A low-density cDNA microarray with a unique reference RNA: pattern recognition analysis for IFN efficacy prediction to HCV as a model.
We have designed and established a low-density (295 genes) cDNA microarray for the prediction of IFN efficacy in hepatitis C patients. To obtain a precise and consistent microarray data, we collected a data set from three spots for each gene (mRNA) and using three different scanning conditions. We also established an artificial reference RNA representing pseudo-inflammatory conditions from established hepatocyte cell lines supplemented with synthetic RNAs to 48 inflammatory genes. We also developed a novel algorithm that replaces the standard hierarchical-clustering method and allows handling of the large data set with ease. This algorithm utilizes a standard space database (SSDB) as a key scale to calculate the Mahalanobis distance (MD) from the center of gravity in the SSDB. We further utilized sMD (divided by parameter k: MD/k) to reduce MD number as a predictive value. The efficacy prediction of conventional IFN mono-therapy was 100% for non-responder (NR) vs. transient responder (TR)/sustained responder (SR) (P < 0.0005). Finally, we show that this method is acceptable for clinical application.
Daiba
Akito
A
JGS Japan Genome Solutions, Inc. 51 Komiya-cho, Hachioji, Tokyo 192-0031, Japan.
Inaba
Niro
N
Ando
Satoshi
S
Kajiyama
Naoki
N
Yatsuhashi
Hiroshi
H
Terasaki
Hiroshi
H
Ito
Atsushi
A
Ogasawara
Masanori
M
Abe
Aki
A
Yoshioka
Junichi
J
Hayashida
Kazuhiro
K
Kaneko
Shuichi
S
Kohara
Michinori
M
Ito
Satoru
S
D000465:Algorithms; D000998:Antiviral Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D020869:Gene Expression Profiling / Q000379:methods; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008957:Models, Genetic; D015233:Models, Statistical; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010363:Pattern Recognition, Automated; D012313:RNA / Q000235:genetics*; D012016:Reference Values; D012680:Sensitivity and Specificity
D000998:Antiviral Agents; D012313:RNA; D007372:Interferons