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A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
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Putative functional genes in idiopathic dilated cardiomyopathy
Nishanth Ulhas Nair1, Avinash Das2, Uri Amit3,4,5,6
1Center for Bioinformatics and Computational Biology, University of Maryland, College Park, Maryland, 20742, USA. nnair@umiacs.umd.edu.
Scientific Reports
|January 10, 2018
Summary
Researchers developed Hridaya, a novel method to identify genes linked to dilated cardiomyopathy (DCM). This approach uncovers potential drug targets and patient subgroups for this complex heart condition.
Area of Science:
- Genomics
- Cardiovascular Research
- Systems Biology
Background:
- Idiopathic dilated cardiomyopathy (DCM) is a complex heart disorder with genetic and environmental factors.
- Numerous genes contributing to DCM remain undiscovered.
Purpose of the Study:
- To develop a genome-wide method, Hridaya, for inferring functional genes underlying DCM.
- To identify novel therapeutic targets and understand DCM patient stratification.
Main Methods:
- Integrated genetic, epigenetic, transcriptomic, phenotypic, and evolutionary data from 213 human heart samples.
- Utilized Hridaya to identify putative functional genes associated with DCM.
- Validated top predicted genes through five genome-wide analyses, including mouse knockdowns and human genotype-phenotype correlations.
Main Results:
- Hridaya identified genes experimentally linked to cardiac complications.
- Predicted genes showed associations with cardiovascular functions, cardiac abnormalities upon knockdown, drug side effects, differential exon usage, and increased cardiomyopathy risk.
- DCM patient stratification based on gene expression revealed two distinct subgroups with differing phenotypes.
Conclusions:
- Hridaya effectively infers functional genes implicated in DCM.
- Identified novel potential drug targets and investigational drugs associated with newly identified functional genes.
- Revealed distinct DCM patient subgroups, paving the way for personalized medicine approaches.
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