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CellMinerCDB: NCATS Is a Web-Based Portal Integrating Public Cancer Cell Line Databases for Pharmacogenomic
William C Reinhold1, Kelli Wilson2, Fathi Elloumi1
1Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
Abstract:
Major advances have been made in the field of precision medicine for treating cancer. However, many open questions remain that need to be answered to realize the goal of matching every patient with cancer to the most efficacious therapy. To facilitate these efforts, we have developed CellMinerCDB: National Center for Advancing Translational Sciences (NCATS; https://discover.nci.nih.gov/rsconnect/cellminercdb_ncats/), which makes available activity information for 2,675 drugs and compounds, including multiple nononcology drugs and 1,866 drugs and compounds unique to the NCATS. CellMinerCDB: NCATS comprises 183 cancer cell lines, with 72 unique to NCATS, including some from previously understudied tissues of origin. Multiple forms of data from different institutes are integrated, including single and combination drug activity, DNA copy number, methylation and mutation, transcriptome, protein levels, histone acetylation and methylation, metabolites, CRISPR, and miscellaneous signatures. Curation of cell lines and drug names enables cross-database (CDB) analyses. Comparison of the datasets is made possible by the overlap between cell lines and drugs across databases. Multiple univariate and multivariate analysis tools are built-in, including linear regression and LASSO. Examples have been presented here for the clinical topoisomerase I (TOP1) inhibitors topotecan and irinotecan/SN-38. This web application provides both substantial new data and significant pharmacogenomic integration, allowing exploration of interrelationships.
Significance:
CellMinerCDB: NCATS provides activity information for 2,675 drugs in 183 cancer cell lines and analysis tools to facilitate pharmacogenomic research and to identify determinants of response.
Insights
A new database, CellMinerCDB: National Center for Advancing Translational Sciences (NCATS), integrates drug activity and genomic data for 2,675 compounds across 183 cancer cell lines. This resource aids precision cancer medicine by facilitating pharmacogenomic research and identifying effective therapies.
Area of Science:
- Pharmacogenomics
- Translational Cancer Research
- Computational Biology
Background:
- Precision medicine aims to match cancer patients with effective therapies, but requires comprehensive data integration.
- Existing resources often lack the breadth of drug compounds and cancer cell line data needed for advanced pharmacogenomic analyses.
- The National Center for Advancing Translational Sciences (NCATS) has developed a novel platform to address these limitations.
Purpose of the Study:
- To introduce CellMinerCDB: NCATS, a web application designed to facilitate precision medicine research in oncology.
- To provide a centralized resource for drug activity, genomic, and other molecular data across a diverse set of cancer cell lines.
- To enable cross-database analyses and exploration of drug response determinants.
Main Methods:
- Developed CellMinerCDB: NCATS, integrating data for 2,675 drugs and 183 cancer cell lines, including 1,866 unique compounds and 72 unique cell lines from NCATS.
- Incorporated diverse data types: single/combination drug activity, DNA copy number, methylation, mutation, transcriptome, protein levels, epigenetics, metabolites, CRISPR, and signatures.
- Implemented data curation for cell lines and drugs to enable cross-database (CDB) analyses and integrated univariate/multivariate analysis tools (e.g., linear regression, LASSO).
Main Results:
- CellMinerCDB: NCATS offers activity data for 2,675 drugs across 183 cancer cell lines, with significant novel data from NCATS.
- The platform integrates multiple molecular data types, enabling comprehensive pharmacogenomic investigations.
- Demonstrated utility with examples using clinical topoisomerase I (TOP1) inhibitors, topotecan and irinotecan/SN-38.
Conclusions:
- CellMinerCDB: NCATS provides a valuable, integrated resource for exploring drug response in cancer.
- The platform supports the discovery of novel therapeutic strategies and biomarkers for precision cancer medicine.
- Facilitates interdisciplinary research by making extensive pharmacogenomic data accessible and analyzable.
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