arXiv subjects

Jiangbin Zheng

Publications and source records attributed to Jiangbin Zheng.

At least 19 recordsLinked to original sources

arXiv2026

MetaGEM: Bottom-Up Reconstruction of Genome-Scale Metabolic Networks via Deep Enzyme-Metabolite Anchoring

Genome-scale metabolic models (GEMs) are essential tools for systems biology and rational chassis design, but conventional top-down reconstruction depends heavily on sequence homology and often leaves unknown enzymes and metabolic dark matter unresolved. Direct reconstruction from metabolomics is also difficult because mapping observed metabolites to reactions is an ill-posed inverse problem with combinatorial ambiguity and possible spurious networks. Here we present MetaGEM, a bottom-up framework that uses enzymes as physical anchors to convert system-level network inference into enzyme-metabolite interaction prediction. MetaGEM uses a multimodal dual-tower architecture that combines protein evolutionary semantics from a protein language model with three-dimensional metabolite representations. It further introduces contrastive learning with hard negative mining to separate structurally similar metabolites and reduce false positive interactions. On a de-homologized benchmark, MetaGEM achieves state-of-the-art enzyme-metabolite prediction performance, with AUROC of 0.9701 and MCC of 0.8033, and remains robust under low sequence identity splits. In downstream reconstruction, MetaGEM generates functional genome-scale metabolic models for Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa. The reconstructed models improve network connectivity, capture promiscuous enzymes, and show strong agreement with experimental phenotype microarray and gene essentiality data. These results indicate that MetaGEM provides a practical route from metabolomic evidence to computable metabolic networks and offers a foundation for automated AI-driven virtual cell reconstruction.

q-bio.QM↗

arXiv2026

TCRTransBench: A Comprehensive Benchmark for Bidirectional TCR-Peptide Sequence Generation

T-cell receptor (TCR) interactions with antigenic peptides underpin adaptive immunity and are pivotal for personalized immunotherapy and vaccine development. Despite recent progress, computational modeling of TCR-peptide specificity remains challenging due to data scarcity, complex sequence dependencies, and the absence of standardized evaluation frameworks. To systematically address these issues, we introduce TCRTransBench, a comprehensive benchmark for bidirectional TCR-peptide sequence generation tasks. Specifically, we define two sequence-to-sequence (seq2seq) tasks: generating antigenic peptides from TCR sequences (TCR2PEP) and generating TCR sequences from antigenic peptides (PEP2TCR). Our framework provides a rigorously curated, MHC-free dataset comprising tens of thousands of validated TCR-peptide pairs, along with diverse evaluation metrics that integrate computational efficiency, sequence accuracy, and biological plausibility. Extensive benchmarking across representative neural architectures, including recurrent, convolutional, and transformer-based models, reveals key trade-offs among performance metrics, highlighting the effectiveness of transformers in capturing intricate biological interactions and the necessity of biologically informed evaluation criteria. TCRTransBench establishes standardized tasks, datasets, and evaluation protocols, laying a robust foundation for future computational advances in immunological sequence modeling and therapeutic protein design.

q-bio.CB↗

arXiv2026

DiffVC: A Non-autoregressive Framework Based on Diffusion Model for Video Captioning

Current video captioning methods usually use an encoder-decoder structure to generate text autoregressively. However, autoregressive methods have inherent limitations such as slow generation speed and large cumulative error. Furthermore, the few non-autoregressive counterparts suffer from deficiencies in generation quality due to the lack of sufficient multimodal interaction modeling. Therefore, we propose a non-autoregressive framework based on Diffusion model for Video Captioning (DiffVC) to address these issues. Its parallel decoding can effectively solve the problems of generation speed and cumulative error. At the same time, our proposed discriminative conditional Diffusion Model can generate higher-quality textual descriptions. Specifically, we first encode the video into a visual representation. During training, Gaussian noise is added to the textual representation of the ground-truth caption. Then, a new textual representation is generated via the discriminative denoiser with the visual representation as a conditional constraint. Finally, we input the new textual representation into a non-autoregressive language model to generate captions. During inference, we directly sample noise from the Gaussian distribution for generation. Experiments on MSVD, MSR-VTT, and VATEX show that our method can outperform previous non-autoregressive methods and achieve comparable performance to autoregressive methods, e.g., it achieved a maximum improvement of 9.9 on the CIDEr and improvement of 2.6 on the B@4, while having faster generation speed. The source code will be available soon.

