Search PubMedSearch

Biomedical subjects

Dongyuan Song

Publications and source records attributed to Dongyuan Song.

2 recordsLinked to original sources

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

SUMMARY: 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. AVAILABILITY AND IMPLEMENTATION: 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.

Single-Cell Analysis

Decoding heterogeneous single-cell perturbation responses.

Understanding how cells respond differently to perturbation is crucial in cell biology, but existing methods often fail to accurately quantify and interpret heterogeneous single-cell responses. Here we introduce the perturbation-response score (PS), a method to quantify diverse perturbation responses at a single-cell level. Applied to single-cell perturbation datasets such as Perturb-seq, PS outperforms existing methods in quantifying partial gene perturbations. PS further enables single-cell dosage analysis without needing to titrate perturbations, and identifies 'buffered' and 'sensitive' response patterns of essential genes, depending on whether their moderate perturbations lead to strong downstream effects. PS reveals differential cellular responses on perturbing key genes in contexts such as T cell stimulation, latent HIV-1 expression and pancreatic differentiation. Notably, we identified a previously unknown role for the coiled-coil domain containing 6 (CCDC6) in regulating liver and pancreatic cell fate decisions. PS provides a powerful method for dose-to-function analysis, offering deeper insights from single-cell perturbation data.

Single-Cell Analysis