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Pharmacogenomic data

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https://www.readbyqxmd.com/read/29331453/are-privacy-enhancing-technologies-for-genomic-data-ready-for-the-clinic-a-survey-of-medical-experts-of-the-swiss-hiv-cohort-study
#1
Jean-Louis Raisaro, Paul J McLaren, Jacques Fellay, Matthias Cavassini, Catherine Klersy, Jean-Pierre Hubaux
PURPOSE: Protecting patient privacy is a major obstacle for the implementation of genomic-based medicine. Emerging privacy-enhancing technologies can become key enablers for managing sensitive genetic data. We studied physicians' attitude toward this kind of technology in order to derive insights that might foster their future adoption for clinical care. METHODS: We conducted a questionnaire-based survey among 55 physicians of the Swiss HIV Cohort Study who tested the first implementation of a privacy-preserving model for delivering genomic test results...
January 10, 2018: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/29300844/link-synthetic-lethality-to-drug-sensitivity-of-cancer-cells
#2
Ruiping Wang, Yue Han, Zhangxiang Zhao, Fan Yang, Tingting Chen, Wenbin Zhou, Xianlong Wang, Lishuang Qi, Wenyuan Zhao, Zheng Guo, Yunyan Gu
Synthetic lethal (SL) interactions occur when alterations in two genes lead to cell death but alteration in only one of them is not lethal. SL interactions provide a new strategy for molecular-targeted cancer therapy. Currently, there are few drugs targeting SL interactions that entered into clinical trials. Therefore, it is necessary to investigate the link between SL interactions and drug sensitivity of cancer cells systematically for drug development purpose. We identified SL interactions by integrating the high-throughput data from The Cancer Genome Atlas, small hairpin RNA data and genetic interactions of yeast...
December 28, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29283070/pharmacogenomics-of-methotrexate-current-status-and-future-outlook
#3
Mengda Cao, Miao Guo, De-Qin Wu, Ling Meng
BACKGROUND: Methotrexate (MTX) is a folate analogue with high therapeutic efficiency in the treatment of cancers and autoimmune diseases. The efficacy and toxicity of MTX may be altered by genetic polymorphisms in genes involved in MTX metabolic pathway. Personalized pharmacotherapy based on gene polymorphisms enables a more efficient, compatible and cost-effective treatment of patients. OBJECTIVE: Present article aims to review genetic polymorphisms associated with MTX pharmacokinetics, toxicity, and outcome, and try to point out future development directions of individualized MTX therapy...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29249361/pharmacogenomics-of-gpcr-drug-targets
#4
Alexander S Hauser, Sreenivas Chavali, Ikuo Masuho, Leonie J Jahn, Kirill A Martemyanov, David E Gloriam, M Madan Babu
Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug- and effector-binding sites in the human population...
December 8, 2017: Cell
https://www.readbyqxmd.com/read/29243231/gaining-mechanistic-insight-into-coproporphyrin-i-as-endogenous-biomarker-for-oatp1b-mediated-drug-drug-interactions-using-population-pharmacokinetic-modelling-and-simulation
#5
Shelby Barnett, Kayode Ogungbenro, Karelle Ménochet, Hong Shen, Yurong Lai, W Griffith Humphreys, Aleksandra Galetin
This study evaluates coproporphyrin I (CPI) as a selective endogenous biomarker of OATP1B-mediated drug-drug interactions (DDIs) relative to clinical probe rosuvastatin using nonlinear mixed-effect modelling. Plasma and urine CPI data in the presence/absence of rifampicin were modelled to describe CPI synthesis, elimination clearances and obtain rifampicin in vivo OATP Ki. The biomarker showed stable inter-occasion baseline concentrations and low inter-individual variability (<25%) in subjects with wild type SLCO1B1...
December 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29229604/transcription-factor-activities-enhance-markers-of-drug-sensitivity-in-cancer
#6
Luz M Garcia-Alonso, Francesco Iorio, Angela Matchan, Nuno A Fonseca, Patricia Jaaks, Gareth Peat, Miguel Pignatelli, Fiammetta Falcone, Cyril H Benes, Ian Dunham, Graham R Bignell, Simon McDade, Mathew J Garnett, Julio Saez-Rodriguez
Transcriptional dysregulation induced by aberrant Transcription factors (TFs) is a key feature of cancer, but its global influence on drug sensitivity has not been examined. Here we infer the transcriptional activity of 127 TFs through analysis of RNA-seq gene expression data newly generated for 448 cancer cell lines, combined with publicly available datasets to survey a total of 1,056 cancer cell lines and 9,250 primary tumors. Predicted TF activities are supported by their agreement with independent shRNA essentiality profiles and homozygous gene deletions, and recapitulate mutant-specific mechanisms of transcriptional dysregulation in cancer...
