Abstract
We developed deconvolution of single-cell expression distribution (DESCEND), a method to recover cross-cell distribution of the true gene expression level from observed counts in single-cell RNA sequencing, allowing adjustment of known confounding cell-level factors. With the recovered distribution, DESCEND provides reliable estimates of distribution-based measurements, such as the dispersion of true gene expression and the probability that true gene expression is positive. This is important, as with better estimates of these measurements, DESCEND clarifies and improves many downstream analyses including finding differentially expressed genes, identifying cell types, and selecting differentiation markers. Another contribution is that we verified using nine public datasets a simple “Poisson-alpha” noise model for the technical noise of unique molecular identifier-based single-cell RNA-sequencing data, clarifying the current intense debate on this issue.
