The Sickle Cell Disease Ontology: enabling universal sickle cell-based knowledge representation

Abstract

Sickle cell disease (SCD) is one of the most common monogenic diseases 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 therapeutic options and ambiguous terminology. This ambiguous terminology has hampered the integration and interoperability of existing SCD knowledge, and SCD research translation. The SCD Ontology (SCDO), which is a community-driven integrative and universal knowledge representation system for SCD, overcomes this issue by providing a controlled vocabulary developed by a group of experts in both SCD and ontology design. 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 is built around the central concept 'hemoglobinopathy', allowing inclusion of non-SCD haemoglobinopathies, such as thalassaemias, which may interfere with or influence SCD phenotypic manifestations. This collaboratively developed ontology constitutes a comprehensive knowledge management system and standardized terminology of various SCD-related factors. The SCDO will promote interoperability of different research datasets, facilitate seamless data sharing and collaborations, including meta-analyses within the SCD community, and support the development and curation of data-basing and clinical informatics in SCD.

Figure 1

Overview of different steps in the remodelling, reviewing and release of the SCDO by curators, domain and ontology experts and independent reviewers.

Figure 2

SCDO evolution before and after the second workshop. Before the ontology was built around the ‘Phenotype’ class and after, the ‘hemoglobinopathy’ class became the central class.

Figure 3

Association between the central class ‘hemoglobinopathy’ and other upper-level classes (close to the root of the ontology) in the SCDO. Properties with an asterisk also link other classes within the ontology, but these could not be shown in detail here.

Figure 4

Distribution of different SCDO concepts per upper-level class with the number of associated terms in the ontology (see Supplementary Section 1 for more details about these classes).

Figure 5

Different properties and axioms defined between different SCDO concepts to satisfy rules set by SCD experts or to answer competency questions. Numbers at the top of bars represent the occurrence frequency of the association in the ontology. ^*Authors: Sickle Cell Disease Ontology Working Group.