arXiv subjects

Zelin Zang

Publications and source records attributed to Zelin Zang.

At least 37 records · Page 2Linked to original sources

arXiv2025

CellScout: Visual Analytics for Mining Biomarkers in Cell State Discovery

Cell state discovery is crucial for understanding biological systems and enhancing medical outcomes. A key aspect of this process is identifying distinct biomarkers that define specific cell states. However, difficulties arise from the co-discovery process of cell states and biomarkers: biologists often use dimensionality reduction to visualize cells in a two-dimensional space. Then they usually interpret visually clustered cells as distinct states, from which they seek to identify unique biomarkers. However, this assumption is often invalid due to internal inconsistencies in a cluster, making the process trial-and-error and highly uncertain. Therefore, biologists urgently need effective tools to help uncover the hidden association relationships between different cell populations and their potential biomarkers. To address this problem, we first designed a machine-learning algorithm based on the Mixture-of-Experts (MoE) technique to identify meaningful associations between cell populations and biomarkers. We further developed a visual analytics system, CellScout, in collaboration with biologists, to help them explore and refine these association relationships to advance cell state discovery. We validated our system through expert interviews, from which we further selected a representative case to demonstrate its effectiveness in discovering new cell states.

cs.HC↗

arXiv2025

Learning Cell-Aware Hierarchical Multi-Modal Representations for Robust Molecular Modeling

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.

cs.LG↗

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

Deep Multi-Manifold Transformation Based Multivariate Time Series Fault Detection

Unsupervised fault detection in multivariate time series plays a vital role in ensuring the stable operation of complex systems. Traditional methods often assume that normal data follow a single Gaussian distribution and identify anomalies as deviations from this distribution. {\color{black} However, this simplified assumption fails to capture the diversity and structural complexity of real-world time series, which can lead to misjudgments and reduced detection performance in practical applications. To address this issue, we propose a new method that combines a neighborhood-driven data augmentation strategy with a multi-manifold representation learning framework.} By incorporating information from local neighborhoods, the augmentation module can simulate contextual variations of normal data, enhancing the model's adaptability to distributional changes. In addition, we design a structure-aware feature learning approach that encourages natural clustering of similar patterns in the feature space while maintaining sufficient distinction between different operational states. Extensive experiments on several public benchmark datasets demonstrate that our method achieves superior performance in terms of both accuracy and robustness, showing strong potential for generalization and real-world deployment.

cs.LG↗

arXiv2025

PCaM: A Progressive Focus Attention-Based Information Fusion Method for Improving Vision Transformer Domain Adaptation

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.

cs.LG↗

arXiv2025

A Review of BioTree Construction in the Context of Information Fusion: Priors, Methods, Applications and Trends

Biological tree (BioTree) analysis is a foundational tool in biology, enabling the exploration of evolutionary and differentiation relationships among organisms, genes, and cells. Traditional tree construction methods, while instrumental in early research, face significant challenges in handling the growing complexity and scale of modern biological data, particularly in integrating multimodal datasets. Advances in deep learning (DL) offer transformative opportunities by enabling the fusion of biological prior knowledge with data-driven models. These approaches address key limitations of traditional methods, facilitating the construction of more accurate and interpretable BioTrees. This review highlights critical biological priors essential for phylogenetic and differentiation tree analyses and explores strategies for integrating these priors into DL models to enhance accuracy and interpretability. Additionally, the review systematically examines commonly used data modalities and databases, offering a valuable resource for developing and evaluating multimodal fusion models. Traditional tree construction methods are critically assessed, focusing on their biological assumptions, technical limitations, and scalability issues. Recent advancements in DL-based tree generation methods are reviewed, emphasizing their innovative approaches to multimodal integration and prior knowledge incorporation. Finally, the review discusses diverse applications of BioTrees in various biological disciplines, from phylogenetics to developmental biology, and outlines future trends in leveraging DL to advance BioTree research. By addressing the challenges of data complexity and prior knowledge integration, this review aims to inspire interdisciplinary innovation at the intersection of biology and DL.

q-bio.PE↗

arXiv2024

Neural Network Diffusion

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}.

cs.LG↗

arXiv2024

FGBERT: Function-Driven Pre-trained Gene Language Model for Metagenomics

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.

q-bio.GN↗

arXiv2024

PhyloGen: Language Model-Enhanced Phylogenetic Inference via Graph Structure Generation

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.

q-bio.PE↗

arXiv2024

Deep Graph Neural Networks via Posteriori-Sampling-based Node-Adaptive Residual Module

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.

cs.LG↗

arXiv2024

Set-CLIP: Exploring Aligned Semantic From Low-Alignment Multimodal Data Through A Distribution View

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.

cs.LG↗

arXiv2024

GenBench: A Benchmarking Suite for Systematic Evaluation of Genomic Foundation Models

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.

q-bio.GN↗

arXiv2024

DiffAug: Enhance Unsupervised Contrastive Learning with Domain-Knowledge-Free Diffusion-based Data Augmentation

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}.

cs.LG↗

arXiv2024

GenURL: A General Framework for Unsupervised Representation Learning

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.

cs.LG↗

arXiv2024

Must: Maximizing Latent Capacity of Spatial Transcriptomics Data

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.

cs.CE↗

arXiv2024

Deep Manifold Graph Auto-Encoder for Attributed Graph Embedding

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.

cs.LG↗

arXiv2024

Deep Manifold Transformation for Protein Representation Learning

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.

q-bio.BM↗

arXiv2024

Graph-level Protein Representation Learning by Structure Knowledge Refinement

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.

cs.LG↗