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Development of a pipeline for exploratory metabolic profiling of infant urine
Numerous metabolic profiling pipelines have been developed to characterize the composition of human biofluids and tissues, the vast majority of these being for studies in adults. To accommodate limited sample volume and to take into account the compositional differences between adult and infant biofluids, we developed and optimized sample handling and analytical procedures for studying urine from newborns. A robust pipeline for metabolic profiling using NMR spectroscopy was established, encompassing sample collection, preparation, spectroscopic measurement, and computational analysis. Longitudinal samples were collected from five infants from birth until 14 months of age. Methods of extraction and effects of freezing and sample dilution were assessed, and urinary contaminants from breakdown of polymers in a range of diapers and cotton wool balls were identified and compared, including propylene glycol, acrylic acid, and tert-butanol. Finally, assessment of urinary profiles obtained over the first few weeks of life revealed a dramatic change in composition, with concentrations of phenols, amino acids, and betaine altering systematically over the first few months of life. Therefore, neonatal samples require more stringent standardization of experimental design, sample handling, and analysis compared to that of adult samples to accommodate the variability and limited sample volume
Improving visualisation and interpretation of metabolome-wide association studies (MWAS):an application in a population based cohort using untargeted 1H NMR metabolic profiling
Workflow for Integrated Processing of Multicohort Untargeted 1H NMR Metabolomics Data in Large-Scale Metabolic Epidemiology
NMR and MS urinary metabolic phenotyping in kidney diseases is fit-for-purpose in the presence of a protease inhibitor
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Improving Visualization and Interpretation of Metabolome-Wide Association Studies: An Application in a Population-Based Cohort Using Untargeted 1H NMR Metabolic Profiling
Improving Visualization and Interpretation of Metabolome-Wide Association Studies: An Application in a Population-Based Cohort Using Untargeted <sup>1</sup>H NMR Metabolic Profiling
<sup>1</sup>H NMR spectroscopy of
biofluids generates reproducible
data allowing detection and quantification of small molecules in large
population cohorts. Statistical models to analyze such data are now
well-established, and the use of univariate metabolome wide association
studies (MWAS) investigating the spectral features separately has
emerged as a computationally efficient and interpretable alternative
to multivariate models. The MWAS rely on the accurate estimation of
a metabolome wide significance level (MWSL) to be applied to control
the family wise error rate. Subsequent interpretation requires efficient
visualization and formal feature annotation, which, in-turn, call
for efficient prioritization of spectral variables of interest. Using
human serum <sup>1</sup>H NMR spectroscopic profiles from 3948 participants
from the Multi-Ethnic Study of Atherosclerosis (MESA), we have performed
a series of MWAS for serum levels of glucose. We first propose an
extension of the conventional MWSL that yields stable estimates of
the MWSL across the different model parameterizations and distributional
features of the outcome. We propose both efficient visualization methods
and a strategy based on subsampling and internal validation to prioritize
the associations. Our work proposes and illustrates practical and
scalable solutions to facilitate the implementation of the MWAS approach
and improve interpretation in large cohort studies