Fig. 1. A multiclass supervised classification system.

This classification system, referred to as a methylation variant pathogenicity (MVP) score, can classify samples using the 43 episignatures in EpiSign v2. Shown here are examples using the Cornelia de Lange syndrome (CdLS) signature (top) and Sotos signature (bottom), applied to over 1,500 samples from subjects with various neurodevelopmental syndromes or from healthy controls. In each case, samples from the respective syndrome all have high scores while samples from other syndromes and controls all have low scores, demonstrating the sensitivity and specificity of the classifier. The likely pathogenic variants described in Fig. 2 (CdLS) and 3 (Sotos) are shown here larger and in red.