cs.CV↗

arXiv2025

Probing Scientific General Intelligence of LLMs with Scientist-Aligned Workflows

Despite advances in scientific AI, a coherent framework for Scientific General Intelligence (SGI)-the ability to autonomously conceive, investigate, and reason across scientific domains-remains lacking. We present an operational SGI definition grounded in the Practical Inquiry Model (PIM: Deliberation, Conception, Action, Perception) and operationalize it via four scientist-aligned tasks: deep research, idea generation, dry/wet experiments, and experimental reasoning. SGI-Bench comprises over 1,000 expert-curated, cross-disciplinary samples inspired by Science's 125 Big Questions, enabling systematic evaluation of state-of-the-art LLMs. Results reveal gaps: low exact match (10--20%) in deep research despite step-level alignment; ideas lacking feasibility and detail; high code executability but low execution result accuracy in dry experiments; low sequence fidelity in wet protocols; and persistent multimodal comparative-reasoning challenges. We further introduce Test-Time Reinforcement Learning (TTRL), which optimizes retrieval-augmented novelty rewards at inference, enhancing hypothesis novelty without reference answer. Together, our PIM-grounded definition, workflow-centric benchmark, and empirical insights establish a foundation for AI systems that genuinely participate in scientific discovery.

cs.AI↗

arXiv2025

Departures: Distributional Transport for Single-Cell Perturbation Prediction with Neural Schrödinger Bridges

Predicting single-cell perturbation outcomes directly advances gene function analysis and facilitates drug candidate selection, making it a key driver of both basic and translational biomedical research. However, a major bottleneck in this task is the unpaired nature of single-cell data, as the same cell cannot be observed both before and after perturbation due to the destructive nature of sequencing. Although some neural generative transport models attempt to tackle unpaired single-cell perturbation data, they either lack explicit conditioning or depend on prior spaces for indirect distribution alignment, limiting precise perturbation modeling. In this work, we approximate Schrödinger Bridge (SB), which defines stochastic dynamic mappings recovering the entropy-regularized optimal transport (OT), to directly align the distributions of control and perturbed single-cell populations across different perturbation conditions. Unlike prior SB approximations that rely on bidirectional modeling to infer optimal source-target sample coupling, we leverage Minibatch-OT based pairing to avoid such bidirectional inference and the associated ill-posedness of defining the reverse process. This pairing directly guides bridge learning, yielding a scalable approximation to the SB. We approximate two SB models, one modeling discrete gene activation states and the other continuous expression distributions. Joint training enables accurate perturbation modeling and captures single-cell heterogeneity. Experiments on public genetic and drug perturbation datasets show that our model effectively captures heterogeneous single-cell responses and achieves state-of-the-art performance.

cs.LG↗

arXiv2025

Multimodal Regression for Enzyme Turnover Rates Prediction

The enzyme turnover rate is a fundamental parameter in enzyme kinetics, reflecting the catalytic efficiency of enzymes. However, enzyme turnover rates remain scarce across most organisms due to the high cost and complexity of experimental measurements. To address this gap, we propose a multimodal framework for predicting the enzyme turnover rate by integrating enzyme sequences, substrate structures, and environmental factors. Our model combines a pre-trained language model and a convolutional neural network to extract features from protein sequences, while a graph neural network captures informative representations from substrate molecules. An attention mechanism is incorporated to enhance interactions between enzyme and substrate representations. Furthermore, we leverage symbolic regression via Kolmogorov-Arnold Networks to explicitly learn mathematical formulas that govern the enzyme turnover rate, enabling interpretable and accurate predictions. Extensive experiments demonstrate that our framework outperforms both traditional and state-of-the-art deep learning approaches. This work provides a robust tool for studying enzyme kinetics and holds promise for applications in enzyme engineering, biotechnology, and industrial biocatalysis.

cs.LG↗

arXiv2025

10K is Enough: An Ultra-Lightweight Binarized Network for Infrared Small-Target Detection

