ArticleBioinformatics (Oxford, England)2024
Pseudobulk with proper offsets has the same statistical properties as generalized linear mixed models in single-cell case-control studies.
Article in Bioinformatics (Oxford, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Decoding epithelial-mesenchymal transitions with multi-omics.Nature reviews. Genetics · 2026Review
- Myasthenia thymus reprograms class-switched B cells into BAFF-dependent survivors.Science advances · 2026Article
- Differential expression analysis in single-cell and spatial RNA-seq without model assumptions.Cell reports methods · 2026Article
- Revisiting differential expression analysis: An updated six-dimensional comparative study.PloS one · 2026Article
- Differential expression analysis in single cell and spatial RNASeq without model assumptions.bioRxiv : the preprint server for biology · 2025Article
- Single-cell dissection of chronic lung allograft dysfunction reveals convergent and distinct fibrotic mechanisms.JCI insight · 2025Article
- Myasthenia thymus reprograms class-switched B cells into BAFF-dependent survivors.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
2 authors.
Funding
Abstract
motivationGeneralized linear mixed models (GLMMs), such as the negative-binomial or Poisson linear mixed model, are widely applied to single-cell RNA sequencing data to compare transcript expression between different conditions determined at the subject level. However, the model is computationally intensive, and its relative statistical performance to pseudobulk approaches is poorly understood.
resultsWe propose offset-pseudobulk as a lightweight alternative to GLMMs. We prove that a count-based pseudobulk equipped with a proper offset variable has the same statistical properties as GLMMs in terms of both point estimates and standard errors. We confirm our findings using simulations based on real data. Offset-pseudobulk is substantially faster (>×10) and numerically more stable than GLMMs. AVAILABILITY AND IMPLEMENTATION: Offset pseudobulk can be easily implemented in any generalized linear model software by tweaking a few options. The codes can be found at https://github.com/hanbin973/pseudobulk_is_mm.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.