Computational identification and validation of alternative splicing in ZSF1 rat RNA-seq data, a preclinical model for type 2 diabetic nephropathy.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Alternative Splicing*; Biomarkers/*analysis ; Computational Biology/*methods ; Diabetes Mellitus, Type 2/*physiopathology ; Diabetic Nephropathies/*genetics ; Exons/*genetics ; Obesity/*complications; Animals ; Diabetic Nephropathies/etiology ; Diabetic Nephropathies/pathology ; Disease Models, Animal ; Gene Expression Regulation ; High-Throughput Nucleotide Sequencing ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology ; Rats ; Rats, Zucker ; Sequence Analysis, RNA ; Validation Studies as Topic
    • Abstract:
      Obese ZSF1 rats exhibit spontaneous time-dependent diabetic nephropathy and are considered to be a highly relevant animal model of progressive human diabetic kidney disease. We previously identified gene expression changes between disease and control animals across six time points from 12 to 41 weeks. In this study, the same data were analysed at the isoform and exon levels to reveal additional disease mechanisms that may be governed by alternative splicing. Our analyses identified alternative splicing patterns in genes that may be implicated in disease pathogenesis (such as Shc1, Serpinc1, Epb4.1l5, and Il-33), which would have been overlooked in standard gene-level analysis. The alternatively spliced genes were enriched in pathways related to cell adhesion, cell-cell interactions/junctions, and cytoskeleton signalling, whereas the differentially expressed genes were enriched in pathways related to immune response, G protein-coupled receptor, and cAMP signalling. Our findings indicate that additional mechanistic insights can be gained from exon- and isoform-level data analyses over standard gene-level analysis. Considering alternative splicing is poorly conserved between rodents and humans, it is noted that this work is not translational, but the point holds true that additional insights can be gained from alternative splicing analysis of RNA-seq data.
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    • Accession Number:
      0 (Biomarkers)
    • Publication Date:
      Date Created: 20180518 Date Completed: 20191023 Latest Revision: 20191023
    • Publication Date:
      20231215
    • Accession Number:
      PMC5955895
    • Accession Number:
      10.1038/s41598-018-26035-x
    • Accession Number:
      29769602