arXiv subjects

Lulu Shang

Publications and source records attributed to Lulu Shang.

3 recordsLinked to original sources

arXiv2026

BaySC: Uncovering Tissue Architecture in Spatial Multi-Omics via Probabilistic Spatial Clustering

Spatial domain identification requires jointly modeling molecular signatures and physical coordinates, yet current tools frequently over-smooth biological boundaries, require user-specified cluster numbers, and lack principled multimodal integration. We introduce BaySC, an integrative Bayesian spatial clustering framework for spatial domain identification. BaySC inherently learns the true number of spatial domains from the data by employing a Mixture of Finite Mixtures (MFM) prior. Tissue topology is modeled via a Markov Random Field (MRF) applied to discrete cellular assignments, a strategy that enforces local spatial coherence without distorting the underlying gene expression features. This enables BaySC to accurately map contiguous tissue layers as well as geographically scattered, transcriptionally identical cell populations. Furthermore, BaySC handles spatial multi-omics data through a weighted log-likelihood fusion mechanism executed via Gibbs sampling. This approach assigns interpretable weights to each modality, allowing users to quantify the biological relevance of different data layers to the final tissue map. Validated across ten single-modal spatial transcriptomics and two spatial multi-omics datasets, BaySC yields highly interpretable probabilistic outputs. It demonstrates competitive accuracy on standard clustering metrics and consistently outperforms existing tools in preserving spatial topography, as measured by spatially-aware Adjusted Rand Index (spARI).

stat.AP↗

arXiv2026

Prototype-driven fusion of pathology and spatial transcriptomics for interpretable survival prediction

Whole slide images (WSIs) enable weakly supervised prognostic modeling via multiple instance learning (MIL). Spatial transcriptomics (ST) preserves in situ gene expression, providing a spatial molecular context that complements morphology. As paired WSI-ST cohorts scale to population level, leveraging their complementary spatial signals for prognosis becomes crucial; however, principled cross-modal fusion strategies remain limited for this paradigm. To this end, we introduce PathoSpatial, an interpretable end-to-end framework integrating co-registered WSIs and ST to learn spatially informed prognostic representations. PathoSpatial uses task-guided prototype learning within a multi-level experts architecture, adaptively orchestrating unsupervised within-modality discovery with supervised cross-modal aggregation. By design, PathoSpatial substantially strengthens interpretability while maintaining discriminative ability. We evaluate PathoSpatial on a triple-negative breast cancer cohort with paired ST and WSIs. PathoSpatial delivers strong and consistent performance across five survival endpoints, achieving superior or comparable performance to leading unimodal and multimodal methods. PathoSpatial inherently enables post-hoc prototype interpretation and molecular risk decomposition, providing quantitative, biologically grounded explanations, highlighting candidate prognostic factors. We present PathoSpatial as a proof-of-concept for scalable and interpretable multimodal learning for spatial omics-pathology fusion.

cs.CV↗

arXiv2024

Single Cells Are Spatial Tokens: Transformers for Spatial Transcriptomic Data Imputation

Spatially resolved transcriptomics brings exciting breakthroughs to single-cell analysis by providing physical locations along with gene expression. However, as a cost of the extremely high spatial resolution, the cellular level spatial transcriptomic data suffer significantly from missing values. While a standard solution is to perform imputation on the missing values, most existing methods either overlook spatial information or only incorporate localized spatial context without the ability to capture long-range spatial information. Using multi-head self-attention mechanisms and positional encoding, transformer models can readily grasp the relationship between tokens and encode location information. In this paper, by treating single cells as spatial tokens, we study how to leverage transformers to facilitate spatial tanscriptomics imputation. In particular, investigate the following two key questions: (1) $\textit{how to encode spatial information of cells in transformers}$, and (2) $\textit{ how to train a transformer for transcriptomic imputation}$. By answering these two questions, we present a transformer-based imputation framework, SpaFormer, for cellular-level spatial transcriptomic data. Extensive experiments demonstrate that SpaFormer outperforms existing state-of-the-art imputation algorithms on three large-scale datasets while maintaining superior computational efficiency.

q-bio.GN↗