Zelin Zang

Zelin Zang, Hao Luo, Kai Wang et al. · stanford

Unsupervised Contrastive learning has gained prominence in fields such as vision, and biology, leveraging predefined positive/negative samples for representation learning. Data augmentation, categorized into hand-designed and model-based methods, has been identified as a crucial component for enhancing contrastive learning. However, hand-designed methods require human expertise in domain-specific data while sometimes distorting the meaning of the data. In contrast, generative model-based approaches usually require supervised or large-scale external data, which has become a bottleneck constraining model training in many domains. To address the problems presented above, this paper proposes DiffAug, a novel unsupervised contrastive learning technique with diffusion mode-based positive data generation. DiffAug consists of a semantic encoder and a conditional diffusion model; the conditional diffusion model generates new positive samples conditioned on the semantic encoding to serve the training of unsupervised contrast learning. With the help of iterative training of the semantic encoder and diffusion model, DiffAug improves the representation ability in an uninterrupted and unsupervised manner. Experimental evaluations show that DiffAug outperforms hand-designed and SOTA model-based augmentation methods on DNA sequence, visual, and bio-feature datasets. The code for review is released at \url{https://github.com/zangzelin/code_diffaug}.

Zelin Zang, Siyuan Li, Di Wu et al. · tsinghua

Manifold learning (ML) aims to seek low-dimensional embedding from high-dimensional data. The problem is challenging on real-world datasets, especially with under-sampling data, and we find that previous methods perform poorly in this case. Generally, ML methods first transform input data into a low-dimensional embedding space to maintain the data's geometric structure and subsequently perform downstream tasks therein. The poor local connectivity of under-sampling data in the former step and inappropriate optimization objectives in the latter step leads to two problems: structural distortion and underconstrained embedding. This paper proposes a novel ML framework named Deep Local-flatness Manifold Embedding (DLME) to solve these problems. The proposed DLME constructs semantic manifolds by data augmentation and overcomes the structural distortion problem using a smoothness constrained based on a local flatness assumption about the manifold. To overcome the underconstrained embedding problem, we design a loss and theoretically demonstrate that it leads to a more suitable embedding based on the local flatness. Experiments on three types of datasets (toy, biological, and image) for various downstream tasks (classification, clustering, and visualization) show that our proposed DLME outperforms state-of-the-art ML and contrastive learning methods.

Siyuan Li, Di Wu, Fang Wu et al. · tsinghua

Masked image modeling, an emerging self-supervised pre-training method, has shown impressive success across numerous downstream vision tasks with Vision transformers. Its underlying idea is simple: a portion of the input image is masked out and then reconstructed via a pre-text task. However, the working principle behind MIM is not well explained, and previous studies insist that MIM primarily works for the Transformer family but is incompatible with CNNs. In this work, we observe that MIM essentially teaches the model to learn better middle-order interactions among patches for more generalized feature extraction. We then propose an Architecture-Agnostic Masked Image Modeling framework (A$^2$MIM), which is compatible with both Transformers and CNNs in a unified way. Extensive experiments on popular benchmarks show that A$^2$MIM learns better representations without explicit design and endows the backbone model with the stronger capability to transfer to various downstream tasks.

Zelin Zang, Lei Shang, Senqiao Yang et al.

Unsupervised domain adaptation (UDA) has proven to be highly effective in transferring knowledge from a label-rich source domain to a label-scarce target domain. However, the presence of additional novel categories in the target domain has led to the development of open-set domain adaptation (ODA) and universal domain adaptation (UNDA). Existing ODA and UNDA methods treat all novel categories as a single, unified unknown class and attempt to detect it during training. However, we found that domain variance can lead to more significant view-noise in unsupervised data augmentation, which affects the effectiveness of contrastive learning (CL) and causes the model to be overconfident in novel category discovery. To address these issues, a framework named Soft-contrastive All-in-one Network (SAN) is proposed for ODA and UNDA tasks. SAN includes a novel data-augmentation-based soft contrastive learning (SCL) loss to fine-tune the backbone for feature transfer and a more human-intuitive classifier to improve new class discovery capability. The SCL loss weakens the adverse effects of the data augmentation view-noise problem which is amplified in domain transfer tasks. The All-in-One (AIO) classifier overcomes the overconfidence problem of current mainstream closed-set and open-set classifiers. Visualization and ablation experiments demonstrate the effectiveness of the proposed innovations. Furthermore, extensive experiment results on ODA and UNDA show that SAN outperforms existing state-of-the-art methods.

Zelin Zang, Shenghui Cheng, Linyan Lu et al.

Dimension reduction (DR) is commonly utilized to capture the intrinsic structure and transform high-dimensional data into low-dimensional space while retaining meaningful properties of the original data. It is used in various applications, such as image recognition, single-cell sequencing analysis, and biomarker discovery. However, contemporary parametric-free and parametric DR techniques suffer from several significant shortcomings, such as the inability to preserve global and local features and the pool generalization performance. On the other hand, regarding explainability, it is crucial to comprehend the embedding process, especially the contribution of each part to the embedding process, while understanding how each feature affects the embedding results that identify critical components and help diagnose the embedding process. To address these problems, we have developed a deep neural network method called EVNet, which provides not only excellent performance in structural maintainability but also explainability to the DR therein. EVNet starts with data augmentation and a manifold-based loss function to improve embedding performance. The explanation is based on saliency maps and aims to examine the trained EVNet parameters and contributions of components during the embedding process. The proposed techniques are integrated with a visual interface to help the user to adjust EVNet to achieve better DR performance and explainability. The interactive visual interface makes it easier to illustrate the data features, compare different DR techniques, and investigate DR. An in-depth experimental comparison shows that EVNet consistently outperforms the state-of-the-art methods in both performance measures and explainability.

