One of the tools that dtp employs in the early stage of drug discovery and development is the nci60 cell line screen. Nci60 cell lines hcc2998 a549 hs578t snb75 ncih23 molt4. Finally, by matching drug sensitivity data for the nci60 cells to their mirna expression profiles, we found numerous drugmirnas pairs, for which the mirna expression and drug sensitivity. Implementation of the nci60 human tumor cell line panel. We next tested whether dna methylation profiling in the nci60 panel predicts drug sensitivity or resistance. An academic research program to identify molecular features of cancers that predict response to anticancer drugs. Highthroughput biological techniques, like microarrays and drug screens, generate an enormous amount of data that may be critically important for cancer researchers and clinicians. This data set includes compounds, as well as with fdaapproved, clinical trial and known mechanismofactions drugs in. Analyses of data from such studies have provided valuable information for understanding cellular processes and developing strategies for the diagnosis and treatment of cancer. Gda, a webbased tool for genomics and drugs integrated. We have suspended the receipt of samples and the nci60 is on hiatus until further notice due to covid19.
Drug sensitivity prediction by cpg island methylation. National cancer institute to screen over 100,000 chemical compounds and natural products since 1990. Nci60 growth inhibition data nci dtp data nci wiki. The data matrices for nci60 lines treated with the 15 drugs at different time points and different concentrations, including baseline experiments zero concentration, were stored in a backend sqlite database. The nci60 database includes drug sensitivity data from more than 50. The us national cancer institute nci 60 human tumour cell line anticancer drug screen nci60 was developed in the late 1980s as an in vitro drugdiscovery tool intended to supplant the use of. The 60 cell lines of the national cancer institute anticancer drug screen nci 60 constitute the most extensively characterized in vitro cancer cell model. The cancer cell line encyclopedia presents the first results from a largescale screen of some 947 cancer cell lines with 24 anticancer drugs, with the aim of identifying specific genomic.
Stanford nci60 cancer microarray project web supplement to the paper from. Here we describe a proteomic data resource for the nci60 cell lines generated by pressure cycling technology and swath mass spectrometry. Aug 07, 2007 given the finding that coxen could predict drug sensitivity, even in cell lines of histological types not included in the nci 60 panel, we wondered whether an analogous algorithm would also have predictive power for chemotherapeutic responses in human patients. Search dtpnci60 drug data by single identifier or list of identifiers, and retrieve activity information as well as additional annotation information. Jun 26, 2018 full release of endpoints calculated from concentration curves. A description of the nci 60 assay and calculations can be found here. Some data and graphics are available in scalable vector graphics svg format. Open source machinelearning algorithms for the prediction of. Quantitative proteome landscape of the nci60 cancer cell lines. It leverages overlaps of cell lines and drugs across databases to examine. Implementation of the nci 60 human tumor cell line panel to screen 2260 cancer drug combinations to generate 3 million data points used to populate a large matrix of antineoplastic agent combinations almanac database. A central assumption of the work described in this paper is that the gene expression and drug sensitivity data that are available for the nci 60 cell lines can be correlated with mutation status of a key regulatory gene, pik3ca.
Systems analysis of the nci60 cancer cell lines by. Parp1 rs1805407 increases sensitivity to parp1 inhibitors in. For access to our cytogenetics spectral karyotyping of the nci60, type nci60 in the ncbis sky database search page. Nci 60 screening methodology nci 60 cell onedose screen general description. Drug sensitivity prediction by cpg island methylation profile. Predictive models of in vitro drug sensitivity have. The mutational status of more than 1,600 genes is determined by targeted massively parallel sequencing, followed by removal of variants likely to be germline events. Quantitative proteome landscape of the nci60 cancer cell. Previous studies have also shown that uptake transporters can influence cytotoxicity by altering the cellular uptake. Identification of potential synthetic lethal genes to p53.
Scientists establish database of genes associated with cancer. Predicting tumor cell line response to drug pairs with deep learning. Of these, decreased uptake of anticancer drugs mediated by efflux transporters represents one of the best studied mechanisms. In addition, the nci 60 provides drug responses for over 21,000 individual agents, making it an unmatched resource for the discovery of new chemotypes based on correlations with genomic data and response patterns for drugs with known targets. The sensitivity of the nci60 to over 100,000 synthetic or natural. Please note the links for more information on the snb19, u251, nci adrres, and mdamb435 cell lines. Nci 60 panel of human cancer cell lines maintained by the developmental therapeutics program of the nci. Nov 26, 2019 this is the first one of a series of files which will be released over the next few months. Nci60 human cancer cell line screen nci60 human tumor. A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery. Sep 12, 2014 for cancer cell lines, the national cancer institute cell line panel nci 60, the cancer cell line encyclopedia ccle, and the collaborative genomics of drug sensitivity in cancer gdsc databases all provide subsets of these forms of data.
