Time-resolved compound repositioning predictions on a texted-mined knowledge network

Mayers, M. D.; Li, T. S.; Queralt-Rosinach, N.; Su, A. I.

doi:10.1101/625459

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bioRxiv · 10.1101/625459

Time-resolved compound repositioning predictions on a texted-mined knowledge network

Mayers, M. D.·Li, T. S.·Queralt-Rosinach, N.·Su, A. I.

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Abstract

BackgroundComputational compound repositioning has the potential for identifying new uses for existing drugs, and new algorithms and data source aggregation strategies provide ever-improving results via in silico metrics. However, even with these advances, the number of compounds successfully repositioned via computational screening remains low. New strategies for algorithm evaluation that more accurately reflect the repositioning potential of a compound could provide a better target for future optimizations.\n\nResultsUsing a text-mined database, we applied a previously described network-based computational repositioning algorithm, yielding strong results via cross-validation, averaging 0.95 AUROC on test-set indications. The text-mined data was then used to build networks corresponding to different time-points in biomedical knowledge. Training the algorithm on contemporary indications and testing on future showed a marked reduction in performance, peaking in performance metrics with the 1985 network at an AUROC of .797. Examining performance reductions due to removal of specific types of relationships highlighted the importance of drug-drug and disease-disease similarity metrics. Using data from future timepoints, we demonstrate that further acquisition of these kinds of data may help improve computational results.\n\nConclusionsEvaluating a repositioning algorithm using indications unknown to input network better tunes its ability to find emerging drug indications, rather than finding those which have been withheld. Focusing efforts on improving algorithmic performance in a time-resolved paradigm may further improve computational repositioning predictions.

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Mayers, M. D., Li, T. S., Queralt-Rosinach, N., Su, A. I.. 2019-05-07. Time-resolved compound repositioning predictions on a texted-mined knowledge network. https://doi.org/10.1101/625459

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