Cytocipherdetermines significantly different populations of cells in single cell RNA-seq data

Abstract

AbstractIdentification of cell types using single cell RNA-seq (scRNA-seq) is revolutionising the study of multicellular organisms. However, typical scRNA-seq analysis often involves post hoc manual curation to ensure clusters are transcriptionally distinct, which is time-consuming, error-prone, and irreproducible. To overcome these obstacles, we developedCytocipher, a bioinformatics method andscversecompatible software package that statistically determines significant clusters. Application ofCytocipherto normal tissue, development, disease, and large-scale atlas data reveals the broad applicability and power ofCytocipherto generate biological insights in numerous contexts. This included the identification of cell types not previously described in the datasets analyzed, such as CD8+ T cell subtypes in human peripheral blood mononuclear cells; cell lineage intermediate states during mouse pancreas development; and subpopulations of luminal epithelial cells over-represented in prostate cancer.Cytocipheralso scales to large datasets with high test performance, as shown by application to the Tabula Sapiens Atlas representing >480,000 cells.Cytocipheris a novel and generalisable method that statistically determines transcriptionally distinct and programmatically reproducible clusters from single cell data.Cytocipheris available athttps://github.com/BradBalderson/Cytocipher.