| Status | 已發表Published |
| Susceptibility to False Discovery in Biomarker Research using Liquid Chromatography–High Resolution Mass Spectrometry based Untargeted Metabolomics Profiling | |
Zhang, P. ; Ang, L.; Lam, M. T.; Wei, R.; Lei, K. M. K.; Zhou, X.; Lam, H. H. N.; He, Q. Y.; Poon, C. W.
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| 2021-06-27 | |
| Source Publication | Clinical and Translational Medicine
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| ISSN | 2001-1326 |
| Pages | e469-e469 |
| Abstract | Background: In recent years, LC-HRMS based untargeted metabolomics profiling has been widely applied to biomarker discovery research. To what extent putative metabolite biomarkers could be false biomarkers had not been investigated until the present study. Methods: Pooled human plasma was spiked separately with two different sets of 11 metabolite standards (22 “true biomarkers”) to mimic plasma samples collected from diseased subjects and non-diseased subjects. Metabolite extracts of individual samples were subjected to biomarker discovery using LC-HRMS. XCMS was employed for feature extraction, grouping and retention time alignment. CAMERA and MS-FLO were used to annotate and remove the redundant peaks. Results: The number of metabolomic features depended on the signal-to-noise ratio threshold used for feature extraction. Using a signal-to-noise ratio threshold value of 5 for feature extraction, 22 true biomarkers and 165 false positive biomarkers were observed. The actual false discovery rate (FDR) was about 88% which was far higher than the FDR cutoff (i.e., 5%) used for data mining. Identifies of 154 false positive biomarkers were deciphered. About 85% (141) of the false positive biomarkers were contributed by in-source fragmentation products, in-source complex, adducts and isotopes of the true biomarkers. About 8% (13) of the false biomarkers were contributed by irrelevant plasma metabolites, and most of them had a fold-change less than 1.5. Conclusions: Biomarker research using LC-HRMS based untargeted metabolomics profiling is highly susceptible to the discovery of false biomarkers. Our findings shed light on how the LC-HRMS approach should be improved for identifying reliable metabolomic biomarkers. |
| Keyword | metabolomics biomarker mass spectrometry false discovery |
| URL | View the original |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 60607 |
| Document Type | Journal article |
| Collection | DEPARTMENT OF BIOMEDICAL SCIENCES |
| Corresponding Author | Poon, C. W. |
| Recommended Citation GB/T 7714 | Zhang, P.,Ang, L.,Lam, M. T.,et al. Susceptibility to False Discovery in Biomarker Research using Liquid Chromatography–High Resolution Mass Spectrometry based Untargeted Metabolomics Profiling[J]. Clinical and Translational Medicine, 2021, e469-e469. |
| APA | Zhang, P.., Ang, L.., Lam, M. T.., Wei, R.., Lei, K. M. K.., Zhou, X.., Lam, H. H. N.., He, Q. Y.., & Poon, C. W. (2021). Susceptibility to False Discovery in Biomarker Research using Liquid Chromatography–High Resolution Mass Spectrometry based Untargeted Metabolomics Profiling. Clinical and Translational Medicine, e469-e469. |
| MLA | Zhang, P.,et al."Susceptibility to False Discovery in Biomarker Research using Liquid Chromatography–High Resolution Mass Spectrometry based Untargeted Metabolomics Profiling".Clinical and Translational Medicine (2021):e469-e469. |
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