Comprehensive Metabolic Fingerprints Characterize Neuromyelitis Optica Spectrum Disorder by Nanoparticle-Enhanced Laser Desorption/Ionization Mass Spectrometry

Abstract

Timely screening of neuromyelitis optica spectrum disorder (NMOSD) and differential diagnosis from myelin oligodendrocyte glycoprotein associated disorder (MOGAD) are the keys to improving the quality of life of patients. Metabolic disturbance occurs with the development of NMOSD. Still, advanced tools are required to probe the metabolic phenotype of NMOSD. Here, we developed a fast nanoparticle-enhanced laser desorption/ionization mass spectrometry assay for multiplexing metabolic fingerprints (MFs) from trace plasma and cerebrospinal fluid (CSF) samples in 30 s. Machine learning of the plasma MFs achieved the timely screening of NMOSD from healthy donors with an area under receiver operator characteristic curve (AUROC) of 0.998, and it comprehensively revealed the dysregulated neurotransmitter and energy metabolisms. Combining comprehensive MFs from both plasma and CSF, we constructed an integrated panel for differential diagnosis of NMOSD versus MOGAD with an AUROC of 0.923. This approach demonstrated performance superior to that of human experts in classifying two diseases, especially in antibody assay-limited regions. Together, this approach provides an advanced nanomaterial-based tool for identifying vulnerable populations below the antibody threshold of aquaporin-4 positivity.

Quantitative Detection of Multiple Cardiovascular Biomarkers by an Antibody Microarray-Based Metal-Enhanced Fluorescence Assay

“…LASSO regression is used to differentiate HDs, ACS patients, and AAS patients because it is one of the most robust machine learning approaches for feature selection and classification. , For the training data set, it is performed to simultaneously distinguish HDs, ACS patients, and AAS patients through the expression levels of 7 cardiovascular biomarkers in 140 clinical plasma samples. The effectiveness of LASSO algorithms is displayed by multigroup ROC curves.…”

Quantitative mass spectrometry imaging: therapeutics & biomolecules

“…20 Interestingly, nanoparticle-enhanced LDI-MS, an ionization technique similar to MALDI, has recently been applied for increasing metabolite sensitivity in both breast cancer and neuromyelitis optica spectrum disorder. 21,22 This ionization technique is efficient for studies involving lower molecular weight metabolites as MALDI matrices can result in ion suppression and matrix peaks. 23 All of these techniques have many variants which allow researchers to tailor their ionization source for specific applications.…”

Plasmonic Alloys Enhanced Metabolic Fingerprints for the Diagnosis of COPD and Exacerbations

“…Additionally, there are very few studies investigating the relationship between particle size and selective LDI. Furthermore, nanoparticles with porous structures enable the enrichment of small metabolites and the exclusion of proteins, achieving selective ionization of metabolites. , Therefore, bimetallic alloys with synergistic effects and mesoporous structure promise to alleviate the constraints of monometallic/metal-composite and nonporous matrixes and advance metabolite analysis toward precise diagnosis.…”