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Published on: December 11, 2016
DepLink: an R Shiny app to systematically link genetic and pharmacologic dependencies of cancer
Tapsya Nayak1, Li-Ju Wang2, Michael Ning1,2
1Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Motivation:
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.
Results:
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 CDK6, 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.
Availability And Implementation:
The DepLink web server, demonstrating examples and detailed user manual are available at https://shiny.crc.pitt.edu/deplink/.
Supplementary Information:
Supplementary data are available at Bioinformatics Advances online.
Insights
DepLink is a new web server that links cancer genetic vulnerabilities and drug sensitivities. It helps researchers identify potential drug targets and treatments by integrating diverse datasets for easier navigation and visualization.
Area of Science:
- Computational biology
- Bioinformatics
- Cancer research
Background:
- Large-scale genetic and pharmacologic dependency maps are crucial for understanding cancer vulnerabilities and drug sensitivities.
- Existing tools lack user-friendly interfaces for systematically linking these complex datasets.
Purpose of the Study:
- To develop DepLink, a web server for linking genetic and pharmacologic cancer dependency maps.
- To enable systematic identification of genetic and drug perturbations with similar cellular effects.
Main Methods:
- DepLink integrates heterogeneous datasets including CRISPR loss-of-function screens, high-throughput pharmacologic screens, and gene expression signatures.
- It features four modules for querying drug-gene interactions, drug mechanisms, and drug similarities.
- Validation was performed by linking drug treatments to gene knockout effects.
Main Results:
- DepLink successfully connects diverse cancer dependency data through its integrated modules.
- A case study using CDK6 demonstrated the tool's ability to identify known inhibitors, novel synergistic partners, and investigational drug insights.
- The web server facilitates navigation and visualization of cancer dependency maps.
Conclusions:
- DepLink provides a user-friendly platform for exploring and linking cancer genetic and pharmacologic data.
- It aids in discovering novel therapeutic strategies and understanding drug mechanisms.
- The tool supports the advancement of precision oncology by connecting complex biological information.
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