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1H NMR Signals from urine excreted protein are a source of bias in probabilistic quotient normalization
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acs.analchem.2c00466.pdf | Published version | 2.14 MB | Adobe PDF | View/Open |
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 NIHR201385 MC_PC19025 1257927 HPRU-2012-10064 |
Keywords: | COVID-19 Humans Magnetic Resonance Spectroscopy Metabolome Metabolomics 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 |
This item is licensed under a Creative Commons License