Fig. 2

User interface of PDR in Ingenuity Variant Analysis. a Users enter phenotypes through a widget that employs autocomplete functionality as well as synonym mapping, and also recognizes HPO identifiers. b Results after running the PDR algorithm are displayed in a table that is rank-ordered by disease score, where rows correspond to unique disease-gene-variant combinations. Each row displays the following information (table headers shown in parentheses): inferred disease (“Disease”), associated gene (“Gene”), variant information if available (“Transcript Variant”), variant pathogenicity classification according to ACMG guidelines (“Classification”), the nature of the gene-disease relationship from OMIM (“Causal”), mode of inheritance (“MOI”), a graphical representation of variant zygosity and functional impact if known (“Case”), and the disease score from Eq. (3) (“Score”), as well as a visual representation of its contributing components by phenotype (“Score Breakdown by Phenotype”). Note, that the picture shown here is an actual screenshot of the result table as it is displayed in Ingenuity Variant Analysis, which also contains a column labeled “Control”. This column has no meaning in the context of the present paper. c Selecting a table row in the user interface leads to the display of the corresponding gene-disease-phenotype sub-network that, besides the causal or disease-correlated gene (orange), the inferred disease (green), and the linked phenotypes (blue), may also contain intermediate nodes of the phenotype-disease hierarchy (gray)