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Abstract
Single cell RNA-seq has revolutionized transcriptomics by providing cell type resolution for differential gene expression and expression quantitative trait loci (eQTL) analyses. However, efficient power analysis methods for single cell data and inter-individual comparisons are lacking. Here, we present scPower; a statistical framework for the design and power analysis of multi-sample single cell transcriptomic experiments. We modelled the relationship between sample size, the number of cells per individual, sequencing depth, and the power of detecting differentially expressed genes within cell types. We systematically evaluated these optimal parameter combinations for several single cell profiling platforms, and generated broad recommendations. In general, shallow sequencing of high numbers of cells leads to higher overall power than deep sequencing of fewer cells. The model, including priors, is implemented as an R package and is accessible as a web tool. scPower is a highly customizable tool that experimentalists can use to quickly compare a multitude of experimental designs and optimize for a limited budget.
scRNASeq data is revolutionizing our understanding of biological systems, but is still expensive to generate. Here, the authors present a statistical framework that facilitates informed multi-sample experimental design to reduce unnecessary costs and maximize the utility of the generated data.
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1 Helmholtz Zentrum München – German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); Technical University Munich, Department of Informatics, Munich, Germany (GRID:grid.6936.a) (ISNI:0000000123222966)
2 Max Planck Institute for Psychiatry, Department of Translational Research, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095)
3 Helmholtz Diabetes Center, Helmholtz Zentrum München – German Research Center for Environmental Health, Institute of Diabetes and Regeneration Research, Neuherberg, Germany (GRID:grid.419548.5); German Center for Diabetes Research (DZD), Neuherberg, Germany (GRID:grid.452622.5); Technical University of Munich, School of Medicine, Munich, Germany (GRID:grid.6936.a) (ISNI:0000000123222966)
4 Helmholtz Diabetes Center, Helmholtz Zentrum München – German Research Center for Environmental Health, Institute of Diabetes and Regeneration Research, Neuherberg, Germany (GRID:grid.6936.a); German Center for Diabetes Research (DZD), Neuherberg, Germany (GRID:grid.452622.5); Technical University of Munich, School of Medicine, Munich, Germany (GRID:grid.6936.a) (ISNI:0000000123222966)
5 Max Planck Institute for Psychiatry, Department of Translational Research, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095); Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Georgia, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502)
6 Helmholtz Zentrum München – German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany (GRID:grid.4567.0) (ISNI:0000 0004 0483 2525); Technical University Munich, Department of Mathematics, Munich, Germany (GRID:grid.6936.a) (ISNI:0000000123222966)