ArticleNature communications2026
FLASH-MM: fast and scalable single-cell differential expression analysis using linear mixed-effects models.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Single-cell RNA sequencing (scRNA-seq) enables detailed comparisons of gene expression across cells and conditions. Single-cell differential expression analysis faces challenges like sample correlation, individual variation, and scalability. We develop a fast and scalable linear mixed-effects model (LMM) estimation algorithm, FLASH-MM, to address these issues. We reformulate aspects of the linear mixed model estimation procedure to make it faster, by reducing computational complexity and memory usage. Simulation studies with scRNA-seq data show that FLASH-MM is accurate, computationally efficient, effectively controls false positive rates, and maintains high statistical power in differential expression analysis. Tests on tuberculosis immune and kidney single cell data demonstrate FLASH-MM's utility in accelerating single-cell differential expression analysis across diverse biological contexts.
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