Benchmarking computational methods for detecting spatial domains and domain-specific spatially variable genes from...

Advances in spatially resolved transcriptomics (SRT) have led to the emergence of numerous computational methods for identifying spatial domains and spatially variable genes (SVGs); however, a comprehensive assessment of existing methods is lacking. We comprehensively benchmarked 19 methods for detecting spatial domains and domain-specific SVGs from SRT data, using 30 real-world datasets covering six SRT technologies and 27 synthetic datasets. We first evaluated the performance of these methods on spatial domain identification in terms of accuracy, stability, generalizability, and scalability. Results reveal that there is no single method that works best for all datasets, and the optimal method depends on the data, especially the SRT platform. Further, we proposed a quantitative strategy to evaluate domain-specific SVG recognition results and assessed the impact of spatial domains on SVG detection. We found that SVG detection based on spatial domains identified by different GNN methods have high accuracy but low concordance. Generally, the more accurate the recognized spatial domains, the higher the number and accuracy of domain-specific SVGs detected. Moreover, integrating spatial clustering results from different methods can lead to more robust and better clustering and SVG results. Practical guidelines were provided for choosing appropriate methods for spatial domain and domain-specific SVG identification.