Human Phenotype Ontology Annotations for Rare Congenital Conditions: Application to Arthrogryposis Multiplex...

Arthrogryposis multiplex congenita (AMC) represents a large, rare group of congenital conditions. This study addressed major challenges in AMC research posed by the lack of systematic frameworks for data collection and the use of inconsistent terminologies and text descriptions. We aimed to systematically review the Human Phenotype Ontology (HPO) terms, encode AMC phenotypic traits as HPO terms, and pilot test the encoding process in a cohort of children with AMC. An international consensus-based dataset for AMC was used to extract phenotypic traits from the fetal period to adulthood. The encoding process was developed by an international expert panel to expand and revise HPO ontology for joint contractures, as the main characterizing traits in AMC. Using a pre-tested mapping algorithm, the HPO mapping process resulted in a 62% complete match, a 12% incomplete match, and a 26% no match. The encoding process included 37 new terms and annotations and 13 re-structures across 10 different joints. The implemented annotations significantly increased the number of available HPO terms for joint contractures in a cohort of children with AMC (p-value = 0.04). Our encoding and annotation approach may be used as a blueprint for systematic HPO (re)annotations for musculoskeletal and non-musculoskeletal phenotypic traits of AMC.