Identification of gene-drug interactions that impact patient survival in TCGA.
Identification of gene-drug interactions that impact patient survival in TCGA.
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DOI：
10.1186/s12859-016-1255-7
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发表时间：
2016-10-06
影响因子：
3
通讯作者：
Qiu P
中科院分区：
文献类型：
--
作者：
Spainhour JC;Qiu P
随着各种疾病的大规模生物数据收集的出现，需要建立数据分析管道和工作流程，以构建综合分析框架。在这里，作者提出了一种利用CNV（拷贝数变异）和TCGA（癌症基因组图谱）项目的临床数据来识别疾病特异性基因-药物相互作用的管道。选择两种癌症类型进行分析，LGG（脑低级别胶质瘤）和GBM（多形性胶质母细胞瘤），因为在某些情况下可能从LGG进展到GBM。然后使用拷贝数和临床数据对暴露于给定药物的患者亚群进行逐个基因的生存分析。已经确定了几种基因-药物相互作用，其中基因的拷贝数与暴露于某种药物的患者的生存有关。伊立替康/HAS2（透明质酸合成酶2）和贝伐单抗/PGAM1（磷酸甘油突变酶1）是本研究中发现的相互作用，并得到独立证实。在结肠癌、乳腺癌和白血病的独立研究（Györffy, breast cancer Res Treat 123:725-731, 2010; Mueller, Mol cancer Ther 11:3024-3032, 2010; Hitosugi, cancer Cell 13:585-600, 2012）表明，这两种相互作用可以提高生存率。虽然该管道产生了几种可能的相互作用，其中生存率的增加与使用特定药物治疗的患者的特定基因拷贝数的正常或增加有关，但没有低拷贝数或完全缺失与生存率的增加有关。这个管道的发展显示了一个有前途的实用程序，以确定可能有益的基因-药物相互作用，可以提高患者的生存，并可能说明一些固有的问题，在这种分析这些数据。本文的在线版本（doi:10.1186/s12859-016-1255-7）包含补充材料，可供授权用户使用。
With the advent of large scale biological data collection for various diseases, data analysis pipelines and workflows need to be established to build frameworks for integrative analysis. Here the authors present a pipeline for identifying disease specific gene-drug interactions using CNV (Copy Number Variation) and clinical data from the TCGA (The Cancer Genome Atlas) project. Two cancer types were selected for analysis, LGG (Brain lower grade glioma) and GBM (Glioblastoma multiforme), due to the possible progression from LGG to GBM in some cases. The copy number and clinical data were then used to preform survival analysis on a gene by gene basis on sub-populations of patients exposed to a given drug. Several gene-drug interactions are identified, where the copy number of a gene is associated to survival of a patient exposed to a certain drug. Both Irinotecan/HAS2 (Hyaluronan synthase 2) and Bevacizumab/PGAM1 (Phosphoglycerate mutase 1) are interactions found in this study with independent confirmation. Independent work in colon, breast cancer and leukemia (Györffy, Breast Cancer Res Treat 123:725-731, 2010; Mueller, Mol Cancer Ther 11:3024–3032, 2010; Hitosugi, Cancer Cell 13:585-600, 2012) showed these two interactions can lead to increased survival. While the pipeline produced several possible interactions where increased survival is linked to normal or increased copy number of a given gene for patients treated with a given drug, no instance of low copy number or full deletion was linked to increased survival. The development of this pipeline shows a promising utility to identify possible beneficial gene-drug interactions that could improve patient survival and may illustrate some of the problems inherent in this kind of analysis on these data. The online version of this article (doi:10.1186/s12859-016-1255-7) contains supplementary material, which is available to authorized users.
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影响因子：
5.7
作者：
Mueller BM;Schraufstatter IU;Goncharova V;Povaliy T;DiScipio R;Khaldoyanidi SK
通讯作者：
Khaldoyanidi SK
影响因子：
30.8
作者：
Weinstein, John N.;Collisson, Eric A.;Mills, Gordon B.;Shaw, Kenna R. Mills;Ozenberger, Brad A.;Ellrott, Kyle;Shmulevich, Ilya;Sander, Chris;Stuart, Joshua M.
通讯作者：
Stuart, Joshua M.
影响因子：
4.8
作者：
Koch, M;Schulze, J;Bruckner-Tuderman, L
通讯作者：
Bruckner-Tuderman, L
影响因子：
64.5
作者：
Hoadley KA;Yau C;Wolf DM;Cherniack AD;Tamborero D;Ng S;Leiserson MDM;Niu B;McLellan MD;Uzunangelov V;Zhang J;Kandoth C;Akbani R;Shen H;Omberg L;Chu A;Margolin AA;Van't Veer LJ;Lopez-Bigas N;Laird PW;Raphael BJ;Ding L;Robertson AG;Byers LA;Mills GB;Weinstein JN;Van Waes C;Chen Z;Collisson EA;Cancer Genome Atlas Research Network;Benz CC;Perou CM;Stuart JM
通讯作者：
Stuart JM
影响因子：
64.5
作者：
Brennan CW;Verhaak RG;McKenna A;Campos B;Noushmehr H;Salama SR;Zheng S;Chakravarty D;Sanborn JZ;Berman SH;Beroukhim R;Bernard B;Wu CJ;Genovese G;Shmulevich I;Barnholtz-Sloan J;Zou L;Vegesna R;Shukla SA;Ciriello G;Yung WK;Zhang W;Sougnez C;Mikkelsen T;Aldape K;Bigner DD;Van Meir EG;Prados M;Sloan A;Black KL;Eschbacher J;Finocchiaro G;Friedman W;Andrews DW;Guha A;Iacocca M;O'Neill BP;Foltz G;Myers J;Weisenberger DJ;Penny R;Kucherlapati R;Perou CM;Hayes DN;Gibbs R;Marra M;Mills GB;Lander E;Spellman P;Wilson R;Sander C;Weinstein J;Meyerson M;Gabriel S;Laird PW;Haussler D;Getz G;Chin L;TCGA Research Network
通讯作者：
TCGA Research Network