Whole Exome-seq profiles of prostate cancer cell lines for copy number and PARADIGM analysis

Genomic studies using paired enzalutamide-sensitive and resistant cell models were performed. After transcriptional and copy number profiling, we used PARADIGM to compare the genomic alterations between the parental V16D and resistant MR49F cell models to identify critically deregulated networks to demonstrate the utility of integrative genomic analysis for therapy selection. There were 607 genes and pathway entities that had PARADIGM scores that fell outside the normally distributed range in the MR49F cell line. The top 64 genes were selected for RNAi validation. The most biologically relevant genes between the V16D and MR49F cell line models under enzalutamide treatment conditions were identified as significant by siRNA analysis and deemed biologically relelvant by network and enrichment analyses. Overall design: Whole Exome-seq profiles of prostate cancer cell lines for copy number analysis

本研究采用配对的恩扎卢胺（enzalutamide）敏感与耐药细胞模型开展基因组学研究。完成转录组与拷贝数谱分析后，我们使用PARADIGM工具比较亲本V16D与耐药MR49F细胞模型间的基因组变异，以鉴定关键失调的调控网络，以此验证整合基因组分析在治疗选择中的应用价值。在MR49F细胞系中，共有607个基因及通路实体的PARADIGM评分偏离正态分布范围。选取排名前64的基因进行RNA干扰（RNAi）验证。本研究通过小干扰RNA（siRNA）分析，鉴定出恩扎卢胺处理条件下V16D与MR49F细胞模型间最具生物学相关性的基因，并通过网络与富集分析确认其生物学意义。整体实验设计：用于拷贝数分析的前列腺癌细胞系全外显子组测序（Whole Exome-seq）谱数据。