Gene expression phenotypes of atherosclerosis.
OBJECTIVE
Fulfilling the promise of personalized medicine by developing individualized diagnostic and therapeutic strategies for atherosclerosis will depend on a detailed understanding of the genes and gene variants that contribute to disease susceptibility and progression. To that end, our group has developed a nonbiased approach congruent with the multigenic concept of complex diseases by identifying gene expression patterns highly associated with disease states in human target tissues.


RESULTS
We have analyzed a collection of human aorta samples with varying degrees of atherosclerosis to identify gene expression patterns that predict a disease state or potential susceptibility. We find gene expression signatures that relate to each of these disease measures and are reliable and robust in predicting the classification for new samples with >93% in each analysis. The genes that provide the predictive power include many previously suspected to play a role in atherosclerosis and additional genes without prior association with atherosclerosis.


CONCLUSIONS
Hence, we are reporting a novel method for generating a molecular phenotype of disease and then identifying genes whose discriminatory capability strongly implicates their potential roles in human atherosclerosis.
Division of Cardiology, Department of Medicine, Duke University, Durham, NC, USA. david.seo@duke.edu.
David
D
Seo
Tao
T
Wang
Holly
H
Dressman
Edward E
EE
Herderick
Edwin S
ES
Iversen
Chunming
C
Dong
Korkut
K
Vata
Carmelo A
CA
Milano
Fabio
F
Rigat
Jennifer
J
Pittman
Joseph R
JR
Nevins
Mike
M
West
Pascal J
PJ
Goldschmidt-Clermont
D001013:Aorta, Thoracic / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D005786:Gene Expression Regulation / Q000235:genetics; D005796:Genes / Q000502:physiology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D010641:Phenotype; D011237:Predictive Value of Tests