Dual fragmentation via collision-induced and oxygen attachment dissociations using water and its radicals for C=C position-resolved lipidomics

Abstract Oxygen attachment dissociation (OAD) is a tandem mass spectrometry (MS/MS) technique for annotating the positions of double bonds (C=C) in complex lipids. Although OAD has been used for untargeted lipidomics, its availability has been limited to the positive ion mode, requiring the independ...

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Main Authors: Hiroaki Takeda, Mami Okamoto, Hidenori Takahashi, Bujinlkham Buyantogtokh, Noriyuki Kishi, Hideyuki Okano, Hiroyuki Kamiguchi, Hiroshi Tsugawa
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Communications Chemistry
Online Access:https://doi.org/10.1038/s42004-025-01525-y
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author Hiroaki Takeda
Mami Okamoto
Hidenori Takahashi
Bujinlkham Buyantogtokh
Noriyuki Kishi
Hideyuki Okano
Hiroyuki Kamiguchi
Hiroshi Tsugawa
author_facet Hiroaki Takeda
Mami Okamoto
Hidenori Takahashi
Bujinlkham Buyantogtokh
Noriyuki Kishi
Hideyuki Okano
Hiroyuki Kamiguchi
Hiroshi Tsugawa
author_sort Hiroaki Takeda
collection DOAJ
description Abstract Oxygen attachment dissociation (OAD) is a tandem mass spectrometry (MS/MS) technique for annotating the positions of double bonds (C=C) in complex lipids. Although OAD has been used for untargeted lipidomics, its availability has been limited to the positive ion mode, requiring the independent use of a collision-induced dissociation (CID) method. In this study, we demonstrated the OAD MS/MS technique in the negative-ion mode for profiling phosphatidylserines, phosphatidylglycerols, phosphatidylinositols, and sulfatides, where the fragmentation mechanism remained consistent with that in the positive ion mode. Furthermore, we proposed optimal conditions for the simultaneous acquisition of CID- and OAD-specific fragment ions, termed OAciD, where oxygen atoms and hydroxy radicals facilitate C=C position-specific fragmentation, while residual water vapor induces cleavage of low-energy covalent bonds as observed in CID. Finally, theoretical fragment ions were implemented in MS-DIAL 5 to accelerate C=C position-resolved untargeted lipidomics. The OAciD methodology was used to illuminate brain region-specific marmoset lipidomes with C=C positional information, including the estimation of C=C positional isomer ratios. We also characterized the profiles of polyunsaturated fatty acid-containing lipids, finding that lipids containing omega-3 fatty acids were enriched in the cerebellum, whereas those containing omega-6 fatty acids were more abundant in the hippocampus and frontal lobe.
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spelling doaj-art-ed9755b930bb4debae15fe0373331e992025-08-20T03:48:05ZengNature PortfolioCommunications Chemistry2399-36692025-05-018111310.1038/s42004-025-01525-yDual fragmentation via collision-induced and oxygen attachment dissociations using water and its radicals for C=C position-resolved lipidomicsHiroaki Takeda0Mami Okamoto1Hidenori Takahashi2Bujinlkham Buyantogtokh3Noriyuki Kishi4Hideyuki Okano5Hiroyuki Kamiguchi6Hiroshi Tsugawa7Department of Biotechnology and Life Science, Tokyo University of Agriculture and TechnologyShimadzu Corporation, 1 Nishinokyo-Kuwabaracho Nakagyo-kuShimadzu Corporation, 1 Nishinokyo-Kuwabaracho Nakagyo-kuDepartment of Biotechnology and Life Science, Tokyo University of Agriculture and TechnologyRIKEN Center for Brain ScienceRIKEN Center for Brain ScienceRIKEN Center for Brain ScienceDepartment of Biotechnology and Life Science, Tokyo University of Agriculture and TechnologyAbstract Oxygen attachment dissociation (OAD) is a tandem mass spectrometry (MS/MS) technique for annotating the positions of double bonds (C=C) in complex lipids. Although OAD has been used for untargeted lipidomics, its availability has been limited to the positive ion mode, requiring the independent use of a collision-induced dissociation (CID) method. In this study, we demonstrated the OAD MS/MS technique in the negative-ion mode for profiling phosphatidylserines, phosphatidylglycerols, phosphatidylinositols, and sulfatides, where the fragmentation mechanism remained consistent with that in the positive ion mode. Furthermore, we proposed optimal conditions for the simultaneous acquisition of CID- and OAD-specific fragment ions, termed OAciD, where oxygen atoms and hydroxy radicals facilitate C=C position-specific fragmentation, while residual water vapor induces cleavage of low-energy covalent bonds as observed in CID. Finally, theoretical fragment ions were implemented in MS-DIAL 5 to accelerate C=C position-resolved untargeted lipidomics. The OAciD methodology was used to illuminate brain region-specific marmoset lipidomes with C=C positional information, including the estimation of C=C positional isomer ratios. We also characterized the profiles of polyunsaturated fatty acid-containing lipids, finding that lipids containing omega-3 fatty acids were enriched in the cerebellum, whereas those containing omega-6 fatty acids were more abundant in the hippocampus and frontal lobe.https://doi.org/10.1038/s42004-025-01525-y
spellingShingle Hiroaki Takeda
Mami Okamoto
Hidenori Takahashi
Bujinlkham Buyantogtokh
Noriyuki Kishi
Hideyuki Okano
Hiroyuki Kamiguchi
Hiroshi Tsugawa
Dual fragmentation via collision-induced and oxygen attachment dissociations using water and its radicals for C=C position-resolved lipidomics
Communications Chemistry
title Dual fragmentation via collision-induced and oxygen attachment dissociations using water and its radicals for C=C position-resolved lipidomics
title_full Dual fragmentation via collision-induced and oxygen attachment dissociations using water and its radicals for C=C position-resolved lipidomics
title_fullStr Dual fragmentation via collision-induced and oxygen attachment dissociations using water and its radicals for C=C position-resolved lipidomics
title_full_unstemmed Dual fragmentation via collision-induced and oxygen attachment dissociations using water and its radicals for C=C position-resolved lipidomics
title_short Dual fragmentation via collision-induced and oxygen attachment dissociations using water and its radicals for C=C position-resolved lipidomics
title_sort dual fragmentation via collision induced and oxygen attachment dissociations using water and its radicals for c c position resolved lipidomics
url https://doi.org/10.1038/s42004-025-01525-y
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