December 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29228590/precision-and-recall-oncology-combining-multiple-gene-mutations-for-improved-identification-of-drug-sensitive-tumours
#7
Stefan Naulaerts, Cuong C Dang, Pedro J Ballester
Cancer drug therapies are only effective in a small proportion of patients. To make things worse, our ability to identify these responsive patients before administering a treatment is generally very limited. The recent arrival of large-scale pharmacogenomic data sets, which measure the sensitivity of molecularly profiled cancer cell lines to a panel of drugs, has boosted research on the discovery of drug sensitivity markers. However, no systematic comparison of widely-used single-gene markers with multi-gene machine-learning markers exploiting genomic data has been so far conducted...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218868/large-scale-integration-of-heterogeneous-pharmacogenomic-data-for-identifying-drug-mechanism-of-action
#8
Yunan Luo, Sheng Wang, Jinfeng Xiao, Jian Peng
A variety of large-scale pharmacogenomic data, such as perturbation experiments and sensitivity profiles, enable the systematical identification of drug mechanism of actions (MoAs), which is a crucial task in the era of precision medicine. However, integrating these complementary pharmacogenomic datasets is inherently challenging due to the wild heterogeneity, high-dimensionality and noisy nature of these datasets. In this work, we develop Mania, a novel method for the scalable integration of large-scale pharmacogenomic data...
2018: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/29199461/biomarkers-delivering-on-the-expectation-of-molecularly-driven-quantitative-health
#9
Jennifer L Wilson, Russ B Altman
Biomarkers are the pillars of precision medicine and are delivering on expectations of molecular, quantitative health. These features have made clinical decisions more precise and personalized, but require a high bar for validation. Biomarkers have improved health outcomes in a few areas such as cancer, pharmacogenetics, and safety. Burgeoning big data research infrastructure, the internet of things, and increased patient participation will accelerate discovery in the many areas that have not yet realized the full potential of biomarkers for precision health...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29197902/a-new-zealand-platform-to-enable-genetic-investigation-of-adverse-drug-reactions
#10
Simran Ds Maggo, Eng Wee Chua, Paul Chin, Simone Cree, John Pearson, Matthew Doogue, Martin A Kennedy
A multitude of factors can affect drug response in individuals. It is now well established that variations in genes, especially those coding for drug metabolising enzymes, can alter the pharmacokinetic and/or pharmacodynamic profile of a drug, impacting on efficacy and often resulting in drug-induced toxicity. The UDRUGS study is an initiative from the Carney Centre for Pharmacogenomics to biobank DNA and store associated clinical data from patients who have suffered rare and/or serious adverse drug reactions (ADRs)...
December 1, 2017: New Zealand Medical Journal
https://www.readbyqxmd.com/read/29186349/gdsctools-for-mining-pharmacogenomic-interactions-in-cancer
#11
Thomas Cokelaer, Elisabeth Chen, Francesco Iorio, Michael P Menden, Howard Lightfoot, Julio Saez-Rodriguez, Mathew J Garnett
Motivation: Large pharmacogenomic screenings integrate heterogeneous cancer genomic data sets as well as anti-cancer drug responses on thousand human cancer cell lines. Mining this data to identify new therapies for cancer sub-populations would benefit from common data structures, modular computational biology tools and user-friendly interfaces. Results: We have developed GDSCTools: a software aimed at the identification of clinically relevant genomic markers of drug response...
November 24, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29186305/systems-bioinformatics-increasing-precision-of-computational-diagnostics-and-therapeutics-through-network-based-approaches
#12
Anastasis Oulas, George Minadakis, Margarita Zachariou, Kleitos Sokratous, Marilena M Bourdakou, George M Spyrou
Systems Bioinformatics is a relatively new approach, which lies in the intersection of systems biology and classical bioinformatics. It focuses on integrating information across different levels using a bottom-up approach as in systems biology with a data-driven top-down approach as in bioinformatics. The advent of omics technologies has provided the stepping-stone for the emergence of Systems Bioinformatics. These technologies provide a spectrum of information ranging from genomics, transcriptomics and proteomics to epigenomics, pharmacogenomics, metagenomics and metabolomics...
November 27, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29171014/the-influence-of-big-clinical-data-and-genomics-on-precision-medicine-and-drug-development
#13
Joshua C Denny, Sara L Van Driest, Wei-Qi Wei, Dan M Roden
Drug development continues to be costly and slow, with medications failing due to lack of efficacy or presence of toxicity. The promise of pharmacogenomic discovery includes tailoring therapeutics based on an individual's genetic makeup, rational drug development, and repurposing medications. Rapid growth of large research cohorts, linked to electronic health record (EHR) data, fuels discovery of new genetic variants predicting drug action, supports Mendelian randomization experiments to show drug efficacy, and suggests new indications for existing medications...
