Combining DI-ESI-MS and NMR datasets for metabolic profiling

Area of Science:

• Metabolomics
• Analytical Chemistry
• Biochemistry

Background:

• Metabolomics datasets are typically acquired using mass spectrometry (MS) or nuclear magnetic resonance (NMR) spectroscopy separately.
• These techniques are fundamentally complementary, and their combined use enhances metabolome coverage and metabolite identification accuracy.
• Integrating MS and NMR data provides a more comprehensive analysis of metabolic changes.

Purpose of the Study:

• To optimize sample preparation, data acquisition, and data handling for simultaneous analysis of metabolomics samples by NMR and direct-infusion electrospray ionization mass spectrometry (DI-ESI-MS).
• To develop protocols for integrating 1D ¹H NMR spectra with DI-ESI-MS data.
• To demonstrate the utility of integrated metabolomics data for identifying metabolites involved in disease processes.

Main Methods:

• Optimization of sample preparation for dual NMR and MS analysis.
• High-throughput positive-ion DI-ESI-MS for complex mixtures.
• Data handling protocols using multiblock bilinear factorizations (multiblock principal component analysis [MB-PCA] and multiblock partial least squares [MB-PLS]).
• Utilized backscaled loadings, accurate mass measurements, and tandem MS for metabolite identification.

Main Results:

• Successfully optimized protocols for simultaneous NMR and DI-ESI-MS analysis from a single sample.
• Demonstrated the effectiveness of multiblock analyses (MB-PCA, MB-PLS) for integrating diverse metabolomics datasets.
• Identified specific metabolites contributing to class separation in neurotoxin-induced cell death models.

Conclusions:

• Integration of NMR and DI-ESI-MS datasets significantly improves metabolome analysis.
• The developed methodology enhances the accuracy and coverage of metabolite identification.
• This integrated approach provides valuable insights into metabolic changes, particularly in studies of neurotoxin involvement in dopaminergic cell death.