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. 2013 Oct 8;9:696. doi: 10.1038/msb.2013.54

Figure 7.

Figure 7

Inferring genetic dependencies on variable cancer genotypes. (A) Schematic outline showing GARP profiles derived from isogenic cell lines on the left and essential gene profile from 72 non-isogenic cell lines on the right. GARP profiles for each cell line, both isogenic and non-isogenic, is represented as sorted dot plots with genes on the x axis and cell lines on the y axis. The yellow dots represent those genes that had a significant GARP score (P-value <0.05). Genes are sorted by their frequency of being essential in the 72 cancer cell lines. The DiE profile contains the significant negative genetic interactions (P-value <0.05, derived as pictured for the PTEN-null case in the lower left box: red dots, synthetic lethal or sick; blue, general essentials; black, not-influenced genes). We model that the enrichment of genes in the DiE profile from the isogenic cell lines will be a key feature in defining the genetic dependencies of the non-isogenic cancer cell lines. (B) Jaccard index (defined as the intersection between the DiE profile of PTEN and the essentials genes (P<0.05) of non-isogenic lines divided by their union) exhibit a higher overlap on average for those lines that are dependent on PTEN/PI3K pathway (shift in mean is significant, P-value <0.002). (C) The Jaccard index distribution for both the PTEN-dependent and PTEN-independent sets are plotted as box plot. Dots are extreme values (outliers; defined as having an Jaccard index more than 3/2 times higher as the upper quartile, which represents 75% of the data), the vertical lines represent the span of maximal to minimal value of non-outliers, the boxes span the upper (75% of the data) to lower (25% of the data) quartiles, the vertical line represents the median. (D) Heat map showing distributions of genes that exhibit negative genetic interaction with PTEN and are at the same time more frequently essential (P<0.05) in the PTEN/PIK3-dependent cell lines compared with PTEN/PI3K-independent lines. Red color histogram shows the frequency in cell lines that are PTEN/PI3K dependent, blue represents the PTEN/PI3K-independent cell lines. Light blue bars give the difference in frequency between the two sets according to which the heat map is sorted (only genes with a difference in frequency >0.1 and more frequent in PTEN/PIK3-dependent cell lines are shown).