Fig. 2

Visual representations of differential disease spectra. In this case selected from a retrospective genetic disease cohort, bradykinesia, developmental regression, dystonia, motor delay, delayed speech and language development, and ptosis were reported. a The global map: a visual map representation of the relationships between the phenotypic features of the case (yellow triangle) and all 7,746 cataloged Online Mendelian Inheritance in Man (OMIM) diseases (gray circles). The two-dimensional space x,y is defined by the first two multidimensional scaling (MDS) components computed from Resnik similarities between all pairs of diseases. A projected map location is calculated for the case via a weighted convex combination of the coordinates of the diseases with the top five similarities to the complete patient phenotypes. The genotypic spectrum of disease for the case, comprising the 174 diseases with known causes in genes variant in the filtered patient exome, is highlighted in orange and is clustered throughout the visual space. b The local/radar map: an improved visual map representation of the relationships between the phenotypic features of the selected clinical case and the 174 genotypic spectrum diseases. The case is placed at the center of the map. The circumferential disease distribution across 360 degrees θ is a linear scaling of the first MDS component computed from Resnik similarities between all pairs of diseases. Radial dissimilarity distance r is computed for each disease as the linear transformation of its similarity to the patient phenotypes. The size and color of disease points indicate the ExAC [42] and MutationTaster [46] pathogenicity of case variants harbored in genes causally linked to top differential intermediate diseases. The map can be progressively filtered to reflect mandatory aspects of clinical phenotype and genotype or manual curation of differential intermediates, as performed by clinicians