Sensitivity and precision We simulated datasets of 10,000 genes with negative binomial distributed counts. To simulate data with realistic moments, the mean and dispersions were drawn from the joint distribution of means and gene-wise dispersion estimates from the Pickrell et al. data, fitting only an intercept term. These datasets were of varying total sample size (m∈{6,8,10,20}), and the samples were split into two equal-sized groups; 80% of the simulated genes had no true differential expression, while for 20% of the genes, true fold changes of 2, 3 and 4 were used to generate counts across the two groups, with the direction of fold change chosen randomly. The simulated differentially expressed genes were chosen uniformly at random among all the genes, throughout the range of mean counts. MA-plots of the true fold changes used in the simulation and the observed fold changes induced by the simulation for one of the simulation settings are shown in Additional file 1: Figure S6.
