Semantic Similarity Analysis Reveals Robust Gene-Disease Relationships in Developmental and Epileptic Encephalopathies.

ABSTRACT: More than 100 genetic etiologies have been identified in developmental and epileptic encephalopathies (DEEs), but correlating genetic findings with clinical features at scale has remained a hurdle because of a lack of frameworks for analyzing heterogenous clinical data. Here, we analyzed 31,742 Human Phenotype Ontology (HPO) terms in 846 individuals with existing whole-exome trio data and assessed associated clinical features and phenotypic relatedness by using HPO-based semantic similarity analysis for individuals with de novo variants in the same gene. Gene-specific phenotypic signatures included associations of SCN1A with "complex febrile seizures" (HP: 0011172; p = 2.1 × 10^-5) and "focal clonic seizures" (HP: 0002266; p = 8.9 × 10^-6), STXBP1 with "absent speech" (

SUBMITTER: Galer PD 

PROVIDER: S-EPMC7536581 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature