MP-MNCA: Morphology-Prior Masked Neighbor Cross-Attention for Efficient Spatial Domain Identification

Abstract

Spatial transcriptomics jointly captures molecular state, tissue morphology, and spatial organization, yet spatial-domain methods are typically compared only at late training checkpoints, obscuring differences in convergence efficiency. We introduce MP-MNCA, a morphology-prior masked neighbor cross-attention framework that preserves the full 3,000 dimensional highly-variable-gene representation while selectively routing molecular information across spatial neighbors, with histological similarity incorporated as a continuous attention prior under a self-supervised masked neighbor-contrastive objective. Across 12 heterogeneous human dorsolateral prefrontal cortex (DLPFC) sections, MP-MNCA is evaluated against established spatial-domain baselines using both convergence trajectories and epoch-wise spatial-domain visualizations. Our results show that MP-MNCA (i) reaches coherent spatial-domain structure in substantially fewer training epochs, as reflected quantitatively by convergence curves and qualitatively by progressive spatial grids, and (ii) maintains strong clustering quality, achieving a mean peak refined ARI of 0.546 versus 0.549 for the strongest baseline (STAIG), while attaining the highest mean refined NMI of 0.657 versus 0.640. Moreover, MP-MNCA outperforms STAIG on 7 of 12 sections in ARI and 11 of 12 in NMI, demonstrating faster convergence without sacrificing spatial-domain quality.