PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data
Dongyuan Song, Jingyi Jessica Li
Abstract
To investigate molecular mechanisms underlying cell state changes, a crucial analysis is to identify differentially expressed (DE) genes along the pseudotime inferred from single-cell RNA-sequencing data. However, existing methods do not account for pseudotime inference uncertainty, and they have either ill-posed p-values or restrictive models. Here we propose PseudotimeDE, a DE gene identification method that adapts to various pseudotime inference methods, accounts for pseudotime inference uncertainty, and outputs well-calibrated p-values. Comprehensive simulations and real-data applications verify that PseudotimeDE outperforms existing methods in false discovery rate control and power.
Topics & Concepts
BiologyInferenceHuman geneticsGeneticsComputational biologyGeneGene expressionSingle cell sequencingRNARNA-SeqCellTranscriptomePhenotypeArtificial intelligenceExome sequencingComputer scienceSingle-cell and spatial transcriptomicsGene Regulatory Network AnalysisCancer Genomics and Diagnostics