The widespread deployment of Infrared Small-Target Detection (IRSTD) algorithms on edge devices necessitates the exploration of model compression techniques. Binarized neural networks (BNNs) are distinguished by their exceptional efficiency in model compression. However, the small size of infrared targets introduces stringent precision requirements for the IRSTD task, while the inherent precision loss during binarization presents a significant challenge. To address this, we propose the Binarized Infrared Small-Target Detection Network (BiisNet), which preserves the core operations of binarized convolutions while integrating full-precision features into the network's information flow. Specifically, we propose the Dot Binary Convolution, which retains fine-grained semantic information in feature maps while still leveraging the binarized convolution operations. In addition, we introduce a smooth and adaptive Dynamic Softsign function, which provides more comprehensive and progressively finer gradient during backpropagation, enhancing model stability and promoting an optimal weight distribution. Experimental results demonstrate that BiisNet not only significantly outperforms other binary architectures but also has strong competitiveness among state-of-the-art full-precision models.

cs.CV↗

arXiv2025

MogaNet: Multi-order Gated Aggregation Network

By contextualizing the kernel as global as possible, Modern ConvNets have shown great potential in computer vision tasks. However, recent progress on multi-order game-theoretic interaction within deep neural networks (DNNs) reveals the representation bottleneck of modern ConvNets, where the expressive interactions have not been effectively encoded with the increased kernel size. To tackle this challenge, we propose a new family of modern ConvNets, dubbed MogaNet, for discriminative visual representation learning in pure ConvNet-based models with favorable complexity-performance trade-offs. MogaNet encapsulates conceptually simple yet effective convolutions and gated aggregation into a compact module, where discriminative features are efficiently gathered and contextualized adaptively. MogaNet exhibits great scalability, impressive efficiency of parameters, and competitive performance compared to state-of-the-art ViTs and ConvNets on ImageNet and various downstream vision benchmarks, including COCO object detection, ADE20K semantic segmentation, 2D&3D human pose estimation, and video prediction. Notably, MogaNet hits 80.0% and 87.8% accuracy with 5.2M and 181M parameters on ImageNet-1K, outperforming ParC-Net and ConvNeXt-L, while saving 59% FLOPs and 17M parameters, respectively. The source code is available at https://github.com/Westlake-AI/MogaNet.

cs.CV↗

arXiv2024

Pan-protein Design Learning Enables Task-adaptive Generalization for Low-resource Enzyme Design

Computational protein design (CPD) offers transformative potential for bioengineering, but current deep CPD models, focused on universal domains, struggle with function-specific designs. This work introduces a novel CPD paradigm tailored for functional design tasks, particularly for enzymes-a key protein class often lacking specific application efficiency. To address structural data scarcity, we present CrossDesign, a domain-adaptive framework that leverages pretrained protein language models (PPLMs). By aligning protein structures with sequences, CrossDesign transfers pretrained knowledge to structure models, overcoming the limitations of limited structural data. The framework combines autoregressive (AR) and non-autoregressive (NAR) states in its encoder-decoder architecture, applying it to enzyme datasets and pan-proteins. Experimental results highlight CrossDesign's superior performance and robustness, especially with out-of-domain enzymes. Additionally, the model excels in fitness prediction when tested on large-scale mutation data, showcasing its stability.

q-bio.QM↗

arXiv2024

DapPep: Domain Adaptive Peptide-agnostic Learning for Universal T-cell Receptor-antigen Binding Affinity Prediction

Identifying T-cell receptors (TCRs) that interact with antigenic peptides provides the technical basis for developing vaccines and immunotherapies. The emergent deep learning methods excel at learning antigen binding patterns from known TCRs but struggle with novel or sparsely represented antigens. However, binding specificity for unseen antigens or exogenous peptides is critical. We introduce a domain-adaptive peptide-agnostic learning framework DapPep for universal TCR-antigen binding affinity prediction to address this challenge. The lightweight self-attention architecture combines a pre-trained protein language model with an inner-loop self-supervised regime to enable robust TCR-peptide representations. Extensive experiments on various benchmarks demonstrate that DapPep consistently outperforms existing tools, showcasing robust generalization capability, especially for data-scarce settings and unseen peptides. Moreover, DapPep proves effective in challenging clinical tasks such as sorting reactive T cells in tumor neoantigen therapy and identifying key positions in 3D structures.

q-bio.QM↗

arXiv2024

CCPL: Cross-modal Contrastive Protein Learning

Effective protein representation learning is crucial for predicting protein functions. Traditional methods often pretrain protein language models on large, unlabeled amino acid sequences, followed by finetuning on labeled data. While effective, these methods underutilize the potential of protein structures, which are vital for function determination. Common structural representation techniques rely heavily on annotated data, limiting their generalizability. Moreover, structural pretraining methods, similar to natural language pretraining, can distort actual protein structures. In this work, we introduce a novel unsupervised protein structure representation pretraining method, cross-modal contrastive protein learning (CCPL). CCPL leverages a robust protein language model and uses unsupervised contrastive alignment to enhance structure learning, incorporating self-supervised structural constraints to maintain intrinsic structural information. We evaluated our model across various benchmarks, demonstrating the framework's superiority.

q-bio.BM↗

arXiv2024

MetaEnzyme: Meta Pan-Enzyme Learning for Task-Adaptive Redesign

Enzyme design plays a crucial role in both industrial production and biology. However, this field faces challenges due to the lack of comprehensive benchmarks and the complexity of enzyme design tasks, leading to a dearth of systematic research. Consequently, computational enzyme design is relatively overlooked within the broader protein domain and remains in its early stages. In this work, we address these challenges by introducing MetaEnzyme, a staged and unified enzyme design framework. We begin by employing a cross-modal structure-to-sequence transformation architecture, as the feature-driven starting point to obtain initial robust protein representation. Subsequently, we leverage domain adaptive techniques to generalize specific enzyme design tasks under low-resource conditions. MetaEnzyme focuses on three fundamental low-resource enzyme redesign tasks: functional design (FuncDesign), mutation design (MutDesign), and sequence generation design (SeqDesign). Through novel unified paradigm and enhanced representation capabilities, MetaEnzyme demonstrates adaptability to diverse enzyme design tasks, yielding outstanding results. Wet lab experiments further validate these findings, reinforcing the efficacy of the redesign process.

q-bio.BM↗

arXiv2024

Progressive Multi-Modality Learning for Inverse Protein Folding

While deep generative models show promise for learning inverse protein folding directly from data, the lack of publicly available structure-sequence pairings limits their generalization. Previous improvements and data augmentation efforts to overcome this bottleneck have been insufficient. To further address this challenge, we propose a novel protein design paradigm called MMDesign, which leverages multi-modality transfer learning. To our knowledge, MMDesign is the first framework that combines a pretrained structural module with a pretrained contextual module, using an auto-encoder (AE) based language model to incorporate prior protein semantic knowledge. Experimental results, only training with the small dataset, demonstrate that MMDesign consistently outperforms baselines on various public benchmarks. To further assess the biological plausibility, we present systematic quantitative analysis techniques that provide interpretability and reveal more about the laws of protein design.

cs.AI↗

arXiv2024

Deciphering RNA Secondary Structure Prediction: A Probabilistic K-Rook Matching Perspective

The secondary structure of ribonucleic acid (RNA) is more stable and accessible in the cell than its tertiary structure, making it essential for functional prediction. Although deep learning has shown promising results in this field, current methods suffer from poor generalization and high complexity. In this work, we reformulate the RNA secondary structure prediction as a K-Rook problem, thereby simplifying the prediction process into probabilistic matching within a finite solution space. Building on this innovative perspective, we introduce RFold, a simple yet effective method that learns to predict the most matching K-Rook solution from the given sequence. RFold employs a bi-dimensional optimization strategy that decomposes the probabilistic matching problem into row-wise and column-wise components to reduce the matching complexity, simplifying the solving process while guaranteeing the validity of the output. Extensive experiments demonstrate that RFold achieves competitive performance and about eight times faster inference efficiency than the state-of-the-art approaches. The code and Colab demo are available in (http://github.com/A4Bio/RFold).

q-bio.BM↗

arXiv2024

VQDNA: Unleashing the Power of Vector Quantization for Multi-Species Genomic Sequence Modeling

Similar to natural language models, pre-trained genome language models are proposed to capture the underlying intricacies within genomes with unsupervised sequence modeling. They have become essential tools for researchers and practitioners in biology. However, the hand-crafted tokenization policies used in these models may not encode the most discriminative patterns from the limited vocabulary of genomic data. In this paper, we introduce VQDNA, a general-purpose framework that renovates genome tokenization from the perspective of genome vocabulary learning. By leveraging vector-quantized codebooks as learnable vocabulary, VQDNA can adaptively tokenize genomes into pattern-aware embeddings in an end-to-end manner. To further push its limits, we propose Hierarchical Residual Quantization (HRQ), where varying scales of codebooks are designed in a hierarchy to enrich the genome vocabulary in a coarse-to-fine manner. Extensive experiments on 32 genome datasets demonstrate VQDNA's superiority and favorable parameter efficiency compared to existing genome language models. Notably, empirical analysis of SARS-CoV-2 mutations reveals the fine-grained pattern awareness and biological significance of learned HRQ vocabulary, highlighting its untapped potential for broader applications in genomics.

