Metabolomics Test Materials for Quality Control: A Study of a Urine Materials Suite

Abstract

There is a lack of experimental reference materials and standards for metabolomics measurements, such as urine, plasma, and other human fluid samples. Reasons include difficulties with supply, distribution, and dissemination of information about the materials. Additionally, there is a long lead time because reference materials need their compositions to be fully characterized with uncertainty, a labor-intensive process for material containing thousands of relevant compounds. Furthermore, data analysis can be hampered by different methods using different software by different vendors. In this work, we propose an alternative implementation of reference materials. Instead of characterizing biological materials based on their composition, we propose using untargeted metabolomic data such as nuclear magnetic resonance (NMR) or gas and liquid chromatography-mass spectrometry (GC-MS and LC-MS) profiles. The profiles are then distributed with the material accompanying the certificate, so that researchers can compare their own metabolomic measurements with the reference profiles. To demonstrate this approach, we conducted an interlaboratory study (ILS) in which seven National Institute of Standards and Technology (NIST) urine Standard Reference Material®s (SRM®s) were distributed to participants, who then returned the metabolomic data to us. We then implemented chemometric methods to analyze the data together to estimate the uncertainties in the current measurement techniques. The participants identified similar patterns in the profiles that distinguished the seven samples. Even when the number of spectral features is substantially different between platforms, a collective analysis still shows significant overlap that allows reliable comparison between participants. Our results show that a urine suite such as that used in this ILS could be employed for testing and harmonization among different platforms. A limited quantity of test materials will be made available for researchers who are willing to repeat the protocols presented here and contribute their data.

RaMP-DB 2.0: a renovated knowledgebase for deriving biological and chemical insight from genes, proteins, and metabolites

“…Furthermore, the harmonization of metabolites across the different resources is not fool-proof. Metabolite identification in large-scale metabolomic experiments is still an unresolved issue, and experiments often yield a mix of different levels of certainty and structural resolution in identified metabolites [34][35][36][37][38][39] . These factors are not taken into account during harmonization or mapping of metabolites across sources.…”

Recurrent Topics in Mass Spectrometry-Based Metabolomics and Lipidomics—Standardization, Coverage, and Throughput

“…The frequent use of SRM 1950 in both metabolomics and lipidomics studies ,,, highlights its key role as a reference point for merged workflows. Another recent interlaboratory study tested seven distinct materials including human urine pools from four SRMs and one research-grade test material (RGTM) provided by NIST . Untargeted analytical profiles for these materials were obtained using a variety of common metabolomics platforms (nuclear magnetic resonance (NMR), GC- and LC-MS), leading to the conclusion that all platforms were able to detect compositional differences despite some platform-dependent differences.…”

Metabolomics for personalized medicine: the input of analytical chemistry from biomarker discovery to point-of-care tests

“…This is, for example, the case for human plasma with the SRM 1950, which is produced by the U.S. National Institute of Standards and Technology (NIST) [31], and which has been used in several inter-laboratory tests [32][33][34][35]. Beyond the case of human blood samples, NIST urine reference materials have been used in an inter-laboratory study involving NMR, GC-MS, and LC-MS untargeted metabolomics analyses [36], and the development of a human stool reference material for metabolomics and metagenomics gut microbiome analysis is envisaged, as highlighted in a workshop report [37].…”