Yehui Yang, Zelin Zang, Changxi Chi et al.

Automated cellular reasoning faces a core dichotomy: supervised methods fall into the Reference Trap and fail to generalize to out-of-distribution cell states, while large language models (LLMs), without grounded biological priors, suffer from a Signal-to-Noise Paradox that produces spurious associations. We propose MAT-Cell, a neuro-symbolic reasoning framework that reframes single-cell analysis from black-box classification into constructive, verifiable proof generation. MAT-Cell injects symbolic constraints through adaptive Retrieval-Augmented Generation (RAG) to ground neural reasoning in biological axioms and reduce transcriptomic noise. It further employs a dialectic verification process with homogeneous rebuttal agents to audit and prune reasoning paths, forming syllogistic derivation trees that enforce logical consistency.Across large-scale and cross-species benchmarks, MAT-Cell significantly outperforms state-of-the-art (SOTA) models and maintains robust per-formance in challenging scenarios where baselinemethods severely degrade. Code is available at https://gith ub.com/jiangliu91/MAT-Cell-A-Mul ti-Agent-Tree-Structured-Reasoni ng-Framework-for-Batch-Level-Sin gle-Cell-Annotation.

Mengran Li, Zelin Zang, Wenbin Xing et al.

Understanding how chemical perturbations propagate through biological systems is essential for robust molecular property prediction. While most existing methods focus on chemical structures alone, recent advances highlight the crucial role of cellular responses such as morphology and gene expression in shaping drug effects. However, current cell-aware approaches face two key limitations: (1) modality incompleteness in external biological data, and (2) insufficient modeling of hierarchical dependencies across molecular, cellular, and genomic levels. We propose CHMR (Cell-aware Hierarchical Multi-modal Representations), a robust framework that jointly models local-global dependencies between molecules and cellular responses and captures latent biological hierarchies via a novel tree-structured vector quantization module. Evaluated on nine public benchmarks spanning 728 tasks, CHMR outperforms state-of-the-art baselines, yielding average improvements of 3.6% on classification and 17.2% on regression tasks. These results demonstrate the advantage of hierarchy-aware, multimodal learning for reliable and biologically grounded molecular representations, offering a generalizable framework for integrative biomedical modeling. The code is in https://github.com/limengran98/CHMR.

Ziyang Song, Zelin Zang, Zuyao Chen et al.

Multimodal Large Language Models (MLLMs) have achieved impressive progress in natural image reasoning, yet their potential in medical imaging remains underexplored, especially in clinical anatomical surgical images. Anatomy understanding tasks demand precise understanding and clinically coherent answers, which are difficult to achieve due to the complexity of medical data and the scarcity of high-quality expert annotations. These challenges limit the effectiveness of conventional Supervised Fine-Tuning (SFT) strategies. While recent work has demonstrated that Group Relative Policy Optimization (GRPO) can enhance reasoning in MLLMs without relying on large amounts of data, we find two weaknesses that hinder GRPO's reasoning performance in anatomy recognition: 1) knowledge cannot be effectively shared between different anatomical structures, resulting in uneven information gain and preventing the model from converging, and 2) the model quickly converges to a single reasoning path, suppressing the exploration of diverse strategies. To overcome these challenges, we propose two novel methods. First, we implement a progressive learning strategy called Anatomical Similarity Curriculum Learning by controlling question difficulty via the similarity of answer choices, enabling the model to master complex problems incrementally. Second, we utilize question augmentation referred to as Group Diversity Question Augmentation to expand the model's search space for difficult queries, mitigating the tendency to produce uniform responses. Comprehensive experiments on the SGG-VQA and OmniMedVQA benchmarks show our method achieves a significant improvement across the two benchmarks, demonstrating its effectiveness in enhancing the medical reasoning capabilities of MLLMs. The code can be found in https://github.com/tomato996/Anatomy-R1

Zelin Zang, Yongjie Xu, Linyan Lu et al.

Dimensional reduction~(DR) maps high-dimensional data into a lower dimensions latent space with minimized defined optimization objectives. The DR method usually falls into feature selection~(FS) and feature projection~(FP). FS focuses on selecting a critical subset of dimensions but risks destroying the data distribution (structure). On the other hand, FP combines all the input features into lower dimensions space, aiming to maintain the data structure; but lacks interpretability and sparsity. FS and FP are traditionally incompatible categories; thus, they have not been unified into an amicable framework. We propose that the ideal DR approach combines both FS and FP into a unified end-to-end manifold learning framework, simultaneously performing fundamental feature discovery while maintaining the intrinsic relationships between data samples in the latent space. In this work, we develop a unified framework, Unified Dimensional Reduction Neural-network~(UDRN), that integrates FS and FP in a compatible, end-to-end way. We improve the neural network structure by implementing FS and FP tasks separately using two stacked sub-networks. In addition, we designed data augmentation of the DR process to improve the generalization ability of the method when dealing with extensive feature datasets and designed loss functions that can cooperate with the data augmentation. Extensive experimental results on four image and four biological datasets, including very high-dimensional data, demonstrate the advantages of DRN over existing methods~(FS, FP, and FS\&FP pipeline), especially in downstream tasks such as classification and visualization.

Kai Wang, Dongwen Tang, Boya Zeng et al.

Diffusion models have achieved remarkable success in image and video generation. In this work, we demonstrate that diffusion models can also \textit{generate high-performing neural network parameters}. Our approach is simple, utilizing an autoencoder and a diffusion model. The autoencoder extracts latent representations of a subset of the trained neural network parameters. Next, a diffusion model is trained to synthesize these latent representations from random noise. This model then generates new representations, which are passed through the autoencoder's decoder to produce new subsets of high-performing network parameters. Across various architectures and datasets, our approach consistently generates models with comparable or improved performance over trained networks, with minimal additional cost. Notably, we empirically find that the generated models are not memorizing the trained ones. Our results encourage more exploration into the versatile use of diffusion models. Our code is available \href{https://github.com/NUS-HPC-AI-Lab/Neural-Network-Diffusion}{here}.

