SYNERGxDB: an integrative pharmacogenomic portal to identify synergistic drug combinations for precision oncology
Open Access
- 22 May 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 48 (W1), W494-W501
- https://doi.org/10.1093/nar/gkaa421
Abstract
Drug-combination data portals have recently been introduced to mine huge amounts of pharmacological data with the aim of improving current chemotherapy strategies. However, these portals have only been investigated for isolated datasets, and molecular profiles of cancer cell lines are lacking. Here we developed a cloud-based pharmacogenomics portal called SYNERGxDB (http://SYNERGxDB.ca/) that integrates multiple high-throughput drug-combination studies with molecular and pharmacological profiles of a large panel of cancer cell lines. This portal enables the identification of synergistic drug combinations through harmonization and unified computational analysis. We integrated nine of the largest drug combination datasets from both academic groups and pharmaceutical companies, resulting in 22 507 unique drug combinations (1977 unique compounds) screened against 151 cancer cell lines. This data compendium includes metabolomics, gene expression, copy number and mutation profiles of the cancer cell lines. In addition, SYNERGxDB provides analytical tools to discover effective therapeutic combinations and predictive biomarkers across cancer, including specific types. Combining molecular and pharmacological profiles, we systematically explored the large space of univariate predictors of drug synergism. SYNERGxDB constitutes a comprehensive resource that opens new avenues of research for exploring the mechanism of action for drug synergy with the potential of identifying new treatment strategies for cancer patients.Funding Information
- Genome Canada (15414)
- Canadian Institutes of Health Research (361454)
- Ontario Institute for Cancer Research (#399980)
This publication has 39 references indexed in Scilit:
- Overcoming drug-resistant lung cancer by paclitaxel loaded dual-functional liposomes with mitochondria targeting and pH-responseBiomaterials, 2015
- DrugComboRanker: drug combination discovery based on target network analysisBioinformatics, 2014
- Randomized Trial of Lapatinib Versus Placebo Added to Paclitaxel in the Treatment of Human Epidermal Growth Factor Receptor 2–Overexpressing Metastatic Breast CancerJournal of Clinical Oncology, 2013
- Genetic heterogeneity and cancer drug resistanceThe Lancet Oncology, 2012
- FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic CancerThe New England Journal of Medicine, 2011
- pROC: an open-source package for R and S+ to analyze and compare ROC curvesBMC Bioinformatics, 2011
- Chemotherapy: Updates and New PerspectivesThe Oncologist, 2011
- DrugBank: a comprehensive resource for in silico drug discovery and explorationNucleic Acids Research, 2006
- THE TOXICITY OF POISONS APPLIED JOINTLY1Annals of Applied Biology, 1939
- Über KombinationswirkungenNaunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 1926