravitational wave data analysis (GWDA) faces significant challenges due to high-dimensional parameter spaces and non-Gaussian, non-stationary artifacts in the interferometer background, which traditional methods have made significant progress in addressing but continue to face limitations. Artificial intelligence (AI), particularly deep learning (DL) algorithms, offers potential advantages, including computational efficiency, scalability, and adaptability, which may complement traditional approaches in tackling these challenges more effectively. In this review, we explore AI-driven approaches to GWDA, covering every stage of the pipeline and presenting first explorations in waveform modeling and parameter estimation. This work represents the most comprehensive review to date, integrating the latest AI advancements with practical GWDA applications. Our meta-analysis reveals insights and trends, highlighting the transformative potential of AI in revolutionizing gravitational wave research and paving the way for future discoveries.

gr-qc↗

arXiv2025

Concept-Driven Deep Learning for Enhanced Protein-Specific Molecular Generation

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.

cs.LG↗

arXiv2025

A quantitative analysis of knowledge-learning preferences in large language models in molecular science

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.

cs.LG↗

arXiv2024

Deep Learning in Single-Cell and Spatial Transcriptomics Data Analysis: Advances and Challenges from a Data Science Perspective

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.

q-bio.GN↗

arXiv2024

ProtFAD: Introducing function-aware domains as implicit modality towards protein function prediction

Protein function prediction is currently achieved by encoding its sequence or structure, where the sequence-to-function transcendence and high-quality structural data scarcity lead to obvious performance bottlenecks. Protein domains are "building blocks" of proteins that are functionally independent, and their combinations determine the diverse biological functions. However, most existing studies have yet to thoroughly explore the intricate functional information contained in the protein domains. To fill this gap, we propose a synergistic integration approach for a function-aware domain representation, and a domain-joint contrastive learning strategy to distinguish different protein functions while aligning the modalities. Specifically, we align the domain semantics with GO terms and text description to pre-train domain embeddings. Furthermore, we partition proteins into multiple sub-views based on continuous joint domains for contrastive training under the supervision of a novel triplet InfoNCE loss. Our approach significantly and comprehensively outperforms the state-of-the-art methods on various benchmarks, and clearly differentiates proteins carrying distinct functions compared to the competitor. Our implementation is available at https://github.com/AI-HPC-Research-Team/ProtFAD.

q-bio.BM↗

arXiv2024

Rapid eccentric spin-aligned binary black hole waveform generation based on deep learning

Accurate waveform templates of binary black holes (BBHs) with eccentric orbits are essential for the detection and precise parameter estimation of gravitational waves (GWs). While SEOBNRE produces accurate time-domain waveforms for eccentric BBH systems, its generation speed remains a critical bottleneck in analyzing such systems. Accelerating template generation is crucial to data analysis improvement and valuable information extraction from observational data. We present SEOBNRE_AIq5e2, an innovative AI-based surrogate model that crafted to accelerate waveform generation for eccentric, spin-aligned BBH systems. SEOBNRE_AIq5e2 incorporates an advanced adaptive resampling technique during training, enabling the generation of eccentric BBH waveforms with mass ratios up to 5, eccentricities below 0.2, and spins $|χ_z|$ up to 0.6. It achieves an impressive generation speed of 4.3 ms per waveform with a mean mismatch of $1.02 \times 10^{-3}$. With the exceptional accuracy and rapid performance, SEOBNRE_AIq5e2 emerges as a promising waveform template for future analysis of eccentric gravitational wave data.

gr-qc↗

arXiv2024

3D-Mol: A Novel Contrastive Learning Framework for Molecular Property Prediction with 3D Information

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.

q-bio.BM↗

arXiv2024

Impact of Domain Knowledge and Multi-Modality on Intelligent Molecular Property Prediction: A Systematic Survey

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.

cs.LG↗

arXiv2024

Dilated convolutional neural network for detecting extreme-mass-ratio inspirals

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.

astro-ph.IM↗

arXiv2024

A Self-feedback Knowledge Elicitation Approach for Chemical Reaction Predictions

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.

cs.LG↗