Comparison of microarray-based mRNA profiling technologies for identification of psychiatric disease and drug signatures.
The gene expression profiles of human postmortem parietal and prefrontal cortex samples of normal controls and patients with bipolar disease, or human neuroblastoma flat (NBFL) cells treated with the mood-stabilizing drug, valproate, were used to compare the performance of Affymetrix oligonucleotide U133A GeneChips and Agilent Human 1 cDNA microarrays. Among those genes represented on both platforms, the oligo array identified 26-53% more differentially expressed genes compared to the cDNA array in the three experiments, when identical fold change and t-test criteria were applied. The increased sensitivity was primarily the result of more robust fold changes measured by the oligonucleotide system. Essentially all gene changes overlapping between the two platforms were co-directional, and ranged from 4 to 19% depending upon the amount of biological variability within and between the comparison groups. Q-PCR validation rates were virtually identical for the two platforms, with 23-24% validation in the prefrontal cortex experiment, and 56% for both platforms in the cell culture experiment. Validated genes included dopa decarboxylase, dopamine beta-hydroxylase, and dihydropyrimidinase-related protein 3, which were decreased in NBFL cells exposed to valproate, and spinocerebellar ataxia 7, which was increased in bipolar disease. The modest overlap but similar validation rates show that each microarray system identifies a unique set of differentially expressed genes, and thus the greatest information is obtained from the use of both platforms.
Psychiatric Genomics Inc., 19 Firstfield Road, Gaithersburg, MD 20878, USA.
Linda W
LW
Jurata
Yury V
YV
Bukhman
Vinod
V
Charles
Frank
F
Capriglione
Jeffrey
J
Bullard
Andrew L
AL
Lemire
Ali
A
Mohammed
Quyen
Q
Pham
Pascal
P
Laeng
Jeffrey A
JA
Brockman
C Anthony
CA
Altar
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010296:Parietal Lobe / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D014635:Valproic Acid / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014635:Valproic Acid