Phenotype-specific estimation of metabolic fluxes using gene expression data.

ABSTRACT: A cell's genome influences its metabolism via the expression of enzyme-related genes, but transcriptome and fluxome are not perfectly correlated as post-transcriptional mechanisms also regulate reaction's kinetics. Here, we addressed the question: given a transcriptome, how unobserved mechanisms of reaction kinetics should be systematically accounted for when inferring the fluxome? To infer the most likely and least biased fluxome, we present Pheflux, a constraint-based model maximizing Shannon's entropy of fluxes per mRNA. Benchmarked against ¹³C fluxes of yeast and bacteria, Pheflux accurately estimates the carbon core metabolism. We applied Pheflux to thousands of normal and tumor cell transcriptomes obtained from The Cancer Genome Atlas. Pheflux showed statistically signific

SUBMITTER: Gonzalez-Arrue N 

PROVIDER: S-EPMC10006673 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature