GC-MoE: Genomics-Guided Cell-Type-Specific Mixture of Experts for Histology-Based Single-Cell Spatial Transcriptomics
Kaito Shiku, Ahtisham Fazeel Abbasi, Ryoma Bise, Yuichiro Iwashita, Kazuya Nishimura, Andreas Dengel, Muhammad Nabeel Asim
Abstract
Histology-based single-cell spatial transcriptomics (ST) estimation aims to predict gene expression for individual cells from histopathological images and cell locations, reducing the need for costly single-cell ST measurements. Unlike existing histology-to-ST methods that mainly predict spot-level profiles for local regions containing multiple cells, this task requires modeling cell-to-cell expression variability, which is strongly structured by cell type. We propose Genomics-Guided Cell-Type-Specific Mixture-of-Experts (GC-MoE), which estimates cell-type probabilities with a routing network and softly combines cell-type-specific experts for gene expression prediction. To further encode cell-type-dependent gene programs, we introduce the Cell-Type-Specific Co-Expression-Aware Predictor (CAP), together with a lightweight Cell-to-Cell Interaction Attention (C2CA) module for neighboring-cell context. Experiments and ablations on public single-cell ST datasets show consistent improvements over existing single-cell and adapted spot-level baselines.
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Classified with taxonomy v2 on Wed, 2 Sept 2026.