Gene set enrichment in eQTL data identifies novel annotations and pathway regulators.
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 g...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-05-01
|
| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000070&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850108054174957568 |
|---|---|
| author | Chunlei Wu David L Delano Nico Mitro Stephen V Su Jeff Janes Phillip McClurg Serge Batalov Genevieve L Welch Jie Zhang Anthony P Orth John R Walker Richard J Glynne Michael P Cooke Joseph S Takahashi Kazuhiro Shimomura Akira Kohsaka Joseph Bass Enrique Saez Tim Wiltshire Andrew I Su |
| author_facet | Chunlei Wu David L Delano Nico Mitro Stephen V Su Jeff Janes Phillip McClurg Serge Batalov Genevieve L Welch Jie Zhang Anthony P Orth John R Walker Richard J Glynne Michael P Cooke Joseph S Takahashi Kazuhiro Shimomura Akira Kohsaka Joseph Bass Enrique Saez Tim Wiltshire Andrew I Su |
| author_sort | Chunlei Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fa80e29c71a0416faaa85e8ff6d947a7 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2008-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-fa80e29c71a0416faaa85e8ff6d947a72025-08-20T02:38:28ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042008-05-0145e100007010.1371/journal.pgen.1000070Gene set enrichment in eQTL data identifies novel annotations and pathway regulators.Chunlei WuDavid L DelanoNico MitroStephen V SuJeff JanesPhillip McClurgSerge BatalovGenevieve L WelchJie ZhangAnthony P OrthJohn R WalkerRichard J GlynneMichael P CookeJoseph S TakahashiKazuhiro ShimomuraAkira KohsakaJoseph BassEnrique SaezTim WiltshireAndrew I SuGenome-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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000070&type=printable |
| spellingShingle | Chunlei Wu David L Delano Nico Mitro Stephen V Su Jeff Janes Phillip McClurg Serge Batalov Genevieve L Welch Jie Zhang Anthony P Orth John R Walker Richard J Glynne Michael P Cooke Joseph S Takahashi Kazuhiro Shimomura Akira Kohsaka Joseph Bass Enrique Saez Tim Wiltshire Andrew I Su Gene set enrichment in eQTL data identifies novel annotations and pathway regulators. PLoS Genetics |
| title | Gene set enrichment in eQTL data identifies novel annotations and pathway regulators. |
| title_full | Gene set enrichment in eQTL data identifies novel annotations and pathway regulators. |
| title_fullStr | Gene set enrichment in eQTL data identifies novel annotations and pathway regulators. |
| title_full_unstemmed | Gene set enrichment in eQTL data identifies novel annotations and pathway regulators. |
| title_short | Gene set enrichment in eQTL data identifies novel annotations and pathway regulators. |
| title_sort | gene set enrichment in eqtl data identifies novel annotations and pathway regulators |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000070&type=printable |
| work_keys_str_mv | AT chunleiwu genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT davidldelano genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT nicomitro genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT stephenvsu genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT jeffjanes genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT phillipmcclurg genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT sergebatalov genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT genevievelwelch genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT jiezhang genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT anthonyporth genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT johnrwalker genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT richardjglynne genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT michaelpcooke genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT josephstakahashi genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT kazuhiroshimomura genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT akirakohsaka genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT josephbass genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT enriquesaez genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT timwiltshire genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators AT andrewisu genesetenrichmentineqtldataidentifiesnovelannotationsandpathwayregulators |