Modelling dropouts for feature selection in scRNASeq experiments

A key challenge of single-cell RNASeq (scRNASeq) is the many genes with zero reads in some cells, but high expression in others. In full-transcript datasets modelling zeros using the Michaelis-Menten equation provides an equal or superior fit to existing scRNASeq datasets compared to other approaches and enables fast and accurate identification of features corresponding to differentially expressed genes without prior identification of cell subpopulations. For datasets tagged with unique molecular identifiers we introduce a depth adjusted negative binomial (DANB) to perform dropout-rate based feature selection. Applying our method to mouse preimplantation embryos revealed clusters corresponding to the inner cell mass and trophectoderm of the blastocyst. Our feature selection method overcomes batch effects to cluster cells from five different datasets by developmental stage rather than experimental origin.