Gene set enrichment in eQTL data identifies novel annotations and pathway regulators.
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Wu, Chunlei, Delano, David, Mitro, Nico, Su, Stephen, Janes, Jeff, Mcclurg, Phillip, Batalov, Sergei, Welch, Genevieve, Zhang, Jie, Orth, Anthony, Walker, John, Glynne, Richard, Cooke, Michael, Takahashi, Joseph, Shimomura, Kazuhiro, Kohsaka, Akira, Bass, Joseph, Saez, Enrique, Wiltshire, Timothy and Su, Andrew (2008) Gene set enrichment in eQTL data identifies novel annotations and pathway regulators. PLoS Genetics, 4 (5). e1000070. ISSN 1553-7404
Abstract
Genome-wide gene expression profiling has been extensively used to generate biological hypotheses based on differential expression. Recently, many studies have used microarrays to measure gene expression levels across genetic mapping populations. These gene expression phenotypes have been used for genome-wide association analyses, an analysis referred to as expression QTL (eQTL) mapping. Here, eQTL analysis was performed in adipose tissue from 28 inbred strains of mice. We focused our analysis on "trans-eQTL bands", defined as instances in which the expression patterns of many genes were all associated to a common genetic locus. Genes comprising trans-eQTL bands were screened for enrichments in functional gene sets representing known biological pathways, and genes located at associated trans-eQTL band loci were considered candidate transcriptional modulators. We demonstrate that these patterns were enriched for previously characterized relationships between known upstream transcriptional regulators and their downstream target genes. Moreover, we used this strategy to identify both novel regulators and novel members of known pathways. Finally, based on a putative regulatory relationship identified in our analysis, we identified and validated a previously uncharacterized role for cyclin H in the regulation of oxidative phosphorylation. We believe that the specific molecular hypotheses generated in this study will reveal many additional pathway members and regulators, and that the analysis approaches described herein will be broadly applicable to other eQTL data sets.
| Item Type: | Article |
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| Date Deposited: | 13 Oct 2015 13:17 |
| Last Modified: | 13 Oct 2015 13:17 |
| URI: | https://oak.novartis.com/id/eprint/82 |