Abstract
Background: An untargeted chemical analysis of bio-fluids provides semi-quantitative data for thousands of chemicals for expanding our understanding about relationships among metabolic pathways, diseases, phenotypes and exposures. During the processing of mass spectral and chromatography data, various signal thresholds are used to control the number of peaks in the final data matrix that is used for statistical analyses. However, commonly used stringent thresholds generate constrained data matrices which may under-represent the detected chemical space, leading to missed biological insights in the exposome research.Methods: We have re-analyzed a liquid chromatography high resolution mass spectrometry data set for a publicly available epidemiology study (n = 499) of human cord blood samples using the MS-DIAL software with minimally possible thresholds during the data processing steps. Peak list for individual files and the data matrix after alignment and gap-filling steps were summarized for different peak height and detection frequency thresholds. Correlations between birth weight and LC/MS peaks in the newly generated data matrix were computed using the spearman correlation coefficient.Results: MS-DIAL software detected on average 23,156 peaks for individual LC/MS file and 63,393 peaks in the aligned peak table. A combination of peak height and detection frequency thresholds that was used in the original publication at the individual file and the peak alignment levels can reject 90% peaks from the untargeted chemical analysis dataset that was generated by MS-DIAL. Correlation analysis for birth weight data suggested that up to 80% of the significantly associated peaks were rejected by the data processing thresholds that were used in the original publication. The re-analysis with minimum possible thresholds recovered metabolic insights about C19 steroids and hydroxy-acyl-carnitines and their relationships with birth weight.Conclusions: Data processing thresholds for peak height and detection frequencies at individual data file and at the alignment level should be used at minimal possible level or completely avoided for mining untargeted chemical analysis data in the exposome research for discovering new biomarkers and mechanisms.
Highlights
Small molecules can function as metabolic substrates and products, signaling molecules, energy equivalents, building blocks, and toxic exposures in the human body [1]
The dataset was collected using an Agilent 1290 Infinity Liquid chromatography system connected to an Agilent quadruple time of flight 6550 mass spectrometry instrument in the ESI positive mode
This study was chosen as a case study because of it’s large sample size, but it has a negligible drift in retention time and mass spectrometry signals (Supplementary Figures 1–5)
Summary
An untargeted chemical analysis of bio-fluids provides semi-quantitative data for thousands of chemicals for expanding our understanding about relationships among metabolic pathways, diseases, phenotypes and exposures. During the processing of mass spectral and chromatography data, various signal thresholds are used to control the number of peaks in the final data matrix that is used for statistical analyses. Commonly used stringent thresholds generate constrained data matrices which may under-represent the detected chemical space, leading to missed biological insights in the exposome research
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