How do i compare drug sensitivity of cell lines with. Drug sensitivity prediction by cpg island methylation. However, such pharmacogenomic datasets are disparate and lack of standardization for cell line and drug identifiers, and used heterogeneous data format for the drug sensitivity measurements. Cellminercdb automatically matches synonymous cell line and drug. Mar, 20 sensitivity reference is the lowest ic 50 value reported for particular drug or cell line. The nci has established a panel of cell lines nci60 and used it to screen compounds for anticancer activity over the last decades 1. Nono and raly proteins are required for yb1 oxaliplatin. Search dtpnci60 drug data by single identifier or list of identifiers, and retrieve activity information as well as. 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. In line with recent advances in neural drug design and sensitivity prediction, we propose a novel architecture for interpretable prediction of anticancer compound sensitivity using a multimodal attentionbased convolutional encoder.
Overexpression of yb1 in breast cancers causes cisplatin resistance. You may have been redirected here from the broad cancer program resource gateway, which is no longer active. Cancer drug resistance database scientific reports. Hcc1143 cell line hms lincs database hms lincs project. Genomics of drug sensitivity in cancer wellcome sanger. We screened a large panel of liver cancer cell lines. Human cancer cell lines are an important resource for research and drug development. Furthermore, by clicking on circles within scatter plots, cell line ic 50 values are directly linked to the cosmic database facilitating integration of drug sensitivity data with detailed cell line information such a tissue type, tumour histology and a description of cell line origin and genotype. If the ic50 is very low then the concentration or amount of drug. The rpmi 8226 myeloma cell line and its multidrug resistant subline 8226dox40 was screened for cytotoxicity in response to 3,000 chemically diverse compounds using a.
One caveat, however, is that the large cell line database comparisons entail far larger numbers of matched. As part of our continuing efforts to characterize and authenticate the cell lines in the cell biology collection, atcc has developed a comprehensive database of short tandem repeat str dna profiles for all of our human cell lines. The cell line name and lineage are listed at the top of the cell line page. Reduced sensitivity to cisplatin may reside in an active drug efflux, like copper efflux systems 42, 43, that preferentially inhibits drug accumulation in the cells. Cancer cell lines have a prominent role in the initial stages of drug discovery, facilitating highthroughput screening of potential drugs. Aug 26, 2019 human cancer cell lines are fundamental models for cancer research and therapeutic strategy development. To view a cell line s information, search for it from the front page.
Clinical drug response can be predicted using baseline. Expression levels were obtained for each of the lines using. A tool for discovering drug sensitivity and gene expression. Nov 25, 2011 yb1 is a multifunctional protein that affects transcription, splicing, and translation. Current therapies suffer from lack of efficacy in a great percentage. On this website, you will find drug response data and genomic. Information about levels of these polypeptides in common cancer cell types and any possible correlation with drug sensitivity in the absence of gene deletion is. Toward explainable anticancer compound sensitivity prediction. Phosphoproteomics data classify hematological cancer cell.
Human cancer cell lines are fundamental models for cancer research and therapeutic strategy development. Cancer cell line encyclopedia ccle 8, genomics of drug sensitivity in cancer. Of particular relevance was the use of dna arraybased methodology by the national cancer institute nci to assess the gene expression profiles of 60 human cancer cell lines of diverse. Implementation of the nci60 human tumor cell line panel to. Anticancer drug clustering in lung cancer based on gene. The databases of cancer cell line encyclopedia ccle 3 and genomics of drug sensitivity in cancer gdsc 4 projects contain gene. Cancer cell line drug sensitivity data are generated from ongoing highthroughput screening performed by the cancer genome project at the wellcome trust sanger institute wtsi and the center for molecular therapeutics at massachusetts general hospital using a collection of cell lines. For this analysis, we have determined the relative sensitivity z score of a cell line to a given drug compared to all other cell lines. New opensource ai machine learning tools to fight cancer. Ncis database of cancer drugs with its database of cell lines a daunting task that involved. Components of the cell death machine and drug sensitivity.
