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Kurt, Z. orcid.org/0000-0003-3186-8091, Cheng, J. orcid.org/0009-0009-2248-1697, Barrere-Cain, R. et al. (12 more authors) (2023) Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse. eLife, 12. RP88266. ISSN 2050-084X
Abstract
Mouse models have been used extensively to study human coronary artery disease (CAD) or atherosclerosis and to test therapeutic targets. However, whether mouse and human share similar genetic factors and pathogenic mechanisms of atherosclerosis has not been thoroughly investigated in a data-driven manner. We conducted a cross-species comparison study to better understand atherosclerosis pathogenesis between species by leveraging multiomics data. Specifically, we compared genetically driven and thus CAD-causal gene networks and pathways, by using human GWAS of CAD from the CARDIoGRAMplusC4D consortium and mouse GWAS of atherosclerosis from the Hybrid Mouse Diversity Panel (HMDP) followed by integration with functional multiomics human (STARNET and GTEx) and mouse (HMDP) databases. We found that mouse and human shared >75% of CAD causal pathways. Based on network topology, we then predicted key regulatory genes for both the shared pathways and species-specific pathways, which were further validated through the use of single cell data and the latest CAD GWAS. In sum, our results should serve as a much-needed guidance for which human CAD-causal pathways can or cannot be further evaluated for novel CAD therapies using mouse models.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023, Kurt, Cheng et al. This article is distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use and redistribution provided that the original author and source are credited. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Social Sciences (Sheffield) > Information School (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Dec 2023 15:25 |
Last Modified: | 13 Dec 2023 15:25 |
Status: | Published |
Publisher: | eLife Sciences Publications, Ltd |
Refereed: | Yes |
Identification Number: | 10.7554/elife.88266.3 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:206610 |
Available Versions of this Item
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Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse. (deposited 01 Dec 2023 13:01)
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Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse. (deposited 13 Dec 2023 15:15)
- Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse. (deposited 13 Dec 2023 15:25) [Currently Displayed]
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Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse. (deposited 13 Dec 2023 15:15)