Jinlin Wu, Felix Holm, Chuxi Chen et al.

While foundation models have advanced surgical video analysis, current approaches rely predominantly on pixel-level reconstruction objectives that waste model capacity on low-level visual details - such as smoke, specular reflections, and fluid motion - rather than semantic structures essential for surgical understanding. We present UniSurg, a video-native foundation model that shifts the learning paradigm from pixel-level reconstruction to latent motion prediction. Built on the Video Joint Embedding Predictive Architecture (V-JEPA), UniSurg introduces three key technical innovations tailored to surgical videos: 1) motion-guided latent prediction to prioritize semantically meaningful regions, 2) spatiotemporal affinity self-distillation to enforce relational consistency, and 3) feature diversity regularization to prevent representation collapse in texture-sparse surgical scenes. To enable large-scale pretraining, we curate UniSurg-15M, the largest surgical video dataset to date, comprising 3,658 hours of video from 50 sources across 13 anatomical regions. Extensive experiments across 17 benchmarks demonstrate that UniSurg significantly outperforms state-of-the-art methods on surgical workflow recognition (+14.6% F1 on EgoSurgery, +10.3% on PitVis), action triplet recognition (39.54% mAP-IVT on CholecT50), skill assessment, polyp segmentation, and depth estimation. These results establish UniSurg as a new standard for universal, motion-oriented surgical video understanding.

Ziyang Song, Zelin Zang, Xiaofan Ye et al.

Multimodal Large Language Models (MLLMs) have shown significant potential in surgical video understanding. With improved zero-shot performance and more effective human-machine interaction, they provide a strong foundation for advancing surgical education and assistance. However, existing research and datasets primarily focus on understanding surgical procedures and workflows, while paying limited attention to the critical role of anatomical comprehension. In clinical practice, surgeons rely heavily on precise anatomical understanding to interpret, review, and learn from surgical videos. To fill this gap, we introduce the Neurosurgical Anatomy Benchmark (NeuroABench), the first multimodal benchmark explicitly created to evaluate anatomical understanding in the neurosurgical domain. NeuroABench consists of 9 hours of annotated neurosurgical videos covering 89 distinct procedures and is developed using a novel multimodal annotation pipeline with multiple review cycles. The benchmark evaluates the identification of 68 clinical anatomical structures, providing a rigorous and standardized framework for assessing model performance. Experiments on over 10 state-of-the-art MLLMs reveal significant limitations, with the best-performing model achieving only 40.87% accuracy in anatomical identification tasks. To further evaluate the benchmark, we extract a subset of the dataset and conduct an informative test with four neurosurgical trainees. The results show that the best-performing student achieves 56% accuracy, with the lowest scores of 28% and an average score of 46.5%. While the best MLLM performs comparably to the lowest-scoring student, it still lags significantly behind the group's average performance. This comparison underscores both the progress of MLLMs in anatomical understanding and the substantial gap that remains in achieving human-level performance.

Xichen Yan, Zelin Zang, Changxi Chi et al.

A critical challenge in single-cell RNA sequencing (scRNA-seq) integration is resolving the tension between eliminating batch effects and maintaining biological fidelity. While recent evidence indicates that batch effects manifest heterogeneously across genes, most existing methods process the transcriptome uniformly, frequently resulting in over-correction and loss of subtle biological signals. To address this, we present scHelix, a dataset-adaptive framework that fundamentally changes how features are processed by explicitly partitioning genes into domain-invariant Anchors and domain-sensitive Variants at the input level. scHelix utilizes a dual-stream sparse diffusion encoder equipped with stop-gradient graph caching to efficiently learn multi-scale structural representations. The core of our approach is a novel asymmetric Align-Refine-Fuse protocol: the unstable Variant stream is first aligned to the robust topology of the Anchor stream, followed by a conservative refinement phase where the Anchor stream absorbs denoised details via bounded residual gating. This divide-and-conquer architecture prevents shortcut learning and ensures robust batch removal without compromising the integrity of biological clusters. Extensive benchmarking demonstrates that scHelix outperforms state-of-the-art methods.

Zelin Zang, Wenyi Gu, Siqi Ma et al.

With the rapid growth of large language models (LLMs) and vision-language models (VLMs) in medicine, simply integrating clinical text and medical imaging does not guarantee reliable reasoning. Existing multimodal models often produce hallucinations or inconsistent chains of thought, limiting clinical trust. We propose a diagnostic framework built upon LLaVA that combines vision-language alignment with logic-regularized reasoning. The system includes an input encoder for text and images, a projection module for cross-modal alignment, a reasoning controller that decomposes diagnostic tasks into steps, and a logic tree generator that assembles stepwise premises into verifiable conclusions. Evaluations on MedXpertQA and other benchmarks show that our method improves diagnostic accuracy and yields more interpretable reasoning traces on multimodal tasks, while remaining competitive on text-only settings. These results suggest a promising step toward trustworthy multimodal medical AI.

Siqi Ma, Jiajie Huang, Fan Zhang et al.

