Integrative cancer pharmacogenomics to establish drug mechanism of action: drug repurposing

• Published in: Pharmacogenomics Vol. 18; no. 16; pp. 1469 - 1472
• Main Authors: El-Hachem, Nehme, Ba-alawi, Wail, Smith, Ian, Mer, Arvind Singh, Haibe-Kains, Benjamin
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2017
• Subjects: Bcl-2 protein; Biological activity; Biology; Cancer; Chemical compounds; Complementarity; Computational Biology - methods; Datasets; Drug development; Drug Discovery - methods; Drug Repositioning - methods; drug repurposing; Drugs; Gene expression; Genomics; Humans; integrative analysis; Ligands; machine learning; Methods; Neoplasms - drug therapy; Pharmacogenetics - methods; Pharmacogenomics; Proteins; Taxonomy; Transcription; cancer; integrative analysis; drug repurposing; pharmacogenomics; machine learning
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs-2017-0132

[...]these approaches integrate a limited number of data layers, despite their high complementarity (18,19). DNF to pinpoint novel drug indications and MoA in the drug development process DNF is the first tool to integrate pharmaco-chemo-genomics high-throughput data, including chemical structures, pharmacological growth inhibition profiles and post-treatment transcriptional perturbations, to develop comprehensive drug taxonomy (20). Since our integrative approach yielded an improved drug taxonomy, we assessed the biological relevance of DNF using a clustering technique known as affinity propagation clustering (29). ABT-737 and navitoclax that showed less off-target effect than obatoclax towards Bcl-2. Besides improving drug classification, a major application of DNF is drug repurposing.