title: RNA-Seq identifies novel myocardial gene expression signatures of heart failure.
abstract: Heart failure is a complex clinical syndrome and has become the most common reason for adult hospitalization in developed countries. Two subtypes of heart failure, ischemic heart disease (ISCH) and dilated cardiomyopathy (DCM), have been studied using microarray platforms. However, microarray has limited resolution. Here we applied RNA sequencing (RNA-Seq) to identify gene signatures for heart failure from six individuals, including three controls, one ISCH and two DCM patients. Using genes identified from this small RNA-Seq dataset, we were able to accurately classify heart failure status in a much larger set of 313 individuals. The identified genes significantly overlapped with genes identified via genome-wide association studies for cardiometabolic traits and the promoters of those genes were enriched for binding sites for transcriptions factors. Our results indicate that it is possible to use RNA-Seq to classify disease status for complex diseases such as heart failure using an extremely small training dataset.
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: yichuan.edwdard.liu@gmail.com.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: mmorley@mail.med.upenn.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Morley
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: bjeff@mail.med.upenn.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Brandimarto
authors.affiliation: Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, United States. Electronic address: sridhar@umiacs.umd.edu.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Hannenhalli
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: huyu1@mail.med.upenn.edu.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Stanford Center for Inherited Cardiovascular Disease, Stanford University School of Medicine, Stanford, CA 94305, United States. Electronic address: euan@stanford.edu.
authors.forename: Euan A
authors.initials: EA
authors.lastname: Ashley
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, United States. Electronic address: TANGW@ccf.org.
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, United States. Electronic address: MORAVEC@ccf.org.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Moravec
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: Kenneth.Margulies@uphs.upenn.edu.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Margulies
authors.affiliation: Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: thomas.cappola@uphs.upenn.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Cappola
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: mingyao@mail.med.upenn.edu.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D055106:Genome-Wide Association Study; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D017202:Myocardial Ischemia / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017423:Sequence Analysis, RNA / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D014157:Transcription Factors
keywords: Disease classification; Heart Failure; RNA-seq