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首页> 外文会议>European conference on applications of evolutionary computation >An Integrated Analysis of Genome-Wide DNA Methylation and Genetic Variants Underlying Etoposide-Induced Cytotoxicity in European and African Populations
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An Integrated Analysis of Genome-Wide DNA Methylation and Genetic Variants Underlying Etoposide-Induced Cytotoxicity in European and African Populations

机译：对欧洲和非洲人口中依托泊苷诱导的细胞毒作用的全基因组DNA甲基化和遗传变异的综合分析

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Genetic variations among individuals account for a large portion of variability in drug response. The underlying mechanism of the variability is still not known, but it is expected to comprise of a wide range of genetic factors that interact and communicate with each other. Here, we present an integrated genome-wide approach to uncover the interactions among genetic factors that can explain some of the inter-individual variation in drug response. The International HapMap consortium generated genotyping data on human lymphoblastoid cell lines of (Center d'Etude du Polymorphisme Humain population - CEU) European descent and (Yoruba population - YRI) African descent. Using genome-wide analysis, Huang et al. identified SNPs that are associated with etoposide, a chemotherapeutic drug, response on the cell lines. Using the same lymphoblastoid cell lines, Fraser et al. generated genome-wide methylation profiles for gene promoter regions. We evaluated associations between candidate SNPs generated by Huang et al and genome-wide methylation sites. The analysis identified a set of methylation sites that are associated with etoposide related SNPs. Using the set of methylation sites and the candidate SNPs, we built an integrated model to explain etoposide response observed in CEU and YRI cell lines. This integrated method can be extended to combine any number of genomics data types to explain many phenotypes of interest.
机译：个体之间的遗传变异占药物反应变异性的很大一部分。变异性的潜在机制仍是未知的，但是预期它包括相互影响和交流的广泛遗传因素。在这里，我们提出了一种全基因组整合的方法来揭示遗传因素之间的相互作用，这些相互作用可以解释药物反应中的个体间差异。国际HapMap联盟生成了人类后裔（Center d'Etude du多态性Humain种群-CEU）欧洲血统和（约鲁巴族-YRI）非洲人血统的人类淋巴母细胞细胞系的基因分型数据。使用全基因组分析，Huang等。鉴定出了与依托泊苷（一种化疗药物）相关的SNP对细胞系的反应。使用相同的淋巴母细胞系，Fraser等。生成基因启动子区域的全基因组甲基化谱。我们评估了由Huang等人生成的候选SNP与全基因组范围的甲基化位点之间的关联。该分析鉴定了一组与依托泊苷相关的SNP相关的甲基化位点。使用一组甲基化位点和候选SNP，我们建立了一个集成模型来解释在CEU和YRI细胞系中观察到的依托泊苷反应。可以扩展此集成方法，以组合任意数量的基因组数据类型来解释许多感兴趣的表型。

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