Aetiology-specific patterns in end-stage heart failure patients identified by functional annotation and classification of microarray data.
BACKGROUND
The objective of the present study was to use gene expression profiling, functional annotations and classification to identify aetiology-specific biological processes and potential molecular markers for different aetiologies of end-stage heart failure.


RESULTS
Individual left ventricular myocardial samples from eleven coronary artery disease and nine dilated cardiomyopathy transplant patients were co-hybridized with pooled RNA from four non-failing hearts on custom-made arrays of 7000 human genes. Significance analysis identified differential expression of 153 and 147 genes, respectively, in coronary artery disease or dilated cardiomyopathy versus non-failing hearts. Analysis of Gene Ontology biological process annotations indicated aetiology-specific patterns, primarily related to genes involved in catabolism and in regulation of protein kinase activity. Gene expression classifiers were obtained and used for class prediction of random samples of coronary artery diseased and dilated cardiomyopathic hearts. Best classifiers frequently included matrix metalloproteinase 3, fibulin 1, ATP-binding cassette, sub-family B member 1 and iroquois homeobox protein 5.


CONCLUSIONS
Combining functional annotation from microarray data and classification analysis constitutes a potent strategy to identify disease-specific biological processes and gene expression markers in e.g. end-stage coronary artery disease and dilated cardiomyopathy.
Beisvag
Vidar
V
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway. vidar.beisvag@utnu.no
Lehre
Per Kristian
PK
Midelfart
Herman
H
Aass
Halfdan
H
Geiran
Odd
O
Sandvik
Arne Kristian
AK
Laegreid
Astrid
A
Komorowski
Jan
J
Ellingsen
Oyvind
O
D000328:Adult; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000209:etiology* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction