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Automatic filtering and substantiation of drug safety signals
Bauer-Mehren, Anna; van Mullingen, Erik M.; Avillach, Paul; Carrascosa, Maria del Carmen; García Serna, Ricard; Piñero, Janet; Singh, Barat; Lopes, Pedro; Oliveira, José Luis; Diallo, Gayo; Ahlberg Helgee, Ernest; Boyer, Scott; Mestres, Jordi; Sanz, Ferran; Kors, Jan A.; Furlong, Laura I.
Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions
This work was supported by the European Commission [EU-ADR, ICT-215847], Innovative Medicines Initiative [eTOX,115002], the AGAUR [to A.B.M.],Instituto de Salud Carlos III FEDER (CP10/00524) and COMBIOMED grants. The Research Unit on Biomedical Informatics (GRIB) is a node of the Spanish NationalInstitute of Bioinformatics (INB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Medicaments -- Efectes secundaris
Medicaments -- Anàlisi
© 2012 Bauer-Mehren et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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