A Strategy for Uncovering the Serum Metabolome by Direct-Infusion High-Resolution Mass Spectrometry
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 character...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/3/460 |
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| author | Xiaoshan Sun Zhen Jia Yuqing Zhang Xinjie Zhao Chunxia Zhao Xin Lu Guowang Xu |
| author_facet | Xiaoshan Sun Zhen Jia Yuqing Zhang Xinjie Zhao Chunxia Zhao Xin Lu Guowang Xu |
| author_sort | Xiaoshan Sun |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T06:11:47Z |
| format | Article |
| id | doaj.art-e4a60a6692b644ef8a095891a29905b5 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-11T06:11:47Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-e4a60a6692b644ef8a095891a29905b52023-11-17T12:37:47ZengMDPI AGMetabolites2218-19892023-03-0113346010.3390/metabo13030460A Strategy for Uncovering the Serum Metabolome by Direct-Infusion High-Resolution Mass SpectrometryXiaoshan Sun0Zhen Jia1Yuqing Zhang2Xinjie Zhao3Chunxia Zhao4Xin Lu5Guowang Xu6CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaDirect 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.https://www.mdpi.com/2218-1989/13/3/460metabolomicsdirect-infusionhigh-resolution mass spectrometryformula assignmentreaction network |
| spellingShingle | Xiaoshan Sun Zhen Jia Yuqing Zhang Xinjie Zhao Chunxia Zhao Xin Lu Guowang Xu A Strategy for Uncovering the Serum Metabolome by Direct-Infusion High-Resolution Mass Spectrometry Metabolites metabolomics direct-infusion high-resolution mass spectrometry formula assignment reaction network |
| title | A Strategy for Uncovering the Serum Metabolome by Direct-Infusion High-Resolution Mass Spectrometry |
| title_full | A Strategy for Uncovering the Serum Metabolome by Direct-Infusion High-Resolution Mass Spectrometry |
| title_fullStr | A Strategy for Uncovering the Serum Metabolome by Direct-Infusion High-Resolution Mass Spectrometry |
| title_full_unstemmed | A Strategy for Uncovering the Serum Metabolome by Direct-Infusion High-Resolution Mass Spectrometry |
| title_short | A Strategy for Uncovering the Serum Metabolome by Direct-Infusion High-Resolution Mass Spectrometry |
| title_sort | strategy for uncovering the serum metabolome by direct infusion high resolution mass spectrometry |
| topic | metabolomics direct-infusion high-resolution mass spectrometry formula assignment reaction network |
| url | https://www.mdpi.com/2218-1989/13/3/460 |
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