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整合癌症药物基因组学研究中的异质药物敏感性数据。

Integrating heterogeneous drug sensitivity data from cancer pharmacogenomic studies.

作者信息

Pozdeyev Nikita, Yoo Minjae, Mackie Ryan, Schweppe Rebecca E, Tan Aik Choon, Haugen Bryan R

机构信息

Department of Medicine, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO, USA.

出版信息

Oncotarget. 2016 Aug 9;7(32):51619-51625. doi: 10.18632/oncotarget.10010.

Abstract

The consistency of in vitro drug sensitivity data is of key importance for cancer pharmacogenomics. Previous attempts to correlate drug sensitivities from the large pharmacogenomics databases, such as the Cancer Cell Line Encyclopedia (CCLE) and the Genomics of Drug Sensitivity in Cancer (GDSC), have produced discordant results. We developed a new drug sensitivity metric, the area under the dose response curve adjusted for the range of tested drug concentrations, which allows integration of heterogeneous drug sensitivity data from the CCLE, the GDSC, and the Cancer Therapeutics Response Portal (CTRP). We show that there is moderate to good agreement of drug sensitivity data for many targeted therapies, particularly kinase inhibitors. The results of this largest cancer cell line drug sensitivity data analysis to date are accessible through the online portal, which serves as a platform for high power pharmacogenomics analysis.

摘要

体外药物敏感性数据的一致性对于癌症药物基因组学至关重要。此前尝试将来自大型药物基因组学数据库(如癌症细胞系百科全书(CCLE)和癌症药物敏感性基因组学(GDSC))的药物敏感性进行关联,结果并不一致。我们开发了一种新的药物敏感性指标,即针对测试药物浓度范围进行调整的剂量反应曲线下面积,它能够整合来自CCLE、GDSC和癌症治疗反应门户(CTRP)的异质性药物敏感性数据。我们发现,对于许多靶向治疗,尤其是激酶抑制剂,药物敏感性数据存在中度到良好的一致性。迄今为止这项最大规模的癌细胞系药物敏感性数据分析结果可通过在线门户获取,该门户作为一个高功效药物基因组学分析平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3326/5239501/f667449b7962/oncotarget-07-51619-g001.jpg

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