A Strategy for Uncovering the Serum Metabolome by Direct-Infusion High-Resolution Mass Spectrometry.
Xiaoshan SunZhen JiaYuqing ZhangXinjie ZhaoChunxia ZhaoXin LuGuo-Wang XuPublished in: Metabolites (2023)
Direct infusion nanoelectrospray high-resolution mass spectrometry (DI-nESI-HRMS) is a promising tool for high-throughput metabolomics analysis. However, metabolite assignment is limited by the inadequate mass accuracy and chemical space of the metabolome database. Here, a serum metabolome characterization method was proposed to make full use of the potential of DI-nESI-HRMS. Different from the widely used database search approach, unambiguous formula assignments were achieved by a reaction network combined with mass accuracy and isotopic patterns filter. To provide enough initial known nodes, an initial network was directly constructed by known metabolite formulas. Then experimental formula candidates were screened by the predefined reaction with the network. The effects of sources and scales of networks on assignment performance were investigated. Further, a scoring rule for filtering unambiguous formula candidates was proposed. The developed approach was validated by a pooled serum sample spiked with reference standards. The coverage and accuracy rates for the spiked standards were 98.9% and 93.6%, respectively. A total of 1958 monoisotopic features were assigned with unique formula candidates for the pooled serum, which is twice more than the database search. Finally, a case study of serum metabolomics in diabetes was carried out using the developed method.
Keyphrases
- high resolution mass spectrometry
- liquid chromatography
- mass spectrometry
- high throughput
- ultra high performance liquid chromatography
- type diabetes
- low dose
- human milk
- gas chromatography
- cardiovascular disease
- staphylococcus aureus
- clinical trial
- escherichia coli
- high resolution
- tandem mass spectrometry
- early stage
- emergency department
- metabolic syndrome
- weight loss
- drinking water
- electronic health record
- neoadjuvant chemotherapy
- drug induced
- biofilm formation
- network analysis