@article{cb2139debdda45c29bb32bdf7651d119,
title = "Directed Non-targeted Mass Spectrometry and Chemical Networking for Discovery of Eicosanoids and Related Oxylipins",
abstract = "Eicosanoids and related oxylipins are critical, small bioactive mediators of human physiology and inflammation. While ∼1,100 distinct species have been predicted to exist, to date, less than 150 of these molecules have been measured in humans, limiting our understanding of their role in human biology. Using a directed non-targeted mass spectrometry approach in conjunction with chemical networking of spectral fragmentation patterns, we find over 500 discrete chemical signals highly consistent with known and putative eicosanoids and related oxylipins in human plasma including 46 putative molecules not previously described. In plasma samples from 1,500 individuals, we find members of this expanded oxylipin library hold close association with markers of inflammation, as well as clinical characteristics linked with inflammation, including advancing age and obesity. These experimental and computational approaches enable discovery of new chemical entities and will shed important insight into the role of bioactive molecules in human health and disease. Watrous et al. describe the integration of directed non-targeted mass spectrometry and computational chemical networking to discover hundreds of previously unrecognized inflammatory oxylipins metabolites in human plasma, providing a foundation for new insight into the role of oxylipins in human biology.",
keywords = "GNPS, directed non-targeted metabolomics, eicosanoids, mass spectrometry, oxylipins, spectral networking",
author = "Watrous, {Jeramie D.} and Niiranen, {Teemu J.} and Lagerborg, {Kim A.} and Mir Henglin and Xu, {Yong Jiang} and Jian Rong and Sonia Sharma and Vasan, {Ramachandran S.} and Larson, {Martin G.} and Aaron Armando and Samia Mora and Oswald Quehenberger and Dennis, {Edward A.} and Susan Cheng and Mohit Jain",
note = "Funding Information: This work was supported by grants from the NIH (K01DK116917 to J.D.W.; R01GM020501, R01DK105961, U19AI135972, P30DK063491, and U54GM069338 to E.A.D. and O.Q.; R01HL134168 to S.C.; R01DK112940, R01HL134811, and K24HL136852 to S.M.; R01CA199376 to S.S.; and S10OD020025, R03AG053287, and R01ES027595 to M.J.), support from the NHLBI to the Framingham Heart Study (contracts N01HC25195 and HHSN268201500001I), as well as generous awards from Foundations, including the American Heart Association (CVGPS Pathway Award to S.C. and M.J.), the Doris Duke Charitable Foundation (no. 2015092 to M.J.), Tobacco-Related Disease Research Program (no. 24RT-0032 to M.J., 24FT-0010 to J.D.W.), UC San Diego Frontiers of Innovation Scholars Program (to K.A.L.), Emil Aaltonen Foundation (to T.J.N.), the Finnish Medical Foundation (to T.J.N.), and the Paavo Nurmi Foundation (to T.J.N.). The funders play no role in the design of the study; the collection, analysis, and interpretation of the data; and the decision to approve publication of the finished manuscript. All authors had full access to all the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. Funding Information: This work was supported by grants from the NIH ( K01DK116917 to J.D.W.; R01GM020501 , R01DK105961 , U19AI135972 , P30DK063491 , and U54GM069338 to E.A.D. and O.Q.; R01HL134168 to S.C.; R01DK112940 , R01HL134811 , and K24HL136852 to S.M.; R01CA199376 to S.S.; and S10OD020025 , R03AG053287 , and R01ES027595 to M.J.), support from the NHLBI to the Framingham Heart Study (contracts N01HC25195 and HHSN268201500001I), as well as generous awards from Foundations, including the American Heart Association (CVGPS Pathway Award to S.C. and M.J.), the Doris Duke Charitable Foundation (no. 2015092 to M.J.), Tobacco-Related Disease Research Program (no. 24RT-0032 to M.J., 24FT-0010 to J.D.W.), UC San Diego Frontiers of Innovation Scholars Program (to K.A.L.), Emil Aaltonen Foundation (to T.J.N.), the Finnish Medical Foundation (to T.J.N.), and the Paavo Nurmi Foundation (to T.J.N.). The funders play no role in the design of the study; the collection, analysis, and interpretation of the data; and the decision to approve publication of the finished manuscript. All authors had full access to all the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",
year = "2019",
month = mar,
day = "21",
doi = "10.1016/j.chembiol.2018.11.015",
language = "English (US)",
volume = "26",
pages = "433--442.e4",
journal = "Cell Chemical Biology",
issn = "2451-9456",
publisher = "Elsevier Inc.",
number = "3",
}