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

Abstract

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is developed and used within a single laboratory. The holistic metabolomic LDT integrating the currently available data on human metabolic pathways, changes in the concentrations of low-molecular-weight compounds in the human blood during diseases and other conditions, and their prevalent location in the body was developed. That is, the LDT uses all of the accumulated metabolic data relevant for disease diagnosis and high-resolution mass spectrometry with data processing by in-house software. In this study, the LDT was applied to diagnose early-stage Parkinson’s disease (PD), which currently lacks available laboratory tests. The use of the LDT for blood plasma samples confirmed its ability for such diagnostics with 73% accuracy. The diagnosis was based on relevant data, such as the detection of overrepresented metabolite sets associated with PD and other neurodegenerative diseases. Additionally, the ability of the LDT to detect normal composition of low-molecular-weight compounds in blood was demonstrated, thus providing a definition of healthy at the molecular level. This LDT approach as a screening tool can be used for the further widespread testing for other diseases, since ‘omics’ tests, to which the metabolomic LDT belongs, cover a variety of them.

Metabolomic Laboratory-Developed Tests: Current Status and Perspectives

“…Despite this, there are currently no clinically and FDA-approved complex metabolic diagnostic tests [ 66 ]. On 25 March 2021, a combined search for “metabolomics and laboratory test” in PubMed showed only two relevant publications, which are a prerequisite for the creation of the first comprehensive metabolomics test designed to diagnose early-stage Parkinson’s disease [ 21 , 22 ].…”

“…The process of interpreting complex metabolomic data can be automated, and the data can be presented in an accessible format [ 22 ]; Unlike scientific metabolomic research, LDT can be reproduced an unlimited number of times according to the created workflow ( Figure 1 ) within one laboratory and can be used by people for independent research of the state of health of their body and regular monitoring of their health, which has a pronounced applied value in the modern world [ 22 ]; The method of direct mass spectrometry of blood plasma, based on which it is possible to implement metabolomic LDT, is characterized by a high processing speed and relatively high reproducibility and was also widely used in metabolomics, in particular, in the laboratory where LDT was developed for the study of cancer, diabetes [ 73 ], and Parkinson’s disease [ 74 ]. The processing of mass spectrometric data was specially developed for high-resolution mass spectra and was successfully used for many years in studies of blood plasma [ 75 ], and now it is implemented in the LDT format [ 22 ]; In the LDT format, various options for diagnosing human health can be implemented, for example, as “confirmation of a person’s healthy state”, “score-based diagnostics”, and “disease diagnosis based on metabolite set overrepresentation” [ 22 ]. In the future, it is possible to create new and more adaptive methods for diagnosing the state of human health; Due to the potentially large number of tests within one laboratory, the cost of metabolomic LDT is expected to be quite low and acceptable for most people.…”

“…LDT results are available to a wide range of clients: physicians and their patients, researchers, citizen scientists, and any educated person. The process of interpreting complex metabolomic data can be automated, and the data can be presented in an accessible format [ 22 ];…”

“…Unlike scientific metabolomic research, LDT can be reproduced an unlimited number of times according to the created workflow ( Figure 1 ) within one laboratory and can be used by people for independent research of the state of health of their body and regular monitoring of their health, which has a pronounced applied value in the modern world [ 22 ];…”

“…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 ].…”