PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data

Published: Nov. 18, 2020, 4:01 p.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.17.387779v1?rss=1 Authors: Song, D., Li, J. J. Abstract: In the investigation of molecular mechanisms underlying cell state changes, a crucial analysis is to identify differentially expressed (DE) genes along a continuous cell trajectory, which can be estimated by pseudotime inference from single-cell RNA-sequencing (scRNA-seq) data. However, existing methods that identify DE genes based on inferred pseudotime do not account for the uncertainty in pseudotime inference. Also, they either have ill-posed p-values that hinder the control of false discovery rate (FDR) or have restrictive models that reduce the power of DE gene identification. To overcome these drawbacks, we propose PseudotimeDE, a robust method that accounts for the uncertainty in pseudotime inference and thus identifies DE genes along cell pseudotime with well-calibrated p-values. PseudotimeDE is flexible in allowing users to specify the pseudotime inference method and to choose the appropriate model for scRNA-seq data. Comprehensive simulations and real-data applications verify that PseudotimeDE provides well-calibrated p-values essential for controlling FDR and downstream analysis and that PseudotimeDE is more powerful than existing methods to identify DE genes. Copy rights belong to original authors. Visit the link for more info