Estimating the false discovery rate using mixed normal distribution for identifying differentially expressed genes in microarray data analysis

Akihiro Hirakawa, Yasunori Sato, Takashi Sozu, Chikuma Hamada, Isao Yoshimura

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)140-148
Number of pages9
JournalCancer Informatics
Volume3
DOIs
Publication statusPublished - 2007
Externally publishedYes

Keywords

  • Differentially expressed genes
  • False discovery rate
  • Microarray
  • Mixed normal distribution
  • Significance analysis of microarray

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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