Two large scale pharmacogenomic studies were published recently in this journal. Two largescale pharmacogenomic studies were published recently in. Inconsistency in large pharmacogenomic studies nature. Background in 2012, two large pharmacogenomic studies, the genomics of drug sensitivity in. Abstract sulfonylureas, a commonlyused class of medication used to treat type 2 diabetes, have been. Recent cancer pharmacogenomic studies profiled large panels of cell lines against hundreds of approved drugs and experimental chemical compounds. Logistics of integrating pharmacogenomic test results into the electronic health record 34,35,37,38,44,45 logistics of incorporating pharmacogenomic testing into the clinical work.
Revisiting inconsistency in large pharmacogenomic studies. Background in 2012, two large pharmacogenomic studies, the genomics of drug sensitivity in cancer gdsc and cancer cell line encyclopedia ccle, were published, each reported gene expression data and measure of drug response for a large number of drugs and hundreds of cell lines. Results from two largescale pharmacogenomic studies, the cancer genome project cgp and the. Genebased medicine will help create more effective treatments for large patient subpopulations and is currently being used in practice to treat individual patients. B haibekains, n elhachem, nj birkbak, ac jin, ah beck, hjwl aerts. Inconsistency in large pharmacogenomic studies abstract. Although the source of inconsistencies in drug response measures between these two wellcontrolled studies.
We received extensive feedback on the comparisons that we performed. In 20, we published a comparative analysis that reported gene expression profiles for the 471 cell lines. Cancer cell line studies have long been used to test efficacy of therapeutic agents and to explore genomic factors predictive of response. Cellline selectivity improves the predictive power of. Abstract two large scale pharmacogenomic studies were published recently in this journal.
This feedback, along with the release of new data, prompted us to revisit our initial analysis. This file shows a summary of the results reported with the supplementary data of cgp and ccle for the 15 compounds assessed by haibekains et al. Genome project cgp6 and the cancer cell line encyclopedia ccle7. Inconsistency in large pharmacogenomic studies genomic data are well correlated between studies. Revisiting inconsistency in large pharmacogenomic studies version 3.
We automated the analysis pipeline so that minimal manual interaction is required to reproduce our results. Pharmacogenomics is the study of how genes affect a persons response to drugs. Although the source of inconsistencies in drug response measures between these two. Integrating pharmacogenomics into pharmacy practice via. Cancer cell line encyclopedia consortium, genomics of drug sensitivity in cancer consortium. Evaluating the consistency of largescale pharmacogenomic. Revisiting inconsistency in large pharmacogenomic studies article pdf available in f research 5. Although the source of inconsistencies remains uncertain, it has potential implications for using these outcome measures to assess genedrug associations or select potential. Discordancy partitioning for validating potentially. Revisiting inconsistency in large pharmacogenomic studies biorxiv. Aerts and john quackenbush no static citation data no static citation data cite. Although the source of inconsistencies remains uncertain, it has potential implications for using.
In this chapter, we look at pharmacogenomic data on antitb drugs from different settings to provide better insight into the role of pharmacogenomics in the treatment of tb, thereby enhancing efficacy and. In my pdf there is something like ia squiggle after in some large fraction. Two largescale pharmacogenomic studies were published recently in this journal. Assessment of modelling strategies for drug response. Cancer cell line studies have long been used to test efficacy of therapeutic agents and to explore genomic factors predictive of response 1,2. Our comparative study triggered intense discussions in the field and we received extensive feedback on our analyses and results from the community. Pharmacogenomic investigations require an increased use of methods designed to study many genes or gene patterns, that is to look simultaneously at the structure and expression of. To seek cancer biomarkers that predict sensitivity to therapeutic agents, large pharmacogenomic studies have been performed. Pharmacokinetics, pharmacodynamics, and pharmacogenomics. The nci60 human tumor cell line anticancer drug screen the nci60 project started in the late 1980s, and is the. Results from two largescale pharmacogenomic studiesthe cancer. Handbook of pharmacogenomics and stratified medicine. Pharmacogenomic agreement between two cancer cell line data sets.
