The Experts below are selected from a list of 32427 Experts worldwide ranked by ideXlab platform
Eileen M Dolan - One of the best experts on this subject based on the ideXlab platform.
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Lymphoblastoid Cell lines in pharmacogenomic discovery and clinical translation
Pharmacogenomics, 2012Co-Authors: Heather E Wheeler, Eileen M DolanAbstract:The ability to predict how an individual patient will respond to a particular treatment is the ambitious goal of personalized medicine. The genetic make up of an individual has been shown to play a role in drug response. For pharmacogenomic studies, human Lymphoblastoid Cell lines (LCLs) comprise a useful model system for identifying genetic variants associated with pharmacologic phenotypes. The availability of extensive genotype data for many panels of LCLs derived from individuals of diverse ancestry allows for the study of genetic variants contributing to interethnic and interindividual variation in susceptibility to drugs. Many genome-wide association studies for drug-induced phenotypes have been performed in LCLs, often incorporating gene-expression data. LCLs are also being used in follow-up studies to clinical findings to determine how an associated variant functions to affect phenotype. This review describes the most recent pharmacogenomic findings made in LCLs, including the translation of some findings to clinical cohorts.
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gender specific differences in expression in human Lymphoblastoid Cell lines
Pharmacogenetics and Genomics, 2007Co-Authors: Wei Zhang, Wasim K Bleibel, Cheryl Roe, Nancy J Cox, Eileen M DolanAbstract:Women and men have different risks for certain diseases and they often respond differently to treatment. These differences could be due to the sex-specific differences in the expression of genes related to primary disease susceptibility or pharmacodynamic targets. To evaluate the sex-specific pattern of gene expression, we compared gene expression levels using a publicly available microarray dataset of 233 (115 women and 118 men) Lymphoblastoid Cell lines. From the 4799 probes meeting a specified minimal level of expression, 10 genes (P<0.005, permutation adjusted false discovery rate less than 50%) located on autosomal chromosomes were identified using a permutation-based approach. These genes were found to be over-represented in certain gene ontology terms of biological process (Cell adhesion, apoptosis, transcription and signal transduction), and molecular function (structural molecule activity, zinc ion binding, transcription factor activity and protein binding). A Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that two known pathways are over-represented: adherens junction and cytokine-cytokine receptor interaction.
Makoto Goto - One of the best experts on this subject based on the ideXlab platform.
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abnormal telomere dynamics of b Lymphoblastoid Cell strains from werner s syndrome patients transformed by epstein barr virus
Oncogene, 1997Co-Authors: Hidetoshi Tahara, Yoshiki Tokutake, Shizuko Maeda, Hiroshi Kataoka, Taro Watanabe, Misako Satoh, Takehisa Matsumoto, Minoru Sugawara, Toshinori Ide, Makoto GotoAbstract:Abnormal telomere dynamics of B-Lymphoblastoid Cell strains from Werner's syndrome patients transformed by Epstein – Barr virus
James J Cai - One of the best experts on this subject based on the ideXlab platform.
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single Cell rna sequencing of a european and an african Lymphoblastoid Cell line
Scientific Data, 2019Co-Authors: Daniel Osorio, Erchin Serpedin, James J CaiAbstract:In biomedical research, Lymphoblastoid Cell lines (LCLs), often established by in vitro infection of resting B Cells with Epstein-Barr virus, are commonly used as surrogates for peripheral blood lymphocytes. Genomic and transcriptomic information on LCLs has been used to study the impact of genetic variation on gene expression in humans. Here we present single-Cell RNA sequencing (scRNA-seq) data on GM12878 and GM18502-two LCLs derived from the blood of female donors of European and African ancestry, respectively. Cells from three samples (the two LCLs and a 1:1 mixture of the two) were prepared separately using a 10x Genomics Chromium Controller and deeply sequenced. The final dataset contained 7,045 Cells from GM12878, 5,189 from GM18502, and 5,820 from the mixture, offering valuable information on single-Cell gene expression in highly homogenous Cell populations. This dataset is a suitable reference for population differentiation in gene expression at the single-Cell level. Data from the mixture provide additional valuable information facilitating the development of statistical methods for data normalization and batch effect correction.
Alison A Motsingerreif - One of the best experts on this subject based on the ideXlab platform.
