title: Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) causes progressive loss of renal function in adults as a consequence of the accumulation of cysts. ADPKD is the most common genetic cause of end-stage renal disease. Mutations in polycystin-1 occur in 87% of cases of ADPKD and mutations in polycystin-2 are found in 12% of ADPKD patients. The complexity of ADPKD has hampered efforts to identify the mechanisms underlying its pathogenesis. No current FDA (Federal Drug Administration)-approved therapies ameliorate ADPKD progression.
  
  
  
  We used the de Almeida laboratory's sensitive new transcriptogram method for whole-genome gene expression data analysis to analyze microarray data from cell lines developed from cell isolates of normal kidney and of both non-cystic nephrons and cysts from the kidney of a patient with ADPKD. We compared results obtained using standard Ingenuity Volcano plot analysis, Gene Set Enrichment Analysis (GSEA) and transcriptogram analysis. Transcriptogram analysis confirmed the findings of Ingenuity, GSEA, and published analysis of ADPKD kidney data and also identified multiple new expression changes in KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways related to cell growth, cell death, genetic information processing, nucleotide metabolism, signal transduction, immune response, response to stimulus, cellular processes, ion homeostasis and transport and cofactors, vitamins, amino acids, energy, carbohydrates, drugs, lipids, and glycans. Transcriptogram analysis also provides significance metrics which allow us to prioritize further study of these pathways.
  
  
  
  Transcriptogram analysis identifies novel pathways altered in ADPKD, providing new avenues to identify both ADPKD's mechanisms of pathogenesis and pharmaceutical targets to ameliorate the progression of the disease.
authors.affiliation: Biocomplexity Institute and Department of Physics, Indiana University, Bloomington, IN, 47405, USA.|Instituto de Física and Instituto Nacional de Ciência e Tecnologia, Universidade Federal do Rio Grande do Sul, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Rita M C
authors.initials: RM
authors.lastname: de Almeida
authors.affiliation: Biocomplexity Institute and Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN, 47405, USA.
authors.forename: Sherry G
authors.initials: SG
authors.lastname: Clendenon
authors.affiliation: AMGEN Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320-1799, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Richards
authors.affiliation: AMGEN Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320-1799, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Boedigheimer
authors.affiliation: AMGEN Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320-1799, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Damore
authors.affiliation: Division of Nephrology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Sandro
authors.initials: S
authors.lastname: Rossetti
authors.affiliation: Division of Nephrology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Britney-Shea
authors.initials: BS
authors.lastname: Herbert
authors.affiliation: Division of Nephrology, Department of Medicine, Richard Roudebush VAMC and Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Wei Min
authors.initials: WM
authors.lastname: Xu
authors.affiliation: Department of Pathology MSC08-4640 and Cancer Research and Treatment Center, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Wandinger-Ness
authors.affiliation: Division of Nephrology, Department of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA.
authors.forename: Heather H
authors.initials: HH
authors.lastname: Ward
authors.affiliation: Biocomplexity Institute and Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN, 47405, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Glazier
authors.affiliation: Division of Nephrology, Department of Medicine, Richard Roudebush VAMC and Indiana University School of Medicine, Indianapolis, IN, 46202, USA. rbacalla@iupui.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Bacallao
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002460:Cell Line; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism* / Q000473:pathology; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D050396:TRPP Cation Channels
keywords: Autosomal dominant polycystic kidney disease; Bioinformatics; Cystic kidney disease; Kidney; Pathway identification; Transcriptogram