Abstract
Today’s high-resolution mass spectrometers (HRMS) allow bioanalysts to perform untargeted/global determinations that can reveal unexpected compounds or concentrations in a patient’s sample. This could be performed for preliminary diagnosis attempts when usual diagnostic processes and targeted determinations fail. We have evaluated an untargeted diagnostic screening (UDS) procedure. UDS is a metabolome analysis that compares one sample (e.g., a patient) with control samples (a healthy population). Using liquid chromatography (LC)-HRMS full-scan analysis of human serum extracts and unsupervised data treatment, we have compared individual samples that were spiked with one xenobiotic or a higher level of one endogenous compound with control samples. After the use of different filters that drastically reduced the number of metabolites detected, the spiked compound was eventually revealed in each test sample and ranked. The proposed UDS procedure appears feasible and reliable to reveal unexpected xenobiotics (toxicology) or higher concentrations of endogenous metabolites. HRMS-based untargeted approaches could be useful as preliminary diagnostic screening when canonical processes do not reveal disease etiology nor establish a clear diagnosis and could reduce misdiagnosis. On the other hand, the risk of overdiagnosis of this approach should be reduced with mandatory biomedical interpretation of the patient’s UDS results and with confirmatory targeted and quantitative determinations.
Highlights
Diagnostic process starts from the patient’s symptoms and history
Metabolites 2018, 8, 39 there are less common diseases and clinical symptoms in which such targeted approaches do not properly reveal disease etiology nor establish a clear diagnosis (Figure 1). Such diseases may benefit from an untargeted diagnostic screening (UDS) approach in which a much larger number of compounds (N > 1000; the metabolome) can be measured in one person’s sample whereas no metabolites are predefined before their measurements (Figure 1) [5,6,7,8,9,10,11]
We have investigated the use of metabolomics for untargeted diagnostic screening (UDS)
Summary
Diagnostic process starts from the patient’s symptoms and history. It is evidence-based and tries to rule in or out different disease possibilities and relies on targeted/knowledge-driven approaches. Metabolites 2018, 8, 39 there are less common diseases and clinical symptoms in which such targeted approaches do not properly reveal disease etiology nor establish a clear diagnosis (Figure 1) Such diseases may benefit from an untargeted diagnostic screening (UDS) approach in which a much larger number of compounds (N > 1000; the metabolome) can be measured in one person’s sample whereas no metabolites are predefined before their measurements (Figure 1) [5,6,7,8,9,10,11]. The risk of overdiagnosis associated with possible false positive hits is discussed
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.