Ion mobility conformational lipid atlas for high confidence lipidomics

Leaptrot, Katrina L.; May, Jody C.; Dodds, James N.; McLean, John A.

doi:10.1038/s41467-019-08897-5

Cited by 157 publications

(159 citation statements)

References 41 publications

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“…PB reaction converts the C=C to an oxetane which can be preferentially fragmented by low-energy collisioninduced dissociation (CID). Other approaches include ion mobility spectrometry (IMS) 36,37 and alternative gas-phase ion activation [38][39][40][41][42][43][44] . These lipid characterizing methods were also compatible with mass spectrometry imaging (MSI) [45][46][47][48][49][50] .…”

mentioning

confidence: 99%

Large-scale lipid analysis with C=C location and sn-position isomer resolving power

Cao¹,

Cheng²,

Yang³

et al. 2020

Nat Commun

144

183

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Lipids play a pivotal role in biological processes and lipid analysis by mass spectrometry (MS) has significantly advanced lipidomic studies. While the structure specificity of lipid analysis proves to be critical for studying the biological functions of lipids, current mainstream methods for large-scale lipid analysis can only identify the lipid classes and fatty acyl chains, leaving the C=C location and sn-position unidentified. In this study, combining photochemistry and tandem MS we develop a simple but effective workflow to enable large-scale and near-complete lipid structure characterization with a powerful capability of identifying C=C location(s) and sn-position(s) simultaneously. Quantitation of lipid structure isomers at multiple levels of specificity is achieved and different subtypes of human breast cancer cells are successfully discriminated. Remarkably, human lung cancer tissues can only be distinguished from adjacent normal tissues using quantitative results of both lipid C=C location and sn-position isomers.

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mentioning

confidence: 99%

Large-scale lipid analysis with C=C location and sn-position isomer resolving power

Cao¹,

Cheng²,

Yang³

et al. 2020

Nat Commun

144

183

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“…The CCS value is a measure of the shape-and sizedependent mobility of an ion in IMS and is unique to every compound. In recent years there have been major efforts to establish lipid CCS databases for DTIMS and traveling wave IMS [65][66][67][68][69]. Blazenovic et al, for example, proposed a system of lipid annotation derived from accurate mass, retention time, CCS, and degree of unsaturation values as well as the number of carbons, which should promote the identification certainty for lipids from untargeted workflows [65].…”

Section: Ion Mobility Spectrometrymentioning

confidence: 99%

“…Blazenovic et al, for example, proposed a system of lipid annotation derived from accurate mass, retention time, CCS, and degree of unsaturation values as well as the number of carbons, which should promote the identification certainty for lipids from untargeted workflows [65]. In a similar fashion, Leaptrot et al introduced an experimentally derived database of CCS values of glycerophospholipids and sphingolipids [67]. Their findings suggest that the main determinant of the CCS value is not fatty acyl chain length but rather the degree of fatty acyl unsaturation.…”

Section: Ion Mobility Spectrometrymentioning

confidence: 99%

Lipidomics from sample preparation to data analysis: a primer

2019

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Lipids are amongst the most important organic compounds in living organisms, where they serve as building blocks for cellular membranes as well as energy storage and signaling molecules. Lipidomics is the science of the large-scale determination of individual lipid species, and the underlying analytical technology that is used to identify and quantify the lipidome is generally mass spectrometry (MS). This review article provides an overview of the crucial steps in MS-based lipidomics workflows, including sample preparation, either liquid-liquid or solid-phase extraction, derivatization, chromatography, ion-mobility spectrometry, MS, and data processing by various software packages. The associated concepts are discussed from a technical perspective as well as in terms of their application. Furthermore, this article sheds light on recent advances in the technology used in this field and its current limitations. Particular emphasis is placed on data quality assurance and adequate data reporting; some of the most common pitfalls in lipidomics are discussed, along with how to circumvent them.

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“…The investigation of the correlation of lipids mass and ion mobility has been a long term interest in ion mobility spectrometry-based lipidomics 26,27 . TIMS and PASEF provide a very efficient way to extend the scope of such studies to complex biological samples.…”

Section: Starting From the Thousands Of 4d Featuresmentioning

confidence: 99%

“…This is particular interesting for lipidomics, as it provides an opportunity to separate otherwise unresolved isomers [22][23][24][25] . Furthermore, the chemical structure of lipids is closely linked to the CCS, which allows predictions by machine learning and could facilitate lipid identification [26][27][28][29] .…”

mentioning

confidence: 99%

Trapped ion mobility spectrometry (TIMS) and parallel accumulation - serial fragmentation (PASEF) enable in-depth lipidomics from minimal sample amounts

Vasilopoulou

Sulek²,

Brunner

et al. 2019

Preprint

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Lipids form a highly diverse group of biomolecules fulfilling central biological functions, ranging from structural components to intercellular signaling. Yet, a comprehensive characterization of the lipidome from limited starting material, for example in tissue biopsies, remains very challenging.Here, we develop a high-sensitivity lipidomics workflow based on nanoflow liquid chromatography and trapped ion mobility spectrometry. Taking advantage of the PASEF principle (Meier et al., PMID: 26538118), we fragmented on average nine precursors in each 100 ms TIMS scans, while maintaining the full mobility resolution of co-eluting isomers. The very high acquisition speed of about 100 Hz allowed us to obtain MS/MS spectra of the vast majority of detected isotope patterns for automated lipid identification. Analyzing 1 uL of human plasma, PASEF almost doubled the number of identified lipids over standard TIMS-MS/MS and allowed us to reduce the analysis time by a factor of three without loss of coverage. Our single-extraction workflow surpasses the plasma lipid coverage of extensive multi-step protocols in common lipid classes and achieves attomole sensitivity. Building on the high precision and accuracy of TIMS collisional cross section measurements (median CV 0.2%), we compiled 1,327 lipid CCS values from human plasma, mouse liver and human cancer cells. Our study establishes PASEF in lipid analysis and paves the way for sensitive, ion mobility-enhanced lipidomics in four dimensions.

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Ion mobility conformational lipid atlas for high confidence lipidomics

Cited by 157 publications

References 41 publications

Large-scale lipid analysis with C=C location and sn-position isomer resolving power

Large-scale lipid analysis with C=C location and sn-position isomer resolving power

Lipidomics from sample preparation to data analysis: a primer

Trapped ion mobility spectrometry (TIMS) and parallel accumulation - serial fragmentation (PASEF) enable in-depth lipidomics from minimal sample amounts

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