Accurate mass and retention time library of serum lipids for type 1 diabetes research

Abstract

Dysregulated lipid species are linked to various disease pathologies and implicated as potential biomarkers for type 1 diabetes (T1D). However, it is challenging to comprehensively profile the blood specimen lipidome with full structural details of every lipid molecule. The commonly used reversed-phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS)-based lipidomics approach is powerful for the separation of individual lipid species, but lipids belonging to different classes may still co-elute and result in ion suppression and misidentification of lipids. Using offline mixed-mode and RPLC-based two-dimensional separations coupled with MS/MS, a comprehensive lipidomic profiling was performed on human sera pooled from healthy and T1D subjects. The elution order of lipid molecular species on RPLC showed good correlations to the total number of carbons in fatty acyl chains and total number of double bonds. This observation together with fatty acyl methyl ester analysis was used to enhance the confidence of identified lipid species. The final T1D serum lipid library database contains 753 lipid molecular species with accurate mass and RPLC retention time uniquely annotated for each of the species. This comprehensive human serum lipid library can serve as a database for high-throughput RPLC-MSbased lipidomic analysis of blood samples related to T1D and other childhood diseases.

Lysophosphatidic acid shifts metabolic and transcriptional landscapes to induce a distinct cellular state in human pluripotent stem cells

“…Article ll lysophosphatidylcholines (LPCs), and signaling lipids as well as other unspecified components (Figure S1B) (Vu et al, 2019;Garcia-Gonzalo and Izpisu ´a Belmonte, 2008). In comparison with lipid-depleted E8 medium, AlbuMAX mitigates the metabolic burden from de novo lipogenesis and shifts cellular metabolism from extensive glycolysis toward glutamine-dependent oxidative metabolism (Zhang et al, 2016).…”

Identification, mapping and relative quantitation of SARS-CoV-2 Spike glycopeptides by Mass-Retention Time Fingerprinting

“…Mass and retention-time databases are already commonly used for small molecule screening identification applications from metabolomics, proteomics, and pesticides to drugs of abuse 17 – 20 . The MRTF database method described here has advantages over other approaches to Spike protein glycan analysis.…”

Advances in analytical tools and current statistical methods used in ultra-high-performance liquid chromatography-mass spectrometry of glycero-, glycerophospho- and sphingolipids

“…HPLC techniques are preferred for their ability to enhance identification by predictable retention time patterns [98], [105] and reduced mass ambiguity [106]. In lipid research, the sub-method UHPLC is preferred over HPLC due to its lower dispersion, substantial decrease in solvent usage, shorter analysis times without compromising resolution, higher resolution performance due to smaller (sub-2 µm) fully porous particles or (sub-3 µm) core-shell material [73] in columns (enabled by higher pressure capabilities) and enhanced retention precision.…”

“…[9], [16], [98], [105] For example, they help to differentiate possible sodium adducts from similar exact masses (e.g. [PC (38:4) In contrast to phenomena in reversed phases, normal phases in HPLC (NP-HPLC) typically separates analytes containing polar functionalities having silanol, amino-or diol groups.…”

“…Nonlinear or second-degree curves between the retention times and total carbon (CN) double bonds (DB) are used for quantitative calculations. [9], [16], [98], [105] For example, they help to differentiate possible sodium adducts from similar exact masses (e.g. [PC (38:4)+Na] + and [PC(40:7)+H] + [9]).…”