Circ Res 2010 May 1;106(9):1459-67. Epub 2010 Apr 1.
Department of Medicine, Center for Pharmacogenomics, Washington University School of Medicine, St Louis, Mo 63110, USA.
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Circ Heart Fail 2011 Sep 18;4(5):659-68. Epub 2011 Jul 18.
Center for Pharmacogenomics, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Background: G-protein receptor kinases (GRKs) modulate cardiac β-adrenergic signaling. GRK5 is upregulated in heart failure, and a gain-of-function polymorphism substituting leucine for wild-type glutamine at amino acid 41 (GRK5-Leu41) is associated with improved outcomes in heart failure and hypertension. GRK5 is distinguished by partial nuclear localization and class II histone deacetylases (HDAC) kinase activity that is postulated to regulate Gαq-stimulated cardiac gene expression. Read More
Mol Vis 2011 23;17:3034-54. Epub 2011 Nov 23.
Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived retinal transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) methods and to evaluate protocols for optimal high-throughput data analysis.
Methods: Retinal mRNA profiles of 21-day-old wild-type (WT) and neural retina leucine zipper knockout (Nrl(-/-)) mice were generated by deep sequencing, in triplicate, using Illumina GAIIx. Read More
Circ Res 2011 Jan 28;108(1):18-26. Epub 2010 Oct 28.
Center for Pharmacogenomics, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Rationale: MicroRNAs (miRs) are expanding our understanding of cardiac disease and have the potential to transform cardiovascular therapeutics. One miR can target hundreds of individual mRNAs, but existing methodologies are not sufficient to accurately and comprehensively identify these mRNA targets in vivo.
Objective: To develop methods permitting identification of in vivo miR targets in an unbiased manner, using massively parallel sequencing of mouse cardiac transcriptomes in combination with sequencing of mRNA associated with mouse cardiac RNA-induced silencing complexes (RISCs). Read More
Circ Res 2011 Dec 27;109(12):1332-41. Epub 2011 Oct 27.
Integrative Biology and Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Rationale: Accurate and comprehensive de novo transcriptome profiling in heart is a central issue to better understand cardiac physiology and diseases. Although significant progress has been made in genome-wide profiling for quantitative changes in cardiac gene expression, current knowledge offers limited insights to the total complexity in cardiac transcriptome at individual exon level.
Objective: To develop more robust bioinformatic approaches to analyze high-throughput RNA sequencing (RNA-Seq) data, with the focus on the investigation of transcriptome complexity at individual exon and transcript levels. Read More