The Edinburgh human metabolic network reconstruction and its functional analysis

Abstract

A better understanding of human metabolism and its relationship with diseases is an important task in human systems biology studies. In this paper, we present a high-quality human metabolic network manually reconstructed by integrating genome annotation information from different databases and metabolic reaction information from literature. The network contains nearly 3000 metabolic reactions, which were reorganized into about 70 human-specific metabolic pathways according to their functional relationships. By analysis of the functional connectivity of the metabolites in the network, the bow-tie structure, which was found previously by structure analysis, is reconfirmed. Furthermore, the distribution of the disease related genes in the network suggests that the IN (substrates) subset of the bow-tie structure has more flexibility than other parts.

Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease

“…The HMR database was constructed 15 by integrating the elements of stoichiometric networks of human metabolism, Recon 1 (ref. 12) and EHMN 13,14 , as well as the Kyoto Encyclopedia of Genes and Genomes (KEGG) database 60 . To generate a generic network for studying the effect of the lipids on the cellular metabolism, we expanded the coverage of the HMR database.…”

“…Several generic (non-cell type-specific) GEMs for human metabolism have been previously constructed [12][13][14][15][16] . However, neither of these generic networks contain extensive lipid metabolism, which is necessary to study the effect of lipids on the underlying molecular mechanism of NAFLD.…”

An integrated computational and experimental study uncovers FUT 9 as a metabolic driver of colorectal cancer

“…A genome‐scale metabolic model (GSMM) is a computer program built around a set of reactions that comprise a metabolic network, accompanied by a mapping of genes and proteins to the reactions they catalyze within the network (Orth et al , 2010). GSMM of human metabolism has become feasible in recent years thanks to the publication of the first full‐fledged genome‐scale human metabolic models [Recon1 (Duarte et al , 2007; Ma et al , 2007)]. In addition to a network of more than 3000 metabolic reactions, Recon1 contains Boolean mappings of approximately 1,500 metabolic genes through their encoded enzymes to these reactions, sub‐cellular compartmentalization of processes and pathways, and manually curated reaction stoichiometry and membrane transporters.…”

Organising metabolic networks: Cycles in flux distributions

“…The present availability of extensive data is allowing the construction of genome scale metabolic networks for an increasing number of species, generally through a careful human driven curation process (Feist et al, 2007;Heinemann et al, 2005;Herrgård et al, 2008;Ma et al, 2007). The topological properties of metabolic networks have been investigated in great details, revealing scale free, modular and hierarchical properties (Jeong et al, 2000;Ravasz et al, 2002;Sales Pardo et al, 2007).…”