Fig. 3

Extension of the DISCOVER test for mutual exclusivity within groups of genes. a Three alternative statistics for measuring the degree of mutual exclusivity within a group of genes. Coverage refers to the number of tumors that have an alteration in at least one of the genes. Exclusivity refers to the number of tumors that have an alteration in exactly one gene. Impurity refers to the number of tumors that have an alteration in more than one gene. b P-value reliability curves comparing DISCOVER with other mutual exclusivity tests. The false positive rate should not exceed the significance level α. In such a case, the calibration curve will be below the diagonal. For all tests but muex, this is the case. The curves for CoMEt, MEGSA, mutex, and TiMEx are mostly overlapping; their false positive rate stays at 0 until the significance level is almost 1. c Sensitivity curves comparing DISCOVER with other mutual exclusivity tests. More sensitive tests will attain higher true positive rates at lower significance levels. Two discontinuities that occur at a significance level of approximately 1×10⁻¹⁶ are marked with dotted lines. First, muex compresses all lower P values to 0; hence, all lower significance levels have the same true positive rate. Second, this significance level coincides with the change from the slower CoMEt exact test to the binomial approximation (see Methods); the two tests seem to behave quite differently