Answering complex medical questions requires not only domain expertise and patient-specific information, but also structured and multi-perspective reasoning. Existing multi-agent approaches often rely on fixed roles or shallow interaction prompts, limiting their ability to detect and resolve fine-grained logical inconsistencies. To address this, we propose \textsc{MedLA}, a logic-driven multi-agent framework built on large language models. Each agent organizes its reasoning process into an explicit logical tree based on syllogistic triads (major premise, minor premise, and conclusion), enabling transparent inference and premise-level alignment. Agents engage in a multi-round, graph-guided discussion to compare and iteratively refine their logic trees, achieving consensus through error correction and contradiction resolution. We demonstrate that \textsc{MedLA} consistently outperforms both static role-based systems and single-agent baselines on challenging benchmarks such as MedDDx and standard medical QA tasks. Furthermore, \textsc{MedLA} scales effectively across both open-source and commercial LLM backbones, achieving state-of-the-art performance and offering a generalizable paradigm for trustworthy medical reasoning.

Zelin Zang, Yuhao Wang, Jinlin Wu et al.

Dimensionality reduction (DR) plays a crucial role in various fields, including data engineering and visualization, by simplifying complex datasets while retaining essential information. However, achieving both high DR accuracy and strong explainability remains a fundamental challenge, especially for users dealing with high-dimensional data. Traditional DR methods often face a trade-off between precision and transparency, where optimizing for performance can lead to reduced explainability, and vice versa. This limitation is especially prominent in real-world applications such as image, tabular, and text data analysis, where both accuracy and explainability are critical. To address these challenges, this work introduces the MOE-based Explainable Deep Manifold Transformation (DMT-ME). The proposed approach combines hyperbolic embeddings, which effectively capture complex hierarchical structures, with Mixture of Experts (MOE) models, which dynamically allocate tasks based on input features. DMT-ME enhances DR accuracy by leveraging hyperbolic embeddings to represent the hierarchical nature of data, while also improving explainability by explicitly linking input data, embedding outcomes, and key features through the MOE structure. Extensive experiments demonstrate that DMT-ME consistently achieves superior performance in both DR accuracy and model explainability, making it a robust solution for complex data analysis. The code is available at https://github.com/zangzelin/code_dmtme

Jingbo Zhou, Yixuan Du, Ruqiong Zhang et al.

Graph Neural Networks (GNNs), a type of neural network that can learn from graph-structured data through neighborhood information aggregation, have shown superior performance in various downstream tasks. However, as the number of layers increases, node representations become indistinguishable, which is known as over-smoothing. To address this issue, many residual methods have emerged. In this paper, we focus on the over-smoothing issue and related residual methods. Firstly, we revisit over-smoothing from the perspective of overlapping neighborhood subgraphs, and based on this, we explain how residual methods can alleviate over-smoothing by integrating multiple orders neighborhood subgraphs to avoid the indistinguishability of the single high-order neighborhood subgraphs. Additionally, we reveal the drawbacks of previous residual methods, such as the lack of node adaptability and severe loss of high-order neighborhood subgraph information, and propose a \textbf{Posterior-Sampling-based, Node-Adaptive Residual module (PSNR)}. We theoretically demonstrate that PSNR can alleviate the drawbacks of previous residual methods. Furthermore, extensive experiments verify the superiority of the PSNR module in fully observed node classification and missing feature scenarios. Our code is available at https://github.com/jingbo02/PSNR-GNN.

Stan Z. Li, Zelin Zang, Lirong Wu

We propose a novel framework, called Markov-Lipschitz deep learning (MLDL), to tackle geometric deterioration caused by collapse, twisting, or crossing in vector-based neural network transformations for manifold-based representation learning and manifold data generation. A prior constraint, called locally isometric smoothness (LIS), is imposed across-layers and encoded into a Markov random field (MRF)-Gibbs distribution. This leads to the best possible solutions for local geometry preservation and robustness as measured by locally geometric distortion and locally bi-Lipschitz continuity. Consequently, the layer-wise vector transformations are enhanced into well-behaved, LIS-constrained metric homeomorphisms. Extensive experiments, comparisons, and ablation study demonstrate significant advantages of MLDL for manifold learning and manifold data generation. MLDL is general enough to enhance any vector transformation-based networks. The code is available at https://github.com/westlake-cairi/Markov-Lipschitz-Deep-Learning.

Zelin Zang, Yehui Yang, Fei Wang et al.

Unsupervised Domain Adaptation (UDA) seeks to transfer knowledge from a labeled source domain to an unlabeled target domain but often suffers from severe domain and scale gaps that degrade performance. Existing cross-attention-based transformers can align features across domains, yet they struggle to preserve content semantics under large appearance and scale variations. To explicitly address these challenges, we introduce the concept of beneficial noise, which regularizes cross-attention by injecting controlled perturbations, encouraging the model to ignore style distractions and focus on content. We propose the Domain-Adaptive Cross-Scale Matching (DACSM) framework, which consists of a Domain-Adaptive Transformer (DAT) for disentangling domain-shared content from domain-specific style, and a Cross-Scale Matching (CSM) module that adaptively aligns features across multiple resolutions. DAT incorporates beneficial noise into cross-attention, enabling progressive domain translation with enhanced robustness, yielding content-consistent and style-invariant representations. Meanwhile, CSM ensures semantic consistency under scale changes. Extensive experiments on VisDA-2017, Office-Home, and DomainNet demonstrate that DACSM achieves state-of-the-art performance, with up to +2.3% improvement over CDTrans on VisDA-2017. Notably, DACSM achieves a +5.9% gain on the challenging "truck" class of VisDA, evidencing the strength of beneficial noise in handling scale discrepancies. These results highlight the effectiveness of combining domain translation, beneficial-noise-enhanced attention, and scale-aware alignment for robust cross-domain representation learning.

Mengran Li, Bo Li, Jiaying Wang et al.

