Fig. 1

Benchmarking of all phenotype-based exome analysis tools on 1000 Genomes Project or in-house exomes. Exomes were generated by randomly inserting known disease variants from the Human Genome Mutation Database (HGMD) into either (a, c, e) 50 unaffected exomes from the 1000 Genomes Project or (b, d, f) 50 in-house generated exomes. These exomes were analyzed using each tool and the ability of each tool to rank the causative variant as the top hit, in the top 10 or top 50 was recorded. Default settings, along with filtering with a minor allele frequency cutoff of 1 %, were used for all tools. Analysis was performed using (a, b) all phenotype annotations (c, d) just three of the terms chosen randomly, or (e, f) with two of these three terms made less-specific and two random terms from the whole of the Human Phenotype Ontology (HPO) added