Identifying Neighborhoods of Coordinated Gene Expression and Metabolite Profiles
Overview
Affiliations
In this paper we investigate how metabolic network structure affects any coordination between transcript and metabolite profiles. To achieve this goal we conduct two complementary analyses focused on the metabolic response to stress. First, we investigate the general size of any relationship between metabolic network gene expression and metabolite profiles. We find that strongly correlated transcript-metabolite profiles are sustained over surprisingly long network distances away from any target metabolite. Secondly, we employ a novel pathway mining method to investigate the structure of this transcript-metabolite relationship. The objective of this method is to identify a minimum set of metabolites which are the target of significantly correlated gene expression pathways. The results reveal that in general, a global regulation signature targeting a small number of metabolites is responsible for a large scale metabolic response. However, our method also reveals pathway specific effects that can degrade this global regulation signature and complicates the observed coordination between transcript-metabolite profiles.
New views on the selection acting on genetic polymorphism in central metabolic genes.
Eanes W Ann N Y Acad Sci. 2016; 1389(1):108-123.
PMID: 27859384 PMC: 5318266. DOI: 10.1111/nyas.13285.
The Human Blood Metabolome-Transcriptome Interface.
Bartel J, Krumsiek J, Schramm K, Adamski J, Gieger C, Herder C PLoS Genet. 2015; 11(6):e1005274.
PMID: 26086077 PMC: 4473262. DOI: 10.1371/journal.pgen.1005274.
NetPathMiner: R/Bioconductor package for network path mining through gene expression.
Mohamed A, Hancock T, Nguyen C, Mamitsuka H Bioinformatics. 2014; 30(21):3139-41.
PMID: 25075120 PMC: 4609018. DOI: 10.1093/bioinformatics/btu501.
What mRNA Abundances Can Tell us about Metabolism.
Hoppe A Metabolites. 2014; 2(3):614-31.
PMID: 24957650 PMC: 3901220. DOI: 10.3390/metabo2030614.
MIRA: mutual information-based reporter algorithm for metabolic networks.
Cicek A, Roeder K, Ozsoyoglu G Bioinformatics. 2014; 30(12):i175-84.
PMID: 24931981 PMC: 4058943. DOI: 10.1093/bioinformatics/btu290.