Development and Implementation of the Sickle Cell Disease Ontology

Abstract

Background: Sickle cell disease (SCD) is the most common monogenic disease in humans with multiple phenotypic expressions that can manifest as both acute and chronic complications. Although described more than a century ago, challenges in comprehensive disease management and collaborative research on this disease are compounded by the complex molecular and clinical phenotypes of SCD, environmental and psychosocial factors, limited number of therapeutic options and ambiguous terminology.  

Methods: Sickle Cell Disease Ontology (SCDO) was a community driven integrative and universal knowledge representation system for SCD, providing a controlled vocabulary developed by multi- and interdisciplinary groups of experts in both SCD and ontology design. The initial concepts in the ontology were generated using existing biological databases and ontologies, literature-based text mining and SCD management guidelines and standards of care from both resources-rich and resources-poor countries. SCDO is built around the central concept 'Hemoglobinopathy', allowing inclusion of non-SCD haemoglobinopathies, such as thalassaemias, which may interfere with SCD phenotypic manifestations.  

Findings: SCDO is the first and most comprehensive standardized human- and machine-readable resource that unambiguously represents terminology and concepts about SCD for researchers, patients and clinicians. It constitutes a comprehensive knowledge management system, standardize terminology of  various SCD related factors, that will promote interoperability of different research datasets.  

Interpretation: This collaboratively developed ontology will help advance research and improve SCD management, by providing a well-structured format by which disease knowledge can be compared, integrated and shared. This will facilitate seamless data sharing and collaborations including meta-analysis within the SCD community and support the development and curation of data-basing and clinical informatics in SCD. The ontology will continue to be developed by the SCD community using best practices and guidelines.  

Funding: The development of the SCDO is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number U24HL135600; National Institutes of Health Common Fund grants U24HG006941 (H3ABioNet) and U01HG009716, Wellcome Trust/AESA Ref: H3A/18/001 and 1U54HG009790-01.

Declaration of Interest: No conflict of interest is declared.

Ethical Approval: No ethics committee approval was required as no patient data is used in this work.

Keywords: Sickle Cell, disease, ontology, data, phenotype