Vitak Sarah A, Torkenczy Kristof A, Rosenkrantz Jimi L, Fields Andrew J, Christiansen Lena, Wong Melissa H, Carbone Lucia, Steemers Frank J, Adey Andrew
Department of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon, USA.
Program in Molecular &Cellular Biosciences, Oregon Health &Science University, Portland, Oregon, USA.
Nat Methods. 2017 Mar;14(3):302-308. doi: 10.1038/nmeth.4154. Epub 2017 Jan 30.
Single-cell genome sequencing has proven valuable for the detection of somatic variation, particularly in the context of tumor evolution. Current technologies suffer from high library construction costs, which restrict the number of cells that can be assessed and thus impose limitations on the ability to measure heterogeneity within a tissue. Here, we present single-cell combinatorial indexed sequencing (SCI-seq) as a means of simultaneously generating thousands of low-pass single-cell libraries for detection of somatic copy-number variants. We constructed libraries for 16,698 single cells from a combination of cultured cell lines, primate frontal cortex tissue and two human adenocarcinomas, and obtained a detailed assessment of subclonal variation within a pancreatic tumor.
单细胞基因组测序已被证明在检测体细胞变异方面具有重要价值，尤其是在肿瘤进化的背景下。目前的技术存在文库构建成本高的问题，这限制了可评估的细胞数量，从而对测量组织内异质性的能力造成了限制。在此，我们提出单细胞组合索引测序（SCI-seq），作为一种同时生成数千个低通量单细胞文库以检测体细胞拷贝数变异的方法。我们从培养的细胞系、灵长类前额叶皮质组织和两种人类腺癌的组合中构建了16698个单细胞的文库，并对胰腺肿瘤内的亚克隆变异进行了详细评估。