Virtual Cell Modeling (VCM) requires models that not only predict perturbation responses, but also support targeted revision when predictions fail. Current LLM-assisted modeling workflows face a refinement-routing problem: prediction discrepancies are observed through executable implementations, but the relevant revision may involve the modeling assumption, representation design, implementation, or task constraint. Without structured feedback propagation across these levels, iterative refinement may repair code while failing to revise the assumption responsible for the discrepancy. We propose CellScientist, a dual-space hierarchical framework that couples a high-level hypothesis space with a low-level executable implementation space. CellScientist represents modeling decisions as structured states, realizes them as admissible programs under task and interface constraints, and routes execution discrepancies back to targeted hypothesis or implementation updates. This enables a closed Hypothesis -> Implementation -> Hypothesis loop where failures become structured signals for model refinement rather than debugging events. Across morphology and transcriptomic benchmarks, with additional single-cell perturbation evaluations, the final executable models selected by CellScientist improve over reference baselines under fixed split and evaluation protocols, while the workflow produces auditable refinement traces.

Yurui Xiang, Xingyi Mao, Rui Sheng et al.

Large language models (LLMs) show promise in medical diagnosis, but real-world deployment remains challenging due to high-stakes clinical decisions and imperfect reasoning reliability. As a result, careful inspection of model behavior is essential for assessing whether diagnostic reasoning is reliable and clinically grounded. However, debugging medical LLMs remains difficult. First, developers often lack sufficient medical domain expertise to interpret model errors in clinically meaningful terms. Second, models can fail across a large and diverse set of instances involving different input types, tasks, and reasoning steps, making it challenging for developers to prioritize which errors deserve focused inspection. Third, developers struggle to identify recurring error patterns across cases, as existing debugging practices are largely instance-centric and rely on manual inspection of isolated failures. To address these challenges, we present VeriLLMed, a visual analytics system that integrates external biomedical knowledge to audit and debug medical LLM diagnostic reasoning. VeriLLMed transforms model outputs into comparable reasoning paths, constructs knowledge graph-grounded reference paths, and identifies three recurring classes of diagnosis errors: relation errors, branch errors, and missing errors. Case studies and expert evaluation demonstrate that VeriLLMed helps developers identify clinically implausible reasoning and generate actionable insights that can inform the improvement of medical LLMs.

Hanchen Xia, Baoyou Chen, Zelin Zang et al.

We propose LaPha, a method for training AlphaZero-like LLM agents in a Poincaré latent space. Under LaPha, the search process can be visualized as a tree rooted at the prompt and growing outward from the origin toward the boundary of the Poincaré ball, where negative curvature provides exponentially increasing capacity with radius. Using hyperbolic geodesic distance to rule-verified correctness, we define a node potential and assign dense process rewards by potential differences. We further attach a lightweight value head on the same shared latent space, enabling self-guided test-time scaling with almost no additional overhead. On MATH-500, LaPha improves Qwen2.5-Math-1.5B from 66.0% to 88.2%. With value-head-guided search, LaPha-1.5B reaches 56.7% accuracy on AIME'24, and LaPha-7B further achieves 60.0% on AIME'24 and 53.3% on AIME'25.

ChenRui Duan, Zelin Zang, Siyuan Li et al.

Phylogenetic trees elucidate evolutionary relationships among species, but phylogenetic inference remains challenging due to the complexity of combining continuous (branch lengths) and discrete parameters (tree topology). Traditional Markov Chain Monte Carlo methods face slow convergence and computational burdens. Existing Variational Inference methods, which require pre-generated topologies and typically treat tree structures and branch lengths independently, may overlook critical sequence features, limiting their accuracy and flexibility. We propose PhyloGen, a novel method leveraging a pre-trained genomic language model to generate and optimize phylogenetic trees without dependence on evolutionary models or aligned sequence constraints. PhyloGen views phylogenetic inference as a conditionally constrained tree structure generation problem, jointly optimizing tree topology and branch lengths through three core modules: (i) Feature Extraction, (ii) PhyloTree Construction, and (iii) PhyloTree Structure Modeling. Meanwhile, we introduce a Scoring Function to guide the model towards a more stable gradient descent. We demonstrate the effectiveness and robustness of PhyloGen on eight real-world benchmark datasets. Visualization results confirm PhyloGen provides deeper insights into phylogenetic relationships.

ChenRui Duan, Zelin Zang, Yongjie Xu et al.

Metagenomic data, comprising mixed multi-species genomes, are prevalent in diverse environments like oceans and soils, significantly impacting human health and ecological functions. However, current research relies on K-mer, which limits the capture of structurally and functionally relevant gene contexts. Moreover, these approaches struggle with encoding biologically meaningful genes and fail to address the One-to-Many and Many-to-One relationships inherent in metagenomic data. To overcome these challenges, we introduce FGBERT, a novel metagenomic pre-trained model that employs a protein-based gene representation as a context-aware and structure-relevant tokenizer. FGBERT incorporates Masked Gene Modeling (MGM) to enhance the understanding of inter-gene contextual relationships and Triplet Enhanced Metagenomic Contrastive Learning (TMC) to elucidate gene sequence-function relationships. Pre-trained on over 100 million metagenomic sequences, FGBERT demonstrates superior performance on metagenomic datasets at four levels, spanning gene, functional, bacterial, and environmental levels and ranging from 1k to 213k input sequences. Case studies of ATP Synthase and Gene Operons highlight FGBERT's capability for functional recognition and its biological relevance in metagenomic research.

Bozhen Hu, Zelin Zang, Jun Xia et al.

Representing graph data in a low-dimensional space for subsequent tasks is the purpose of attributed graph embedding. Most existing neural network approaches learn latent representations by minimizing reconstruction errors. Rare work considers the data distribution and the topological structure of latent codes simultaneously, which often results in inferior embeddings in real-world graph data. This paper proposes a novel Deep Manifold (Variational) Graph Auto-Encoder (DMVGAE/DMGAE) method for attributed graph data to improve the stability and quality of learned representations to tackle the crowding problem. The node-to-node geodesic similarity is preserved between the original and latent space under a pre-defined distribution. The proposed method surpasses state-of-the-art baseline algorithms by a significant margin on different downstream tasks across popular datasets, which validates our solutions. We promise to release the code after acceptance.

