Ran Li, Dongyi Wan, Junnan Liang, Huifang Liang, Haohao Huang, Ganxun Li
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引用次数: 0
摘要
在包括肿瘤发生在内的多种生物过程中,普遍观察到启动子活性的改变。越来越多的证据表明,采用数量性状位点定位方法可以有效地理解启动子活性的遗传基础。利用来自The Cancer Genome Atlas的基因型数据,并使用proActiv计算相应的启动子活性值,我们系统地评估了遗传变异对启动子活性的影响,并鉴定出100万个启动子活性定量性状位点(paqtl)为顺式和反式作用。此外,利用来自全基因组关联研究(GWAS)目录的数据,我们发现了130万个paqtl与已知的GWAS连锁不平衡区域重叠。值得注意的是,~ 9324个paqtl与患者预后有显著关联。此外,研究启动子活性对泛癌症患者中1000个推定抗肿瘤治疗反应的影响,发现了43亿个显著关联。此外,在启动子活性和免疫细胞丰度之间发现了约25,000个显著关联。最后,构建了一个用户友好的数据门户,Pancan-paQTL (https://www.hbpding.com/PancanPaQTL/),供用户浏览、搜索和下载感兴趣的数据。panan - paqtl是一个全面的多维数据库,可以对多种癌症类型的启动子活性、药物反应和免疫浸润相关的遗传变异进行功能和临床研究。
Pan-cancer analysis of promoter activity quantitative trait loci
Abstract Altered promoter activity has been generally observed in diverse biological processes, including tumorigenesis. Accumulating evidence suggests that employing a quantitative trait locus mapping approach is effective in comprehending the genetic basis of promoter activity. By utilizing genotype data from The Cancer Genome Atlas and calculating corresponding promoter activity values using proActiv, we systematically evaluated the impact of genetic variants on promoter activity and identified >1.0 million promoter activity quantitative trait loci (paQTLs) as both cis- and trans-acting. Additionally, leveraging data from the genome-wide association study (GWAS) catalog, we discovered >1.3 million paQTLs that overlap with known GWAS linkage disequilibrium regions. Remarkably, ∼9324 paQTLs exhibited significant associations with patient prognosis. Moreover, investigating the impact of promoter activity on >1000 imputed antitumor therapy responses among pan-cancer patients revealed >43 000 million significant associations. Furthermore, ∼25 000 significant associations were identified between promoter activity and immune cell abundance. Finally, a user-friendly data portal, Pancan-paQTL (https://www.hbpding.com/PancanPaQTL/), was constructed for users to browse, search and download data of interest. Pancan-paQTL serves as a comprehensive multidimensional database, enabling functional and clinical investigations into genetic variants associated with promoter activity, drug responses and immune infiltration across multiple cancer types.