Gatto, Francesco;
Miess, Heike;
Schulze, Almut;
Nielsen, Jens;
(2015)
Flux balance analysis predicts essential genes in clear cell renal cell carcinoma metabolism.
Scientific Reports
, 5
, Article 10738. 10.1038/srep10738.
Preview |
Text
srep10738.pdf - Published Version Download (2MB) | Preview |
Abstract
Flux balance analysis is the only modelling approach that is capable of producing genome-wide predictions of gene essentiality that may aid to unveil metabolic liabilities in cancer. Nevertheless, a systemic validation of gene essentiality predictions by flux balance analysis is currently missing. Here, we critically evaluated the accuracy of flux balance analysis in two cancer types, clear cell renal cell carcinoma (ccRCC) and prostate adenocarcinoma, by comparison with large-scale experiments of gene essentiality in vitro. We found that in ccRCC, but not in prostate adenocarcinoma, flux balance analysis could predict essential metabolic genes beyond random expectation. Five of the identified metabolic genes, AGPAT6, GALT, GCLC, GSS and RRM2B, were predicted to be dispensable in normal cell metabolism. Hence, targeting these genes may selectively prevent ccRCC growth. Based on our analysis, we discuss the benefits and limitations of flux balance analysis for gene essentiality predictions in cancer metabolism and its use for exposing metabolic liabilities in ccRCC, whose emergent metabolic network enforces outstanding anabolic requirements for cellular proliferation.
| Type: | Article |
|---|---|
| Title: | Flux balance analysis predicts essential genes in clear cell renal cell carcinoma metabolism |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/srep10738 |
| Publisher version: | https://doi.org/10.1038/srep10738 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL SLASH UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of S&HS UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of S&HS > Dept of Economics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10161560 |
Archive Staff Only
 |
View Item |
