Fig. 6

Hard priors in the context of cancer somatic mutations. The universe of all tests (dark blue) includes all identified somatic mutations, regardless of frequency within cancer cells or recurrence across individuals. Hard priors often restrict tests to loss-of-function mutations (light blue) characteristic of tumor suppressors (green) and to recurrent non-synonymous mutations (light blue) characteristic of oncogenes (green). These priors may exclude unanticipated classes of driver mutations, for example structural variants (green) in which copy-number amplifications lead to changes in gene activities that drive cancer. While oracular hard priors have the property that all true findings are within the subset selected for testing, in real-world applications true findings will fall outside the prior and can increase the false-negative rate