The Pharmacorank Search Tool for the Retrieval of Prioritized Protein Drug Targets and Drug Repositioning Candidates According to Selected Diseases

摘要

We present the Pharmacorank search tool as an objective means to obtain prioritized protein drug targets and their associated medications according to user-selected diseases. This tool could be used to obtain prioritized protein targets for the creation of novel medications or to predict novel indications for medications that already exist. To prioritize the proteins associated with each disease, a gene similarity profiling method based on protein functions is implemented. The priority scores of the proteins are found to correlate well with the likelihoods that the associated medications are clinically relevant in the disease's treatment. When the protein priority scores are plotted against the percentage of protein targets that are known to bind medications currently indicated to treat the disease, which we termed the pertinency score, a strong correlation was observed. The correlation coefficient was found to be 0.9978 when using a weighted second-order polynomial fit. As the highly predictive fit was made using a broad range of diseases, we were able to identify a general threshold for the pertinency score as a starting point for considering drug repositioning candidates. Several repositioning candidates are described for proteins that have high predicated pertinency scores, and these provide illustrative examples of the applications of the tool. We also describe focused reviews of repositioning candidates for Alzheimer's disease. Via the tool's URL, https://protein.som.geisinger.edu/Pharmacorank/, an open online interface is provided for interactive use; and there is a site for programmatic access.