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1H NMR Signals from urine excreted protein are a source of bias in probabilistic quotient normalization

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Title: 1H NMR Signals from urine excreted protein are a source of bias in probabilistic quotient normalization
Authors: Correia, GDS
Takis, PG
Sands, CJ
Kowalka, AM
Tan, T
Turtle, L
Ho, A
Semple, MG
Openshaw, PJM
Baillie, JK
Takáts, Z
Lewis, MR
Item Type: Journal Article
Abstract: Normalization to account for variation in urinary dilution is crucial for interpretation of urine metabolic profiles. Probabilistic quotient normalization (PQN) is used routinely in metabolomics but is sensitive to systematic variation shared across a large proportion of the spectral profile (>50%). Where 1H nuclear magnetic resonance (NMR) spectroscopy is employed, the presence of urinary protein can elevate the spectral baseline and substantially impact the resulting profile. Using 1H NMR profile measurements of spot urine samples collected from hospitalized COVID-19 patients in the ISARIC 4C study, we determined that PQN coefficients are significantly correlated with observed protein levels (r2 = 0.423, p < 2.2 × 10–16). This correlation was significantly reduced (r2 = 0.163, p < 2.2 × 10–16) when using a computational method for suppression of macromolecular signals known as small molecule enhancement spectroscopy (SMolESY) for proteinic baseline removal prior to PQN. These results highlight proteinuria as a common yet overlooked source of bias in 1H NMR metabolic profiling studies which can be effectively mitigated using SMolESY or other macromolecular signal suppression methods before estimation of normalization coefficients.
Issue Date: 17-May-2022
Date of Acceptance: 6-Apr-2022
URI: http://hdl.handle.net/10044/1/96567
DOI: 10.1021/acs.analchem.2c00466
ISSN: 0003-2700
Publisher: American Chemical Society (ACS)
Start Page: 6919
End Page: 6923
Journal / Book Title: Analytical Chemistry
Volume: 94
Issue: 19
Copyright Statement: © 2022 The Authors. Published by American Chemical Society. This work is published under CC BY licence.
Sponsor/Funder: Medical Research Council (MRC)
National Institute for Health Research
UKRI MRC COVID-19 Rapid Response Call
UK Research and Innovation
National Institute for Health Research
Funder's Grant Number: MR/R502121/1
Keywords: COVID-19
Magnetic Resonance Spectroscopy
Proton Magnetic Resonance Spectroscopy
0301 Analytical Chemistry
0399 Other Chemical Sciences
Analytical Chemistry
Publication Status: Published
Open Access location: https://doi.org/10.1021/acs.analchem.2c00466
Online Publication Date: 2022-05-03
Appears in Collections:Department of Metabolism, Digestion and Reproduction
National Heart and Lung Institute
Faculty of Medicine

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