The intracellular effects and overall efficacies of anticancer therapies can vary significantly by tumor type. However,what confuses me is that where can i download the nci 60 data. Second, the analysis provides the most robust geneexpression database yet available to the hundreds, or probably thousands, of laboratories that are using the nci60 drug activity and molecular characterization databases. Finally, by matching drug sensitivity data for the nci 60 cells to their mirna expression profiles, we found numerous drug mirnas pairs, for which the mirna expression and drug sensitivity. Data analysis in accordance with the in vitro cell line screening project ivclsp for the dtp anticancer drug discovery program this method uses seven absorbance measurements zero, control growth and test growth in the presence of drug at the five concentration levels. First, we used compare analysis to correlate methylation of each marker with drug response at the gi. Pdf predicting invitro drug sensitivity using random forests. As of early 2007 all compounds submitted to the nci 60 cell screen are tested initially at a single high dose 105 m in the full nci 60 cell panel. The nci tpw system operates under the centos version 6. The national cancer institute developmental therapeutics program. Work to identify novel drugtarget interactions using compound activity from the nci developmental therapeutics program dtp and omic profiling data of the nci60 cancer cell lines in collaboration with the developmental therapeutics branch at the.
Jun 23, 2009 in addition to its role as an integrative resource for the nci 60, the cellminer package also serves as a shell for incorporation of molecular profile data on other cell or tissue sample types. To illustrate mining strategies supporting therapeutic. Predicting in vitro drug sensitivity using random forests. This paper describes the relationship between the gene expression patterns and compound sensitivity patterns measured by the developmental therapeutics program. These files will contain a successively curated structure set of all records of the open nci database. They have been tested for sensitivity to more than 100,000 potential chemotherapy agents and have been profiled extensively at the dna, rna, protein, functional, and pharmacologic levels. A plug in for most browsers and operating systems is available from adobe. Methods identification of candidates of druggable synthetic lethal genes to p53. Cellminer is a relational database tool for storing, querying, integrating, and downloading molecular profile data on the nci 60 and other cancer cell. The national cancer institute drug pair screening effort against 60. At this moment, the nci 60 cells constitute the most extensively and diversely characterized cell panel anywhere, and several databases have been generated based on these cell lines, such as drug activity database for 30,000 chemically defined.
The nci has established a panel of cell lines nci 60 and used it to screen compounds for anticancer activity over the last decades 1. Cellminer greatly broadens applications of the extensive nci60 database for. Using drug response data to identify molecular effectors, and. Indeed, as our group at nci reported april 27 in cancer research, this new database has already borne fruit. Nci60 analysis tools this page provides automation of several commonly done analyses. Cellminercdb for integrative crossdatabase genomics and. A strategy for predicting the chemosensitivity of human. Molecular and pharmacologic profiling of the nci 60 cell panel offers the possibility of identifying pathways involved in drug resistance or sensitivity. However, a critical missing component of previous analyses has been the inability to place the massive amounts of omic data in the context of functional protein signaling networks, which often contain many of the drug targets for new targeted therapeutics. I am working on nci60 database for data mining purpose. Nci almanac tool for research on cancer drug combinations. A description of the nci60 assay and calculations can be found here. The database serves as reference to query the abundance and distribution of proteins in each cell line as well as protein signature for drug sensitivity and resistance. Nci60 analysis tools national institutes of health.
Mutation hotspots on the gene were pcr amplified and sequenced, and the trace data were analyzed with software designed to detect mutations. Predicting invitro drug sensitivity using random forests. Implementation of the nci60 human tumor cell line panel to screen 2260 cancer drug combinations to generate 3 million data points used to populate a large matrix of antineoplastic agent combinations almanac database. Predictive models for each drug are individually created by combining two data sources. The 60 cell lines of the national cancer institute anticancer drug screen nci60 constitute the most extensively characterized in vitro cancer cell model.
Dtp drug activities are measured for 50% growth inhibition. For additional drug, dataset and molecular target data see the nci developmental therapeutics program site. Gda is a webserver designed to facilitate the integrative analysis of genomic and drug response data available from two major cancer cell line screens i. New webbased tools make systems pharmacology more accessible. The web client interface pages are written in html, css, and javascript. Precision medicine is a rapidly growing area of modern medical science and open source machinelearning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. National cancer institute has used a panel of 60 diverse human cancer cell lines the nci 60 to screen 100,000 chemical compounds for anticancer activity.
