Identifying disease-associated pathways in one-phenotype data based on reversal gene expression orderings

Due to the invasiveness nature of tissue biopsy, it is common that investigators cannot collect sufficient normal controls for comparison with diseased samples. We developed a pathway enrichment tool, DRFunc, to detect significantly disease-disrupted pathways by incorporating normal controls from other experiments. The method was validated using both microarray and RNA-seq expression data for different cancers. The high concordant differentially ranked (DR) gene pairs were identified between cases and controls from different independent datasets. The DR gene pairs were used in the DRFunc algorithm to detect significantly disrupted pathways in one-phenotype expression data by combing controls from other studies. The DRFunc algorithm was exemplified by the detection of significant pathways in glioblastoma samples. The algorithm can also be used to detect altered pathways in the datasets with weak expression signals, as shown by the analysis on the expression data of chemotherapy-treated breast cancer samples.