BCseq: accurate single cell RNA-seq quantification with bias correction

With rapid technical advances, single cell RNA-seq (scRNA-seq) has been used to detect cell subtypes exhibiting distinct gene expression profiles and to trace cell transitions in development and disease. However, the potential of scRNA-seq for new discoveries is constrained by the robustness of subsequent data analysis. Here we propose a robust model, BCseq (bias-corrected sequencing analysis), to accurately quantify gene expression from scRNA-seq. BCseq corrects inherent bias of scRNA-seq in a data adaptive manner and effectively removes technical noise. BCseq rescues dropouts through weighted consideration of similar cells. Cells with higher sequencing depths contribute more to the quantification nonlinearly. Furthermore, BCseq assigns a quality score for the expression of each gene in each cell, providing users an objective measure to select genes for downstream analysis. In comparison to existing scRNA-seq methods, BCseq demonstrates increased robustness in detection of differentially expressed (DE) genes and cell subtype classification.