The development of a translational informatics knowledgebase (TIK) that is assay-centric and captures relevant information from chemogenomics, proteomics and phenomics requires appropriate annotations for each of the classes of objects within the TIK system. Careful curation is required at all levels, including chemical, biological assay with target, phenotype, pathway, detection, etc. - aspects that are both enabled and required within the BARD system. Here we describe the process of annotating and evaluating an external screening set, the bioactivity component of DrugMatrix (baDM). The complete DrugMatrix dataset is freely available at https://ntp.niehs.nih.gov/drugmatrix/index.html, offered by the National Toxicology Program (NTP). baDM assays were extracted from ChEMBL (https://www.ebi.ac.uk/chembldb/), with additional re-evaluation against the complete NTP set. Assay information was  extracted from the original assay provider, Eurofins Panlabs (https://www.eurofinspanlabs.com/Catalog/AssayCatalog/AssayCatalog.aspx?search). The baDM set from ChEMBL contains 871 chemicals, measured in 131 assays, with 7055 exact Ki or IC50 values. BARD leverages BioAssay Ontology (BAO) and BAO annotations including biochemical information (e.g., reference compound structures and bioactivities) were added for all baDM assays. Target curation was required for 37 proteins, with complete target reassignment in some cases (e.g., 'central imidazoline I2 receptors' are in fact an allosteric site of monoamine oxidases A or B). A regression analysis of the complete baDM matrix shows target relationships at the bioactivity level: Highly correlated sets (R^2 >= 0.5) were observed within the adrenergic, dopaminergic, muscarinic, opioid and serotonergic receptor family subtypes, as well as within the calcium channel L-type sites, with up to 87 chemicals.

Data curation and formal BioAssay Ontology (BAO)-based annotations of the DrugMatrix enable bioactivity-based target-relationship analysis and demonstrate incorporation of external datasets into the BioAssay Research Database (BARD)

246th National Meeting (2013)

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