Skip to main content
Open Access Publications from the University of California

UC San Diego

UC San Diego Previously Published Works bannerUC San Diego

A systems approach to predict oncometabolites via context-specific genome-scale metabolic networks.

  • Author(s): Nam, Hojung
  • Campodonico, Miguel
  • Bordbar, Aarash
  • Hyduke, Daniel R
  • Kim, Sangwoo
  • Zielinski, Daniel C
  • Palsson, Bernhard O
  • et al.

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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View