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Untargeted lipidomics, also called global lipidomics, aims at comprehensive and unbiased analysis of the lipidome in a biological matrix. One advantage of untargeted lipidomics is the ability to theoretically measure all lipids that are readily detectable. Untargeted lipidomics is eximious for discovering novel lipids and defining differential lipids. Therefore, it is well suited for screening novel lipid biomarkers in relation to diseases. Alfa Chemistry based on the sensitive and stable systems of separation, characterization, identification, analysis, and the professional technical teams to provide you with fast, accurate untargeted lipidomics study service.

Applications of Untargeted Lipidomics

Untargeted lipidomics analysis provides a plethora of lipid features in a single run, therefore, it is very suitable for screening biomarkers of diseases and enzyme annotation ^[1].

• Screening of biomarkers. Untargeted lipidomics is a powerful approach to discover not only lipids that can be used as diagnostic biomarkers, but also those that are therapeutically effective against diseases or are potential drug targets. Researches have discovered that untargeted metabolomics has been studied for human disease biomarker discovery such as Alzheimer's disease, atherosclerosis, cardiovascular disease, cancer, diabetes, obesity and others.
• Enzyme annotation. There are many lipid-metabolizing enzymes remain to be an notated. Given that the endogenous substrates and products of such enzymes are unknown. Untargeted lipidomics is a favorable approach to reveal novel lipid metabolic pathways regulated by these enzymes, which can expanded our understanding of the lipid metabolism regulated by this family of enzymes.

Alfa Chemistry's Analytical Strategies

High-resolution MS (HRMS) has powerful mass resolution and high mass accuracy that is favorable for the elucidation of lipid structural composition. It has been hailed as the preferred tool for untargeted lipidomics analysis. In Alfa Chemistry, several outstanding representatives HRMS instruments such as (Quadruple) time-of-flight MS (Q-TOF MS), Orbitrap MS, and Fourier Transform Ion Cyclotron Resonance MS (FTICR MS) are used in this study. Based on the HRMS, two popular analytics platforms are built for study of untargeted lipidomics include direct injection-HRMS (DI-HRMS) and liquid chromatography-HRMS (LC-HRMS). Introduction about these two analytics platforms is as follows.

• DI-HRMS-based untargeted lipidomics. DI-HRMS-based lipidomics is usually called shotgun lipidomics, in which lipids extracted from biological samples are directly introduced into the ion source at a constant concentration either by an LC autosampler or by a chip-based automated syringe. Such technique shows a high-throughput analysis ability, because it avoids the time consuming separation step and enables high quality data acquisition of hundreds of thousands of lipids only in minutes ^[2].
• LC-HRMS-based untargeted lipidomics. In this technique, samples are separated by liquid chromatography prior to MS detection, so the LC-HRMS can alleviate the ion suppression and provide explicit identification of isomeric or isobaric lipids to a great extent, which is benefiting accurate identification of individual lipid molecular species in untargeted lipidomics.

Alfa Chemistry's Workflow

The typical workflow of untargeted lipidomics studies is as follows.

Sample preparation

Fast and efficient sample processing to ensure sample integrity and reduce the difference between samples.

MS-based profiling platforms

HRMS platform is used to determine the exact mass of lipid and thereby discriminate each lipid species from its isobaric compounds.

Data processing

The data-processing step includes noise filtering, peak picking and alignment, and normalization.

Data analysis

Multivariate analysis methods, such as principal component analysis, partial least squares-discriminant analysis, and orthogonal PLS-DA, are employed to extract biologically relevant features.

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References

1. Lee H. C., and Yokomizo T. Applications of mass spectrometry-based targeted and non-targeted lipidomics[J]. Biochemical and Biophysical Research Communications, 2018, 504(3): 576-581.
2. Xu T., et al. Recent advances in analytical strategies for mass spectrometry-based lipidomics[J]. Analytica Chimica Acta, 2020, 1137: 156-169.