Fig. 2

Perturbation clones have distinct genomic features. A. Manhattan plots showing the differentially expressed genes for cells with sgRNAs from two independent genomic regions. X-axis: genes ordered by chromosomal coordinate. Y-axis: significance differential gene expression. Positive values: up-regulated genes; negative values: down-regulated genes. Note that these distinct perturbations share the same sets of differential expressed genes in chromosome 5 and chromosome 19. B. We sequenced 1225 and 578 cells with sgRNAs targeting chr5:91296670–91,297,170 and chr14:92760258–92,760,758, respectively. Shown is the overlap of cells, which is statistically significant (p = 3.42e-35, hypergeometric p-value). C. We randomly selected 400 cells from either major clonal cells or other cells. The Manhattan plots show that the signals come from clonal cells. D. Clone 18 represents most of the overlapping cells in 2B. (top) For all 483 cells in clone 18, the heatmap shows the z-score normalized expression of all genes ordered by chromosomal coordinate. (bottom) Average values across all cells. The putative segmental deletions of chromosomes 5 and 19 are consistent with the differentially expressed genes in Fig. 2A. E. For each of the 54 major clones identified, the heatmap shows the z-score normalized expression of all genes ordered by chromosomal coordinate. F. For Clone 0, shown is the average z-score normalized expression of genes, ordered by chromosomal coordinate. Several tumor suppressors (red) and oncogenes (red) that overlap potential regions of segmental amplification or deletion, respectively, are labeled. G. Power analysis indicates the p-value of sgRNA overlap in two sequenced cells as a function of sgRNA library size and the number of sgRNAs detected per cell. We assume that clonal cells share 75% of detected sgRNAs