Synthesis of pharmacokinetic pathways through knowledge acquisition and automated reasoning

Biological pathways are seen as highly critical in our understanding of the mechanism of biological functions. To collect information about pathways, manual curation has been the most popular method. However, pathway annotation is regarded as heavily time-consuming, as it requires expert curators to identify and collect information from different sources. Even with the pieces of biological facts and interactions collected from various sources, curators have to apply their biological knowledge to arrange the acquired interactions in such a way that together they perform a common biological function as a pathway. In this paper, we propose a novel approach for automated pathway synthesis that acquires facts from hand-curated knowledge bases. To comprehend the incompleteness of the knowledge bases, our approach also obtains facts through automated extraction from Medline abstracts. An essential component of our approach is to apply logical reasoning to the acquired facts based on the biological knowledge about pathways. By representing such biological knowledge, the reasoning component is capable of assigning ordering to the acquired facts and interactions that is necessary for pathway synthesis. We demonstrate the feasibility of our approach with the development of a system that synthesizes pharmacokinetic pathways. We evaluate our approach by reconstructing the existing pharmacokinetic pathways available in PharmGKB. Our results show that not only that our approach is capable of synthesizing these pathways but also uncovering information that is not available in the manually annotated pathways.