Peer group normalization and urine to blood context in steroid metabolomics: the case of CAH and obesity.

[congenital adrenal hyperplasia]

Traditional interpretation of GC -MS output involved the semi-quantitative estimation of outstanding low or high specific metabolites and the ratio between metabolites . Here , we utilize a systems biology approach to steroid metabolomics of a complex steroid-related disorder , using an all-inclusive analysis of the steroidal pathway in the form of a subject steroidal fingerprint and disease signature , providing novel methods of normalization and visualization . The study compares 324 normal children to pure enzymatic deficiency in 27 untreated 21 -hydroxylase CAH patients and to complex disease in 70 children with obesity . Steroid profiles were created by quantitative data generated by GC -MS analyses . A novel peer -group normalization method defined each individual subject 's control group in a multi-dimensional space of metadata parameters . Classical steroid pathway visualization was enhanced by adding urinary end-product sub-nodes and by color coding of semi-quantitative metabolic concentrations and enzymatic activities . Unbiased automated data analysis confirmed the common knowledge for CAH - the inferred 17 -hydroxyprogesterone was up-regulated and the inferred 21 -hydroxylase enzyme activity was down-regulated . In childhood obesity , we observe a general decrease of both glucocorticoid and mineralocorticoid metabolites , increased androgens , up-regulation of 17 ,20 -lyase , 17 -OHase and 11 β-HSD 1 activity and down-regulation of 21 -OHase enzymatic activity . Our study proved novel normalization and visualization techniques are to be useful in identifying subject fingerprint and disease signature in enzymatic deficiency and insufficiency , while demonstrating hypothesis generation in a complex disease such as childhood obesity .