However, not all important cancer types are included in the panel, nor are drug responses of the panel predictive of clinical efficacy in patients. For a complete description of the cellminer options, go to the home tab above. One important goal of precision cancer medicine is the accurate prediction of optimal drug therapies from the genomic profiles of individual patient tumors. A web application that facilitates comprehensive proteome analysis of the nci60 cell line panel. For other bioinformatic tools and database resources from gbg go to the discover website home page.
The nci60 panel of 60 human cancer celllines of nine different tissues of origin has been extensively characterized in biological, molecular and pharmacological studies. Analysis for gene expression data of the nci 60 cancer. Therefore, improvements to model selection are beneficial. Can drug sensitivity data on the nci60 or analogous screening panels be extrapolated to predict the sensitivity of cell lines and cell line types not included. Being able to new webbased tools make systems pharmacology more accessible using data from the nci 60 center for cancer research national cancer institute.
Please try our experimental interactive site cellminercdb for exploring nci60 data in. A central assumption of the work described in this paper is that the gene expression and drug sensitivity data that are available for the nci60 cell lines can be correlated with mutation status of. The nci60 human tumor cell lines screen has served the global cancer research community for 20 years. The nci60 cancer cell line panel is a group of 60 human cancer cell lines used by the national cancer institute nci for the screening of compounds to detect potential anticancer activity. The nci60 cell line set is likely the most molecularly profiled set of human tumor cell lines in the world. Correlation of pik3ca mutations with gene expression and drug. Using the nci almanac, we identified several different drug combinations that have never before been tested together in humans but that nevertheless had powerful cellkilling effects in a number of the nci 60 cell lines. Developmental therapeutics program link to analysis tools for exploring the drug sensitivity database, the gene expression database, and other drug targets measured by the dtp. The people involved in the stanford nci60 cancer microarray project. To illustrate mining strategies supporting therapeutic studies. We have suspended the receipt of samples and the nci 60 is on hiatus until further notice due to covid19. Matched pairs of cdna clones and oligonucleotide sequences representing 1,493 unigene clusters with r 0.
In addition to its role as an integrative resource for the nci60, the cellminer package also serves as a shell for incorporation of molecular profile data on other cell or tissue sample types. Cellminer is a relational database tool for storing, querying, integrating, and downloading molecular profile data on the nci60 and other cancer cell. Ccle has been aggregated to facilitate numerous advances in cancer biology and drug discovery. Read correlation of pik3ca mutations with gene expression and drug sensitivity in nci60 cell lines, biochemical and biophysical research communications on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. The screen was implemented in fully operational form in 1990 and utilizes 60 different human tumor cell lines to identify and characterize novel compounds with growth inhibition or killing of tumor cell lines. We demonstrate the value of proteome data in predicting drug. Systems analysis of the nci60 cancer cell lines by alignment. Open source machinelearning algorithms for the prediction. Profiling slco and slc22 genes in the nci60 cancer cell.
The nci60 human tumor cell lines screen has served the global. National cancer institute has used a panel of 60 diverse human cancer cell lines the nci60 to screen 100,000 chemical compounds for anticancer activity. Access nci60 drug response and omics data using rcellminer. The rcellminer is an r package that provides a wide range of functionality to help r users to access and explore molecular profiling and drug response data in the nci60. Scientists establish database of genes associated with cancer drug resistance. It utilizes a panel of 60 human tumor cell lines, chosen both for their ability to perform consistently under the conditions of the assay, and to represent a variety of tumor types 3. For cancer cell lines, the national cancer institute cell line panel nci60, the cancer cell line encyclopedia ccle, and the collaborative genomics of drug sensitivity in cancer gdsc databases all provide subsets of these forms of data. The nci60 dataset includes drug activity data for over 21,000. Karyotypic complexity of the nci60 drugscreening panel. Full release of endpoints calculated from concentration curves. The nci 60 human tumor cell lines screen has served the global cancer research community for 20 years. Panel of human cancer cell lines provides valuable database for drug discovery and bioinformatics. This is the first one of a series of files which will be released over the next few months. The cancer cell line encyclopedia enables predictive.
