EXPANDS: expanding ploidy and allele frequency on nested subpopulations.
EXPANDS: expanding ploidy and allele frequency on nested subpopulations.
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DOI：
10.1093/bioinformatics/btt622
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发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
Petritsch C
中科院分区：
文献类型：
--
作者：
Andor N;Harness JV;Müller S;Mewes HW;Petritsch C
动机：几种癌症类型由多个基因和表型不同的亚群组成。这种肿瘤内异质性的潜在机制可以通过克隆进化模型来解释，即生长有利的突变导致癌细胞亚克隆的扩增。许多癌症的复发表型可能是这些共存的亚群对治疗反应不平等的结果。计算推断肿瘤进化和亚群多样性的方法正在出现，它们有望提高对复发的遗传和分子决定因素的理解。结果：为了解决人类肿瘤内的细胞亚群动力学，我们开发了一种生物信息学方法，扩展。它估计肿瘤中携带特定突变的细胞的比例。通过将细胞频率建模为概率分布，expansion可以预测细胞在克隆扩展之前积累的突变。我们评估了扩展在一个全基因组测序乳腺癌中的表现，并对从TCGA获得的118个多形性胶质母细胞瘤样本进行了SP分析。我们的研究结果揭示了原发性胶质母细胞瘤的亚克隆多样性程度，复发期间的亚群动态，并提供了一组在最适应的亚群中突变的候选基因。总之，expansion可以根据测序数据预测肿瘤纯度和亚克隆组成。可用性和实现：extensions可在http://code.google.com/p/expands（本文中使用的matlab版本）和http://cran.r-project.org/web/packages/expands （R版本）下载。补充信息：补充数据可在Bioinformatics在线获取。
Motivation: Several cancer types consist of multiple genetically and phenotypically distinct subpopulations. The underlying mechanism for this intra-tumoral heterogeneity can be explained by the clonal evolution model, whereby growth advantageous mutations cause the expansion of cancer cell subclones. The recurrent phenotype of many cancers may be a consequence of these coexisting subpopulations responding unequally to therapies. Methods to computationally infer tumor evolution and subpopulation diversity are emerging and they hold the promise to improve the understanding of genetic and molecular determinants of recurrence. Results: To address cellular subpopulation dynamics within human tumors, we developed a bioinformatic method, EXPANDS. It estimates the proportion of cells harboring specific mutations in a tumor. By modeling cellular frequencies as probability distributions, EXPANDS predicts mutations that accumulate in a cell before its clonal expansion. We assessed the performance of EXPANDS on one whole genome sequenced breast cancer and performed SP analyses on 118 glioblastoma multiforme samples obtained from TCGA. Our results inform about the extent of subclonal diversity in primary glioblastoma, subpopulation dynamics during recurrence and provide a set of candidate genes mutated in the most well-adapted subpopulations. In summary, EXPANDS predicts tumor purity and subclonal composition from sequencing data. Availability and implementation: EXPANDS is available for download at http://code.google.com/p/expands (matlab version - used in this manuscript) and http://cran.r-project.org/web/packages/expands (R version). Contact: claudia.petritsch@ucsf.edu Supplementary information: Supplementary data are available at Bioinformatics online.
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影响因子：
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作者：
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发表时间：
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期刊：
Bioinformatics (Oxford, England)
影响因子：
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