ce‐Subpathway: Identification of ce RNA ‐mediated subpathways via joint power of ce RNA s and pathway topologies

Competing endogenous RNA s (ce RNA s) represent a novel mechanism of gene regulation that may mediate key subpathway regions and contribute to the altered activities of pathways. However, the classical methods used to identify pathways fail to specifically consider ce RNA s within the pathways and key regions impacted by them. We proposed a powerful strategy named ce‐Subpathway for the identification of ce RNA ‐mediated functional subpathways. It provided an effective level of pathway analysis via integrating ce RNA s, differentially expressed ( DE ) genes and their key regions within the given pathways. We respectively analysed one pulmonary arterial hypertension ( PAH ) and one myocardial infarction ( MI ) data sets and demonstrated that ce‐Subpathway could identify many subpathways whose corresponding entire pathways were ignored by those non‐ce RNA ‐mediated pathway identification methods. And these pathways have been well reported to be associated with PAH / MI ‐related cardiovascular diseases. Further evidence showed reliability of ce RNA interactions and robustness/reproducibility of the ce‐Subpathway strategy by several data sets of different cancers, including breast cancer, oesophageal cancer and colon cancer. Survival analysis was finally applied to illustrate the clinical application value of the ce RNA ‐mediated functional subpathways using another data sets of pancreatic cancer. Comprehensive analyses have shown the power of a joint ce RNA s/ DE genes and subpathway strategy based on their topologies.