Drug repurposing using transcriptomics: principles and unmet needs in cardiovascular disease.

Area of Science:

• Genomics and Bioinformatics
• Cardiovascular Medicine
• Pharmacology

Background:

• Cardiovascular disease is a leading global cause of death, with slow therapeutic development.
• Drug repurposing offers a cost-effective strategy to accelerate cardiovascular drug development.
• Transcriptomics and 'Omics' era provide new avenues for drug discovery and repurposing.

Purpose of the Study:

• To review signature mapping principles and workflows for transcriptome-based drug repurposing.
• To highlight features of analysis pipelines and databases for signature mapping.
• To identify limitations and unmet needs in current transcriptomic approaches for cardiovascular drug repurposing.

Main Methods:

• Review of signature mapping methodologies.
• Analysis of existing transcriptomic databases and pipelines.
• Comparison of statistical gene prioritization versus pathway-based approaches.

Main Results:

• Signature mapping utilizes statistical models for transcriptome-based drug repurposing.
• Current pipelines prioritize statistically significant genes, differing from traditional pharmacology.
• Pipeline outcomes are sensitive to data quality and reproducibility issues.

Conclusions:

• Existing RNA-seq databases primarily focus on cancer, lacking cardiovascular disease data.
• High-quality cardiovascular molecular data is crucial for effective transcriptomic-based drug repurposing.
• Interdisciplinary collaboration and cardiovascular biobanks are needed to advance this field.