Evaluating the Predictive Accuracy of Reactome's Curated Biological Pathways

Abstract

Reactome is a database of human biological pathways manually curated from the primary literature and peer-reviewed by experts. To evaluate the utility of Reactome pathways for predicting functional consequences of genetic perturbations, we compared predictions of perturbation effects based on Reactome pathways against published empirical observations. Ten cancer-relevant Reactome pathways, representing diverse biological processes such as signal transduction, cell division, DNA repair, and transcriptional regulation, were selected for testing. For each pathway, root input nodes and key pathway outputs were defined. We then used pathway-diagram-derived logic graphs to predict, either by inspection by biocurators or using a novel algorithm MP-BioPath, the effects of bidirectional perturbations (upregulation/activation or downregulation/inhibition) of single root inputs on the status of key outputs. These predictions were then compared to published empirical tests.