Fig. 3: Overlap of compensation and toxicity identifies ARGOS genes.

a All gene classes are spread along the genome and densities using a Gaussian estimator with a 1 Mb bandwidth show clustering only in gene-dense regions (cf. Supplementary Fig. S4a). b Compensated genes (110) are dropping out more strongly in the ORF screen than hyperactivated (451) and non-regulated genes. Boxes show median ± quartile, whiskers 1.5x inter-quartile range, and P-values from a two-sided t test. c The overlap of compensated and toxic genes identifies eight genes, five of which are amplified in over 15% of TCGA tumors (upward pointing triangles). Numbers include only genes present in both CCLE and TCGA, numbers in brackets include all genes present in data. d Prioritization of protein complexes with ARGOS genes (Fisher’s Exact test on CORUM complexes, y-axis) and their toxicity (Wald statistic of a linear regression model for ORF dropout, x-axis) identifies the HDP-RNP and U1A spliceosomal complexes. Paraspeckle genes in the HDP-RNP complex are both compensated and toxic, while nonhomologous end-joining (NHEJ) genes show no effect or the opposite trend. Complexes without evidence of compensation and toxicity are shaded gray and yellow, respectively.