The success of this study illustrates several important points in the study design of pharmacogenomic gwas. In 2012, two large pharmacogenomic studies, the genomics of drug sensitivity in cancer gdsc and cancer cell line encyclopedia ccle, were published, each reported gene expression data and measures of drug response for a large number of drugs and hundreds of cell lines. Controversy in pharmacogenomics harvard university. The opportunity to study validation of models arose with the generation of two major pharmacogenomic datasets the genome drug sensitivity in cancer gdsc project 1,2. Genomewide association studies in pharmacogenomics. Request pdf inconsistency in large pharmacogenomic studies two large scale pharmacogenomic studies were published recently in this journal. Data sharing and research reproducibility in pharmacogenomics benjamin haibekains. Before initiating abacavir antiretroviral therapy, his physician orders genetic testing to determine whether he carries the hlab5701 allele, knowing that js would develop fever, rash. This file shows a summary of the results reported with the supplementary data of cgp and ccle for. Addressing the inconsistency of pharmacogenomic datasets. Two largescale pharmacogenomic studies were published recently 3,4. Pubmed abstract publisher full text free full text. This relatively new field combines pharmacology the science of drugs and genomics the study of genes and their functions to develop effective, safe medications and doses that will be tailored to a persons genetic makeup. Inconsistency in large pharmacogenomic studies github.
Inconsistency in large pharmacogenomic studies by benjamin haibekains, nehme elhachem, nicolai juul birkbak, andrew c. Genomic medicine, which uses dna variation to individualise and improve human health, is the subject of this series of papers. Pharmacogenomic studies of drugs used in the treatment of tb can promote understanding of intersubject variations in treatment response. Revisiting inconsistency in large pharmacogenomic studies read the latest article version by zhaleh safikhani, petr smirnov, mark freeman, nehme elhachem, adrian she, quevedo rene, anna goldenberg, nicolai j. In 20, we published a comparative analysis that reported gene expression profiles for the 471. The curated and structured aspects of our package make it easy to compare large scale pharmacogenomic studies. While we found good concordance in gene expression profiles, there was substantial inconsistency in the drug responses reported by the gdsc and ccle projects. In 20 we reported inconsistency in the drug sensitivity phenotypes measured by the. First, large collaborative samples can provide a valuable resource for collecting a critical mass of subjects with a rare phenotype. Pdf revisiting inconsistency in large pharmacogenomic. This feedback, along with the release of new data, prompted us to revisit our initial analysis, which we made available on biorxiv figure 1c. Genomic heterogeneity in human cancers complicates genecentric personalized medicine. The nci60 human tumor cell line anticancer drug screen the nci60 project started in the late 1980s, and is the first kind of such efforts.
Inconsistency in large pharmacogenomic studies europe pmc. In 2012, two large pharmacogenomic studies, the genomics of drug sensitivity in cancer gdsc and cancer cell line encyclopedia ccle, were published, each reported gene expression. We sought to reproduce and extend our published comparison of gdsc and ccle studies haibekains et al. Genomic medicine 2 pharmacogenomics dan m roden, howard l mcleod, mary v relling, marc s williams, george a mensah, josh f peterson, sara l van driest genomic medicine, which uses dna variation to individualise and improve human health, is the subject of this series of papers. Consistency in large pharmacogenomic studies nature. The resulting datasets present a unique opportunity to characterize mechanisms associated with drug response, with 471 cell lines and 15. Largescale pharmacogenomic study of sulfonylureas and the. Pharmacokinetics, pharmacodynamics, and pharmacogenomics by simon w. The idea that genetic variation can be used to individualise drug therapythe topic addressed hereis often viewed as within reach for genomic medicine. Inconsistency in large pharmacogenomic studies core. Charge pharmacogenomics working group a full list of authors and affiliations appears at the end of the article. The overarching goal of these screens is to measure sensitivity of cell lines to chemical perturbations, correlate these measures to genomic features, and thereby develop novel predictors of drug. Code for revisiting inconsistency in large pharmacogenomic studies full reproducibility of the analysis results. We will describe how to fully reproduce the figures and tables reported in the main manuscript.
Pdf in 20, we published a comparative analysis of mutation and gene expression profiles and drug sensitivity measurements for 15 drugs characterized. Revisiting inconsistency in large pharmacogenomic studies ncbi. Case study js is a 35 yearold man who has recently been diagnosed as hiv positive. Find, read and cite all the research you need on researchgate. An r package for analysis of large pharmacogenomic datasets petrsmirnov1 zhalehsa. Pdf pharmacogenomics holds great promise for the development of biomarkers of drug response and the. Inconsistency in large pharmacogenomic studies ncbi nih. Towards pathwaycentric cancer therapies via pharmacogenomic profiling analysis of erk signalling pathway haiyun wang 1, xiaoqi zheng2, teng fei 3,4, jinzeng wang 1, xujuan li1, yin liu 1 and fan zhang5 abstract background. Second, rare phenotypes are sampled from the extreme tail of drug response distributions. For showing inconsistency of ccle and gdsc data sets, key factors like aspects or, methods or, sources discussed by different papers have been summarized here.
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