# PseudotimeDE-fast: fast testing of differential gene expression along cell pseudotime

## TL;DR

PseudotimeDE-fast is a new method for quickly and accurately finding genes that change expression over time in single-cell RNA sequencing data.

## Contribution

PseudotimeDE-fast introduces a scalable and computationally efficient approach for differential gene expression analysis along pseudotime with well-calibrated P-values.

## Key findings

- PseudotimeDE-fast delivers comparable or better performance than existing methods.
- The method offers substantial improvements in computational efficiency.
- It handles uncertainty in pseudotime inference to produce valid P-values.

## Abstract

Identifying differentially expressed (DE) genes along cell pseudotime is crucial for understanding dynamic biological processes captured by single-cell RNA sequencing. However, existing DE methods either produce invalid P-values by ignoring the uncertainty in pseudotime inference or struggle to scale with the growing size of modern datasets. To address these limitations, we introduce PseudotimeDE-fast, a scalable method for detecting DE genes along pseudotime with well-calibrated P-values. Through comprehensive simulations and real-data analyses, we demonstrate that PseudotimeDE-fast delivers comparable or superior performance to existing approaches while offering substantial improvements in computational efficiency.

PseudotimeDE-fast is implemented in R with Rcpp acceleration and released under the MIT license. The source code is available at: https://github.com/dsong-lab/PseudotimeDE.