Accurity: accurate tumor purity and ploidy inference from tumor-normal WGS data by jointly modelling somatic copy number alterations and heterozygous germline single-nucleotide-variants.
Accurity: accurate tumor purity and ploidy inference from tumor-normal WGS data by jointly modelling somatic copy number alterations and heterozygous germline single-nucleotide-variants.
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DOI：
10.1093/bioinformatics/bty043
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发表时间：
2018-06-15
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影响因子：
--
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肿瘤纯度和倍性对肿瘤样本的下一代序列分析有重大影响，并可能改变结果的生物学和临床解释。尽管存在几种专用于根据癌症基因组图谱 (TCGA) 肿瘤正常全基因组测序 (WGS) 数据估计肿瘤纯度和/或倍性的计算方法，但仍然缺乏一种准确、快速且全自动的方法，该方法适用于广泛的测序覆盖范围、肿瘤纯度水平和肿瘤内异质性水平。我们描述了一种称为 Accurity 的计算方法，通过联合建模 SCNA 和杂合种系单核苷酸变异体 (HGSNV)，从肿瘤正常 WGS 数据推断肿瘤纯度、肿瘤细胞倍性和体细胞拷贝数改变 (SCNA) 的绝对等位基因拷贝数。计算机模拟和真实测序数据的结果表明，即使在几种现有方法表现不佳的低纯度、高倍性和低覆盖率环境中，Accurity 也是高度准确和稳健的。考虑到肿瘤纯度和倍性，准确性显着增加了不同拷贝数之间的信号/噪声间隙。我们希望 Accurity 可用于临床识别癌症诊断生物标志物。 Accurity 是用 C++/Rust 实现的，可从 http://www.yfish.org/software/ 获取。 补充数据可在生物信息学在线获取。
Tumor purity and ploidy have a substantial impact on next-gen sequence analyses of tumor samples and may alter the biological and clinical interpretation of results. Despite the existence of several computational methods that are dedicated to estimate tumor purity and/or ploidy from The Cancer Genome Atlas (TCGA) tumor-normal whole-genome-sequencing (WGS) data, an accurate, fast and fully-automated method that works in a wide range of sequencing coverage, level of tumor purity and level of intra-tumor heterogeneity, is still missing. We describe a computational method called Accurity that infers tumor purity, tumor cell ploidy and absolute allelic copy numbers for somatic copy number alterations (SCNAs) from tumor-normal WGS data by jointly modelling SCNAs and heterozygous germline single-nucleotide-variants (HGSNVs). Results from both in silico and real sequencing data demonstrated that Accurity is highly accurate and robust, even in low-purity, high-ploidy and low-coverage settings in which several existing methods perform poorly. Accounting for tumor purity and ploidy, Accurity significantly increased signal/noise gaps between different copy numbers. We are hopeful that Accurity is of clinical use for identifying cancer diagnostic biomarkers. Accurity is implemented in C++/Rust, available at http://www.yfish.org/software/. Supplementary data are available at Bioinformatics online.
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DOI：
10.1093/annonc/mdu479
发表时间：
2015-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Favero F;Joshi T;Marquard AM;Birkbak NJ;Krzystanek M;Li Q;Szallasi Z;Eklund AC
通讯作者：
Eklund AC
影响因子：
12.3
作者：
Mayrhofer M;DiLorenzo S;Isaksson A
通讯作者：
Isaksson A
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Navin N;Kendall J;Troge J;Andrews P;Rodgers L;McIndoo J;Cook K;Stepansky A;Levy D;Esposito D;Muthuswamy L;Krasnitz A;McCombie WR;Hicks J;Wigler M
通讯作者：
Wigler M
影响因子：
9.5
作者：
Alkodsi, Amjad;Louhimo, Riku;Hautaniemi, Sampsa
通讯作者：
Hautaniemi, Sampsa