Abstract The study of gene expression quantitative trait loci (eQTL) is an effective approach to illuminate the functional roles of genetic variants. Computational methods have been developed for eQTL mapping using gene expression data from microarray or RNA-seq technology. Application of these methods for eQTL mapping in tumor tissues is problematic because tumor tissues are composed of both tumor and infiltrating normal cells (e.g., immune cells) and eQTL effects may vary between tumor and infiltrating normal cells. To address this challenge, we have developed a new method for eQTL mapping using RNA-seq data from tumor samples. Our method separately estimates the eQTL effects in tumor and infiltrating normal cells using both total expression and allele-specific expression (ASE). We demonstrate that our method controls Type I error rate and has higher power than some alternative approaches. We applied our method to study RNA-seq data from The Cancer Genome Atlas and illustrated the similarities and differences of eQTL effects in tumor and normal cells. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.

中文翻译：

---

绘制不纯肿瘤样品中的肿瘤特异性表达 QTL

摘要 基因表达数量性状位点（eQTL）的研究是阐明遗传变异功能作用的有效方法。已经开发了使用来自微阵列或 RNA-seq 技术的基因表达数据的 eQTL 映射的计算方法。在肿瘤组织中应用这些方法进行 eQTL 定位是有问题的，因为肿瘤组织由肿瘤和浸润的正常细胞（例如免疫细胞）组成，并且 eQTL 效应可能因肿瘤和浸润的正常细胞而异。为了应对这一挑战，我们开发了一种使用来自肿瘤样本的 RNA-seq 数据进行 eQTL 映射的新方法。我们的方法使用总表达和等位基因特异性表达 (ASE) 分别估计肿瘤和浸润正常细胞中的 eQTL 效应。我们证明我们的方法控制了 I 类错误率，并且比一些替代方法具有更高的能力。我们应用我们的方法研究来自癌症基因组图谱的 RNA-seq 数据，并说明了肿瘤和正常细胞中 eQTL 效应的异同。本文的补充材料，包括对可用于复制作品的材料的标准化描述，可作为在线补充材料获得。