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Automatic Filtering and Substantiation of Drug Safety Signals

Figure 1

Schematic representation of the signal substantiation process.

The signal substantiation process involves the automatic search for evidences that support the causal inference of the potential signal. A. Signal substantiation through proteins. The profile of targets of the drug and its metabolites is obtained by in silico profiling methods (Drug-Target-Profile). The profile of proteins associated with the clinical event is obtained by mining DisGeNET (Event-Protein Profile). The profiles are compared to find proteins in common in both profiles (Drug-Event Linking Proteins). The evidences that support the association of the drug and event with the Drug-Event Linking proteins are explored to determine if they support the causal inference of the signal. B. Signal substantiation through pathways. Proteins in the Drug-Target-Profile and in the Event-Protein Profile are searched in The Human Protein Atlas database to determine if they are expressed in the same tissue and cell type. Proteins that share expression at both levels (tissue and cell type) are used to query Reactome database, and pathways that contain at least one protein from the Drug-Target-Profile and one protein from the Event-Protein Profile are retrieved. Then, these pathways are explored to determine if they support the causal inference of the signal.

Figure 1

doi: https://doi.org/10.1371/journal.pcbi.1002457.g001