Evidence-aware Integration and Domain Identification of Spatial Transcriptomics Data

Spatial transcriptomics (ST) enables joint profiling of gene expression and spatial positions, thereby revealing spatially resolved biological functions. However, many existing ST analysis methods often fail to explicitly quantify the belief and uncertainty in decisions caused by noisy ST data, making it difficult to handle spots of varying quality in a fine-grained manner. In addition, domain identification is a fundamental and critical task in ST, but commonly used models that separate expression learning and clustering often struggle to learn cluster-friendly latent representations effectively. To address these issues, we propose PREST, a prototype-based evidence-aware integration framework for ST data. PREST performs multi-scale representation learning with fine-grained attention fusion and introduces learnable class prototypes to quantify belief and uncertainty in model decisions. We aim to align overall belief scores with latent semantic information to enhance uncertainty quantification and prototype learning, thereby promoting the learning of clustering-friendly representations. PREST further integrates an uncertainty-aware reconstruction module and spatial regularization to reduce overfitting to unreliable spots and promote denoised, discriminative representations. Extensive experiments on several benchmark datasets validate the effectiveness and superiority of our proposed PREST across various downstream tasks.