Abstract

Effective control of false discovery rate is key for multiplicity problems. Here, we consider incorporating informative covariates from external datasets in the multiple testing procedure to boost statistical power while maintaining false discovery rate control. In particular, we focus on the statistical analysis of innovative high-dimensional spatial transcriptomic data while incorporating external multi-omics data that provide distinct but complementary information to the detection of spatial expression patterns. We extend OrderShapeEM, an efficient covariate-assisted multiple testing procedure that incorporates one auxiliary study, to make it permissible to incorporate multiple external omics studies, to boost statistical power of spatial expression pattern detection. Specifically, we first use a recently proposed computationally efficient statistical analysis method, spatial pattern recognition via kernels, to produce the primary test statistics for spatial transcriptomic data. Afterwards, we construct the auxiliary covariate by combining information from multiple external omics studies, such as bulk or single-cell RNA-seq data and genome wise association study data, using the Cauchy combination rule. Finally, we extend and implement the integrative analysis method OrderShapeEM on the primary p-values along with auxiliary data incorporating multi-omics information for efficient covariate-assisted spatial expression analysis. We conduct a series of realistic simulations to evaluate the performance of our method with known ground truth. Four case studies in mouse olfactory bulb, mouse cerebellum, human breast cancer and human heart tissues further demonstrate the substantial power gain of our method in detecting genes with spatial expression patterns compared to existing classic approaches that do not utilize any external information.