Cancer Research · 2012 · 931 citations · 41 references
PharmacyMolecular MedicineSystems BiologyDrug DiscoveryGenomic Data AnalysisTranscriptomicsCancer TranscriptomicsCellular Response ProfilingDrug DatabasesDrug Information ResourcesGenomic DatabasesTranscriptomic ProfilingBioactivity DatabasesCancer BioinformaticsCancer Genomics DatabasesCell Line Response DatabasesData OrganizationData RetrievalMolecular Medicine IntegrationSystems Biology Integration
High‑throughput databases are essential in molecular medicine, yet their unwieldy nature limits analysis, especially for the extensively characterized NCI‑60 cell line database. This report introduces CellMiner, a web application designed to improve the use of the NCI‑60 database. CellMiner provides rapid retrieval of 22,379 gene and 360 miRNA transcripts and 20,503 compound activity reports, converts differential levels into quantitative patterns via a novel pattern‑matching tool, and supports iterative, user‑specific queries across the NCI‑60. Using CellMiner, the authors demonstrated in silico discovery of multidrug resistance mechanisms, doxorubicin activity, colon‑specific genes and miRNAs, and drug‑matching patterns for erlotinib, gefitinib, afatinib, and lapatinib. Cancer Res 72(14):3499–511; ©2012 AACR.
Abstract High-throughput and high-content databases are increasingly important resources in molecular medicine, systems biology, and pharmacology. However, the information usually resides in unwieldy databases, limiting ready data analysis and integration. One resource that offers substantial potential for improvement in this regard is the NCI-60 cell line database compiled by the U.S. National Cancer Institute, which has been extensively characterized across numerous genomic and pharmacologic response platforms. In this report, we introduce a CellMiner (http://discover.nci.nih.gov/cellminer/) web application designed to improve the use of this extensive database. CellMiner tools allowed rapid data retrieval of transcripts for 22,379 genes and 360 microRNAs along with activity reports for 20,503 chemical compounds including 102 drugs approved by the U.S. Food and Drug Administration. Converting these differential levels into quantitative patterns across the NCI-60 clarified data organization and cross-comparisons using a novel pattern match tool. Data queries for potential relationships among parameters can be conducted in an iterative manner specific to user interests and expertise. Examples of the in silico discovery process afforded by CellMiner were provided for multidrug resistance analyses and doxorubicin activity; identification of colon-specific genes, microRNAs, and drugs; microRNAs related to the miR-17-92 cluster; and drug identification patterns matched to erlotinib, gefitinib, afatinib, and lapatinib. CellMiner greatly broadens applications of the extensive NCI-60 database for discovery by creating web-based processes that are rapid, flexible, and readily applied by users without bioinformatics expertise. Cancer Res; 72(14); 3499–511. ©2012 AACR.
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