Zelin Zang, Liangyu Li, Yongjie Xu et al.

Spatial transcriptomics (ST) technologies have revolutionized the study of gene expression patterns in tissues by providing multimodality data in transcriptomic, spatial, and morphological, offering opportunities for understanding tissue biology beyond transcriptomics. However, we identify the modality bias phenomenon in ST data species, i.e., the inconsistent contribution of different modalities to the labels leads to a tendency for the analysis methods to retain the information of the dominant modality. How to mitigate the adverse effects of modality bias to satisfy various downstream tasks remains a fundamental challenge. This paper introduces Multiple-modality Structure Transformation, named MuST, a novel methodology to tackle the challenge. MuST integrates the multi-modality information contained in the ST data effectively into a uniform latent space to provide a foundation for all the downstream tasks. It learns intrinsic local structures by topology discovery strategy and topology fusion loss function to solve the inconsistencies among different modalities. Thus, these topology-based and deep learning techniques provide a solid foundation for a variety of analytical tasks while coordinating different modalities. The effectiveness of MuST is assessed by performance metrics and biological significance. The results show that it outperforms existing state-of-the-art methods with clear advantages in the precision of identifying and preserving structures of tissues and biomarkers. MuST offers a versatile toolkit for the intricate analysis of complex biological systems.

Bozhen Hu, Zelin Zang, Cheng Tan et al.

Protein representation learning is critical in various tasks in biology, such as drug design and protein structure or function prediction, which has primarily benefited from protein language models and graph neural networks. These models can capture intrinsic patterns from protein sequences and structures through masking and task-related losses. However, the learned protein representations are usually not well optimized, leading to performance degradation due to limited data, difficulty adapting to new tasks, etc. To address this, we propose a new \underline{d}eep \underline{m}anifold \underline{t}ransformation approach for universal \underline{p}rotein \underline{r}epresentation \underline{l}earning (DMTPRL). It employs manifold learning strategies to improve the quality and adaptability of the learned embeddings. Specifically, we apply a novel manifold learning loss during training based on the graph inter-node similarity. Our proposed DMTPRL method outperforms state-of-the-art baselines on diverse downstream tasks across popular datasets. This validates our approach for learning universal and robust protein representations. We promise to release the code after acceptance.

Changxi Chi, Yufei Huang, Jun Xia et al.

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.

Zelin Zang, WenZhe Li, Fei Chen et al.

In single-cell research, tracing and analyzing high-throughput single-cell differentiation trajectories is crucial for understanding complex biological processes. Key to this is the modeling and generation of hierarchical data that represents the intrinsic structure within datasets. Traditional methods face limitations in terms of computational cost, performance, generative capacity, and stability. Recent VAEs based approaches have made strides in addressing these challenges but still require specialized network modules for each tree branch, limiting their stability and ability to capture deep hierarchical relationships. To overcome these challenges, we introduce diffusion-based approach called HDTree. HDTree captures tree relationships within a hierarchical latent space using a unified hierarchical codebook and quantized diffusion processes to model tree node transitions. This method improves stability by eliminating branch-specific modules and enhancing generative capacity through gradual hierarchical changes simulated by the diffusion process. HDTree's effectiveness is demonstrated through comparisons on both general-purpose and single-cell datasets, where it outperforms existing methods in terms of accuracy and performance. These contributions provide a new tool for hierarchical lineage analysis, enabling more accurate and efficient modeling of cellular differentiation paths and offering insights for downstream biological tasks. The code of HDTree is available at anonymous link https://anonymous.4open.science/r/code_HDTree_review-A8DB.

Zelin Zang, Fei Wang, Liangyu Li et al.

Unsupervised Domain Adaptation (UDA) aims to transfer knowledge from a labeled source domain to an unlabeled target domain. Recent UDA methods based on Vision Transformers (ViTs) have achieved strong performance through attention-based feature alignment. However, we identify a key limitation: foreground object mismatch, where the discrepancy in foreground object size and spatial distribution across domains weakens attention consistency and hampers effective domain alignment. To address this issue, we propose the Progressive Focus Cross-Attention Mechanism (PCaM), which progressively filters out background information during cross-attention, allowing the model to focus on and fuse discriminative foreground semantics across domains. We further introduce an attentional guidance loss that explicitly directs attention toward task-relevant regions, enhancing cross-domain attention consistency. PCaM is lightweight, architecture-agnostic, and easy to integrate into existing ViT-based UDA pipelines. Extensive experiments on Office-Home, DomainNet, VisDA-2017, and remote sensing datasets demonstrate that PCaM significantly improves adaptation performance and achieves new state-of-the-art results, validating the effectiveness of attention-guided foreground fusion for domain adaptation.

Zijia Song, Zelin Zang, Yelin Wang et al.

Multimodal fusion breaks through the boundaries between diverse modalities and has already achieved notable performances. However, in many specialized fields, it is struggling to obtain sufficient alignment data for training, which seriously limits the use of previously effective models. Therefore, semi-supervised learning approaches are attempted to facilitate multimodal alignment by learning from low-alignment data with fewer matched pairs, but traditional techniques like pseudo-labeling may run into troubles in the label-deficient scenarios. To tackle these challenges, we reframe semi-supervised multimodal alignment as a manifold matching issue and propose a new methodology based on CLIP, termed Set-CLIP. Specifically, by designing a novel semantic density distribution loss, we constrain the latent representation distribution with fine granularity and extract implicit semantic alignment from unpaired multimodal data, thereby reducing the reliance on numerous strictly matched pairs. Furthermore, we apply coarse-grained modality adaptation and unimodal self-supervised guidance to narrow the gaps between modality spaces and improve the stability of representation distributions. Extensive experiments conducted on a range of tasks in various fields, including protein analysis, remote sensing, and the general vision-language field, validate the efficacy of our proposed Set-CLIP method. Especially with no paired data for supervised training, Set-CLIP is still outstanding, which brings an improvement of 144.83% over CLIP.

