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Temporal Signal Pattern Recognition in Mass Spectrometry: A Method for Rapid Identification and Accurate Quantification of Biomarkers for Inborn Errors of Metabolism with Quality Assurance.
- Source :
-
Analytical chemistry [Anal Chem] 2017 Aug 01; Vol. 89 (15), pp. 8112-8121. Date of Electronic Publication: 2017 Jul 11. - Publication Year :
- 2017
-
Abstract
- Mass spectrometry (MS)-based metabolomic initiatives that use conventional separation techniques are limited by low sample throughput and complicated data processing that contribute to false discoveries. Herein, we introduce a new strategy for unambiguous identification and accurate quantification of biomarkers for inborn errors of metabolism (IEM) from dried blood spots (DBS) with quality assurance. A multiplexed separation platform based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) was developed to provide comparable sample throughput to flow injection analysis-tandem MS (FIA-MS/MS) but with greater selectivity as required for confirmatory testing and discovery-based metabolite profiling of volume-restricted biospecimens. Mass spectral information is encoded temporally within a separation by serial injection of three or more sample pairs, each having a unique dilution pattern, alongside a quality control (QC) that serves as a reference in every run to facilitate between-sample comparisons and/or batch correction due to system drift. Optimization of whole blood extraction conditions on DBS filter paper cut-outs was first achieved to maximize recovery of a wide range of polar metabolites from DBS extracts. An interlaboratory comparison study was also conducted using a proficiency test and retrospective neonatal DBS that demonstrated good agreement between MSI-CE-MS and validated FIA-MS/MS methods within an accredited facility. Our work demonstrated accurate identification of various IEM based on reliable measurement of a panel of primary or secondary biomarkers above an upper cutoff concentration limit for presumptive screen-positive cases without stable isotope-labeled reagents. Additionally, nontargeted metabolite profiling by MSI-CE-MS with temporal signal pattern recognition revealed new biomarkers for early detection of galactosemia, such as N-galactated amino acids, that are a novel class of pathognomonic marker due to galactose stress in affected neonates.
- Subjects :
- Dried Blood Spot Testing
Electrophoresis, Capillary
Humans
Infant, Newborn
Metabolism, Inborn Errors metabolism
Quality Control
Signal Processing, Computer-Assisted
Spectrometry, Mass, Electrospray Ionization standards
Biomarkers analysis
Metabolism, Inborn Errors diagnosis
Spectrometry, Mass, Electrospray Ionization methods
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6882
- Volume :
- 89
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Analytical chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28648083
- Full Text :
- https://doi.org/10.1021/acs.analchem.7b01727