HEARTSVG: a fast and accurate method for identifying spatially variable genes in large-scale spatial transcriptomics.

Abstract

Identifying spatially variable genes (SVGs) is crucial for understanding the spatiotemporal characteristics of diseases and tissue structures, posing a distinctive challenge in spatial transcriptomics research. We propose HEARTSVG, a distribution-free, test-based method for fast and accurately identifying spatially variable genes in large-scale spatial transcriptomic data. Extensive simulations demonstrate that HEARTSVG outperforms state-of-the-art methods with higher <math xmlns="http://www.w3.org/1998/Math/MathML"> <msub><mrow><mi>F</mi></mrow> <mrow><mn>1</mn></mrow> </msub> </math> scores (average <math xmlns="http://www.w3.org/1998/Math/MathML"> <msub><mrow><mi>F</mi></mrow> <mrow><mn>1</mn></mrow> </msub> </math> Score=0.948), improved computational efficiency, scalability, and reduced false positives (FPs). Through analysis of twelve real datasets from various spatial transcriptomic technologies, HEARTSVG identifies a greater number of biologically significant SVGs (average AUC = 0.792) than other comparative methods without prespecifying spatial patterns. Furthermore, by clustering SVGs, we uncover two distinct tumor spatial domains characterized by unique spatial expression patterns, spatial-temporal locations, and biological functions in human colorectal cancer data, unraveling the complexity of tumors.