Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis
The availability of genome-wide transcriptomic and proteomic datasets is ever-increasing and often not used beyond initial publication. Here, we applied module-based coexpression network analysis to a comprehensive catalog of 35 mouse genome-wide liver expression datasets (encompassing more than 380...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227524000300 |
| _version_ | 1797238085808816128 |
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| author | James A. Votava Steven V. John Zhonggang Li Shuyang Chen Jing Fan Brian W. Parks |
| author_facet | James A. Votava Steven V. John Zhonggang Li Shuyang Chen Jing Fan Brian W. Parks |
| author_sort | James A. Votava |
| collection | DOAJ |
| description | The availability of genome-wide transcriptomic and proteomic datasets is ever-increasing and often not used beyond initial publication. Here, we applied module-based coexpression network analysis to a comprehensive catalog of 35 mouse genome-wide liver expression datasets (encompassing more than 3800 mice) with the goal of identifying and validating unknown genes involved in cholesterol metabolism. From these 35 datasets, we identified a conserved module of genes enriched with cholesterol biosynthetic genes. Using a systematic approach across the 35 datasets, we identified three genes (Rdh11, Echdc1, and Aldoc) with no known role in cholesterol metabolism. We then performed functional validation studies and show that each gene is capable of regulating cholesterol metabolism. For the glycolytic gene, Aldoc, we demonstrate that it contributes to de novo cholesterol biosynthesis and regulates cholesterol and triglyceride levels in mice. As Aldoc is located within a genome-wide significant genome-wide association studies locus for human plasma cholesterol levels, our studies establish Aldoc as a causal gene within this locus. Through our work, we develop a framework for leveraging mouse genome-wide liver datasets for identifying and validating genes involved in cholesterol metabolism. |
| first_indexed | 2024-04-24T17:30:02Z |
| format | Article |
| id | doaj.art-02b187e0368b45c69abe663312fb39e4 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-24T17:30:02Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-02b187e0368b45c69abe663312fb39e42024-03-28T06:36:41ZengElsevierJournal of Lipid Research0022-22752024-03-01653100525Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesisJames A. Votava0Steven V. John1Zhonggang Li2Shuyang Chen3Jing Fan4Brian W. Parks5Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USAMorgridge Institute for Research, Madison, WI, USADepartment of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USADepartment of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USADepartment of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA; Morgridge Institute for Research, Madison, WI, USADepartment of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA; For correspondence: Brian W. ParksThe availability of genome-wide transcriptomic and proteomic datasets is ever-increasing and often not used beyond initial publication. Here, we applied module-based coexpression network analysis to a comprehensive catalog of 35 mouse genome-wide liver expression datasets (encompassing more than 3800 mice) with the goal of identifying and validating unknown genes involved in cholesterol metabolism. From these 35 datasets, we identified a conserved module of genes enriched with cholesterol biosynthetic genes. Using a systematic approach across the 35 datasets, we identified three genes (Rdh11, Echdc1, and Aldoc) with no known role in cholesterol metabolism. We then performed functional validation studies and show that each gene is capable of regulating cholesterol metabolism. For the glycolytic gene, Aldoc, we demonstrate that it contributes to de novo cholesterol biosynthesis and regulates cholesterol and triglyceride levels in mice. As Aldoc is located within a genome-wide significant genome-wide association studies locus for human plasma cholesterol levels, our studies establish Aldoc as a causal gene within this locus. Through our work, we develop a framework for leveraging mouse genome-wide liver datasets for identifying and validating genes involved in cholesterol metabolism.http://www.sciencedirect.com/science/article/pii/S0022227524000300WGCNAcholesteroltriglycerideslipid metabolismALDOCRDH11 |
| spellingShingle | James A. Votava Steven V. John Zhonggang Li Shuyang Chen Jing Fan Brian W. Parks Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis Journal of Lipid Research WGCNA cholesterol triglycerides lipid metabolism ALDOC RDH11 |
| title | Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis |
| title_full | Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis |
| title_fullStr | Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis |
| title_full_unstemmed | Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis |
| title_short | Mining cholesterol genes from thousands of mouse livers identifies aldolase C as a regulator of cholesterol biosynthesis |
| title_sort | mining cholesterol genes from thousands of mouse livers identifies aldolase c as a regulator of cholesterol biosynthesis |
| topic | WGCNA cholesterol triglycerides lipid metabolism ALDOC RDH11 |
| url | http://www.sciencedirect.com/science/article/pii/S0022227524000300 |
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