Plenary Lecture

The Use of the NCI-60 Cancerous Cell-Lines and CellMiner as a Foundation for the Exploration of Pharmacogenomics

Dr. William C. Reinhold
Genomics and Bioinformatics Group
Developmental Therapeutics Branch, NCI, NIH
USA
E-mail: wcr@mail.nih.gov

Abstract: Determining the level of influence of the molecular alterations found in cancer on pharmacological responses from the omic perspective is prerequisite to making treatment of oncology more effective and specific. How to do this, however, remains to be determined. A high-quality and extensive set of molecular and pharmacological data is provided by the NCI-60 cancerous cell lines, providing a solid basis for these types of assessments. Robust, high-quality activity profiles are generated by the Developmental Therapeutics Program (https://dtp.cancer.gov). A significant assortment of molecular and phenotypic information is available for comparison to these activity profiles through the CellMiner web-application (http://discover.nci.nih.gov/cellminer). CellMiner provides access to both the activity data for 21,768 compounds, including 108 Food and Drug Administration (FDA)-approved, 70 clinical trial drugs, as well as molecular data including i) transcript expression for 25,772 genes, ii) genetic variants for 16,568 genes, iii) transcript expression for 360 microRNAs, iv) protein levels for 94 genes, v) DNA copy number (from aCGH) for 23,413 genes, and soon vi DNA methylation levels for 17,559 genes. “Cell line signatures” may be generated for each of these data types, facilitating their comparison. In addition “Pattern comparisons” may be generated for any input pattern of interest to 87,419 activity, molecular and phenotypic patterns (For CellMiner 1.7). A combination of the data and functionalities available in our CellMiner web application will be presented, including informative examples of data integration, and translationally relevant results.

Brief Biography of the Speaker: William Reinhold is currently operating as facility head of the Genomics and Bioinformatics Group in the Laboratory of Molecular Pharmacology. He has been a part of this section since April 1998, working with first John N. Weinstein, and then Yves Pommier. He has been central in generating multiple datasets for the NCI-60 cancerous cell lines, available at the CellMiner web-application at http://discover.nci.nih.gov/cellminer/. His activities include running the web site, and maintaining the contracts required to do so as a Contracting Officer Representative (COR). He helps in the dissemination and interpretation of this data, encouraging and facilitating collaborations. Currently his research includes the collection of data for the NCI-60 cancerous cell lines, and the development of software to facilitate the use of this data in systems pharmacology. He currently provides easy integration for 20, 602 compounds (including 108 FDA-approved drugs, and 77 in clinical trial). Molecular parameters include transcript levels for 26,065 genes, and 350 microRNAs, aCGH DNA copy numbers for 23,413 genes, and mutational status for 12,706 genes. Prior to this period of time he has also held positions with the Laboratory of Molecular Pharmacology (Sept. 1996 to April 1998), Laboratory of Biological Chemistry and Medicine Branch in the NCI (February 1992 - September 1996), at the National Institutes of Neurological Diseases and Stroke (Sept.-1989 to Feb.-1992), National Institutes of Allergies and Infectious Diseases June 1982 to Aug. 1989), as well as in private industry, working for Gibco BRL (April 1981 to Feb. 1982), and Meloy Laboratories (Jan. 1978 to April 1981). He received his B.S. in Biochemistry from the University of Maryland in 1978, and has 84 peer reviewed publications to date.

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