Abstract
BACKGROUND: Although many efforts have been made to develop comprehensive disease resources that capture rare disease information for the purpose of clinical decision making and education, there is no standardized protocol for defining and harmonizing rare diseases across multiple resources. This introduces data redundancy and inconsistency that may ultimately increase confusion and difficulty for the wide use of these resources. To overcome such encumbrances, we report our preliminary study to identify phenotypical similarity among genetic and rare diseases (GARD) that are presenting similar clinical manifestations, and support further data harmonization. OBJECTIVE: To support rare disease data harmonization, we aim to systematically identify phenotypically similar GARD diseases from a disease-oriented integrative knowledge graph and determine their similarity types. METHODS: We identified phenotypically similar GARD diseases programmatically with 2 methods: (1) We measured disease similarity by comparing disease mappings between GARD and other rare disease resources, incorporating manual assessment; 2) we derived clinical manifestations presenting among sibling diseases from disease classifications and prioritized the identified similar diseases based on their phenotypes and genotypes. RESULTS: For disease similarity comparison, approximately 87% (341/392) identified, phenotypically similar disease pairs were validated; 80% (271/392) of these disease pairs were accurately identified as phenotypically similar based on similarity score. The evaluation result shows a high precision (94%) and a satisfactory quality (86% F measure). By deriving phenotypical similarity from Monarch Disease Ontology (MONDO) and Orphanet disease classification trees, we identified a total of 360 disease pairs with at least 1 shared clinical phenotype and gene, which were applied for prioritizing clinical relevance. A total of 662 phenotypically similar disease pairs were identified and will be applied for GARD data harmonization. CONCLUSIONS: We successfully identified phenotypically similar rare diseases among the GARD diseases via 2 approaches, disease mapping comparison and phenotypical similarity derivation from disease classification systems. The results will not only direct GARD data harmonization in expanding translational science research but will also accelerate data transparency and consistency across different disease resources and terminologies, helping to build a robust and up-to-date knowledge resource on rare diseases.