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Nonparametric Testing for DNA Copy Number Induced Differential mRNA Gene Expression
Author(s) -
van Wieringen Wessel N.,
van de Wiel Mark A.
Publication year - 2009
Publication title -
biometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.298
H-Index - 130
eISSN - 1541-0420
pISSN - 0006-341X
DOI - 10.1111/j.1541-0420.2008.01052.x
Subject(s) - dna microarray , nonparametric statistics , computational biology , copy number variation , biology , gene , statistical hypothesis testing , gene expression , false discovery rate , multiple comparisons problem , genetics , gene dosage , comparative genomic hybridization , gene expression profiling , bioinformatics , statistics , mathematics , genome
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.