PXD015518

PXD015518 is an original dataset announced via ProteomeXchange.

Title	A fibroblast-specific genome-scale model focused on fatty acid alpha-oxidation
Description	Refsum disease is an inborn error of metabolism that is characterized by a defect in peroxisomal α-oxidation of the branched-chain fatty acid phytanic acid. After clinical suspicion of this disorder, including progressive retinitis pigmentosa and polyneuropathy, Refsum disease is biochemically diagnosed by elevated levels of phytanic acid in plasma and tissues of the patient. To date, no cure exists for Refsum disease, but phytanic acid levels in patients can be reduced by plasmapheresis and a strict diet. In recent years, computational models have become valuable tools to provide insight into the complex behaviour of metabolic networks. Besides the comprehensive models that contain all known metabolic reactions within the human body, several tissue- and cell-type-specific models have been developed. However, while systems biology approaches are widely used for complex diseases, only few studies have been published for inborn errors of metabolism. In this study, we reconstructed a fibroblast-specific genome-scale model based on the recently published, FAD-curated model, based on Recon3D reconstruction. We used transcriptomics, exo-metabolomics, and proteomics data, which we obtained from healthy controls and Refsum disease patient fibroblasts incubated with phytol, a precursor of phytanic acid. Our model correctly represents the metabolism of phytanic acid and displays fibroblast-specific metabolic functions. Using this model, we investigated the metabolic phenotype of Refsum disease at the genome scale, and we studied the effect of phytanic acid on cell metabolism. We identified 20 metabolites that were predicted to discriminate between Healthy and Refsum’s Disease patients, whereof several with a link to amino acid metabolism. Ultimately, these insights in metabolic changes may provide leads for pathophysiology and therapy.
HostingRepository	PRIDE
AnnounceDate	2020-03-20
AnnouncementXML	Submission_2020-03-19_23:46:02.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Justina C. Wolters
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-20 01:25:24	ID requested
⏵ 1	2020-03-19 23:46:03	announced

Wegrzyn AB, Herzog K, Gerding A, Kwiatkowski M, Wolters JC, Dolga AM, van Lint AEM, Wanders RJA, Waterham HR, Bakker BM, Fibroblast-specific genome-scale modelling predicts an imbalance in amino acid metabolism in Refsum disease. FEBS J, 287(23):5096-5113(2020) [pubmed]

submitter keyword: Refsum, model, fibroblasts, human, fatty acid alpha-oxidation

Wolters JC
contact affiliation	​Dr. J.C. Wolters Principal investigator University Medical Center Groningen Laboratory of Pediatrics Visiting address: Antonius Deusinglaan 1 (ERIBA 6th floor), 9713 AV Groningen, The Netherlands Mail address: P.O.Box 196, 9700 AD Groningen, The Netherlands HPC XB23/Room 3226.0657 Phone: +31 (0) 50 3636276 www.labpediatricsrug.nl
contact email	justina.c.wolters@rug.nl
lab head
Justina C. Wolters
contact affiliation	University Medical Center Groningen
contact email	justina.c.wolters@rug.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/03/PXD015518

PRIDE project URI

• PRIDE
  1. PXD015518
     1. Label: PRIDE project
     2. Name: A fibroblast-specific genome-scale model focused on fatty acid alpha-oxidation