Label-free Proteomics for Discovering Biomarker Candidates for Controlling Krypton Misuse in Castrated Horses (Geldings)
| Autor: | Peter Curl, Stewart C. Mechie, Hiu Wing Cheung, Anil Prabhu, Terence S.M. Wan, Kin-Sing Wong, Timmy L.S. Choi, Wai Him Kwok, Emmie N.M. Ho |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Proteomics 0301 basic medicine Quantitative proteomics Computational biology Biochemistry Gas Chromatography-Mass Spectrometry 03 medical and health sciences Animals Medicine Data-independent acquisition Horses Doping in Sports 030102 biochemistry & molecular biology business.industry Label free proteomics Krypton Mass spectral library General Chemistry Blood proteins 030104 developmental biology Proteome Biomarker (medicine) business Biomarkers |
| Zdroj: | Journal of Proteome Research. 19:1196-1208 |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/acs.jproteome.9b00724 |
| Popis: | Recent advances in label-free quantitative proteomics may support its application in identifying and monitoring biomarkers for the purpose of doping control in equine sports. In this study, we developed a workflow of label-free quantitative proteomics to propose plasma protein biomarkers in horses after administration with krypton (Kr), a potential erythropoiesis-stimulating agent. Plasma proteomes were profiled by using nanoliquid chromatography-high-resolution mass spectrometry. An in-house mass spectral library consisting of 1121 proteins was compiled using samples collected from geldings (castrated horses) in the administration trial and geldings in training. A data-independent acquisition method was used to quantify an array of plasma proteins across plasma samples from the administration trial. Statistical analyses proposed a profile of 83 biomarker candidates that successfully differentiated Kr-administered samples from control samples, with the ability to detect Kr exposure for up to 13 days (the last sample collected in the administration trial). The model also correctly classified 32 in-training geldings as untreated controls. This is significantly longer than the 1 h detection time of plasma Kr using headspace gas chromatography-tandem mass spectrometry. Bioinformatic analyses enriched biomarker candidates relevant to complement activation and iron metabolism. The upregulation of transferrin receptor protein 1, one of the candidates related to iron metabolism, in plasma after Kr administration was validated by selected reaction monitoring of corresponding peptides. These results have demonstrated label-free quantitative proteomics as a promising approach to propose plasma protein biomarkers to enhance doping control. Data are available via ProteomeXchange with identifier PXD017262. |
| Databáze: | OpenAIRE |
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