Charting a Course to Lipidomics Success
Researchers use ion mobility-mass spectrometry to create a "lipid atlas."
Ryan De Vooght-Johnson | | Quick Read
Lipids are involved in a wide range of biological processes and implicated in numerous diseases, but their complex structures can challenge conventional mass spectrometry techniques. Now, chemists from Vanderbilt University have advanced lipid research using high-precision ion mobility coupled to mass spectrometry (IM-MS) (1, 2).
IM-MS provides information on both shape and mass of molecules, but early setups were often “home-built” and far from user-friendly. When Jody May, Katrina Leaptrot, and members of John McLean’s team from Vanderbilt first gained access to new, commercialized high-precision instrumentation in 2012 they used it to collect as much data as they could on lipids, carbohydrates, peptides, metabolites, and small molecules (3).
Making good use of the speed and precision of IM-MS in their latest work (1), they compiled a structural database – or atlas – of hundreds of mass-resolved collision cross sections (CCS), which can be used to match lipids to their molecular shapes. Surprisingly, the lipid measurements were highly predictable. May explains: “Because we were conducting measurements in the gas phase, we weren’t initially expecting that the lipid’s primary structural aspects (head groups, tails, and so on) would be reflected in the analysis. The predictability we witnessed increases our confidence in the results and allows us to anticipate measurements for lipids that we didn’t see in our experiments but that may appear in future studies.” The potential uses of the lipid atlas are many. “Any research area or disease studies that look at lipids can benefit from our study,” says lead author Leaptrot. Lipid biomarkers are thought to be associated with many diseases, including cancer, depression, multiple sclerosis, Alzheimer’s, and Parkinson’s.
A Unified CCS Compendium of IMMS measurements established by the group includes the lipid atlas data as well as around 3,500 additional measurements spanning a dozen classes of molecules (4, 5). The authors provide tools for making CCS calculations from IM measurements and guidelines for submitting data to the compendium – to help others add their own entries to the atlas.
Previous IM-MS work mainly focused on small molecules and inorganic compounds (6), but, says Leaptrot, “Lipid studies have remained relatively few in number, and this work is a big step toward filling that knowledge gap. Moreover, there are many isomeric and isobaric lipids that do not separate with mass spectrometry alone. Thus, ion mobility provides an additional dimension of separation that allows us to distinguish more lipid features in each complex sample.”
- KL Leaptrot et al., “Ion mobility conformational lipid atlas for high confidence lipidomics”, Nat Commun, 10 [Epub ahead of print] (2019). DOI: 10.1038/s41467-019-08897-5.
- H Hall, Vanderbilt University, “New lipid shape atlas holds key to early disease detection” (2019). Available at: bit.ly/2TMAkuA. Accessed March 12, 2019.
- JC May et al., “Conformational ordering of biomolecules in the gas phase: nitrogen collision cross sections measured on a prototype high resolution drift tube ion mobility-mass spectrometer”, Anal Chem, 86, 2107–2116 (2014). DOI: 10.1021/ac4038448.
- McClean Research Group, “Unified CCS Compendium” (2019). Available at: bit.ly/2O0fPFB. Accessed March 12, 2019
- JA Picache et al., “Collision cross section compendium to annotate and predict multi-omic compound identities”, Chem Sci, 10, 983-993 (2019). DOI: 10.1039/C8SC04396E
- JC May et al., “Ion mobility collision cross section compendium”, Anal Chem, 89 (2) 1032-1044 (2017). DOI: 10.1021/acs.analchem.6b04905