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

Scientific Reports
Chi ZhangShanrong Zhao

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 tr...Continue Reading

References

Oct 19, 2001·Oncogene·K S Ravichandran
Apr 12, 2002·The Journal of Biological Chemistry·Andrea VenturaPier Giuseppe Pelicci
Sep 20, 2002·Journal of the American Society of Nephrology : JASN·Erwin P Böttinger, Markus Bitzer
Feb 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Claudio NapoliPierGiuseppe Pelicci
Mar 29, 2005·FEBS Letters·Núria López-BigasRoderic Guigó
Aug 30, 2007·Nature Reviews. Genetics·Guey-Shin Wang, Thomas A Cooper
Dec 25, 2007·BMC Evolutionary Biology·Ramil N NurtdinovMikhail S Gelfand
Nov 4, 2008·Nature·Eric T WangChristopher B Burge
Jan 6, 2009·FEMS Microbiology Ecology·Cindy J Smith, A Mark Osborn
Dec 19, 2009·Journal of the American Society of Nephrology : JASN·Youhua Liu
Apr 17, 2010·Nucleic Acids Research·Kasper D HansenSandrine Dudoit
Nov 9, 2010·Nature Methods·Yarden KatzChristopher B Burge
Jun 8, 2011·BMC Genomics·Lauren M McIntyreSergey V Nuzhdin
Nov 8, 2011·Annual Review of Physiology·Anna Greka, Peter Mundel
Dec 30, 2011·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Allan J CollinsLawrence Agodoa
Mar 1, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mélanie PicheryJean-Philippe Girard
Mar 7, 2012·Immunologic Research·Marija MilovanovicMiodrag L Lukic
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Apr 23, 2013·Oxidative Medicine and Cellular Longevity·Elena De MarchiPaolo Pinton
Oct 4, 2014·Current Opinion in Immunology·Corinne Cayrol, Jean-Philippe Girard
Dec 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Shihao ShenYi Xing
Apr 5, 2016·Nature Biotechnology·Nicolas L BrayLior Pachter
Apr 10, 2016·The Journal of Biological Chemistry·Alexey TomilovGino Cortopassi
Sep 8, 2016·Nature Medicine·Stanley Chun-Wei Lee, Omar Abdel-Wahab
Feb 24, 2017·Drugs·Sheridan M Hoy
Mar 7, 2017·Nature Methods·Rob PatroCarl Kingsford
Apr 8, 2017·International Journal of Molecular Sciences·Wei-Yu ChenJenq-Lin Yang
Apr 21, 2017·Clinical Science·Zeyuan LuMingyu Liang

❮ Previous
Next ❯

Citations

Dec 3, 2020·International Journal of Molecular Sciences·Cláudia BessaVânia Gonçalves

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
nucleotide exchange

Software Mentioned

IPA
Ensembl
Ingenuity Pathway
edgeR
glmQLFit
RSEM
Bioconductor package
R
STAR
Kallisto

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.