Phenotypic similarity and clinical disease-drug associations. A disease-drug pair is considered a known clinical association if treatment of patients affected by this disease with this drug is indicated, contraindicated, has been tested in phase 3 and 4 clinical trials, or represents a case where the disease has been reported as a side effect of the drug (ADR-diseases). (A) Enrichment of clinical relationships. 'All' refers to the combined set of the four relation types. Here, each type represents a separate benchmark set. (B-E) Enrichment of shortest path lengths among ADR-disease associations (B), contraindications (C), clinical trial associations (D) and indications (E). The number of known clinical associations in each distance category is given in parentheses. The dashed black lines reflect performance at random expectation.