Predicting anticancer drug sensitivity by methylation. Fiftynine cell lines from the nci 60 anticancer drug discovery panel were obtained from richard camalier of the national cancer institute developmental therapeutics program. Panels of cell lines such as the nci60 have long been used to test drug candidates for their ability to inhibit proliferation. Mar 28, 2012 the cancer cell line encyclopedia presents the first results from a largescale screen of some 947 cancer cell lines with 24 anticancer drugs, with the aim of identifying specific genomic. For a detailed description of the functionalities and how to use them, see reinhold, cancer res, 2012. The basis of this first file is the version of the open nci database as provided by dtp in december 2010 2d coordinates sd file with 266,151 records. Using the nci almanac, we identified several different drug combinations that have never before been tested together in humans but that nevertheless had powerful cellkilling effects in a number of the nci60 cell lines. Program link to analysis tools for exploring the drug sensitivity database, the. Development of cancer therapeutics partially depends upon selection of appropriate animal models. We developed the diaexpert 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. Panels of cell lines such as the nci 60 have long been used to test drug candidates for their ability to inhibit proliferation.
I have not found a perticular website where i can download the nci 60. Correlation of pik3ca mutations with gene expression and drug sensitivity in nci60 cell lines. Correlation of pik3ca mutations with gene expression and. This page provides automation of several commonly done analyses. Scientists establish database of genes associated with cancer drug resistance date. In addition, the nci60 provides drug responses for over 21,000 individual agents, making it an unmatched resource for the discovery of new chemotypes based on correlations with genomic data and response patterns for drugs with known targets. Mtt data were then analyzed using the compusyn software.
The sensitivity of the nci 60 to over 100,000 synthetic or natural compounds derived from a wide range of academic and industrial sources has been measured, constructing the most comprehensive open resource for cancer pharmacology. The nci almanac database therefore constitutes a valuable resource. This panel represents the most common solid and soft tumors derived from 9 different tissues such as blood, lung, colon, kidney, breast, skin, prostate. For access to our cytogenetics spectral karyotyping of the nci 60, type nci 60 in the ncbis sky database search page. Using drug response data to identify molecular effectors. Expression of micrornas in the nci60 cancer celllines. Knowledge of the intrinsic and adaptive drug resistance mechanisms of tumors. The results were integrated into a combined database and set of interactive. The results were integrated into a combined database and set of interactive analysis tools, designated the nci transcriptional pharmacodynamics workbench nci tpw, that allows exploration of geneexpression modulation by molecular pathway, drug target, and association with drug sensitivity.
Please try our experimental interactive site cellminercdb for exploring nci 60 data in. The sensitivity of the nci60 to over 100,000 synthetic or natural compounds derived from a wide range of academic and industrial sources has been measured, constructing the most comprehensive open resource for cancer pharmacology. The nci60, a panel of 60 diverse human cancer cell lines used by the developmental therapeutics program of the u. Fortynine human tumor xenografts at in vivo passages 1, 4 and 10 were subjected to cdna microarray analysis yielding a dataset of 823 affymetrix hgu3 plus 2. Integrating the nci60 data with omics for drug discovery. The nci60 human tumour cell line anticancer drug screen. The resulting collection encompasses 36 tumor types.
Please note the links for more information on the snb19, u251, nciadrres, and mdamb435 cell lines. The nci60 cell lines are a set of human tumor cell lines collected by the national cancer institute nci over the last 20 years to accomplish drug screening tests of more than 100,000 chemical compounds and natural extracts. Scientists establish database of genes associated with. In addition to its role as an integrative resource for the nci60, the. Html table with samples plain html table image gallery simply count hits entire db nsc number file cactvs hitlist records alchemy cactvs binary cerius cml compass ctx gaussian input jcampcs molconnz molfile pdb smd 4 sdfile smiles sybyl2 vrml 2. Work on tools to conduct complex pathway analyses using the aggregated pathway commons database. To identify patterns of drug induced gene modulation that occur in different cancer cell types, we measured geneexpression changes across the nci 60 cell line panel after exposure to 15 anticancer agents. Dec 15, 2005 we profiled the mutation status of the pik3ca gene in the national cancer institute nci 60 panel of human cancer cell lines maintained by the developmental therapeutics program of the nci.
The nci60 cancer cell line panel has been used over the course of several. The nci transcriptional pharmacodynamics workbench. Implementation of the nci60 human tumor cell line panel to. We asked, therefore, whether it would be possible to extrapolate from that rich. Fiftynine cell lines from the nci60 anticancer drug discovery panel were obtained from richard camalier of the national cancer institute developmental therapeutics program. Molecular and pharmacologic profiling of the nci60 cell panel offers the possibility of identifying pathways involved in drug resistance or sensitivity. Feb 10, 2006 read correlation of pik3ca mutations with gene expression and drug sensitivity in nci 60 cell lines, biochemical and biophysical research communications on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
320 1441 1470 1288 819 802 1402 1289 944 1275 669 44 951 689 50 113 176 134 523 1302 453 248 206 543 862 1089 884 771 1238 1228 1256 403 1326 327 1199 400 1077 477 795 351 133 144