Recent advances in spatial transcriptomics (ST) and cost reductions have enabled large-scale multi-slice ST data generation, enhancing the statistical power to detect subtle biological signals. However, cross-slice inconsistencies and data quality variability present significant analytical challenges. To overcome these limitations, we developed MUSE, a computational framework designed for multislice joint embedding, spatial domain identification, and gene expression imputation. Specifically, MUSE integrates a two-module architecture to ensure robust cross-slice alignment and data harmonization. The alignment module models each slice as a graph and employs optimal transport to align cells across slices while preserving spatial continuity. The optimization module further refines integration by incorporating an alignment loss, allowing lower-quality data to leverage structural information from higher-quality slices. Additionally, MUSE generates virtual neighbors from aligned cells, enriching contextual information and mitigating data sparsity. These design principles enable seamless integration with existing single-slice methods, extending their applicability to multi-slice ST analysis. To comprehensively evaluate its performance, we applied MUSE to 12 real and 48 simulated datasets spanning a range of data qualities. Across all metrics, MUSE consistently outperformed existing methods in cross-slice consistency, spatial domain identification, and gene expression imputation. To promote accessibility and adoption, we provide MUSE as an open-source software package. As multi-slice ST datasets become increasingly prevalent, MUSE provides a robust and extensible framework designed to effectively integrate growing numbers of slices, thereby advancing the analysis of tissue architectures and spatial gene expression in complex biological systems.
Temporal Graph Neural Networks (TGNNs) have become indispensable for analyzing dynamic graphs in critical applications such as social networks, communication systems, and financial networks. However, the robustness of TGNNs against adversarial attacks, particularly sophisticated attacks that exploit the temporal dimension, remains a significant challenge. Existing attack methods for Spatio-Temporal Dynamic Graphs (STDGs) often rely on simplistic, easily detectable perturbations (e.g., random edge additions/deletions) and fail to strategically target the most influential nodes and edges for maximum impact. We introduce the High Impact Attack (HIA), a novel restricted black-box attack framework specifically designed to overcome these limitations and expose critical vulnerabilities in TGNNs. HIA leverages a data-driven surrogate model to identify structurally important nodes (central to network connectivity) and dynamically important nodes (critical for the graph's temporal evolution). It then employs a hybrid perturbation strategy, combining strategic edge injection (to create misleading connections) and targeted edge deletion (to disrupt essential pathways), maximizing TGNN performance degradation. Importantly, HIA minimizes the number of perturbations to enhance stealth, making it more challenging to detect. Comprehensive experiments on five real-world datasets and four representative TGNN architectures (TGN, JODIE, DySAT, and TGAT) demonstrate that HIA significantly reduces TGNN accuracy on the link prediction task, achieving up to a 35.55% decrease in Mean Reciprocal Rank (MRR) - a substantial improvement over state-of-the-art baselines. These results highlight fundamental vulnerabilities in current STDG models and underscore the urgent need for robust defenses that account for both structural and temporal dynamics. Code and Data are available at https://github.com/ryandhjeon/hia.
Large pre-trained models have achieved notable success across a range of downstream tasks. However, recent research shows that a type of adversarial attack ($\textit{i.e.,}$ backdoor attack) can manipulate the behavior of machine learning models through contaminating their training dataset, posing significant threat in the real-world application of large pre-trained model, especially for those customized models. Therefore, addressing the unique challenges for exploring vulnerability of pre-trained models is of paramount importance. Through empirical studies on the capability for performing backdoor attack in large pre-trained models ($\textit{e.g.,}$ ViT), we find the following unique challenges of attacking large pre-trained models: 1) the inability to manipulate or even access large training datasets, and 2) the substantial computational resources required for training or fine-tuning these models. To address these challenges, we establish new standards for an effective and feasible backdoor attack in the context of large pre-trained models. In line with these standards, we introduce our EDT model, an \textbf{E}fficient, \textbf{D}ata-free, \textbf{T}raining-free backdoor attack method. Inspired by model editing techniques, EDT injects an editing-based lightweight codebook into the backdoor of large pre-trained models, which replaces the embedding of the poisoned image with the target image without poisoning the training dataset or training the victim model. Our experiments, conducted across various pre-trained models such as ViT, CLIP, BLIP, and stable diffusion, and on downstream tasks including image classification, image captioning, and image generation, demonstrate the effectiveness of our method. Our code is available in the supplementary material.
Spatial transcriptomics has transformed genomic research by measuring spatially resolved gene expressions, allowing us to investigate how cells adapt to their microenvironment via modulating their expressed genes. This essential process usually starts from cell-cell communication (CCC) via ligand-receptor (LR) interaction, leading to regulatory changes within the receiver cell. However, few methods were developed to connect them to provide biological insights into intercellular regulation. To fill this gap, we propose iMiracle, an iterative multi-view graph neural network that models each cell's intercellular regulation with three key features. Firstly, iMiracle integrates inter- and intra-cellular networks to jointly estimate cell-type- and micro-environment-driven gene expressions. Optionally, it allows prior knowledge of intra-cellular networks as pre-structured masks to maintain biological relevance. Secondly, iMiracle employs iterative learning to overcome the sparsity of spatial transcriptomic data and gradually fill in the missing edges in the CCC network. Thirdly, iMiracle infers a cell-specific ligand-gene regulatory score based on the contributions of different LR pairs to interpret inter-cellular regulation. We applied iMiracle to nine simulated and eight real datasets from three sequencing platforms and demonstrated that iMiracle consistently outperformed ten methods in gene expression imputation and four methods in regulatory score inference. Lastly, we developed iMiracle as an open-source software and anticipate that it can be a powerful tool in decoding the complexities of inter-cellular transcriptional regulation.
Heterogeneous networks contain multiple types of nodes and links, with some link types encapsulating hierarchical structure over entities. Hierarchical relationships can codify information such as subcategories or one entity being subsumed by another and are often used for organizing conceptual knowledge into a tree-structured graph. Hyperbolic embedding models learn node representations in a hyperbolic space suitable for preserving the hierarchical structure. Unfortunately, current hyperbolic embedding models only implicitly capture the hierarchical structure, failing to distinguish between node types, and they only assume a single tree. In practice, many networks contain a mixture of hierarchical and non-hierarchical structures, and the hierarchical relations may be represented as multiple trees with complex structures, such as sharing certain entities. In this work, we propose a new hyperbolic representation learning model that can handle complex hierarchical structures and also learn the representation of both hierarchical and non-hierarchic structures. We evaluate our model on several datasets, including identifying relevant articles for a systematic review, which is an essential tool for evidence-driven medicine and node classification.
