Author + information
- Thomas Gerard Di Salvo,
- Cristi Galindo,
- Evan Brittain,
- Travis Clark,
- Yan Guo,
- Yan Ru Su,
- Tarek bsi,
- Simon Maltais,
- Douglas Sawyer and
- Anna Hemnes
The right ventricular (RV) transcriptome in human heart failure (HF) has not been widely reported.
We performed RNAseq (30M target reads/cDNA library, paired-end 50 bp sequencing by Illumina HiSeq 25009) on 5 unused donor RVs (DON) and 22 explanted HF RVs. We used a novel sum of ranks approach across three analytic platforms (DESeq, edgeR and baySeq) to determine differentially expressed genes (DEGs, adjusted p <0.05), Cufflinks for isoforms and DAVID, GSEA and Ingenuity for networks.
The HF RV transcriptome (Table) included 13,019 protein coding (average 6 isoforms per gene), 2,085 long non-coding RNA (lncRNA) and 1,064 pseudogenes (PSG). Although the abundance of mitochondrial and contractile protein gene transcripts was anticipated, the high abundance of many lncRNA and PSG transcripts was not. There were 850-1,000 DEGs between DON and HF RVs with prominent differences in cytoskeletal, basement membrane, extracellular matrix, inflammatory mediator, hemostasis, membrane transport and transcription factor genes, lncRNAs and pseudogenes. Gene ontology/network analyses highlighted differences in cell-cell and transmembrane signaling, wound healing, extracellular matrix signaling, inflammation, hematopoiesis and hemostasis.
|Total in ENCODE (GRch37_63, Gencode.v16.lncRNA)||Expressed in Normal RV (% ENCODE)||Expressed in Failing RV (% ENCODE)|
|Total number||56, 340||15,169 (27%)||17,247 (31%)|
|Protein-coding||20,007||12,086 (60%)||13,019 (65%)|
|Long non-coding RNA||13,220||1,474 (11%)||2,085 (16%)|
|Pseudogenes||13,196||793 (6%)||1,064 (8%)|
|Total number||174,930||77,768 (44%)||83,793 (48%)|
|Protein coding (full/partial length)||125,376||71, 792 (57%)||76,033 (61%)|
|Long non-coding RNA transcripts||22,444||3,905 (17%)||5,102 (23%)|
By comprehensive profiling of the polyadenylated mRNA transcriptome, RNAseq identifies protein coding genes, lncRNAs, pseudogenes, gene ontologies and networks of interest in the human failing RV.
Sunday, March 30, 2014, 3:45 p.m.-4:30 p.m.
Session Title: Novel Biomarkers in Heart Failure
Abstract Category: 13. Heart Failure and Cardiomyopathies: Basic
Presentation Number: 1222-205
- 2014 American College of Cardiology Foundation