LipidOz enables automated elucidation of lipid carbon-carbon double bond positions from ozone-induced dissociation mass spectrometry data

Dylan H Ross; Joon-Yong Lee; Aivett Bilbao; Daniel J Orton; Josie G Eder; Meagan C Burnet; Brooke L Deatherage Kaiser; Jennifer E Kyle; Xueyun Zheng

doi:10.1038/s42004-023-00867-9

LipidOz enables automated elucidation of lipid carbon-carbon double bond positions from ozone-induced dissociation mass spectrometry data

Commun Chem. 2023 Apr 19;6(1):74. doi: 10.1038/s42004-023-00867-9.

Authors

Dylan H Ross¹, Joon-Yong Lee^{1

2}, Aivett Bilbao¹, Daniel J Orton¹, Josie G Eder¹, Meagan C Burnet¹, Brooke L Deatherage Kaiser¹, Jennifer E Kyle¹, Xueyun Zheng³

Affiliations

¹ Pacific Northwest National Laboratory, Richland, WA, 99354, USA.
² PrognomiQ, Inc, San Mateo, CA, 94403, USA.
³ Pacific Northwest National Laboratory, Richland, WA, 99354, USA. xueyun.zheng@pnnl.gov.

Abstract

Lipids play essential roles in many biological processes and disease pathology, but unambiguous identification of lipids is complicated by the presence of multiple isomeric species differing by fatty acyl chain length, stereospecifically numbered (sn) position, and position/stereochemistry of double bonds. Conventional liquid chromatography-mass spectrometry (LC-MS/MS) analyses enable the determination of fatty acyl chain lengths (and in some cases sn position) and number of double bonds, but not carbon-carbon double bond positions. Ozone-induced dissociation (OzID) is a gas-phase oxidation reaction that produces characteristic fragments from lipids containing double bonds. OzID can be incorporated into ion mobility spectrometry (IMS)-MS instruments for the structural characterization of lipids, including additional isomer separation and confident assignment of double bond positions. The complexity and repetitive nature of OzID data analysis and lack of software tool support have limited the application of OzID for routine lipidomics studies. Here, we present an open-source Python tool, LipidOz, for the automated determination of lipid double bond positions from OzID-IMS-MS data, which employs a combination of traditional automation and deep learning approaches. Our results demonstrate the ability of LipidOz to robustly assign double bond positions for lipid standard mixtures and complex lipid extracts, enabling practical application of OzID for future lipidomics.