A flexible rank-based framework for detecting copy number aberrations from array data.
A flexible rank-based framework for detecting copy number aberrations from array data.
复制标题
一种灵活的基于等级的框架，用于检测阵列数据中的拷贝数畸变。
DOI：
10.1093/bioinformatics/btp063
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
Thomas,RomanK
中科院分区：
文献类型：
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作者：
LaFramboise,Thomas;Winckler,Wendy;Thomas,RomanK
动机：DNA 拷贝数畸变（遗传性和散发性）是导致多种人类疾病的重要因素。因此，拷贝数表征是一个深入研究的领域。基于探针杂交的阵列是用于以高通量方式测量拷贝数的重要工具。结果：在本文中，我们提出了一种简单但强大的非参数基于排名的方法来检测原始阵列拷贝数测量的删除和增益。我们使用三种不同的基于排名的统计数据来检测三种不同的分子现象——体细胞损伤、种系缺失和种系增益。该方法稳健且严格基于统计理论，从而能够对每个假定的像差进行有意义的统计显着性分配。我们通过将其应用于来自三个不同阵列平台的数据来展示我们的方法的灵活性。通过将我们的方法应用于已发表的特征良好的样本，我们证明了我们的方法与现有方法相比具有优势。功率模拟显示出对合理质量的阵列数据的精确灵敏度。结论：我们灵活的基于排名的框架适用于多种平台，包括单核苷酸多态性阵列和阵列比较基因组杂交，并且可以可靠地检测基因组 DNA 的增益或丢失，无论是遗传的、从头的还是体细胞的。可用性：包含此处描述的方法的 R 包RankCopy，并且可以从作者的网站免费获得(http://mendel.gene.cwru.edu/laframboiselab/)。联系方式：Thomas.LaFramboise@case.edu补充信息：补充数据可在生物信息学在线获取。
Motivation:DNA copy number aberration—both inherited and sporadic—is a significant contributor to a variety of human diseases. Copy number characterization is therefore an area of intense research. Probe hybridization-based arrays are important tools used to measure copy number in a high-throughput manner.Results:In this article, we present a simple but powerful nonparametric rank-based approach to detect deletions and gains from raw array copy number measurements. We use three different rank-based statistics to detect three separate molecular phenomena—somatic lesions, germline deletions and germline gains. The approach is robust and rigorously grounded in statistical theory, thereby enabling the meaningful assignment of statistical significance to each putative aberration. We demonstrate the flexibility of our approach by applying it to data from three different array platforms. We show that our method compares favorably with established approaches by applying it to published well-characterized samples. Power simulations demonstrate exquisite sensitivity for array data of reasonable quality.Conclusions:Our flexible rank-based framework is suitable for multiple platforms including single nucleotide polymorphism arrays and array comparative genomic hybridization, and can reliably detect gains or losses of genomic DNA, whether inherited,de novo, or somatic.Availability:An R packageRankCopycontaining the methods described here, and is freely available from the author's web site (http://mendel.gene.cwru.edu/laframboiselab/).Contact:Thomas.LaFramboise@case.eduSupplementary information:Supplementary data are available atBioinformaticsonline.