Mar 29, 2012 the bottom curve indicates drug response, measured as the area over the doseresponse curve activity area, for each cell line. Im looking to create a database of cell lines i use and their characterisitcs i. However, their clinical relevance remains controversial. Immortalized cancer cell lines are the most widelyused models to study. Modeled after common scientific and business applications, hcs. Dr francesco iorio, first author and a postdoctoral researcher at both emblebi. Our model is based on the three key pillars of drug sensitivity. The sensitivity patterns of the cell lines were correlated with extensive genomic.
Cancer cell line encyclopedia consortium genomics of drug sensitivity in cancer consortium pharmacogenomic agreement between two cancer cell line data sets. Cell line data base cell line data base cldb, the first database set up within the interlab project, contains detailed information on human and animal cell lines that are available in many italian. The genomics of drug sensitivity in cancer provides public access to data on the sensitivity of genomically characterized cancer cell lines to select compounds. Cellminercdb for integrative crossdatabase genomics and. It leverages overlaps of cell lines and drugs across databases to. Comprehensive characterization of circular rnas in. Encircling the regions of the pharmacogenomic landscape that. According to some studies, susceptibility of cells to anticancer drug induced apoptosis is markedly inhibited by targeted deletion of genes encoding apoptotic protease activating factor 1 apaf1 or certain caspases. Pharmacological profiling of these anticancer drugs were collected from ccle and cosmic databases. Correlation between multiple baseline cancer genomics data and relative drug sensitivity has been explored in a number of public resources, such as cellminer 12, 21, genomics drug sensitivity in cancer gdsc, 22, or cancerdp 23, 24, where data can be enriched for compound andor cell line numerosity but cannot be extended to user. Generation of cisplatinresistant ovarian cancer cell lines. Cancerrxgene genomics of drug sensitivity in cancer. Additionally, vehicle treated parental cell line was kept in culture during this period as control cell line.
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. Cancer cell lines for drug discovery and development. Next, we adapted a categorical modeling approach that utilized a naive bayes classification and discrete sensitivity calls, or. The study tested paccmanns ability to predict drug sensitivity on over 200,000 drugcell line pairs in the genomics of drug sensitivity in cancer gdsca database that characterizes human. Dec 10, 2019 a major challenge in cancer treatment is predicting clinical response to anticancer drugs on a personalized basis. The human ht29 colon adenocarcinoma cell line was obtained from the american type culture collection atcc and maintained in mccoys 5a media supplemented with. Drug database for cell line experiments with before vs. Modeled after common scientific and business applications, hcs studio cell analysis software packages our cellbased quantitative analysis software into a simple, easily navigated user interface. Integrated pancancer gene expression and drug sensitivity. Cancer cell line drug sensitivity data are generated from ongoing. In summary, the heterogeneity of pancancer cell lines and structurally diverse drugs in largescale pharmacogenomic databases makes the. Jun 30, 2006 of particular relevance was the use of dna arraybased methodology by the national cancer institute nci to assess the gene expression profiles of 60 human cancer cell lines of diverse tissue origin nci60 set, with a view to determining associations with the extensive drug sensitivity data accumulated on this cell line cohort so far. In this study, we tested the hypothesis that yb1 also confers oxaliplatin resistance in colorectal adenocarcinomas.
The genomics of drug sensitivity in cancer gdsc is the largest cancer cell line ccl panel available to date. Networkbased clustering for drug sensitivity prediction in. As part of our continuing efforts to characterize and authenticate the cell lines in the cell biology collection, atcc has developed a comprehensive. Users of hcs studio cell analysis software start with more than 30 preestablished assays figure 1 that can be optimized to cell line and particular phenotype. However, the available annotations of cell lines are sparse, incomplete, and distributed in multiple. Components of the cell death machine and drug sensitivity of. To view a cell lines information, search for it from the front page.
