气候变化领域集成服务门户(CCPortal): Genome-scale metabolic network reconstruction of model animals as a platform for translational research

CCPortal

DOI	10.1073/pnas.2102344118
	Genome-scale metabolic network reconstruction of model animals as a platform for translational research
	Wang H.; Robinson J.L.; Kocabas P.; Gustafsson J.; Anton M.; Cholley P.-E.; Huang S.; Gobom J.; Svensson T.; Uhlen M.; Zetterberg H.; Nielsen J.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:30
英文摘要	Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (Mus musculus), Rat1 (Rattus norvegicus), Zebrafish1 (Danio rerio), Fruitfly1 (Drosophila melanogaster), and Worm1 (Caenorhabditis elegans). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer’s disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications. https://doi.org/10.1073/pnas.2102344118
英文关键词	Alzheimer’s disease; Animal model; Aβ deposition; Genome-scale model; Translational medicine
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238461
作者单位	Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, SE-412 96, Sweden; Department of Biology and Biological Engineering, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Chalmers University of Technology, Gothenburg, SE-412 96, Sweden; Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, 405 30, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Mölndal, 431 30, Sweden; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kgs, Lyngby, Denmark; Department of Protein Science, Science for Life Laboratory, KTH–Royal Institute of Technology, Stockholm, SE-100 44, Sweden; Wallenberg Center for Protein Research, KTH–Royal Institute of Technology, Stockholm, SE-100 44, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, 431 30, Sweden;...
推荐引用方式 GB/T 7714	Wang H.,Robinson J.L.,Kocabas P.,et al. Genome-scale metabolic network reconstruction of model animals as a platform for translational research[J],2021,118(30).
APA	Wang H..,Robinson J.L..,Kocabas P..,Gustafsson J..,Anton M..,...&Nielsen J..(2021).Genome-scale metabolic network reconstruction of model animals as a platform for translational research.Proceedings of the National Academy of Sciences of the United States of America,118(30).
MLA	Wang H.,et al."Genome-scale metabolic network reconstruction of model animals as a platform for translational research".Proceedings of the National Academy of Sciences of the United States of America 118.30(2021).