Powerful and accurate detection of temporal gene expression patterns from multi-sample multi-stage single cell transcriptomics data with TDEseq

ABSTRACT We present a non-parametric statistical method called TDEseq that takes full advantage of smoothing splines basis functions to account for the dependence of multiple time points, and uses hierarchical structure linear additive mixed models to model the correlated cells within an individual. As a result, TDEseq demonstrates powerful performance in identifying four potential temporal expression patterns within a specific cell type. Extensive simulation studies and the analysis of four published scRNA-seq datasets show that TDEseq can produce well-calibrated p-values and up to 20% power gain over the existing methods for detecting temporal gene expression patterns.