To address these issues, we developed pharmacodb, a webapplication assembling the largest in vitro drug screens in a single database, and allowing users. Jul, 2018 the cancer cell line encyclopedia ccle barretina et al. Since several mechanisms of resistance to platinumbased compounds have been described 44, a final explanation cannot be provided without the execution of further studies. Using a pharmacogenomics database of 1,001 cancer cell lines, we trained deep neural networks for prediction of drug response and assessed their performance on multiple clinical cohorts. At this moment, the nci60 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. Cancerdr is a database of 148 anticancer drugs and their effectiveness against around cancer cell lines. Drug sensitivity prediction by cpg island methylation profile. For each of the three tested drugs, we trained seven different models by. Data are represented by rectangles and processes by ovals. Apr 29, 20 we assessed the ability of phosphoproteomics data in predicting the drug sensitivity profiles of our panel of cell lines against the three tested inhibitors through a leaveone cell line out loclo approach based on lasso regression, detailed in the methods section. On this website, you will find drug response data and genomic markers of sensitivity. Cancer cell line drug sensitivity data are generated from ongoing highthroughput screening performed by the cancer genome project at the wellcome trust. This is an increase of 70% compared to previous releases. Human lung adenocarcinoma cell cultures derived from.
The cancer cell line encyclopedia enables predictive modeling. Data and scientific tools from many of our cancer research projects can now be accessed via broad data, software and tools. News cancerrxgene genomics of drug sensitivity in cancer. Pharmacological profiling of these anticancer drugs were collected from ccle and cosmic. Similarly, we investigated whether intended drug targets are expressed in the corresponding cell lines and, if so, whether the drug is active in this cell line, exploiting proteomics data of nci60. Current pharmacogenomic databases focus on cataloguing and.
Sensitivity reference is the lowest ic 50 value reported for particular drug or cell line. Robust multiarray average rmanormalized transcriptomic data and drug sensitivity data area under the curve auc and ic 50 were downloaded for a 860 cancer cell lines and 481 drugs from the cancer therapeutics response portal ctrp, b 1,065 cancer cell lines and 266 drugs from the genomics of drug sensitivity in cancer gdsc database, and c 60 cancer cell. This dataset contains drug sensitivity data growthinhibition, gi for 265 drugs screened against 1001 cell lines derived from 29 tissues, together with basal transcriptional profiles of the cells among other omics data. Drug combination sensitivity scoring facilitates the. Please see below for a partial list of resources or refer to the list of cancerrelated data, software and tools. Researchers create recordsized, integrated cellular cancer database. The mutation data table displays a list of mutations specifics to the cell line or gene. The final cell line collection spans 36 cancer types. We focused on the model performance for predicting new drug combinations within the same cell line, as the set of drug combinations in the training data did not overlap with that in the test data. Cancer program scientific tools and resources broad institute.
Databases and web tools for cancer genomics study sciencedirect. The central heatmap shows the ccle features in the model continuous zscore for expression and copynumber, dark red for discrete mutation calls, across all cell lines xaxis. The sensitivity of cancer cells to anticancer drugs is a crucial factor for. Hepatocellular carcinomas hccs are heterogeneous aggressive tumors with low rates of response to treatment at advanced stages. Hcc cell lines consist of two groups according to their drug response profiles. Drug resistance is a common cause of treatment failure in cancer patients and encompasses a multitude of different mechanisms. A major challenge in cancer treatment is predicting clinical response to anticancer drugs on a personalized basis. Obtained results were visualized using java tree view software.
The cancer cell line encyclopedia ccle barretina et al. We therefore assembled all ccle genomic data types into a matrix wherein each feature was converted to a zscore across all lines supplementary methods. Data flow diagram showing our approach to predicting in vivo drug sensitivity. The databases of cancer cell line encyclopedia ccle 3 and. Expression levels were obtained for each of the lines using affymetrix u3 plus 2. Compounds selected for screening are anticancer therapeutics. Description, genomics of drug sensitivity in cancer is a database of gene expression, genotype, and drug sensitivity data for human cancer cell lines.
