Nonparametric Testing for DNA Copy Number Induced Differential mRNA Gene Expression
Article first published online: 13 MAY 2008
© 2008, The International Biometric Society
Volume 65, Issue 1, pages 19–29, March 2009
How to Cite
van Wieringen, W. N. and van de Wiel, M. A. (2009), Nonparametric Testing for DNA Copy Number Induced Differential mRNA Gene Expression. Biometrics, 65: 19–29. doi: 10.1111/j.1541-0420.2008.01052.x
- Issue published online: 17 MAR 2009
- Article first published online: 13 MAY 2008
- Received October 2007. Revised February 2008. Accepted February 2008.
- Array CGH;
- Nonparametric statistics;
- Permutation test;
Summary The central dogma of molecular biology relates DNA with mRNA. Array CGH measures DNA copy number and gene expression microarrays measure the amount of mRNA. Methods that integrate data from these two platforms may uncover meaningful biological relationships that further our understanding of cancer. We develop nonparametric tests for the detection of copy number induced differential gene expression. The tests incorporate the uncertainty of the calling of genomic aberrations. The test is preceded by a “tuning algorithm” that discards certain genes to improve the overall power of the false discovery rate selection procedure. Moreover, the test statistics are “shrunken” to borrow information across neighboring genes that share the same array CGH signature. For each gene we also estimate its effect, its amount of differential expression due to copy number changes, and calculate the coefficient of determination. The method is illustrated on breast cancer data, in which it confirms previously reported findings, now with a more profound statistical underpinning.