Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD.
Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD.
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DOI：
10.1186/s40246-016-0095-x
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发表时间：
2016-11-21
期刊：
影响因子：
4.5
通讯作者：
Bacallao RL
中科院分区：
文献类型：
--
作者：
de Almeida RM;Clendenon SG;Richards WG;Boedigheimer M;Damore M;Rossetti S;Harris PC;Herbert BS;Xu WM;Wandinger-Ness A;Ward HH;Glazier JA;Bacallao RL
常染色体显性遗传性多囊肾病（ADPKD）由于囊肿的积累导致成人肾功能进行性丧失。ADPKD是终末期肾病最常见的遗传原因。多囊蛋白-1突变发生在87%的ADPKD病例中，多囊蛋白-2突变发生在12%的ADPKD患者中。ADPKD的复杂性阻碍了确定其发病机制的努力。目前没有FDA（联邦药物管理局）批准的治疗改善ADPKD进展。我们使用de Almeida实验室的灵敏的新转录图方法进行全基因组基因表达数据分析，以分析从正常肾脏细胞分离物和ADPKD患者肾脏的非囊性肾单位和囊肿细胞分离物开发的细胞系的微阵列数据。我们比较了使用标准的Incidity火山图分析、基因集富集分析（GSEA）和转录图分析获得的结果。转录图分析证实了Incidity、GSEA和已发表的ADPKD肾脏数据分析的结果，并确定了KEGG中多个新的表达变化。（京都基因和基因组百科全书）与细胞生长，细胞死亡，遗传信息处理，核苷酸代谢，信号转导，免疫反应，对刺激的反应，细胞过程，离子稳态和运输和辅因子，维生素，氨基酸、能量、碳水化合物、药物、脂质和聚糖。转录图分析还提供了重要性指标，使我们能够优先考虑这些途径的进一步研究。转录图分析确定了ADPKD中改变的新途径，为确定ADPKD的发病机制和改善疾病进展的药物靶点提供了新的途径。本文的在线版本（doi：10.1186/s40246-016-0095-x）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1186/s40246-016-0095-x) contains supplementary material, which is available to authorized users.
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