However, there is no characterization of circular rnas circrnas in a large. Patri, a genomics data integration tool for biomarker discovery. Hcs studio cell analysis software thermo fisher scientific us. Using this colorectal cancer cell line panel, we have shown a clear relationship between 5fluorouracil sensitivity and mismatch repair status in a subset of 77 cell lines using a relatively high. The aim of the present study was to identify drugs effective on multidrug resistant cells. Hcs studio cell analysis software thermo fisher scientific. Cancerdr coveres 116 drug targets correspond to these anticancer drugs and provide the comprehensive information about these targets such as their function, structure, and their gene. Driven by intuitive icons, you can simply choose the assay and magnification of the optimized protocol, confirm settings, and begin the scan.
How to define drugresistant or sensitive cell line when. The cell line drug sensitivity data were integrated with large genomic datasets in the cosmic database to identify molecular markers of cancer drug response. Datasets cell line numbers i the genomics of drug sensitivity in cancer project is a collaboration between the cancer genome project at the wellcome sanger institute uk and the center for molecular therapeutics, massachusetts general hospital cancer center usa. Measurement of drug resistance cisplatin sensitivity was determined in the parental sensitive. Fixed cell gr measures of 33 breast cell lines and pdx lines to 16 small molecule perturbagens from library plate ii. When examining drug sensitivities across a panel of cell lines, i am not sure that a fixedtime measure is appropriate e. If the ic50 is very low then the concentration or amount of drug needed to kill the cell line is also very low which means the cell line is more sensitive.
For example, a recent report describing the cancer cell line encyclopedia ccle. Analysis of liver cancer cell lines identifies agents with. Hcs studio cell analysis software hcs studio cell analysis software is the engine behind thermo scientific high content products. However, there is no characterization of circular rnas circrnas in a large number of cancer cell lines.
Such efforts should be greatly aided by robust preclinical. Recent data have shown that yb1 is also overexpress in colorectal cancer. They also compared the genomic similarities between the lines and. Cancer program scientific tools and resources broad. Cancer cell lines genomics of drug sensitivity in cancer. This means that drug sensitivity testing in cell lines can be used to figure out how a tumour is likely to respond to a drug.
Drug sensitivity in cancer cell lines is not tissuespecific. The cancer cell line encyclopedia provides public access to genomic data, analysis and visualization for about cell lines. Here, we apply four circrna identification algorithms to heuristically characterize the expression landscape of circrnas across human cancer cell lines from ccle polyaenriched. Yang w, soares j, greninger p, edelman ej, lightfoot h et al. Genomic correlates of drug sensitivity may be extracted by predictive models using machine learning techniques 6,10. Quantitative scoring of differential drug sensitivity for individually optimized anticancer therapies. Ic50 is expressed as a concentration so the higher the concentration of drug needed to kill the cell line the more resistant that cell line is. The systematic translation of cancer genomic data into knowledge of tumor biology and therapeutic avenues remains challenging. We screened a large panel of liver cancer cell lines lccls to identify agents that might be effective against hcc and markers of therapeutic response.
Furthermore, by clicking on circles within scatter plots, cell line ic 50 values are directly linked to the cosmic database facilitating integration of drug sensitivity data with detailed cell line. We have characterised human cancer cell lines and screened them with 100s of compounds. 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. Cancer cell lines for drug discovery and development cancer. General hospitals genomics of drug sensitivity in cancer database. Robust multiarray average rmanormalized transcriptomic data and drug sensitivity data area under the curve auc and ic 50 were downloaded for a 860 cancer cell lines and 481. Data are gene expression profile of 917 human cancer cell lines. According to some studies, susceptibility of cells to anticancer druginduced apoptosis is markedly inhibited by targeted deletion of genes encoding apoptotic protease activating. Anticancer drug sensitivity prediction in cell lines from. Lung cancer is the leading cause of cancer related deaths and malignant pleural effusion mpe is a frequent complication. All cell lines were grown in rpmi or dmemf12 medium. You may have been redirected here from the broad cancer program resource. Is there any software to create a database of cell lines. As part of our continuing efforts to characterize and authenticate the cell lines in the cell biology collection, atcc has developed a comprehensive database of short tandem repeat.
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