Similar compounds searching system by using the gene expression microarray database.
Numbers of microarrays have been examined and several public and commercial databases have been developed. However, it is not easy to compare in-house microarray data with those in a database because of insufficient reproducibility due to differences in the experimental conditions. As one of the approach to use these databases, we developed the similar compounds searching system (SCSS) on a toxicogenomics database. The datasets of 55 compounds administered to rats in the Toxicogenomics Project (TGP) database in Japan were used in this study. Using the fold-change ranking method developed by Lamb et al. [Lamb, J., Crawford, E.D., Peck, D., Modell, J.W., Blat, I.C., Wrobel, M.J., Lerner, J., Brunet, J.P., Subramanian, A., Ross, K.N., Reich, M., Hieronymus, H., Wei, G., Armstrong, S.A., Haggarty, S.J., Clemons, P.A., Wei, R., Carr, S.A., Lander, E.S., Golub, T.R., 2006. The connectivity map: using gene-expression signatures to connect small molecules, genes, and disease. Science 313, 1929-1935] and criteria called hit ratio, the system let us compare in-house microarray data and those in the database. In-house generated data for clofibrate, phenobarbital, and a proprietary compound were tested to evaluate the performance of the SCSS method. Phenobarbital and clofibrate, which were included in the TGP database, scored highest by the SCSS method. Other high scoring compounds had effects similar to either phenobarbital (a cytochrome P450s inducer) or clofibrate (a peroxisome proliferator). Some of high scoring compounds identified using the proprietary compound-administered rats have been known to cause similar toxicological changes in different species. Our results suggest that the SCSS method could be used in drug discovery and development. Moreover, this method may be a powerful tool to understand the mechanisms by which biological systems respond to various chemical compounds and may also predict adverse effects of new compounds.
Toyoshiba
Hiroyoshi
H
Development Research Center, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 17-85 Jusohonmachi 2-chome, Yodogawa-ku, Osaka 532-8686, Japan. toyoshiba hiroyoshi@takeda.co.jp
Sawada
Hiroshi
H
Naeshiro
Ichiro
I
Horinouchi
Akira
A
D000284:Administration, Oral; D000818:Animals; D016208:Databases, Factual; D015870:Gene Expression; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D013329:Structure-Activity Relationship; D043922:Toxicogenetics / Q000379:methods*; D015262:Xenobiotics / Q000737:chemistry / Q000633:toxicity*
D015262:Xenobiotics