Magnetique: an interactive web application to explore transcriptome signatures of heart failure

Area of Science:

• Cardiovascular Biology
• Genomics
• Bioinformatics

Background:

• Heart failure (HF) research is hindered by limited accessibility and usability of RNA-sequencing (RNA-seq) data.
• A need exists for intuitive tools to explore the complex transcriptional landscape of HF.

Purpose of the Study:

• To develop an interactive web application for exploring HF transcriptomes.
• To provide researchers with a user-friendly platform for analyzing RNA-seq data in HF.

Main Methods:

• Re-analysis of the Myocardial Applied Genomics Network RNA-seq dataset, including patients with dilated (DCM) and hypertrophic (HCM) cardiomyopathy, and non-failing donors (NFD).
• Differential gene expression analysis, pathway signature identification, and signaling network reconstruction using inferred transcription factor activities.
• Analysis of differential RNA transcript isoform usage (DTU) and prediction of RNA-binding protein (RBP) interactions.

Main Results:

• Identified 201 differentially expressed genes in the DCM vs. HCM comparison, with notable associations to ERK1/ERK2 signaling pathway alterations.
• Discovered 149 differently used RNA transcripts in DCM vs. HCM, including O-linked N-acetylglucosamine (GlcNAc) transferase (OGT).
• Reconstructed RBP-target interaction networks, highlighting CPEB1 as differentially expressed in DCM vs. HCM.

Conclusions:

• Magnetique is the first online application offering interactive exploration of the HF transcriptome at the RNA isoform level.
• The application integrates transcription factor signaling and RBP:RNA interaction networks for comprehensive analysis.
• Source code for analysis and the web application are publicly available to facilitate HF research.