MicroRNA profiling by array of NCI-60 human cancer cell-lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Patnaik SK
PROVIDER: S-ECPF-MTAB-327 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description:Advances in the understanding of cancer cell biology and response to drug treatment have benefited from new molecular technologies and methods for integrating information from multiple sources. The NCI-60, a panel of 60 diverse human cancer cell lines, has been used by the National Cancer Institute to screen >100,000 chemical compounds and natural product extracts for anticancer activity. The NCI-60 has also been profiled for mRNA and protein expression, mutational status, chromosomal aberrations, and DNA copy number, generating an unparalleled public resource for integrated chemogenomic studies. Recently, microRNAs have been shown to target particular sets of mRNAs, thereby preventing translation or accelerating mRNA turnover. To complement the existing NCI-60 datasets, we have measured expression levels of microRNAs in the NCI-60.
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| S-ECPF-GEOD-5949 | biostudies-other
Project description:BackgroundDrugs can influence the whole metabolic system by targeting enzymes which catalyze metabolic reactions. The existence of interactions between drugs and metabolic reactions suggests a potential way to discover drug targets.ResultsIn this paper, we present a computational method to predict new targets for approved anti-cancer drugs by exploring drug-reaction interactions. We construct a Drug-Reaction Network to provide a global view of drug-reaction interactions and drug-pathway interactions. The recent reconstruction of the human metabolic network and development of flux analysis approaches make it possible to predict each metabolic reaction's cell line-specific flux state based on the cell line-specific gene expressions. We first profile each reaction by its flux states in NCI-60 cancer cell lines, and then propose a kernel k-nearest neighbor model to predict related metabolic reactions and enzyme targets for approved cancer drugs. We also integrate the target structure data with reaction flux profiles to predict drug targets and the area under curves can reach 0.92.ConclusionsThe cross validations using the methods with and without metabolic network indicate that the former method is significantly better than the latter. Further experiments show the synergism of reaction flux profiles and target structure for drug target prediction. It also implies the significant contribution of metabolic network to predict drug targets. Finally, we apply our method to predict new reactions and possible enzyme targets for cancer drugs.
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Project description:Affymetrix GeneChip miRNA arrays were used to profile the expression of microRNAs in cells of sixty NCI-60 cancer cell-lines
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Project description:Comparison between cell lines from 9 different cancer tissue of origin types (Breast, Central Nervous System, Colon, Leukemia, Melanoma, Non-Small Cell Lung, Ovarian, Prostate, Renal) from NCI-60 panel Experiment Overall Design: cell lines from 9 different cancer tissue of origin types
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Project description:The NCI-60 panel of 60 human cancer cell-lines of nine different tissues of origin has been extensively characterized in biological, molecular and pharmacological studies. Analyses of data from such studies have provided valuable information for understanding cellular processes and developing strategies for the diagnosis and treatment of cancer. Here, Affymetrix® GeneChip™ miRNA version 1 oligonucleotide microarrays were used to quantify 847 microRNAs to generate an expression dataset of 495 (58.4%) microRNAs that were identified as expressed in at least one cell-line of the NCI-60 panel. Accuracy of the microRNA measurements was partly confirmed by reverse transcription and polymerase chain reaction assays. Similar to that seen among the four existing NCI-60 microRNA datasets, the concordance of the new expression dataset with the other four was modest, with mean Pearson correlation coefficients of 0.37-0.54. In spite of this, comparable results with different datasets were noted in clustering of the cell-lines by their microRNA expression, differential expression of microRNAs by the lines' tissue of origin, and correlation of specific microRNAs with the doubling-time of cells or their radiation sensitivity. Mutation status of the cell-lines for the TP53, PTEN and BRAF but not CDKN2A or KRAS cancer-related genes was found to be associated with changes in expression of specific microRNAs. The microRNA dataset generated here should be valuable to those working in the field of microRNAs as well as in integromic studies of the NCI-60 panel.
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Project description:Here we describe a proteomic data resource for the NCI-60 cell lines generated by pressure cycling technology and SWATH mass spectrometry. We developed the DIA-expert software to curate and visualize the SWATH data, leading to reproducible detection of over 3,100 SwissProt proteotypic proteins and systematic quantification of pathway activities. Stoichiometric relationships of interacting proteins for DNA replication, repair, the chromatin remodeling NuRD complex, β-catenin, RNA metabolism, and prefoldins are more evident than that at the mRNA level. The data are available in CellMiner (discover.nci.nih.gov/cellminercdb and discover.nci.nih.gov/cellminer), allowing casual users to test hypotheses and perform integrative, cross-database analyses of multi-omic drug response correlations for over 20,000 drugs. We demonstrate the value of proteome data in predicting drug response for over 240 clinically relevant chemotherapeutic and targeted therapies. In summary, we present a novel proteome resource for the NCI-60, together with relevant software tools, and demonstrate the benefit of proteome analyses.
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