Flux balance analysis predicts essential genes in clear cell renal cell carcinoma metabolism
Artikel i vetenskaplig tidskrift, 2015

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.

Författare

Francesco Gatto

Chalmers, Biologi och bioteknik, Systembiologi

H. Miess

Cancer Research UK

A. Schulze

Biocenter University of Wurzburg

Comprehensive Cancer Center Mainfranken

Cancer Research UK

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Scientific Reports

2045-2322 (ISSN)

Vol. 5 Art. no. 10738-

Infrastruktur

C3SE (Chalmers Centre for Computational Science and Engineering)

Styrkeområden

Livsvetenskaper och teknik

Ämneskategorier

Bioinformatik och systembiologi

DOI

10.1038/srep10738