ncDRMarker

ncDRMarker prioritizes candidate non-coding RNAs associated with drug resistance by integrating heterogeneous mRNA–miRNA–lncRNA networks and applying an extended random walk with restart algorithm to identify chemoresistance biomarkers.

Key Features:

• Heterogeneous network integration: Constructs an mRNA-miRNA-lncRNA composite network by integrating experimentally validated protein–protein, miRNA–target gene, and miRNA–lncRNA interactions.
• Extended random walk with restart (RWR): Applies an RWR algorithm tailored for heterogeneous networks to prioritize ncRNAs linked to chemoresistance.
• Cross-validation and ROC performance: Evaluates performance using leave-one-out cross-validation (LOOCV) and ROC analysis with AUCs reported between 0.881 and 0.951, including assessments under incomplete-network scenarios.
• KEGG pathway enrichment: Performs KEGG pathway enrichment analysis to characterize biological functions and cancer-related pathways associated with identified ncRNAs.
• Statistical validation on NCI-60: Validates candidate ncRNAs across NCI-60 cancer cell lines using the Wilcoxon rank-sum test, including identification of miR-92a-3p distinguishing tamoxifen and paclitaxel sensitivity.
• Hub ncRNA identification: Identifies hub ncRNAs such as miR-124-3p that are implicated in resistance to multiple drugs and participate in multiple cancer-related pathways.

Scientific Applications:

• Biomarker discovery: Prioritizes ncRNA biomarkers associated with chemoresistance in cancer for downstream experimental validation.
• Mechanistic insight: Links identified ncRNAs to KEGG pathways to elucidate potential mechanisms underlying drug resistance.
• Comparative drug resistance analysis: Distinguishes sensitive versus resistant cell lines for specific drugs (e.g., tamoxifen and paclitaxel) using ncRNA signatures validated on NCI-60.

Methodology:

Constructs a composite mRNA-miRNA-lncRNA network from experimentally validated protein–protein, miRNA–target gene, and miRNA–lncRNA interactions; applies an extended random walk with restart on this heterogeneous network; evaluates performance with LOOCV and ROC AUC; performs KEGG pathway enrichment and validates candidates using the Wilcoxon rank-sum test on NCI-60 cell line data.