PriorCD

PriorCD prioritizes candidate cancer drugs by integrating pathway activity profiles and drug activity data from the NCI-60 cancer cell lines to construct a drug-drug functional similarity network and compute repurposing scores.

Key Features:

• Drug-Drug Functional Similarity Network: Constructs a functional similarity network by integrating pathway activity profiles with drug activity data to assess drug similarity at the pathway level.
• Use of NCI-60 data: Utilizes pathway and drug activity data derived from the NCI-60 cancer cell lines for network construction and analysis.
• Global Network Propagation Algorithm: Applies a global network propagation algorithm to prioritize candidate drugs across the constructed network.
• Random Walk with Restart: Uses the random walk with restart algorithm to calculate drug repurposing scores based on approved therapeutic drugs for specific cancers.
• Statistical Validation: Employs permutation tests to assess the statistical significance of calculated drug repurposing scores.

Scientific Applications:

• Breast cancer evaluation: PriorCD was evaluated using breast cancer datasets to prioritize candidate drugs based on similarity to approved therapies.
• Ovarian cancer evaluation: PriorCD was evaluated using ovarian cancer datasets to prioritize candidate drugs based on similarity to approved therapies.
• Cross-validation performance: Cross-validation on drugs approved for these cancers yielded area under the ROC curve (AUROC) values greater than 0.82.
• Pathway-level comparison: The pathway-level approach was reported to be more effective than classical gene-based methods for identifying candidate drugs with similar therapeutic effects.

Methodology:

Integrate pathway activity profiles with drug activity data from NCI-60 to construct a drug-drug functional similarity network; apply a global network propagation algorithm; compute repurposing scores using random walk with restart seeded by approved therapeutic drugs for specific cancers; assess score significance with permutation tests.