4.6 Article

Transcriptomics-based network medicine approach identifies metformin as a repurposable drug for atrial fibrillation

期刊

CELL REPORTS MEDICINE
卷 3, 期 10, 页码 -

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CELL PRESS
DOI: 10.1016/j.xcrm.2022.100749

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资金

  1. National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) [R00HL138272, K99HL138272]
  2. NIH National Institute on Aging [R01AG076448, R01AG066707, U01AG073323, NIH R01HL111314, P01HL158502]
  3. American Heart Association Atrial Fibrillation Strategically Focused Research Network [18SFRN34110067, 18SFRN34170013, 18SFRN34170442]
  4. NIH National Center for Research Resources for Case Western Reserve University [UL1-RR024989]
  5. Cleveland Clinic Department of Cardiovascular Medicine philanthropy research funds
  6. Tomsich Atrial Fibrillation Research Fund
  7. Howard Hughes Medical Institute Gilliam Fellowship [GT14941]

向作者/读者索取更多资源

This study utilizes network proximity analysis and functional testing to identify metformin as a candidate repurposed drug for atrial fibrillation, showing significant association with reduced risk of the condition.
Effective drugs for atrial fibrillation (AF) are lacking, resulting in significant morbidity and mortality. This study demonstrates that network proximity analysis of differentially expressed genes from atrial tissue to drug tar-gets can help prioritize repurposed drugs for AF. Using enrichment analysis of drug-gene signatures and functional testing in human inducible pluripotent stem cell (iPSC)-derived atrial-like cardiomyocytes, we identify metformin as a top repurposed drug candidate for AF. Using the active compactor, a new design analysis of large-scale longitudinal electronic health record (EHR) data, we determine that metformin use is significantly associated with a reduced risk of AF (odds ratio = 0.48, 95%, confidence interval [CI] 0.36- 0.64, p < 0.001) compared with standard treatments for diabetes. This study utilizes network medicine meth-odologies to identify repurposed drugs for AF treatment and identifies metformin as a candidate drug.

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