Fig. 1

Workflow schematic of Phenotype-Driven Ranking. PDR uses both, genomic data and observed phenotypes to infer likely diseases and their associated causal or correlated variant-affected genes. Only those genes are considered that pass Confidence (filtering by call quality, read depth, and genotype quality), Common Variant (filtering by population allele frequencies using 1000 Genomes, NHLBI-EVS, ExAC, and Allele Frequency Community), and Predicted Deleterious (filtering by known pathogenicity from published literature and HGMD, and variant type like coding, regulatory, non-coding, or loss or gain of function) filters in Ingenuity Variant Analysis. PDR itself employs a heuristic scoring algorithm that is based on linking phenotypes to diseases in a large-scale, hierarchical network of phenotype-phenotype, and phenotype-disease relationships