Accurate Spatial Gene Expression Prediction by Integrating Multi-Resolution Features

Recent advancements in Spatial Transcriptomics (ST) technology have facilitated detailed gene expression anal-ysis within tissue contexts. However, the high costs and methodological limitations of ST necessitate a more ro-bust predictive model. In response, this paper introduces TRIPLEX, a novel deep learning framework designed to predict spatial gene expression from Whole Slide Images (WSIs). TRIPLEX uniquely harnesses multi-resolution features, capturing cellular morphology at individual spots, the local context around these spots, and the global tissue organization. By integrating these features through an ef-fective fusion strategy, TRIPLEX achieves accurate gene ex-pression prediction. Our comprehensive benchmark study, conducted on three public ST datasets and supplemented with Visium data from 10X Genomics, demonstrates that TRIPLEX outperforms current state-of-the-art models in Mean Squared Error (MSE), Mean Absolute Error (MAE), and Pearson Correlation Coefficient (PCC). The model's predictions align closely with ground truth gene expression profiles and tumor annotations, underscoring TRIPLEX's potential in advancing cancer diagnosis and treatment.