Diagnosis of Parkinson’s Disease by A Metabolomics-Based Laboratory-Developed Test (LDT)

Abstract

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is designed, manufactured and used in the same laboratory (i.e., an in-house test). In this study, a metabolomics-based LDT was developed. This test involves a blood plasma preparation, direct-infusion mass spectrometry analysis with a high-resolution mass spectrometer, alignment and normalization of mass peaks using original algorithms, metabolite annotation by a biochemical context-driven algorithm, detection of overrepresented metabolic pathways and results in a visualization in the form of a pathway names cloud. The LDT was applied to detect early stage Parkinson’s disease (PD)—the diagnosis of which currently requires great effort due to the lack of available laboratory tests. In a case–control study (n = 56), the LDT revealed a statistically sound pattern in the PD-relevant pathways. Usage of the LDT for individuals confirmed its ability to reveal this pattern and thus diagnose PD at the early-stage (1–2.5 stages, according to Hoehn and Yahr scale). The detection of this pattern by LDT could diagnose PD with a specificity of 64%, sensitivity of 86% and an accuracy of 75%. Thus, this LDT can be used for further widespread testing.

Holistic Metabolomic Laboratory-Developed Test (LDT): Development and Use for the Diagnosis of Early-Stage Parkinson’s Disease

“…The selection of PD to test this LDT was not an accident. Previously, it has been shown that an LDT can reveal the pathway overrepresentation efficient for the diagnosis of PD [ 12 ], thus making it reasonable to complete LDT development by introducing metabolic data about diseases, different organism conditions, and metabolite location. Figure 3 shows the representation scores for each participant in this study and each metabolite set.…”

“…The details of the application of this algorithm for blood plasma samples have been described previously [ 17 ]. The next release of this algorithm with updated source code to make it more suitable for blood samples was recently used in the LDT [ 12 ] and applied in this work.…”

“…Selected metabolites in the case-control or individual sample studies were projected on these metabolite sets, and the obtained results were compared with the projections, which were performed 30,000 times with the same number of randomly selected metabolites. The obtained results were normalized to produce a metabolite set representation score for each set as described previously [ 12 ]. This score also was used to visualize the results as a metabolite set names cloud in which the font size is related.…”

“…Recently, we established an LDT that can reveal overrepresentation of pathways, providing a basis for diagnosis [ 12 ]. The LDT workflow included blood sample preparation, high-resolution mass spectrometry, pre-processing of mass spectra, a compound annotation algorithm, and a statistical model testing the retrieved metabolic data against human pathways.…”

Metabolomic Laboratory-Developed Tests: Current Status and Perspectives

“…Several LDTs have been published for the diagnosis of various diseases, including genetic disorders, cancer, infections, and other disorders [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Among them, research papers on metabolomics have been published that describe the early diagnosis of Parkinson’s disease [ 21 , 22 ].…”