全基因组增强剂基因调控图将因果变异与人类癌症风险的基因相关联
Pingting Ying1,2,3, Can Chen1,2,3, Zequn Lu1,2,3
1Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, 430071, China.
Nature communications
|September 25, 2023
概括
这项研究使用活动对接触 (ABC) 模型绘制基因调节图,通过影响多个基因表达和激活促进癌症通路来识别与结直肠癌 (CRC) 风险相关的变异.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 全基因组关联研究 (GWAS) 确定了复杂特征的众多变体,主要是在非编码DNA中.
- 了解非编码变体的功能机制仍然是生物学中的一个重大挑战.
研究的目的:
- 通过整合多omics数据来应用活动对接触 (ABC) 模型来评估增强剂基因调节.
- 识别和功能性描述与结直肠癌 (CRC) 风险相关的调节变异.
主要方法:
- 集成的多omics数据与ABC模型预测20种癌症类型的增强剂基因连接.
- 在结直肠癌 (CRC) 组织中确定了超过30,000个增强剂基因连接.
- 利用大规模的人口队列和功能分析来验证特定的CRC风险变异.
主要成果:
- 该ABC模型成功地将调节变异与向基因联系起来,超过了以前的方法.
- 在20种癌症类型中确定了544,849个增强剂基因连接.
- 证明rs4810856变异是一种基因基因特异增强剂,通过促进激活p-AKT信号的PREX1,CSE1L和STAU1的表达来增加CRC风险.
结论:
- 该研究提供了全面的监管地图,并强调了ABC模型在破译非编码变体函数方面的力量.
- 一个单一的遗传变异可以调节多个基因,并通过特定的信号通路对癌症病因有所贡献.
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