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Updated and enhanced pig cardiac transcriptome based on long-read RNA sequencing and proteomics

  • Torsten Müller
    Affiliations
    German Cancer Research Center (DKFZ), Functional and Structural Genomics, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany

    Heidelberg University, Medical Faculty, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany
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  • Etienne Boileau
    Affiliations
    Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, Heidelberg, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany
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  • Sweta Talyan
    Affiliations
    Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, Heidelberg, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany
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  • Dorothea Kehr
    Affiliations
    German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany

    Division of Molecular and Translational Cardiology, Department of Internal Medicine III, Heidelberg University Hospital, INF 410, 69120 Heidelberg, Germany
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  • Karl Varadi
    Affiliations
    German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany

    Division of Molecular and Translational Cardiology, Department of Internal Medicine III, Heidelberg University Hospital, INF 410, 69120 Heidelberg, Germany
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  • Martin Busch
    Affiliations
    German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany

    Division of Molecular and Translational Cardiology, Department of Internal Medicine III, Heidelberg University Hospital, INF 410, 69120 Heidelberg, Germany
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  • Patrick Most
    Affiliations
    German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany

    Division of Molecular and Translational Cardiology, Department of Internal Medicine III, Heidelberg University Hospital, INF 410, 69120 Heidelberg, Germany

    Center for Translational Medicine, Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA
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  • Jeroen Krijgsveld
    Affiliations
    German Cancer Research Center (DKFZ), Functional and Structural Genomics, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany

    Heidelberg University, Medical Faculty, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany
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  • Christoph Dieterich
    Correspondence
    Corresponding author at: Section of Bioinformatics and Systems Cardiology, Department of Internal Medicine III, University Hospital Heidelberg, Analysezentrum III-Klaus Tschira Institute, Im Neuenheimer Feld 669, 69120 Heidelberg, Germany.
    Affiliations
    Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, Heidelberg, Germany

    German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany
    Search for articles by this author
Published:October 09, 2020DOI:https://doi.org/10.1016/j.yjmcc.2020.10.005

      Highlights

      • Pig models are essential for translational cardiac research.
      • The pig cardiac transcriptome annotation is improved using Nanopore long-read sequencing and traditional RNA-seq.
      • 15,926 transcripts are assembled, stratified into coding and non-coding, integrated with Ensembl and NCBI.
      • Results are validated by TMT mass-spectrometry and reflect the cardiac proteome diversity.

      Abstract

      Clinically translatable large animal models have become indispensable for cardiovascular research, clinically relevant proof of concept studies and for novel therapeutic interventions. In particular, the pig has emerged as an essential cardiovascular disease model, because its heart, circulatory system, and blood supply are anatomically and functionally similar to that of humans. Currently, molecular and omics-based studies in the pig are hampered by the incompleteness of the genome and the lack of diversity of the corresponding transcriptome annotation. Here, we employed Nanopore long-read sequencing and in-depth proteomics on top of Illumina RNA-seq to enhance the pig cardiac transcriptome annotation. We assembled 15,926 transcripts, stratified into coding and non-coding, and validated our results by complementary mass spectrometry. A manual review of several gene loci, which are associated with cardiac function, corroborated the utility of our enhanced annotation. All our data are available for download and are provided as tracks for integration in genome browsers. We deem this resource as highly valuable for molecular research in an increasingly relevant large animal model.

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