O. Vieira & R.Mathiesen Labs | Novel lipid-based methodology and the potential in diagnosis of chronic diseases

AAAG_OtíliaRune

An exciting new study carried by Otília V. Vieira, leader of the Lysosomes in Chronic Human Pathologies and Infection Lab, in collaboration with Rune Mathiesen, leader of the Computational and Experimental Biology Lab was just published on EBioMedicine, a Lanchet group journal, titled “Shotgun mass spectrometry-based lipid profiling identifies and distinguishes between chronic inflammatory diseases”. Their method of lipid analysis could become a new diagnosis methodology for identifying different chronic diseases. Read what Otília Vieira had to say to about this research:

What discoveries led you to the research described in your publication?

Blood plasma lipids have long been regarded as a promising biomarker which often present strong dysregulation in chronic diseases. However, previous mass spectrometry methods for lipid identification and quantitation were limited by throughput and reproducibility because of the need of liquid chromatography separation of the analytes before mass spectrometry measurements. New state of art instrumentation enable analysis of lower sample amount, more reproducible measurements and a higher throughput for analysis of the full plasma lipid content.

In this study, we compare deep lipid profiles of major chronic inflammatory diseases such as cardiovascular (CVD), ischemic stroke (IS), systemic lupus erythematosus (SLE) and healthy control volunteers using shotgun lipidomics, a fast and highly sensitive method for lipidome analysis, alleviating the above mentioned shortcomings.

What were you trying to understand and what is the main discovery of this work?

We wanted to access the capability of state-of-the-art shotgun mass spectrometry in terms of separating inflammatory diseases based on lipid profiling of as little as 1 microliter of blood plasma. We found that the obtained lipidomes enabled a clear separation in groups of the studied chronic inflammatory diseases as well as the control groups for each experiment.

Figure1
Outline of study concepts

Why is this important?

The more lipids that are identified and quantified, the better will be our capacity to diagnose the physiological states and understand the etiology of the diseases which in addition has value for development of new therapeutics.

Can you use an analogy to help us understand your work?

The amount of blood needed for the proposed analysis can be obtained from a finger prick rather than traditional blood extraction. Just like the ones used for measurement of blood sugar levels and now in some rapid Covid-19 tests. Furthermore, the shotgun mass spectrometry approach enables faster analysis per sample enabling cost effective studies in large cohorts.

What questions remain to be asked?

We still need to access if the methodology is robust when the study is scaled up with multiple batches and laboratories. Furthermore, the methodology needs to be validated in larger cohorts including more patients and hospitals. Another question is if the detection of the lipids can be further optimized and if it is possible to develop a lipid test not dependent of mass spectrometry equipment, not available in all hospitals. A final interesting question is concerning the dysregulation of proteins in these clinical samples, which constitute an interesting follow up study to evaluate if a similar tendency of separation of chronic diseases also holds up.

You can read the full article here. This publication already warranted a commentary in the same journal which you can also read here. Furthermore, the research was highlighted in a science piece on Público newspaper, which you can access here.

Fig2

Separation of the disease groups by Linear discriminant analysis (LDA) based on selected lipids. a) LDA plots demonstrating separation of CVD, SLE, IS and control. b) LDA base separation of CVD severity and control samples. c) First LDA component versus SLE and control. d) First LDA component versus IS and control.

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