RNA-seq profiles of C. elegans with various dietary conditions and gene perturbations related to vitamin B12 metabolism

ABSTRACT: Genome-scale metabolic network models (MNMs) can be used with a mathematical modeling tool called flux balance analysis to gain insights into metabolism at a systems level. Such models represent metabolism of an organism as a whole and do not automatically reveal how the flux overall is wired, i.e., which reactions carry flux, and which do not, and measuring flux at a large scale is challenging. Enzyme levels, as proxied by mRNA levels, can be used to predict reaction fluxes. However, integrating gene expression data with MNMs only partly constrains flux models. Here, we derive how metabolism is wired in unperturbed animals using a large-scale Worm Perturb-Seq dataset. We present a highly constrained, semi-quantitative optimal flux distribution that reflects how metabolism is wired in the animal at the adult stage. We discover several features about C. elegans metabolism that were heretofore unknown, including cyclic flux through the pentose phosphate pathway, and the primary use of amino acids and bacterial RNA as an energy source, all of which we validated by isotope tracing. Our strategy for inferring metabolic wiring based solely on gene expression should be applicable to a variety of systems, including human cells. This dataset includes the RNA-seq profiles collected during the proof-of-concept studies on the metrics used for predicting flux wiring from Worm Perturb-Seq dataset. It includes three sets of data: the profiles of animals fed live versus paraformaldehyde-killed (PFA killed) bacteria; the profiles of gene knockdowns in propionate degradation metabolism under a gradient of vitamin B12 supplementation; and the profiles of gene knockdowns in Met/SAM cycle under vitamin B12 and choline supplementations.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE255866 | GEO | 2024/11/20

REPOSITORIES: GEO