q-bio.GN↗

arXiv2024

Inter- and intra-uncertainty based feature aggregation model for semi-supervised histopathology image segmentation

Acquiring pixel-level annotations is often limited in applications such as histology studies that require domain expertise. Various semi-supervised learning approaches have been developed to work with limited ground truth annotations, such as the popular teacher-student models. However, hierarchical prediction uncertainty within the student model (intra-uncertainty) and image prediction uncertainty (inter-uncertainty) have not been fully utilized by existing methods. To address these issues, we first propose a novel inter- and intra-uncertainty regularization method to measure and constrain both inter- and intra-inconsistencies in the teacher-student architecture. We also propose a new two-stage network with pseudo-mask guided feature aggregation (PG-FANet) as the segmentation model. The two-stage structure complements with the uncertainty regularization strategy to avoid introducing extra modules in solving uncertainties and the aggregation mechanisms enable multi-scale and multi-stage feature integration. Comprehensive experimental results over the MoNuSeg and CRAG datasets show that our PG-FANet outperforms other state-of-the-art methods and our semi-supervised learning framework yields competitive performance with a limited amount of labeled data.

cs.CV↗

arXiv2024

Advances of Deep Learning in Protein Science: A Comprehensive Survey

Protein representation learning plays a crucial role in understanding the structure and function of proteins, which are essential biomolecules involved in various biological processes. In recent years, deep learning has emerged as a powerful tool for protein modeling due to its ability to learn complex patterns and representations from large-scale protein data. This comprehensive survey aims to provide an overview of the recent advances in deep learning techniques applied to protein science. The survey begins by introducing the developments of deep learning based protein models and emphasizes the importance of protein representation learning in drug discovery, protein engineering, and function annotation. It then delves into the fundamentals of deep learning, including convolutional neural networks, recurrent neural networks, attention models, and graph neural networks in modeling protein sequences, structures, and functions, and explores how these techniques can be used to extract meaningful features and capture intricate relationships within protein data. Next, the survey presents various applications of deep learning in the field of proteins, including protein structure prediction, protein-protein interaction prediction, protein function prediction, etc. Furthermore, it highlights the challenges and limitations of these deep learning techniques and also discusses potential solutions and future directions for overcoming these challenges. This comprehensive survey provides a valuable resource for researchers and practitioners in the field of proteins who are interested in harnessing the power of deep learning techniques. By consolidating the latest advancements and discussing potential avenues for improvement, this review contributes to the ongoing progress in protein research and paves the way for future breakthroughs in the field.

q-bio.BM↗

arXiv2024

Cross-Gate MLP with Protein Complex Invariant Embedding is A One-Shot Antibody Designer

Antibodies are crucial proteins produced by the immune system in response to foreign substances or antigens. The specificity of an antibody is determined by its complementarity-determining regions (CDRs), which are located in the variable domains of the antibody chains and form the antigen-binding site. Previous studies have utilized complex techniques to generate CDRs, but they suffer from inadequate geometric modeling. Moreover, the common iterative refinement strategies lead to an inefficient inference. In this paper, we propose a \textit{simple yet effective} model that can co-design 1D sequences and 3D structures of CDRs in a one-shot manner. To achieve this, we decouple the antibody CDR design problem into two stages: (i) geometric modeling of protein complex structures and (ii) sequence-structure co-learning. We develop a novel macromolecular structure invariant embedding, typically for protein complexes, that captures both intra- and inter-component interactions among the backbone atoms, including C$α$, N, C, and O atoms, to achieve comprehensive geometric modeling. Then, we introduce a simple cross-gate MLP for sequence-structure co-learning, allowing sequence and structure representations to implicitly refine each other. This enables our model to design desired sequences and structures in a one-shot manner. Extensive experiments are conducted to evaluate our results at both the sequence and structure levels, which demonstrate that our model achieves superior performance compared to the state-of-the-art antibody CDR design methods.

q-bio.BM↗