Leveraging Lymphoblastoid Cell Lines for Drug Response Modeling

A. Motsinger-Reif, Daniel M. Rotroff
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Abstract

Lymphoblastoid cell lines (LCL) are becoming popular tools for modeling drug response. LCLs, and other in vitro assays, offer the ability to test many drugs, doses, and biological samples relatively quickly and inexpensively. In addition, a unique advantage to LCLs is that they are available from a large cohort of individuals, providing the capability to test for genetic variability on a scale not readily available in other in vitro systems. Since oftentimes the genotype data is publically available, the experimental costs can be limited to the cost of the drug response phenotyping. Here we describe several advantages and limitations of LCLs. In addition we review several important aspects of LCL experimental design and statistical analysis. Lastly, we present an example of LCLs being successfully used to identify candidate single nucleotide polymorphisms and genes for variability in response to a chemotherapeutic used to treat chronic myeloid leukemia.
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利用淋巴母细胞样细胞系进行药物反应建模
淋巴母细胞系(LCL)正在成为模拟药物反应的流行工具。lcl和其他体外测定法能够相对快速和廉价地检测多种药物、剂量和生物样品。此外,lcl的一个独特优势是,它们可以从大量个体中获得,从而提供了在其他体外系统中难以获得的规模上测试遗传变异性的能力。由于基因型数据通常是公开的,实验成本可以限制在药物反应表型的成本。在这里,我们描述了lcl的几个优点和局限性。此外,我们回顾了LCL实验设计和统计分析的几个重要方面。最后,我们提出了一个lcl被成功地用于鉴定候选单核苷酸多态性和基因变异的例子,这些基因对用于治疗慢性髓性白血病的化疗反应。
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