Untargeted urine metabolomics reveals a biosignature for muscle respiratory chain deficiencies

dc.contributor.authorVenter, Leonie
dc.contributor.authorLindeque, Zander
dc.contributor.authorJansen van Rensburg, Peet
dc.contributor.authorVan der Westhuizen, Francois
dc.contributor.authorSmuts, Izelle
dc.contributor.authorLouw, Roan
dc.date.accessioned2016-02-10T12:27:46Z
dc.date.issued2015-02
dc.description.abstractMitochondrial diseases are a heterogeneous group of disorders characterised by impaired mitochondrial oxidative phosphorylation system. Most often for mitochondrial disease, where no metabolic diagnostic biomarkers exist, a deficiency is diagnosed after analysing the respiratory chain enzymes (complexes I-IV) in affected tissues or by identifying one of an ever expanding number of DNA mutations. This presents a great challenge to identify cases to undergo the invasive diagnostic procedures required. An untargeted liquid chromatography mass spectrometry metabolomics approach was used to search for a metabolic biosignature that can distinguish respiratory chain deficient (RCD) patients from clinical controls (CC). A cohort of 37 ethnically diverse cases was used. Sample preparation, liquid chromatography time-of-flight mass spectrometry methods and data processing methods were standardised. Furthermore the developed methodology used reverse phase chromatography in conjunction with positive electrospray ionisation and hydrophilic interaction chromatography with negative electrospray ionisation. Urine samples of 37 patients representing two different experimental groups were analysed. The two experimental groups comprised of patients with confirmed RCDs and CC. After a variety of data mining steps and statistical analyses a list of 12 features were compiled with the ability to distinguish between patients with RCDs and CC. Although the features of the biosignature needs to be identified and the biosignature validated, this study demonstrates the value of untargeted metabolomics to identify a metabolic biosignature to possibly be applied in the selection criteria for RCDs.en_ZA
dc.description.embargo2016-02-28
dc.description.librarianhb2015en_ZA
dc.description.sponsorshipNorth-West University, Potchefstroom Campusen_ZA
dc.description.urihttp://link.springer.com/journal/11306en_ZA
dc.identifier.citationVenter, L, Lindeque, Z, Van Rensburg, PJ, Van der Westhuizen, F, Smuts, I & Louw, R 2015, 'Untargeted urine metabolomics reveals a biosignature for muscle respiratory chain deficiencies', Metabolomics, vol. 11, no. 1, pp. 111-121.en_ZA
dc.identifier.issn1573-3882 (print)
dc.identifier.issn1573-3890 (online)
dc.identifier.other10.1007/s11306-014-0675-5
dc.identifier.urihttp://hdl.handle.net/2263/51328
dc.language.isoenen_ZA
dc.publisherSpringeren_ZA
dc.rights© Springer Science+Business Media New York 2014. The original publication is available at : http://link.springer.comjournal/11306.en_ZA
dc.subjectMetabolomicsen_ZA
dc.subjectUrinary biomarkeren_ZA
dc.subjectLC–MSen_ZA
dc.subjectRespiratory chain deficient (RCD)en_ZA
dc.subjectClinical controls (CC)en_ZA
dc.titleUntargeted urine metabolomics reveals a biosignature for muscle respiratory chain deficienciesen_ZA
dc.typePostprint Articleen_ZA

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