通过缩放单细胞基因组测序定义的克隆分解和DNA复制状态
Emma Laks1, Andrew McPherson2, Hans Zahn3
1Department of Molecular Oncology, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; Genome Science and Technology Graduate Program, University of British Columbia, Vancouver, BC, Canada.
Cell
|November 16, 2019
概括
研究人员开发了一个可扩展的单细胞全基因组测序平台 (DLP+) 来分析瘤进化. 这种平台可以精确测量克隆基因型和突变过程,进步我们对癌症发展的理解.
科学领域:
- 基因组学
- 癌症生物学
- 生物信息学
背景情况:
- 了解瘤进化需要对个体瘤细胞基因组进行准确的分析.
- 现有的方法在单细胞水平上解决克隆基因型和突变过程时存在局限性.
研究的目的:
- 开发和验证可扩展的单细胞全基因组测序平台 (DLP+),用于全面的瘤分析.
- 研究 mitotic 错误分离率的变化及其与细胞形态和 ploidy 状态的相关性.
- 在多克隆瘤群体中实现高分辨率的克隆基因型,类型和染色体形.
主要方法:
- 使用商品仪器,基于图像的对象识别和开源计算工具开发DLP+平台.
- 来自各种样本的51926个单细胞基因组和匹配的细胞图像的大数据集的生成.
- 对基因组和图像数据的分析,以将细胞形态与基因组组合相关联,并推断克隆结构.
主要成果:
- 大规模单细胞基因组资源的成功生成.
- 在不同的组织类型和基因型中识别线粒错分离率的变化.
- 细胞形态和基因组态状态之间的相关性.
- 高分辨率的克隆基因型和族系由共享拷贝数的细胞聚合得出,克服了批量解卷的限制.
- 通过联合分析在多克隆群体中定义克隆特异性染色体形.
结论:
- DLP+为单细胞全基因组测序提供了一个可扩展和有效的平台,对于研究瘤进化至关重要.
- 该平台为线粒错误,细胞形态和基因组关系以及瘤内部复杂的克隆结构提供了新的洞察力.
- 这种方法能够以前所未有的分辨率精确地描述瘤异质性和进化轨迹.
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