Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD

Rita M C De Almeida, Sherry G. Clendenon, William G. Richards, Michael Boedigheimer, Michael Damore, Sandro Rossetti, Peter C. Harris, Brittney-Shea Herbert, Wei Min Xu, Angela Wandinger-Ness, Heather H. Ward, James A. Glazier, Robert Bacallao

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1-24
Number of pages24
JournalHuman Genomics
Volume10
Issue number1
DOIs
StatePublished - Nov 21 2016

Fingerprint

Autosomal Dominant Polycystic Kidney
Gene Expression Profiling
Cysts
Kidney
Disease Progression
Pharmaceutical Preparations
Genome
Encyclopedias
Genes
Mutation
Nephrons
Ion Transport
Microarray Analysis
Automatic Data Processing
Vitamins
Chronic Kidney Failure
Polysaccharides
Signal Transduction
Homeostasis
Cell Death

Keywords

  • Autosomal dominant polycystic kidney disease
  • Bioinformatics
  • Cystic kidney disease
  • Kidney
  • Pathway identification
  • Transcriptogram

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

Cite this

De Almeida, R. M. C., Clendenon, S. G., Richards, W. G., Boedigheimer, M., Damore, M., Rossetti, S., ... Bacallao, R. (2016). Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD. Human Genomics, 10(1), 1-24. https://doi.org/10.1186/s40246-016-0095-x

Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD. / De Almeida, Rita M C; Clendenon, Sherry G.; Richards, William G.; Boedigheimer, Michael; Damore, Michael; Rossetti, Sandro; Harris, Peter C.; Herbert, Brittney-Shea; Xu, Wei Min; Wandinger-Ness, Angela; Ward, Heather H.; Glazier, James A.; Bacallao, Robert.

In: Human Genomics, Vol. 10, No. 1, 21.11.2016, p. 1-24.

Research output: Contribution to journalArticle

De Almeida, RMC, Clendenon, SG, Richards, WG, Boedigheimer, M, Damore, M, Rossetti, S, Harris, PC, Herbert, B-S, Xu, WM, Wandinger-Ness, A, Ward, HH, Glazier, JA & Bacallao, R 2016, 'Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD', Human Genomics, vol. 10, no. 1, pp. 1-24. https://doi.org/10.1186/s40246-016-0095-x
De Almeida RMC, Clendenon SG, Richards WG, Boedigheimer M, Damore M, Rossetti S et al. Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD. Human Genomics. 2016 Nov 21;10(1):1-24. https://doi.org/10.1186/s40246-016-0095-x
De Almeida, Rita M C ; Clendenon, Sherry G. ; Richards, William G. ; Boedigheimer, Michael ; Damore, Michael ; Rossetti, Sandro ; Harris, Peter C. ; Herbert, Brittney-Shea ; Xu, Wei Min ; Wandinger-Ness, Angela ; Ward, Heather H. ; Glazier, James A. ; Bacallao, Robert. / Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD. In: Human Genomics. 2016 ; Vol. 10, No. 1. pp. 1-24.
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abstract = "Background: 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. Results: 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. Conclusions: 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.",
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AU - Rossetti, Sandro

AU - Harris, Peter C.

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