title: Using CellMiner 1.6 for Systems Pharmacology and Genomic Analysis of the NCI-60.
abstract: The NCI-60 cancer cell line panel provides a premier model for data integration, and systems pharmacology being the largest publicly available database of anticancer drug activity, genomic, molecular, and phenotypic data. It comprises gene expression (25,722 transcripts), microRNAs (360 miRNAs), whole-genome DNA copy number (23,413 genes), whole-exome sequencing (variants for 16,568 genes), protein levels (94 genes), and cytotoxic activity (20,861 compounds). Included are 158 FDA-approved drugs and 79 that are in clinical trials. To improve data accessibility to bioinformaticists and non-bioinformaticists alike, we have developed the CellMiner web-based tools. Here, we describe the newest CellMiner version, including integration of novel databases and tools associated with whole-exome sequencing and protein expression, and review the tools. Included are (i) "Cell line signature" for DNA, RNA, protein, and drugs; (ii) "Cross correlations" for up to 150 input genes, microRNAs, and compounds in a single query; (iii) "Pattern comparison" to identify connections among drugs, gene expression, genomic variants, microRNA, and protein expressions; (iv) "Genetic variation versus drug visualization" to identify potential new drug:gene DNA variant relationships; and (v) "Genetic variant summation" designed to provide a synopsis of mutational burden on any pathway or gene group for up to 150 genes. Together, these tools allow users to flexibly query the NCI-60 data for potential relationships between genomic, molecular, and pharmacologic parameters in a manner specific to the user's area of expertise. Examples for both gain- (RAS) and loss-of-function (PTEN) alterations are provided.
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. wcr@mail.nih.gov pommier@nih.gov.
authors.forename: William C
authors.initials: WC
authors.lastname: Reinhold
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. Systems Research and Applications Corp., Fairfax, Virginia.
authors.forename: Margot
authors.initials: M
authors.lastname: Sunshine
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. Systems Research and Applications Corp., Fairfax, Virginia. HiThru Analytics LLC, Laurel, Maryland.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Varma
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. Developmental Therapeutics Program, DCTD, NCI, NIH, Bethesda, Maryland.
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, Bethesda, Maryland. wcr@mail.nih.gov pommier@nih.gov.
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods*; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D059472:Exome; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D014644:Genetic Variation; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D012984:Software; D064878:Web Browser
chemical_list: D000970:Antineoplastic Agents