DORGE: Discovery of Oncogenes and tumoR suppressor genes using Genetic and Epigenetic features
Open Access
- 13 November 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (46), eaba6784
- https://doi.org/10.1126/sciadv.aba6784
Abstract
Data-driven discovery of cancer driver genes, including tumor suppressor genes (TSGs) and oncogenes (OGs), is imperative for cancer prevention, diagnosis, and treatment. Although epigenetic alterations are important for tumor initiation and progression, most known driver genes were identified based on genetic alterations alone. Here, we developed an algorithm, DORGE (Discovery of Oncogenes and tumor suppressoR genes using Genetic and Epigenetic features), to identify TSGs and OGs by integrating comprehensive genetic and epigenetic data. DORGE identified histone modifications as strong predictors for TSGs, and it found missense mutations, super enhancers, and methylation differences as strong predictors for OGs. We extensively validated DORGE-predicted cancer driver genes using independent functional genomics data. We also found that DORGE-predicted dual-functional genes (both TSGs and OGs) are enriched at hubs in protein-protein interaction and drug-gene networks. Overall, our study has deepened the understanding of epigenetic mechanisms in tumorigenesis and revealed previously undetected cancer driver genes.Funding Information
- National Institutes of Health (R01HG007538)
- National Institutes of Health (R01CA193466)
- National Institutes of Health (R01CA228140)
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