美国加州大学旧金山分校Chun Jimmie Ye研究小组，开发出用于单细胞RNA测序数据差异表达分析的矩方法框架。2024年10月24日，《细胞》杂志在线发表了这项成果。

研究人员表示，单细胞RNA测序（scRNA-seq）数据的差异表达分析对于表征实验因素如何影响基因表达分布至关重要。然而，区分生物和技术来源的细胞间变异性以及评估细胞组之间定量比较的统计显著性仍然具有挑战性。

研究人员推出了Memento，这是一个用于从scRNA-seq数据中进行均值表达、变异性和基因相关性的稳健且高效的差异分析工具，能够扩展到数百万个细胞和数千个样本。

研究人员将Memento应用于70000个气管上皮细胞，以识别干扰素应答基因；160000个CRISPR-Cas9干扰的T细胞以重建基因调控网络；120万个外周血单核细胞（PBMC）以绘制细胞类型特异性定量性状位点（QTL）；以及5000万个细胞的CELLxGENE Discover语料库以比较任意细胞组。

在所有情况下，Memento识别出的均值表达显著性和可重复性差异均超过现有方法。它还识别了变异性和基因相关性的差异，提示由扰动引起的不同转录调控机制。

附：英文原文

Title: Method of moments framework for differential expression analysis of single-cell RNA sequencing data

Author: Min Cheol Kim, Rachel Gate, David S. Lee, Andrew Tolopko, Andrew Lu, Erin Gordon, Eric Shifrut, Pablo E. Garcia-Nieto, Alexander Marson, Vasilis Ntranos, Chun Jimmie Ye

Issue&Volume: 2024-10-24

Abstract: Differential expression analysis of single-cell RNA sequencing (scRNA-seq) data is central for characterizing how experimental factors affect the distribution of gene expression. However, distinguishing between biological and technical sources of cell-cell variability and assessing the statistical significance of quantitative comparisons between cell groups remain challenging. We introduce Memento, a tool for robust and efficient differential analysis of mean expression, variability, and gene correlation from scRNA-seq data, scalable to millions of cells and thousands of samples. We applied Memento to 70,000 tracheal epithelial cells to identify interferon-responsive genes, 160,000 CRISPR-Cas9 perturbed T cells to reconstruct gene-regulatory networks, 1.2 million peripheral blood mononuclear cells (PBMCs) to map cell-type-specific quantitative trait loci (QTLs), and the 50-million-cell CELLxGENE Discover corpus to compare arbitrary cell groups. In all cases, Memento identified more significant and reproducible differences in mean expression compared with existing methods. It also identified differences in variability and gene correlation that suggest distinct transcriptional regulation mechanisms imparted by perturbations.

DOI: 10.1016/j.cell.2024.09.044

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01144-9