Fig. 3

PHMDS methylation variant pathogenicity (MVP) score applied to PHMDS samples, controls, and over 1500 samples from patients with other neurodevelopmental syndromes. A SVM classifier was used to generate a score from zero to one for each subject as the probability of having a DNA methylation profile similar to what is observed in the PHMDS epi-signature. The Y-axis represents scores generated for each of the patient/control individuals on the X-axis. Every circle represents a single sample. The PHMDS large deletion samples, the matched controls used for probe selection and 75% of all other samples (controls and samples from patients with other neurodevelopmental syndromes) were used for training the classifier (blue). The PHMDS small deletion samples and remaining 25% of the controls and neurodevelopmental samples were used for testing (grey). Other neurodevelopmental conditions include subjects diagnosed with imprinting defects (Angelman, Prader-Willi, Beckwith-Wiedemann and Silver-Russell syndromes), non-syndromic autism spectrum disorders, BAFopathies, RASopathies, autosomal dominant cerebellar ataxia, deafness, and narcolepsy, ATRX, Borjeson-Forssman-Lehmann syndrome, Coffin-Lowry, Cornelia de Lange, CHARGE, Claes-Jensen, Down, Dup7, Floating-Harbor, Fragile X, Genitopatellar, Kabuki, Kleefstra, Rett, Sotos, Weaver, Cerebellar ataxia, deafness, and narcolepsy, immunodeficiency-centromeric instability-facial anomalies syndrome 1, Epileptic encephalopathy, Koolen–De Vries syndrome, SBBYSS syndrome, Rubinstein-Taybi syndrome 1, Rhaman syndrome, Helsmoortel-van der Aa syndrome, Autosomal dominant Mental retardation, X-linked Mental retardation, Tatton-Brown-Rahman syndrome Wiedemann-Steiner syndrome and Williams syndromes