Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
UTHealth Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nucleic Acids Res. 2018 Jan 4;46(D1):D776-D780. doi: 10.1093/nar/gkx993.
The adaptation of CRISPR/Cas9 systems for pooled library genetic knockout screens in mammalian cells has substantially advanced the state of the art in human functional genomics. Screening panels of cell lines for genes whose knockout imposes a significant fitness defect has dramatically expanded our catalog of high-confidence essential genes, and has already proven useful in identifying tumor-specific essential genes for the development of targeted therapies. However, nonexperts currently lack an easy to use way to access this data and to identify whether their genes of interest are essential across different genetic backgrounds. The volume of screening data is expected to grow massively, making the problem more intractable. Here we describe PICKLES, the database of Pooled In vitro CRISPR Knockout Library Essentiality Screens, where end users can display and download raw or normalized essentiality profiles for more that 18 000 protein-coding genes across more than 50 cell lines. An additional data set with 15,000 genes targeted by pooled library shRNA in over 100 cell lines is also included. Researchers can see at a glance the relative fitness defect and tissue specificity of their genes of interest, generate and save figures locally, and download all raw data. The database is available at http://pickles.hart-lab.org.
CRISPR/Cas9 系统在哺乳动物细胞中的pooled library genetic knockout 筛选中的应用，大大提高了人类功能基因组学的水平。对细胞系进行基因敲除会导致明显适应性缺陷的基因筛选面板，极大地扩展了我们的高可信度必需基因目录，并且已经在鉴定针对靶向治疗的肿瘤特异性必需基因方面证明是有用的。然而，非专家目前缺乏一种简单易用的方法来访问这些数据，并确定他们感兴趣的基因在不同的遗传背景下是否是必需的。预计筛选数据的数量将大量增加，使问题更加棘手。在这里，我们描述了 PICKLES，这是一个 Pooled In vitro CRISPR Knockout Library Essentiality Screens 数据库，终端用户可以在 50 多个细胞系中显示和下载超过 18000 个编码蛋白基因的原始或标准化必需性图谱。还包括一个针对超过 100 个细胞系的 pooled library shRNA 靶向的 15000 个基因的附加数据集。研究人员可以一目了然地看到他们感兴趣的基因的相对适应性缺陷和组织特异性，生成并本地保存图形，并下载所有原始数据。该数据库可在 http://pickles.hart-lab.org 上获得。