Zicheng Liu, Jiahui Li, Siyuan Li et al.

The Genomic Foundation Model (GFM) paradigm is expected to facilitate the extraction of generalizable representations from massive genomic data, thereby enabling their application across a spectrum of downstream applications. Despite advancements, a lack of evaluation framework makes it difficult to ensure equitable assessment due to experimental settings, model intricacy, benchmark datasets, and reproducibility challenges. In the absence of standardization, comparative analyses risk becoming biased and unreliable. To surmount this impasse, we introduce GenBench, a comprehensive benchmarking suite specifically tailored for evaluating the efficacy of Genomic Foundation Models. GenBench offers a modular and expandable framework that encapsulates a variety of state-of-the-art methodologies. Through systematic evaluations of datasets spanning diverse biological domains with a particular emphasis on both short-range and long-range genomic tasks, firstly including the three most important DNA tasks covering Coding Region, Non-Coding Region, Genome Structure, etc. Moreover, We provide a nuanced analysis of the interplay between model architecture and dataset characteristics on task-specific performance. Our findings reveal an interesting observation: independent of the number of parameters, the discernible difference in preference between the attention-based and convolution-based models on short- and long-range tasks may provide insights into the future design of GFM.

Ge Wang, Zelin Zang, Jiangbin Zheng et al.

This paper focuses on learning representation on the whole graph level in an unsupervised manner. Learning graph-level representation plays an important role in a variety of real-world issues such as molecule property prediction, protein structure feature extraction, and social network analysis. The mainstream method is utilizing contrastive learning to facilitate graph feature extraction, known as Graph Contrastive Learning (GCL). GCL, although effective, suffers from some complications in contrastive learning, such as the effect of false negative pairs. Moreover, augmentation strategies in GCL are weakly adaptive to diverse graph datasets. Motivated by these problems, we propose a novel framework called Structure Knowledge Refinement (SKR) which uses data structure to determine the probability of whether a pair is positive or negative. Meanwhile, we propose an augmentation strategy that naturally preserves the semantic meaning of the original data and is compatible with our SKR framework. Furthermore, we illustrate the effectiveness of our SKR framework through intuition and experiments. The experimental results on the tasks of graph-level classification demonstrate that our SKR framework is superior to most state-of-the-art baselines.

Siyuan Li, Zicheng Liu, Zelin Zang et al.

Unsupervised representation learning (URL), which learns compact embeddings of high-dimensional data without supervision, has made remarkable progress recently. However, the development of URLs for different requirements is independent, which limits the generalization of the algorithms, especially prohibitive as the number of tasks grows. For example, dimension reduction methods, t-SNE, and UMAP optimize pair-wise data relationships by preserving the global geometric structure, while self-supervised learning, SimCLR, and BYOL focus on mining the local statistics of instances under specific augmentations. To address this dilemma, we summarize and propose a unified similarity-based URL framework, GenURL, which can smoothly adapt to various URL tasks. In this paper, we regard URL tasks as different implicit constraints on the data geometric structure that help to seek optimal low-dimensional representations that boil down to data structural modeling (DSM) and low-dimensional transformation (LDT). Specifically, DMS provides a structure-based submodule to describe the global structures, and LDT learns compact low-dimensional embeddings with given pretext tasks. Moreover, an objective function, General Kullback-Leibler divergence (GKL), is proposed to connect DMS and LDT naturally. Comprehensive experiments demonstrate that GenURL achieves consistent state-of-the-art performance in self-supervised visual learning, unsupervised knowledge distillation (KD), graph embeddings (GE), and dimension reduction.

Zihan Liu, Yun Luo, Zelin Zang et al.

Gray-box graph attacks aim at disrupting the performance of the victim model by using inconspicuous attacks with limited knowledge of the victim model. The parameters of the victim model and the labels of the test nodes are invisible to the attacker. To obtain the gradient on the node attributes or graph structure, the attacker constructs an imaginary surrogate model trained under supervision. However, there is a lack of discussion on the training of surrogate models and the robustness of provided gradient information. The general node classification model loses the topology of the nodes on the graph, which is, in fact, an exploitable prior for the attacker. This paper investigates the effect of representation learning of surrogate models on the transferability of gray-box graph adversarial attacks. To reserve the topology in the surrogate embedding, we propose Surrogate Representation Learning with Isometric Mapping (SRLIM). By using Isometric mapping method, our proposed SRLIM can constrain the topological structure of nodes from the input layer to the embedding space, that is, to maintain the similarity of nodes in the propagation process. Experiments prove the effectiveness of our approach through the improvement in the performance of the adversarial attacks generated by the gradient-based attacker in untargeted poisoning gray-box setups.

Di Wu, Siyuan Li, Zelin Zang et al.

Self-supervised contrastive learning has demonstrated great potential in learning visual representations. Despite their success in various downstream tasks such as image classification and object detection, self-supervised pre-training for fine-grained scenarios is not fully explored. We point out that current contrastive methods are prone to memorizing background/foreground texture and therefore have a limitation in localizing the foreground object. Analysis suggests that learning to extract discriminative texture information and localization are equally crucial for fine-grained self-supervised pre-training. Based on our findings, we introduce cross-view saliency alignment (CVSA), a contrastive learning framework that first crops and swaps saliency regions of images as a novel view generation and then guides the model to localize on foreground objects via a cross-view alignment loss. Extensive experiments on both small- and large-scale fine-grained classification benchmarks show that CVSA significantly improves the learned representation.

