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As a reflection of real world biological events triggered by a stimulus, it is important to facilitate the incorporation of known molecular events for inferring (unknown) possible pathways and hypothetic drug interactions. Here, we propose a new Ontology-Driven Hypothetic Assertion (OHA) framework including pathway generation, drug interaction detection, simulation model generation, numerical simulation, and hypothetic assertion. Potential drug interactions are detected from drug metabolic pathways dynamically generated by molecular events triggered after the administration of certain drugs. Numerical simulation enables to estimate the degree of side effects caused by the predicted drug interactions. New hypothetic assertions of the potential drug interactions and simulation are deduced from the Drug Interaction Ontology (DIO) written in Web Ontology Language (OWL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The concept of the Ontology-Driven Hypothetic Assertion (OHA) framework was demonstrated with known interactions between irinotecan (CPT-11) and ketoconazole. Four drug interactions that involved cytochrome p450 (CYP3A4) and albumin as potential drug interaction proteins were automatically detected from Drug Interaction Ontology (DIO). The effect of the two interactions involving CYP3A4 were quantitatively evaluated with numerical simulation. The co-administration of ketoconazole may increase AUC and Cmax of SN-38(active metabolite of irinotecan) to 108% and 105%, respectively. We also estimates the potential effects of genetic variations: the AUC and Cmax of SN-38 may increase to 208% and 165% respectively with the genetic variation UGT1A1*28\/*28 which reduces the expression of UGT1A1 down to 30%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrate that the Ontology-Driven Hypothetic Assertion framework is a promising approach for<jats:italic>in silico<\/jats:italic>prediction of drug interactions. The following future researches for the<jats:italic>in silico<\/jats:italic>prediction of individual differences in the response to the drug and drug interactions after the administration of multiple drugs: expansion of the Drug Interaction Ontology for other drugs, and incorporation of virtual population model for genetic variation analysis, as well as refinement of the pathway generation rules, the drug interaction detection rules, and the numerical simulation models.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2105-9-s6-s11","type":"journal-article","created":{"date-parts":[[2008,5,28]],"date-time":"2008-05-28T18:15:46Z","timestamp":1211998546000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Drug interaction prediction using ontology-driven hypothetical assertion framework for pathway generation followed by numerical simulation"],"prefix":"10.1186","volume":"9","author":[{"given":"Takeshi","family":"Arikuma","sequence":"first","affiliation":[]},{"given":"Sumi","family":"Yoshikawa","sequence":"additional","affiliation":[]},{"given":"Ryuzo","family":"Azuma","sequence":"additional","affiliation":[]},{"given":"Kentaro","family":"Watanabe","sequence":"additional","affiliation":[]},{"given":"Kazumi","family":"Matsumura","sequence":"additional","affiliation":[]},{"given":"Akihiko","family":"Konagaya","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2008,5,28]]},"reference":[{"issue":"2","key":"2622_CR1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S0022-3565(24)37858-9","volume":"287","author":"H Okuda","year":"1998","unstructured":"Okuda H, Ogura K, Kato A, Takubo H, Watanabe T: A possible mechanism of eighteen patient deaths caused by interactions of sorivudine, a new antiviral drug, with oral 5-fluorouracil prodrugs. 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