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Background  Natural language processing has long been applied in various applications for biomedical knowledge inference and discovery. Enrichment analysis based on named entity recognition is a classic application for inferring enriched associations in terms of specific biomedical entities such as gene, chemical, and mutation.    Objective  The aim of this study was to investigate the effect of pathway enrichment evaluation with respect to biomedical text-mining results and to develop a novel metric to quantify the effect.    Methods  Four biomedical text mining methods were selected to represent natural language processing methods on drug-related gene mining. Subsequently, a pathway enrichment experiment was performed by using the mined genes, and a series of inverse pathway frequency (IPF) metrics was proposed accordingly to evaluate the effect of pathway enrichment. Thereafter, 7 IPF metrics and traditional  P  value metrics were compared in simulation experiments to test the robustness of the proposed metrics.    Results  IPF metrics were evaluated in a case study of rapamycin-related gene set. By applying the best IPF metrics in a pathway enrichment simulation test, a novel discovery of drug efficacy of rapamycin for breast cancer was replicated from the data chosen prior to the year 2000. Our findings show the effectiveness of the best IPF metric in support of knowledge discovery in new drug use. Further, the mechanism underlying the drug-disease association was visualized by Cytoscape.    Conclusions  The results of this study suggest the effectiveness of the proposed IPF metrics in pathway enrichment evaluation as well as its application in drug use discovery.

A Novel Metric to Quantify the Effect of Pathway Enrichment Evaluation With Respect to Biomedical Text-Mined Terms: Development and Feasibility Study