Zelin Zang, Siyuan Li, Di Wu et al.

Unsupervised attributed graph representation learning is challenging since both structural and feature information are required to be represented in the latent space. Existing methods concentrate on learning latent representation via reconstruction tasks, but cannot directly optimize representation and are prone to oversmoothing, thus limiting the applications on downstream tasks. To alleviate these issues, we propose a novel graph embedding framework named Deep Manifold Attributed Graph Embedding (DMAGE). A node-to-node geodesic similarity is proposed to compute the inter-node similarity between the data space and the latent space and then use Bergman divergence as loss function to minimize the difference between them. We then design a new network structure with fewer aggregation to alleviate the oversmoothing problem and incorporate graph structure augmentation to improve the representation's stability. Our proposed DMAGE surpasses state-of-the-art methods by a significant margin on three downstream tasks: unsupervised visualization, node clustering, and link prediction across four popular datasets.

Stan Z. Li, Lirong Wu, Zelin Zang

High dimensional data analysis for exploration and discovery includes three fundamental tasks: dimensionality reduction, clustering, and visualization. When the three associated tasks are done separately, as is often the case thus far, inconsistencies can occur among the tasks in terms of data geometry and others. This can lead to confusing or misleading data interpretation. In this paper, we propose a novel neural network-based method, called Consistent Representation Learning (CRL), to accomplish the three associated tasks end-to-end and improve the consistencies. The CRL network consists of two nonlinear dimensionality reduction (NLDR) transformations: (1) one from the input data space to the latent feature space for clustering, and (2) the other from the clustering space to the final 2D or 3D space for visualization. Importantly, the two NLDR transformations are performed to best satisfy local geometry preserving (LGP) constraints across the spaces or network layers, to improve data consistencies along with the processing flow. Also, we propose a novel metric, clustering-visualization inconsistency (CVI), for evaluating the inconsistencies. Extensive comparative results show that the proposed CRL neural network method outperforms the popular t-SNE and UMAP-based and other contemporary clustering and visualization algorithms in terms of evaluation metrics and visualization.

Stan Z. Li, Zelin Zang, Lirong Wu

Manifold learning-based encoders have been playing important roles in nonlinear dimensionality reduction (NLDR) for data exploration. However, existing methods can often fail to preserve geometric, topological and/or distributional structures of data. In this paper, we propose a deep manifold learning framework, called deep manifold transformation (DMT) for unsupervised NLDR and embedding learning. DMT enhances deep neural networks by using cross-layer local geometry-preserving (LGP) constraints. The LGP constraints constitute the loss for deep manifold learning and serve as geometric regularizers for NLDR network training. Extensive experiments on synthetic and real-world data demonstrate that DMT networks outperform existing leading manifold-based NLDR methods in terms of preserving the structures of data.

Siyuan Li, Haitao Lin, Zelin Zang et al.

Dimension reduction (DR) aims to learn low-dimensional representations of high-dimensional data with the preservation of essential information. In the context of manifold learning, we define that the representation after information-lossless DR preserves the topological and geometric properties of data manifolds formally, and propose a novel two-stage DR method, called invertible manifold learning (inv-ML) to bridge the gap between theoretical information-lossless and practical DR. The first stage includes a homeomorphic sparse coordinate transformation to learn low-dimensional representations without destroying topology and a local isometry constraint to preserve local geometry. In the second stage, a linear compression is implemented for the trade-off between the target dimension and the incurred information loss in excessive DR scenarios. Experiments are conducted on seven datasets with a neural network implementation of inv-ML, called i-ML-Enc. Empirically, i-ML-Enc achieves invertible DR in comparison with typical existing methods as well as reveals the characteristics of the learned manifolds. Through latent space interpolation on real-world datasets, we find that the reliability of tangent space approximated by the local neighborhood is the key to the success of manifold-based DR algorithms.

Lirong Wu, Zicheng Liu, Zelin Zang et al.

Though manifold-based clustering has become a popular research topic, we observe that one important factor has been omitted by these works, namely that the defined clustering loss may corrupt the local and global structure of the latent space. In this paper, we propose a novel Generalized Clustering and Multi-manifold Learning (GCML) framework with geometric structure preservation for generalized data, i.e., not limited to 2-D image data and has a wide range of applications in speech, text, and biology domains. In the proposed framework, manifold clustering is done in the latent space guided by a clustering loss. To overcome the problem that the clustering-oriented loss may deteriorate the geometric structure of the latent space, an isometric loss is proposed for preserving intra-manifold structure locally and a ranking loss for inter-manifold structure globally. Extensive experimental results have shown that GCML exhibits superior performance to counterparts in terms of qualitative visualizations and quantitative metrics, which demonstrates the effectiveness of preserving geometric structure.

Linyan Lu, Zhaohui Yang, Mingzhe Chen et al.

In this paper, a machine learning based deployment framework of unmanned aerial vehicles (UAVs) is studied. In the considered model, UAVs are deployed as flying base stations (BS) to offload heavy traffic from ground BSs. Due to time-varying traffic distribution, a long short-term memory (LSTM) based prediction algorithm is introduced to predict the future cellular traffic. To predict the user service distribution, a KEG algorithm, which is a joint K-means and expectation maximization (EM) algorithm based on Gaussian mixture model (GMM), is proposed for determining the service area of each UAV. Based on the predicted traffic, the optimal UAV positions are derived and three multi-access techniques are compared so as to minimize the total transmit power. Simulation results show that the proposed method can reduce up to 24\% of the total power consumption compared to the conventional method without traffic prediction. Besides, rate splitting multiple access (RSMA) has the lower required transmit power compared to frequency domain multiple access (FDMA) and time domain multiple access (TDMA).