Correcting transcription factor gene sets for copy number and promoter methylation variations.

Correcting transcription factor gene sets for copy number and promoter methylation variations.
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DOI:
10.1002/ddr.21220
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发表时间:
2014-09
影响因子:
3.8
通讯作者:
Ochs, Michael F.
Ochs, Michael F.
中科院分区:
医学3区
文献类型:
--
作者:
Rathi, Komal S.;Gaykalova, Daria A.;Hennessey, Patrick;Califano, Joseph A.;Ochs, Michael F.

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Gene set analysis provides a method to generate statistical inferences across sets of linked genes, primarily using high-throughput expression data. Common gene sets include biological pathways, operons, and targets of transcriptional regulators. In higher eukaryotes, especially when dealing with diseases with strong genetic and epigenetic components such as cancer, copy number loss and gene silencing through promoter methylation can eliminate the possibility that a gene is transcribed. This, in turn, can adversely affect the estimation of transcription factor or pathway activity from a set of target genes, since some of the targets may not be responsive to transcriptional regulation. Here we introduce a simple filtering approach that removes genes from consideration if they show copy number loss or promoter methylation and demonstrate the improvement in inference of transcription factor activity in a simulated data set based on the background expression observed in normal head and neck tissue.
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