Since 2002 we have been testing and refining a methodology for ontology development that is now being used by multiple groups of researchers in different life science domains. Gary Merrill, in a recent paper in this journal, describes some of the reasons why this methodology has been found attractive by researchers in the biological and biomedical sciences. At the same time he assails the methodology on philosophical grounds, focusing specifically on our recommendation that ontologies developed for scientific purposes should be constructed in such a way that their terms are seen as referring to what we call universals or types in reality. As we show, Merrill's critique is of little relevance to the success of our realist project, since it not only reveals no actual errors in our work but also criticizes views on universals that we do not in fact hold. However, it nonetheless provides us with a valuable opportunity to clarify the realist methodology, and to show how some of its principles are being applied, especially within the framework of the OBO (Open Biomedical Ontologies) Foundry initiative.

The National Cancer Institute's (NCI) Thesaurus is a biomedical reference ontology. The NCI Thesaurus is represented using Description Logic, more specifically Ontylog, a Description logic implemented by Apelon, Inc. We are exploring the use of the DL species of the Web Ontology Language (OWL DL)-a W3C recommended standard for ontology representation-instead of Ontylog for representing the NCI Thesaurus. We have studied the requirements for knowledge representation of the NCI Thesaurus, and considered how OWL DL (and its implementation in Protégé-OWL) satisfies these requirements. In this paper, we discuss the areas where OWL DL was sufficient for representing required components, where tool support that would hide some of the complexity and extra levels of indirection would be required, and where language expressiveness is not sufficient given the representation requirements. Because many of the knowledge-representation issues that we encountered are very similar to the issues in representing other biomedical terminologies and ontologies in general, we believe that the lessons that we learned and the approaches that we developed will prove useful and informative for other researchers.

The purpose of this study was to evaluate, revise, and extend the Informed Consent Ontology (ICO) for expressing clinical permissions, including reuse of residual clinical biospecimens and health data. This study followed a formative evaluation design and used a bottom-up modeling approach. Data were collected from the literature on US federal regulations and a study of clinical consent forms. Eleven federal regulations and fifteen permission-sentences from clinical consent forms were iteratively modeled to identify entities and their relationships, followed by community reflection and negotiation based on a series of predetermined evaluation questions. ICO included fifty-two classes and twelve object properties necessary when modeling, demonstrating appropriateness of extending ICO for the clinical domain. Twenty-six additional classes were imported into ICO from other ontologies, and twelve new classes were recommended for development. This work addresses a critical gap in formally representing permissions clinical permissions, including reuse of residual clinical biospecimens and health data. It makes missing content available to the OBO Foundry, enabling use alongside other widely-adopted biomedical ontologies. ICO serves as a machine-interpretable and interoperable tool for responsible reuse of residual clinical biospecimens and health data at scale.