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synergistic chemotherapy drug response is a genetic trait in Lymphoblastoid Cell lines
Frontiers in Genetics, 2019Co-Authors: Kyle R Roell, Tammy M Havener, David M Reif, John Jack, Howard L Mcleod, Tim Wiltshire, Alison A MotsingerreifAbstract:Lymphoblastoid Cell lines (LCL) are a highly successful model for evaluating the genetic etiology of cancer drug response, but applications using this model have typically focused on single drugs. Combination therapy is quite common in modern chemotherapy treatment since drugs often work synergistically, and it is an important progression in the use of the LCL model to expand work for drug combinations. In the present work, we demonstrate that synergy occurs and can be quantified in LCLs across a range of clinically important drug combinations. LCLs have been commonly employed in association mapping in cancer pharmacogenomics, but it is so far untested as to whether synergistic effects have a genetic etiology. Here we use Cell lines from extended pedigrees to demonstrate that there is a substantial heritable component to synergistic drug response. Additionally, we perform linkage mapping in these pedigrees to identify putative regions linked to this important phenotype. This demonstration supports the premise of expanding the use of LCL model to perform association mapping for combination therapies.
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genome wide association and pharmacological profiling of 29 anticancer agents using Lymphoblastoid Cell lines
Pharmacogenomics, 2014Co-Authors: Chad Brown, Tammy M Havener, John Jack, Howard L Mcleod, Marisa W Medina, Ronald M Krauss, Alison A MotsingerreifAbstract:Aim: Association mapping with Lymphoblastoid Cell lines (LCLs) is a promising approach in pharmacogenomics research, and in the current study we utilized LCLs to perform association mapping for 29 chemotherapy drugs. Materials & methods: Currently, we use LCLs to perform genome-wide association mapping of the cytotoxic response of 520 European–Americans to 29 different anticancer drugs; the largest LCL study to date. A novel association approach using a multivariate analysis of covariance design was employed with the software program MAGWAS, testing for differences in the dose–response profiles between genotypes without making assumptions about the response curve or the biologic mode of association. Additionally, by classifying 25 of the 29 drugs into eight families according to structural and mechanistic relationships, MAGWAS was used to test for associations that were shared across each drug family. Finally, a unique algorithm using multivariate responses and multiple linear regressions across pairs of ...
David Gurwitz - One of the best experts on this subject based on the ideXlab platform.
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human Lymphoblastoid Cell line panels novel tools for assessing shared drug pathways
Pharmacogenomics, 2010Co-Authors: Ayelet Morag, Julia Kirchheiner, Moshe Rehavi, David GurwitzAbstract:Aims: While powerful in silico tools are emerging for predicting drug targets and pathways, general in vitro tools for assessing such predictions are lacking. We present a novel in vitro method for distinguishing shared versus distinct drug pathways based on comparative Cell growth inhibition profiles across a small panel of human Lymphoblastoid Cell lines (LCLs) from individual donors. Materials & methods: LCLs from unrelated healthy donors were examined in parallel for growth inhibition profiles of various drugs, including antidepressants (paroxetine, fluoxetine, fluvoxamine, citalopram, amitriptyline and imipramine); anticancer drugs (5-fluorouracil, 6-mercaptopurine, azathioprine, methotrexate and resveratrol); steroid drugs (dexamethasone, beclomethasone and prednisolone); and antipsychotic drugs (haloperidol and clozapine). Cell growth was assessed by the colorimetric 2,3-bis(2-methoxy-4-nitro-5-sulfophenly)-5[(phenylamino) carbonyl]-2H-tetrazolium hydroxide method following 72 h of drug exposure. Results: LCLs from unrelated individuals exhibited a wide range of sensitivities to growth inhibition by a given drug, which were independent of basal Cell replication rates. Yet, each individual Cell line demonstrated a consistent sensitivity to multiple drugs from the same family. High goodness-of-fit values (R 2 > 0.6) were consistently observed for plots comparing the growth-inhibition profiles for paired drugs sharing a similar pathway, for example antidepressants, steroid drugs, antipsychotics, or 6-mercaptopurine compared with azathioprine, but not for drugs with different pathways. The method’s utility is demonstrated by the observation that chlorpheniramine, an antihistamine drug long suspected to also possess antidepressantlike properties, exhibits a growth-inhibition profile very similar to antidepressants. Conclusion: Comparing the growth-inhibition profiles of drugs (or compounds) of interest with the profiles of drugs with known pathways may assist in drug pathway classification. The method is useful for in vitro assessment of in silicogenerated drug pathway predictions and for distinguishing shared versus distinct pathways for compounds of interest. Comparative transcriptomics ana lysis of human Lymphoblastoid Cell lines exhibiting ‘edge’ sensitivities can subsequently be utilized in the search for drug response biomarkers for personalized pharmacotherapy. The limitations and advantages of the method are discussed.
