Open pipelines for integrated tumor genome profiles reveal differences between pancreatic cancer tumors and cell lines.

Open pipelines for integrated tumor genome profiles reveal differences between pancreatic cancer tumors and cell lines.
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DOI:
10.1002/cam4.360
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发表时间:
2015-03
期刊:
影响因子:
4
通讯作者:
Rossi, Michael R.
Rossi, Michael R.
中科院分区:
医学3区
文献类型:
--
作者:
Goecks, Jeremy;El-Rayes, Bassel F.;Maithel, Shishir K.;Khoury, H. Jean;Taylor, James;Rossi, Michael R.

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我们描述了开放的、可重复的管道,这些管道创建了癌症的综合基因组图谱,并使用该图谱来查找与疾病和潜在有用的药物相关的突变。这些管道分析高通量癌症外显子组和转录组序列数据以及公共数据库,以寻找相关突变和药物。我们开发的三个管道是:(1)外显子组分析管道,它使用整个或靶向肿瘤外显子组序列数据来生成推定变异列表(不需要匹配的正常数据); (2)转录组分析流程,处理整个肿瘤转录组序列(RNA-seq)数据以计算基因表达并发现潜在的基因融合; (3) 综合变异分析流程,使用外显子组流程中的肿瘤变异和转录组流程中的肿瘤基因表达来识别所有基因和高表达基因中的有害和可药物突变。这些管道被集成到流行的网络平台 Galaxy(http://usegalaxy.org/cancer)中,使其可访问且可重复,从而提供了一种在临床研究中进行标准化、分布式分析的方法。我们使用我们的管道来识别胰腺腺癌细胞系和原发性肿瘤之间的相似性和差异。
We describe open, reproducible pipelines that create an integrated genomic profile of a cancer and use the profile to find mutations associated with disease and potentially useful drugs. These pipelines analyze high-throughput cancer exome and transcriptome sequence data together with public databases to find relevant mutations and drugs. The three pipelines that we have developed are: (1) an exome analysis pipeline, which uses whole or targeted tumor exome sequence data to produce a list of putative variants (no matched normal data are needed); (2) a transcriptome analysis pipeline that processes whole tumor transcriptome sequence (RNA-seq) data to compute gene expression and find potential gene fusions; and (3) an integrated variant analysis pipeline that uses the tumor variants from the exome pipeline and tumor gene expression from the transcriptome pipeline to identify deleterious and druggable mutations in all genes and in highly expressed genes. These pipelines are integrated into the popular Web platform Galaxy at http://usegalaxy.org/cancer to make them accessible and reproducible, thereby providing an approach for doing standardized, distributed analyses in clinical studies. We have used our pipeline to identify similarities and differences between pancreatic adenocarcinoma cancer cell lines and primary tumors.
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