Fig. 1

Overview of the DISCOVER method. a The input to the method is a binary alteration matrix with genes in the rows and tumors in the columns. The following panels illustrate how the two genes highlighted in red and green are tested for co-occurrence. b To identify co-occurrences or mutual exclusivities, a null distribution is estimated that describes the overlap in alterations of two genes expected by chance. Co-occurrence and mutual exclusivity correspond to the tails of this distribution. c In the binomial model, a single alteration probability is estimated per gene that applies to all tumors. The expected number of alterations per gene matches the observed number. The expected number of alterations per tumor does not match the observed number. The product of two genes’ alteration probabilities gives the probability of overlap by chance, which multiplied by the number of tumors gives the expected number of tumors with alterations in both genes, in this case 0.8. d In the Poisson-binomial model, gene alteration probabilities are estimated for each tumor individually. The expected number of alterations both per gene and per tumor match the observed numbers. The product of two gene alteration probabilities is also computed per tumor. The expected number of tumors with alterations in both genes according to this model is 1.5