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 Food and Drug Administration (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 pharmacological parameters in a manner specific to the user’s area of expertise. Examples for both gain- (RAS) and loss- (PTEN) of-function alterations are provided.

Screening of Conditionally Reprogrammed Patient-Derived Carcinoma Cells Identifies ERCC3–MYC Interactions as a Target in Pancreatic Cancer

“…To determine if the hits we observed were uniquely active in PDAC, we benchmarked the cytotoxicity profile we generated in the PDAC cell models to public data reporting systematic analyses of drug chemosensitivity for NCI-60 panel of cell lines [27] which are available in CellMiner [28, 29]. The NCI-60 panel does not include PDAC cell lines.…”

The NCI-60 Methylome and Its Integration into CellMiner

“…Both the NCI and CEPB obtained the cell lines from the Developmental Therapeutics Program (DTP) (12,16,17). For the NCI dataset, cells were grown and DNA isolated as described previously (18,19).…”

“…For comparisons between methylation levels and transcript expression z scores, we used the methylation and transcript “Cell line signatures” (16). Expression versus methylation correlations, heat-map and histogram were generated using The R Project for Statistical Computing (22).…”

Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin

“…B PLAU mRNA expression levels correlate with the SMB release. The levels of SMB released in the presence of Plg and a2AP were used as a query pattern and correlated with the expression levels of about 26,000 genes across the NCI-60 panel, using the CellMiner web tool [32]. The table shows A-D Human ascites and urine samples were immunoprecipitated with HU3-conjugated beads, and eluted material was analysed by MALDI-TOF mass spectrometry.…”