title: Correlation network analysis for data integration and biomarker selection.
abstract: 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.
authors.affiliation: BG Medicine Inc., 610N Lincoln Street, Waltham, MA, USA. aadourian@bg-medicine.com
authors.forename: Aram
authors.initials: A
authors.lastname: Adourian
authors.forename: Ezra
authors.initials: E
authors.lastname: Jennings
authors.forename: Raji
authors.initials: R
authors.lastname: Balasubramanian
authors.forename: Wade M
authors.initials: WM
authors.lastname: Hines
authors.forename: Doris
authors.initials: D
authors.lastname: Damian
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Plasterer
authors.forename: Clary B
authors.initials: CB
authors.lastname: Clish
authors.forename: Paul
authors.initials: P
authors.lastname: Stroobant
authors.forename: Robert
authors.initials: R
authors.lastname: McBurney
authors.forename: Elwin R
authors.initials: ER
authors.lastname: Verheij
authors.forename: Ivana
authors.initials: I
authors.lastname: Bobeldijk
authors.forename: Jan
authors.initials: J
authors.lastname: van der Greef
authors.forename: Johan
authors.initials: J
authors.lastname: Lindberg
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kenne
authors.forename: Ulf
authors.initials: U
authors.lastname: Andersson
authors.forename: Heike
authors.initials: H
authors.lastname: Hellmold
authors.forename: Kerstin
authors.initials: K
authors.lastname: Nilsson
authors.forename: Hugh
authors.initials: H
authors.lastname: Salter
authors.forename: Ina
authors.initials: I
authors.lastname: Schuppe-Koistinen
mesh_terms: 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
chemical_list: D015415:Biomarkers; D008055:Lipids; D009952:Ornithine; D016695:Glycosyltransferases