Methods for the differential integrative omic analysis of plasma from a transgenic disease animal model.
Multitiered quantitative analysis of biological systems is rapidly becoming the desired approach to study hierarchical functional interactions between proteins and metabolites. We describe here a novel systematic approach to analyze organisms with complex metabolic regulatory networks. By using precise analytical methods to measure biochemical constituents and their relative abundance in whole plasma of transgenic ApoE*3-Leiden mice and an isogenic wild-type control group, simultaneous snapshots of metabolic and protein states were obtained. Novel data processing and multivariate analysis tools such as Impurity Resolution Software (IMPRESS) and Windows-based linear fit program (WINLIN) were used to compare protein and metabolic profiles in parallel. Canonical correlations of the resulting data show quantitative relationships between heterogeneous components in the TG animals. These results, obtained solely from whole plasma analysis allowed us, in a rapid manner, to corroborate previous findings as well as find new events pertaining to dominant and peripheral events in lipoprotein metabolism of a genetically modified mammalian organism in relation to ApoE3, a key mediator of lipoprotein metabolism.
Davidov
Eugene
E
Beyond Genomics, Inc., Waltham, Massachusetts, USA.
Clish
Clary B
CB
Oresic
Matej
M
Meys
Michael
M
Stochaj
Wayne
W
Snell
Philip
P
Lavine
Gary
G
Londo
Thomas R
TR
Adourian
Aram
A
Zhang
Xiang
X
Johnston
Mark
M
Morel
Nicole
N
Marple
Edward W
EW
Plasterer
Thomas N
TN
Neumann
Eric
E
Verheij
Elwin
E
Vogels
Jack T W E
JT
Havekes
Louis M
LM
van der Greef
Jan
J
Naylor
Stephen
S
D000818:Animals; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000097:blood* / Q000737:chemistry; D001161:Arteriosclerosis / Q000235:genetics*; D002853:Chromatography, Liquid; D003433:Crosses, Genetic; D005260:Female; D005799:Genes, Dominant; D005821:Genetic Techniques; D006801:Humans; D006951:Hyperlipoproteinemias / Q000235:genetics*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015999:Multivariate Analysis; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D025341:Principal Component Analysis; D011506:Proteins / Q000737:chemistry; D012984:Software; D013997:Time Factors; D014357:Trypsin / Q000737:chemistry
D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D008074:Lipoproteins; D010455:Peptides; D011506:Proteins; D014357:Trypsin