While genomic and proteomic information describe the overall cellular machinery available to an organism, the metabolic profile of an individual at a given time provides a canvas as to the current physiological state. Concentration levels of relevant metabolites vary under different conditions, in particular, in the presence or absence of different disorders. Metabolite concentrations thus mediate an important link between chemistry and biology, contributing to a systems-wide understanding of biological processes and pathways. However, there are a number of challenges in (...) the ontological representation of such information. Firstly, concentration information is numeric and ranges over continuous values, while ontologies consist of discrete classes. Secondly, ontologies usually model only what is certain, and their logical formalisms are adapted to reasoning from certain axioms to logical deductions, however, the link between chemicals and diseases via concentration levels, like many threshold phenomena, is both uncertain and vague. In this paper we evaluate the representation of this knowledge using a combination of concrete domains and probabilistic reasoning. We parse concentration values from HMDB and create an ontology able to distinguish normal from abnormal concentrations and able to evaluate a probabilistic risk category for the presence of an associated disorder. (shrink)

Ontologies aim to represent what is general, by means of universal statements. In contrast, dispositional predications capture knowledge about what is likely to happen if a certain set of circumstances obtain, which is crucial in investigative research such as in drug discovery and systems biology, where entities which are constitutionally dissimilar can nevertheless have similar behavior in a biological context. While such dispositional properties are increasingly included in biomedical ontologies, the circumstances under which the dispositions are realized are seldom explicitly (...) modeled, and doing so is problematic due to the necessary restriction to binary relations in OWL ontologies. In this paper we address this shortcoming, focusing on the bioactivity of small molecules at varying levels of concentration within a living organism as our problem domain, although our approach is generalizable to other problems. We discuss the ontological nature and representation of dispositions and their realization; consider the nature of concentrations and their representation; and finally we detail an approach to linking dispositions to the conditions for their realization which regards conditions as triggers for the process in which the disposition is realized. (shrink)