A genome-scale metabolic model of Drosophila melanogaster for integrative analysis of brain diseases

Abstract

High conservation of the disease-associated genes between fly and human facilitates the common use of Drosophila melanogaster to study metabolic disorders under controlled laboratory conditions. However, metabolic modeling studies are highly limited for this organism. We here report a comprehensively curated genome-scale metabolic network model of Drosophila using an orthology-based approach. The gene coverage and metabolic information of the orthology-based draft model were expanded via Drosophila-specific KEGG and MetaCyc databases, with several curation steps to avoid metabolic redundancy and stoichiometric inconsistency. Further, we performed literature-based curations to improve gene-reaction associations, subcellular metabolite locations, and updated various metabolic pathways including cholesterol metabolism. The performance of the resulting Drosophila model, termed iDrosophila1 (8,230 reactions, 6,990 metabolites, and 2,388 genes), was assessed using flux balance analysis in comparison with the other currently available fly models leading to superior or comparable results. We also evaluated transcriptome-based prediction capacity of the iDrosophila1, where differential metabolic pathways during Parkinsons disease could be successfully elucidated. Overall, iDrosophila1 is promising to investigate systems-level metabolic alterations in response to genetic and environmental perturbations.