期刊
PLOS COMPUTATIONAL BIOLOGY
卷 10, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pcbi.1003837
关键词
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资金
- U.S. Department of Energy [DE-SC0004917]
- NNF Center for Biosustainability at the Technical University of Denmark
- National Research Foundation (NRF) of Korea - Ministry of Education, Science and Technology (MEST) [NRF-2011-357-C00142]
- U.S. Department of Energy (DOE) [DE-SC0004917] Funding Source: U.S. Department of Energy (DOE)
Altered metabolism in cancer cells has been viewed as a passive response required for a malignant transformation. However, this view has changed through the recently described metabolic oncogenic factors: mutated isocitrate dehydrogenases (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) that produce oncometabolites that competitively inhibit epigenetic regulation. In this study, we demonstrate in silico predictions of oncometabolites that have the potential to dysregulate epigenetic controls in nine types of cancer by incorporating massive scale genetic mutation information (collected from more than 1,700 cancer genomes), expression profiling data, and deploying Recon 2 to reconstruct context-specific genome-scale metabolic models. Our analysis predicted 15 compounds and 24 substructures of potential oncometabolites that could result from the loss-of-function and gain-of-function mutations of metabolic enzymes, respectively. These results suggest a substantial potential for discovering unidentified oncometabolites in various forms of cancers.
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