Abstract Akihiro Hirakawa¹, Yasunori Sato¹, Takashi Sozu², Chikuma Hamada³, Isao Yoshimura³

¹Genetics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan. ²The Center for Advanced Medical Engineering and Informatics, Osaka University, Suita, Osaka, Japan. ³Faculty of Engineering, Tokyo University of Science, Shinjuku-ku, Tokyo, Japan.

Abstract

The recent development of DNA microarray technology allows us to measure simultaneously the expression levels of thousands of genes and to identify truly correlated genes with anticancer drug response (differentially expressed genes) from many candidate genes. Significance Analysis of Microarray (SAM) is often used to estimate the false discovery rate (FDR), which is an index for optimizing the identifiability of differentially expressed genes, while the accuracy of the estimated FDR by SAM is not necessarily confirmed. We propose a new method for estimating the FDR assuming a mixed normal distribution on the test statistic and examine the performance of the proposed method and SAM using simulated data. The simulation results indicate that the accuracy of the estimated FDR by the proposed method and SAM, varied depending on the experimental conditions. We applied both methods to actual data comprised of expression levels of 12,625 genes of 10 responders and 14 non-responders to docetaxel for breast cancer. The proposed method identified 280 differentially expressed genes correlated with docetaxel response using a cut-off value for achieving FDR <0.01 to prevent false-positive genes, although 92 genes were previously thought to be correlated with docetaxel response ones.

Discussion
No comments yet...Be the first to comment.

 CONNOTEA  CITEULIKE FACEBOOK LINKED IN