Mass spectrometric signatures of the blood plasma metabolome for disease diagnostics

Abstract

In metabolomics, a large number of small molecules can be detected in a single run. However, metabolomic data do not include the absolute concentrations of each metabolite. Generally, mass spectrometry analyses provide metabolite concentrations that are derived from mass peak intensities, and the peak intensities are strictly dependent on the type of mass spectrometer used, as well as the technical characteristics, options and protocols applied. To convert mass peak intensities to actual concentrations, calibration curves have to be generated for each metabolite, and this represents a significant challenge depending on the number of metabolites that are detected and involved in metabolome-based diagnostics. To overcome this limitation, and to facilitate the development of diagnostic tests based on metabolomics, mass peak intensities may be expressed in quintiles. The present study demonstrates the advantage of this approach. The examples of diagnostic signatures, which were designed in accordance to this approach, are provided for lung and prostate cancer (leading causes of mortality due to cancer in developed countries) and impaired glucose tolerance (which precedes type 2 diabetes, the most common endocrinology disease worldwide).

A Metabolomics Approach to Pharmacotherapy Personalization

“…The effectiveness of this approach for metabolic profiling has been confirmed in a series of experiments [ 42 , 43 , 47 , 48 , 51 ], and it appears to be a method that can be optimized for metabolomics-based clinical tests. The high efficiency of DIMS was demonstrated in the metabolomic diagnosis of prostate cancer and lung cancer patients, as well as in the diagnosis of impaired glucose tolerance using mass spectrometers equipped with electrospray ionization (ESI) ion sources [ 42 , 47 , 52 ]. Additionally, DIMS provides an opportunity to compare mass spectrometric metabolite profiles obtained for the same type of sample in different laboratories.…”

“…Additionally, DIMS provides an opportunity to compare mass spectrometric metabolite profiles obtained for the same type of sample in different laboratories. This is a key requirement for implementing any omics-based testing in the clinic [ 52 ].…”

Parkinson’s Disease: Available Clinical and Promising Omics Tests for Diagnostics, Disease Risk Assessment, and Pharmacotherapy Personalization

“…One of the technologies most suitable for clinical use is metabolomic profiling by direct injection of a low-molecular fraction of a blood sample into an electrospray ionization source of a mass spectrometer. This method has shown outstanding results for diagnostics of many socially significant diseases and does not require complex sample preparation and any preliminary separation, which simplifies the adaptation of this metabolomic analysis for implementation in clinical diagnostic practice [110][111][112][113][114][115][116][117].…”

Metabolomic blood test: purpose, implementation and interpretation of data

“…Это свойство позволяет достоверно идентифицировать вещество и может использоваться как самостоятельно, так и дополнять другие способы идентификации. Ниже, в качестве примера, приведена массспектрометрическая сигнатура рака лёгкого, записанная в унифицированной форме и совместимая с прямым масс-спектрометрическим анализом крови [34]: m/z квантиль : 151,075 0,87 ; 153,024 0,92 ; 210,935 0,70 ; 268,891 0,64 ; 270,888 0,87 ; 278,088 0,76 ; 391,086 0,80 ; 477,087 0,81 ; 478,091 0,86 ; 479,085 0,74 ; 480,089 0,63 ; 481,091 0,73 .…”