Perturb-Seq combines CRISPR (clustered regularly interspaced short palindromic repeats)-based genetic screens with single-cell RNA sequencing readouts for high-content phenotypic screens. Despite the rapid accumulation of Perturb-Seq datasets, there remains a lack of a user-friendly platform for their efficient reuse. Here, we developed PerturbDB (http://research.gzsys.org.cn/perturbdb), a platform to help users unveil gene functions using Perturb-Seq datasets. PerturbDB hosts 66 Perturb-Seq datasets, which encompass 4 518 521 single-cell transcriptomes derived from the knockdown of 10 194 genes across 19 different cell lines. All datasets were uniformly processed using the Mixscape algorithm. Genes were clustered by their perturbed transcriptomic phenotypes derived from Perturb-Seq data, resulting in 421 gene clusters, 157 of which were stable across different cellular contexts. Through integrating chemically perturbed transcriptomes with Perturb-Seq data, we identified 552 potential inhibitors targeting 1409 genes, including an mammalian target of rapamycin (mTOR) signaling inhibitor, retinol, which was experimentally verified. Moreover, we developed a ‘Cancer’ module to facilitate the understanding of the regulatory role of genes in cancer using Perturb-Seq data. An interactive web interface has also been developed, enabling users to visualize, analyze and download all the comprehensive datasets available in PerturbDB. PerturbDB will greatly drive gene functional studies and enhance our understanding of the regulatory roles of genes in diseases such as cancer.

中文翻译：

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PerturbDB 用于揭示基因功能和调控网络


Perturb-Seq 将基于 CRISPR（成簇规则间隔短回文重复）的遗传筛选与单细胞 RNA 测序读数相结合，以进行高内涵表型筛选。尽管 Perturb-Seq 数据集快速积累，但仍然缺乏用户友好的平台来实现其有效重用。在这里，我们开发了PerturbDB（http://research.gzsys.org.cn/perturbdb），一个帮助用户使用Perturb-Seq数据集揭示基因功能的平台。 PerturbDB 拥有 66 个 Perturb-Seq 数据集，其中包含 4 518 521 个单细胞转录组，这些转录组源自 19 个不同细胞系的 10 194 个基因的敲除。所有数据集均使用 Mixscape 算法进行统一处理。根据来自 Perturb-Seq 数据的扰动转录组表型对基因进行聚类，产生 421 个基因簇，其中 157 个在不同的细胞环境中保持稳定。通过将化学扰动的转录组与 Perturb-Seq 数据整合，我们鉴定了针对 1409 个基因的 552 种潜在抑制剂，其中包括经过实验验证的哺乳动物雷帕霉素靶标 (mTOR) 信号抑制剂视黄醇。此外，我们开发了一个“癌症”模块，以促进使用 Perturb-Seq 数据了解基因在癌症中的调节作用。还开发了一个交互式 Web 界面，使用户能够可视化、分析和下载 PerturbDB 中可用的所有综合数据集。 PerturbDB 将极大地推动基因功能研究，并增强我们对基因在癌症等疾病中的调控作用的理解。