Detection of gene cis-regulatory element perturbations in single-cell transcriptomes
Contour maps depicting raw (left) and adjusted (middle, right) p-values for detecting down-regulation of target gene given fraction of monoallelic and biallelic loss for Msh2. p-values are calculated by simulating partial and full loss of genes within each gene bucket corresponding to the observed monoallelic and biallelic loss for the given number of treatment cells, and then performing differential expression via Wilcoxon rank sum. p-values are adjusted either for all genes tested (middle), or for the set of genes with baseline mean expression above the gene with the lowest baseline mean expression in that bucket, i.e. after independent filtering (right). Vertical lines indicate base expression of genes in control population with (red) and without (black) targeted sequencing. Black horizontal lines indicate the actual number of treatment cells observed, while horizontal green dashed lines indicate the minimum number of cells required to achieve significance at corrected p-value < 0.05 to detect differential expression of Msh2 with transcript-targeted sequencing.