MEATRD: Multimodal Anomalous Tissue Region Detection Enhanced with Spatial Transcriptomics

The detection of anomalous tissue regions (ATRs) within affected tissues is crucial in clinical diagnosis and pathological studies. Conventional automated ATR detection methods, primarily based on histology images alone, falter in cases where ATRs and normal tissues have subtle visual differences. The recent spatial transcriptomics (ST) technology profiles gene expressions across tissue regions, offering a molecular perspective for detecting ATRs. However, there is a dearth of ATR detection methods that effectively harness complementary information from both histology images and ST. To address this gap, we propose MEATRD, a novel ATR detection method that integrates histology image and ST data. MEATRD is trained to reconstruct image patches and gene expression profiles of normal tissue spots (inliers) from their multimodal embeddings, followed by learning a one-class classification AD model based on latent multimodal reconstruction errors. This strategy harmonizes the strengths of reconstruction-based and one-class classification approaches. At the heart of MEATRD is an innovative masked graph dual-attention transformer (MGDAT) network, which not only facilitates cross-modality and cross-node information sharing but also addresses the model over-generalization issue commonly seen in reconstruction-based AD methods. Additionally, we demonstrate that modality-specific, task-relevant information is collated and condensed in multimodal bottleneck encoding generated in MGDAT, marking the first theoretical analysis of the informational properties of multimodal bottleneck encoding. Extensive evaluations across eight real ST datasets reveal MEATRD's superior performance in ATR detection, surpassing various state-of-the-art AD methods. Remarkably, MEATRD also proves adept at discerning ATRs that only show slight visual deviations from normal tissues.

Dual Advancement of Representation Learning and Clustering for Sparse and Noisy Images

Sparse and noisy images (SNIs), like those in spatial gene expression data, pose significant challenges for effective representation learning and clustering, which are essential for thorough data analysis and interpretation. In response to these challenges, we propose Dual Advancement of Representation Learning and Clustering (DARLC), an innovative framework that leverages contrastive learning to enhance the representations derived from masked image modeling. Simultaneously, DARLC integrates cluster assignments in a cohesive, end-to-end approach. This integrated clustering strategy addresses the "class collision problem" inherent in contrastive learning, thus improving the quality of the resulting representations. To generate more plausible positive views for contrastive learning, we employ a graph attention network-based technique that produces denoised images as augmented data. As such, our framework offers a comprehensive approach that improves the learning of representations by enhancing their local perceptibility, distinctiveness, and the understanding of relational semantics. Furthermore, we utilize a Student's t mixture model to achieve more robust and adaptable clustering of SNIs. Extensive experiments, conducted across 12 different types of datasets consisting of SNIs, demonstrate that DARLC surpasses the state-of-the-art methods in both image clustering and generating image representations that accurately capture gene interactions. Code is available at https://github.com/zipging/DARLC.

Domain Adaptive and Fine-grained Anomaly Detection for Single-cell Sequencing Data and Beyond

Fined-grained anomalous cell detection from affected tissues is critical for clinical diagnosis and pathological research. Single-cell sequencing data provide unprecedented opportunities for this task. However, current anomaly detection methods struggle to handle domain shifts prevalent in multi-sample and multi-domain single-cell sequencing data, leading to suboptimal performance. Moreover, these methods fall short of distinguishing anomalous cells into pathologically distinct subtypes. In response, we propose ACSleuth, a novel, reconstruction deviation-guided generative framework that integrates the detection, domain adaptation, and fine-grained annotating of anomalous cells into a methodologically cohesive workflow. Notably, we present the first theoretical analysis of using reconstruction deviations output by generative models for anomaly detection in lieu of domain shifts. This analysis informs us to develop a novel and superior maximum mean discrepancy-based anomaly scorer in ACSleuth. Extensive benchmarks over various single-cell data and other types of tabular data demonstrate ACSleuth's superiority over the state-of-the-art methods in identifying and subtyping anomalies in multi-sample and multi-domain contexts. Our code is available at https://github.com/Catchxu/ACsleuth.