Nayak Tapsya, Wang Li-Ju, Ning Michael, Rubannelsonkumar Gabriela, Jin Eric, Zheng Siyuan, Houghton Peter J, Huang Yufei, Chiu Yu-Chiao, Chen Yidong
Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA.
Bioinform Adv. 2023 Jun 12;3(1):vbad076. doi: 10.1093/bioadv/vbad076. eCollection 2023.
Large-scale genetic and pharmacologic dependency maps are generated to reveal genetic vulnerabilities and drug sensitivities of cancer. However, user-friendly software is needed to systematically link such maps.
Here, we present DepLink, a web server to identify genetic and pharmacologic perturbations that induce similar effects on cell viability or molecular changes. DepLink integrates heterogeneous datasets of genome-wide CRISPR loss-of-function screens, high-throughput pharmacologic screens and gene expression signatures of perturbations. The datasets are systematically connected by four complementary modules tailored for different query scenarios. It allows users to search for potential inhibitors that target a gene (Module 1) or multiple genes (Module 2), mechanisms of action of a known drug (Module 3) and drugs with similar biochemical features to an investigational compound (Module 4). We performed a validation analysis to confirm the capability of our tool to link the effects of drug treatments to knockouts of the drug's annotated target genes. By querying with a demonstrating example of , the tool identified well-studied inhibitor drugs, novel synergistic gene and drug partners and insights into an investigational drug. In summary, DepLink enables easy navigation, visualization and linkage of rapidly evolving cancer dependency maps.
The DepLink web server, demonstrating examples and detailed user manual are available at https://shiny.crc.pitt.edu/deplink/.
Supplementary data are available at online.
生成大规模的遗传和药理学依赖性图谱以揭示癌症的遗传脆弱性和药物敏感性。然而，需要用户友好的软件来系统地关联这些图谱。
在此，我们展示了DepLink，一个用于识别对细胞活力或分子变化产生相似影响的遗传和药理学扰动的网络服务器。DepLink整合了全基因组CRISPR功能丧失筛选、高通量药理学筛选和扰动基因表达特征的异构数据集。这些数据集通过针对不同查询场景量身定制的四个互补模块进行系统连接。它允许用户搜索靶向一个基因（模块1）或多个基因（模块2）的潜在抑制剂、已知药物的作用机制（模块3）以及与研究化合物具有相似生化特征的药物（模块4）。我们进行了一项验证分析，以确认我们的工具将药物治疗效果与药物注释靶基因敲除相联系的能力。通过使用一个示例进行查询，该工具识别出了经过充分研究的抑制剂药物、新型协同基因和药物伙伴，并对一种研究药物有了深入了解。总之，DepLink能够轻松导航、可视化和关联快速发展的癌症依赖性图谱。
DepLink网络服务器、示例演示和详细用户手册可在https://shiny.crc.pitt.edu/deplink/获取。
补充数据可在网上获取。
