Correlation network analysis for data integration and biomarker selection.
High-throughput biomolecular profiling techniques such as transcriptomics, proteomics and metabolomics are increasingly being used in in vivo studies to recognize and characterize effects of xenobiotics on organs and systems. Of particular interest are biomarkers of treatment-related effects which are detectable in easily accessible biological fluids such as blood. A fundamental challenge in such biomarker studies is selecting among the plethora of biomolecular changes induced by a compound and revealed by molecular profiling, to identify biomarkers which are exclusively or predominantly due to specific processes. In this work we present a cross-compartment correlation network approach, involving no a priori supervision or design, to integrate proteomic, metabolomic and transcriptomic data for selecting circulating biomarkers. The case study we present is the identification of biomarkers of drug-induced hepatic toxicity effects in a rodent model. Biomolecular profiling of both blood plasma and liver tissue from Wistar Hannover rats administered a toxic compound yielded many hundreds of statistically significant molecular changes. We exploited drug-induced correlations between blood plasma analytes and liver tissue molecules across study animals in order to nominate selected plasma molecules as biomarkers of drug-induced hepatic alterations of lipid metabolism and urea cycle processes.
Adourian
Aram
A
BG Medicine Inc., 610N Lincoln Street, Waltham, MA, USA. aadourian@bg-medicine.com
Jennings
Ezra
E
Balasubramanian
Raji
R
Hines
Wade M
WM
Damian
Doris
D
Plasterer
Thomas N
TN
Clish
Clary B
CB
Stroobant
Paul
P
McBurney
Robert
R
Verheij
Elwin R
ER
Bobeldijk
Ivana
I
van der Greef
Jan
J
Lindberg
Johan
J
Kenne
Kerstin
K
Andersson
Ulf
U
Hellmold
Heike
H
Nilsson
Kerstin
K
Salter
Hugh
H
Schuppe-Koistinen
Ina
I
D000818:Animals; D015415:Biomarkers; D016695:Glycosyltransferases / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D009952:Ornithine / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D049490:Systems Biology
D015415:Biomarkers; D008055:Lipids; D009952:Ornithine; D016695:Glycosyltransferases