Quantitative Age-specific Variability of Plasma Proteins in Healthy Neonates, Children and Adults

Abstract

Human blood plasma is a complex biological fluid containing soluble proteins, sugars, hormones, electrolytes, and dissolved gasses. As plasma interacts with a wide array of bodily systems, changes in protein expression, or the presence or absence of specific proteins are regularly used in the clinic as a molecular biomarker tool. A large body of literature exists detailing proteomic changes in pathologic contexts, however little research has been conducted on the quantitation of the plasma proteome in age-specific, healthy subjects, especially in pediatrics. In this study, we utilized SWATH-MS to identify and quantify proteins in the blood plasma of healthy neonates, infants under 1 year of age, children between 1-5 years, and adults. We identified more than 100 proteins that showed significant differential expression levels across these age groups, and we analyzed variation in protein expression across the age spectrum. The plasma proteomic profiles of neonates were strikingly dissimilar to the older children and adults. By extracting the SWATH data against a large human spectral library we increased protein identification more than 6-fold (940 proteins) and confirmed the concentrations of several of these using ELISA. The results of this study map the variation in expression of proteins and pathways often implicated in disease, and so have significant clinical implication.

Quantitative Proteomics by SWATH‐MS Suggest an Association Between Circulating Exosomes and Maternal Metabolic Changes in Gestational Diabetes Mellitus

“…The SWATH Acquisition Microapp 2.0 in PeakView 2.2 (SCIEX) was used to create a spectral library file. This local library was extended using the R package SwathXtend (version 2.3) with a published SWATH dataset of healthy human plasma . The extended library was used for all subsequent SWATH analysis.…”

“…This local library was extended using the R package SwathXtend (version 2.3) [24] with a published SWATH dataset of healthy human plasma. [25] The extended library was used for all subsequent SWATH analysis. Processing settings for the SWATH Microapp: two peptides per protein, three transitions per peptide, peptide confidence threshold corresponding to 1% global FDR, and FDR threshold of 1% was used.…”

Analysis of the plasma proteome using iTRAQ and TMT‐based Isobaric labeling

“…Until validated these should be considered possible anomalies due to variations at the population level or from longitudinal changes or even from poorly characterized and unsuitable proteotypic peptides. Recent useful examples in the literature have considered changes with maturation and hereditary differences on the basis of the studies of twins . As a simpler directive, it is useful to recognize the depletion targets by their different aliases.…”

Analysis of housekeeping genes in the peripheral blood of retinoblastoma patients

“…The analysis revealed that the levels of these six housekeeping genes between the groups have significant differences between the control groups ( Supplementary Figure 1 and Supplementary Table 1). These differences can only be attributed to the age, so far, only a couple of studies have compared the levels of proteins in blood samples between children and adults 29,30 , in those cases, they observed also a significant differential expression levels of more than 100 proteins across the ages. Later we measure the levels of Rb mRNA into the three groups' pediatric controls, patients and adults' controls.…”