Abstract
Holistic human proteome maps are expected to complement comprehensive profile assessment of health and disease phenotypes. However, methodologies to analyze proteomes in human tissue or body fluid samples at relevant scale and performance are still limited in clinical research. Their deployment and demonstration in large enough human populations are even sparser. In the present study, we have characterized and compared the plasma proteomes of two large independent cohorts of obese and overweight individuals using shotgun mass spectrometry (MS)-based proteomics. Herein, we showed, in both populations from different continents of about 500 individuals each, the concordance of plasma protein MS measurements in terms of variability, gender-specificity, and age-relationship. Additionally, we replicated several known and new associations between proteins, clinical and molecular variables, such as insulin and glucose concentrations. In conclusion, our MS-based analyses of plasma samples from independent human cohorts proved the practical feasibility and efficiency of a large and unified discovery/replication approach in proteomics, which was also recently coined “rectangular” design.
Highlights
Holistic human proteome maps are expected to complement comprehensive profile assessment of health and disease phenotypes
The first cohort under study was composed of 577 overweight and obese patients of the Weight Management Clinical program of The Ottawa Hospital; those patients underwent low calorie diet (LCD) to reduce their weight during a period of 6 to 12 weeks
It was composed of 425 overweight and obese participants who followed 8 weeks of controlled LCD, randomized into 6 months of weight maintenance phase
Summary
Holistic human proteome maps are expected to complement comprehensive profile assessment of health and disease phenotypes. These proteins were so strongly correlated, that even for some small subsets of the cohorts, they could potentially be identified (but with the risk of finding together false positive and negative discoveries as illustrated by the large SD bars obtained with such small numbers of samples).
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