Refinement of a Methodology for Untargeted Detection of Serum Albumin Adducts in Human Populations

Chemical Research in Toxicology
George W PrestonDavid H Phillips

Abstract

Covalently modified blood proteins (e.g., serum albumin adducts) are increasingly being viewed as potential biomarkers via which the environmental causes of human diseases may be understood. The notion that some (perhaps many) modifications have yet to be discovered has led to the development of untargeted adductomics methods, which attempt to capture entire populations of adducts. One such method is fixed-step selected reaction monitoring (FS-SRM), which analyses distributions of serum albumin adducts via shifts in the mass of a tryptic peptide [Li et al. (2011) Mol. Cell. Proteomics 10, M110.004606]. Working on the basis that FS-SRM might be able to detect biological variation due to environmental factors, we aimed to scale the methodology for use in an epidemiological setting. Development of sample preparation methods led to a batch workflow with increased throughput and provision for quality control. Challenges posed by technical and biological variation were addressed in the processing and interpretation of the data. A pilot study of 20 smokers and 20 never-smokers provided evidence of an effect of smoking on levels of putative serum albumin adducts. Differences between smokers and never-smokers were most apparent in putat...Continue Reading

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Citations

Feb 17, 2018·BMC Public Health·Michelle C TurnerUNKNOWN EXPOsOMICS Consortium
Sep 24, 2019·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Mariana Zuccherato BocatoFernando Barbosa
May 28, 2019·Toxics·George W Preston, David H Phillips
Jul 17, 2020·Chemical Research in Toxicology·Gabriele SabbioniBilly W Day
Nov 14, 2021·Archives of Toxicology·Gabriele Sabbioni, Billy W Day

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay

Software Mentioned

MS
TQ
R
FS
R script
MATLAB

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