November 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29167564/whole-transcriptome-sequencing-analyses-reveal-molecular-markers-of-blood-pressure-response-to-thiazide-diuretics
#14
Ana Caroline C Sá, Amy Webb, Yan Gong, Caitrin W McDonough, Somnath Datta, Taimour Y Langaee, Stephen T Turner, Amber L Beitelshees, Arlene B Chapman, Eric Boerwinkle, John G Gums, Steven E Scherer, Rhonda M Cooper-DeHoff, Wolfgang Sadee, Julie A Johnson
Thiazide diuretics (TD) are commonly prescribed anti-hypertensives worldwide. However, <40% of patients treated with thiazide monotherapy achieve BP control. This study uses whole transcriptome sequencing to identify novel molecular markers associated with BP response to TD. We assessed global RNA expression levels in whole blood samples from 150 participants, representing patients in the upper and lower quartile of BP response to TD from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) (50 whites) and from PEAR-2 (50 whites and 50 blacks)...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29163177/assessment-of-pharmacogenomic-panel-assay-for-prediction-of-taxane-toxicities-preliminary-results
#15
Raffaele Di Francia, Luigi Atripaldi, Salvo Di Martino, Carla Fierro, Tommaso Muto, Anna Crispo, Sabrina Rossetti, Gaetano Facchini, Massimiliano Berretta
Backbone: Paclitaxel and docetaxel are the primary taxane anticancer drugs regularly used to treat, breast, gastric, ovarian, head/neck, lung, and genitourinary neoplasm. Suspension of taxane treatments compromising patient benefits is more frequently caused by peripheral neuropathy and allergy, than to tumor progression. Several strategies for preventing toxicity have been investigated so far. Recently, findings on the genetic variants associated with toxicity and resistance to taxane-based chemotherapy have been reported...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29160303/the-pnpla3-i148m-variant-is-associated-with-transaminase-elevations-in-type-2-diabetes-patients-treated-with-basal-insulin-peglispro
#16
S Pillai, S Duvvuru, P Bhatnagar, W Foster, M Farmen, S Shankar, C Harris, E Bastyr, B Hoogwerf, A Haupt
Basal insulin peglispro (BIL) is a novel insulin with hepato-preferential action. In phase 3 trials, BIL showed significantly improved glycemic control but higher levels of transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), triglycerides (TGs) and liver fat content (LFC) compared with insulin glargine (GL). As variants in PNPLA3 (I148M) and TM6SF2 (E167K) are associated with nonalcoholic fatty liver disease, we assessed these variants in type 2 diabetes (T2D) patients randomized to receive BIL (n=1822) or GL (n=1270) in three phase 3 trials...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29160301/new-insights-into-the-pharmacogenomics-of-antidepressant-response-from-the-gendep-and-star-d-studies-rare-variant-analysis-and-high-density-imputation
#17
C Fabbri, K E Tansey, R H Perlis, J Hauser, N Henigsberg, W Maier, O Mors, A Placentino, M Rietschel, D Souery, G Breen, C Curtis, L Sang-Hyuk, S Newhouse, H Patel, M Guipponi, N Perroud, G Bondolfi, M O'Donovan, G Lewis, J M Biernacka, R M Weinshilboum, A Farmer, K J Aitchison, I Craig, P McGuffin, R Uher, C M Lewis
Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29160300/genome-wide-association-study-identifies-the-common-variants-in-cyp3a4-and-cyp3a5-responsible-for-variation-in-tacrolimus-trough-concentration-in-caucasian-kidney-transplant-recipients
#18
W S Oetting, B Wu, D P Schladt, W Guan, R P Remmel, R B Mannon, A J Matas, A K Israni, P A Jacobson
The immunosuppressant tacrolimus (TAC) is metabolized by both cytochrome P450 3A4 (CYP3A4) and CYP3A5 enzymes. It is common for European Americans (EA) to carry two CYP3A5 loss-of-function (LoF) variants that profoundly reduces TAC metabolism. Despite having two LoF alleles, there is still considerable variability in TAC troughs and identifying additional variants in genes outside of the CYP3A5 gene could provide insight into this variability. We analyzed TAC trough concentrations in 1345 adult EA recipients with two CYP3A5 LoF alleles in a genome-wide association study...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29141462/a-safety-review-of-medications-used-for-labour-induction
#19
Lili Sheibani, Deborah A Wing
Induction of labour is a commonly performed procedure around the world. There are various medications used for induction including those commonly used for cervical ripening (prostaglandins) and oxytocin. The ideal agent is one that decreases the time to achieving delivery without compromising maternal or neonatal safety. The 'optimal safe agent' remains undetermined. Areas covered: This article reviews the safety of currently used induction agents. Prostaglandins and oxytocin have proven to be effective in labour induction, and their profiles will be reviewed in this article...
November 15, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29123971/concepts-of-genomics-in-kidney-transplantation
#20
William S Oetting, Casey Dorr, Rory P Remmel, Arthur J Matas, Ajay K Israni, Pamala A Jacobson
Purpose of review: Identification of genetic variants to aid in individualized treatment of solid organ allograft recipients would improve graft survival. We will review the current state of knowledge for associations of variants with transplant outcomes. Recent findings: Many studies have yet to exhibit robust and reproducible results, however, pharmacogenomic studies focusing on cytochrome P450 (CYP) enzymes, transporters and HLA variants have shown strong associations with outcomes and have relevance towards drugs used in transplant...
June 2017: Current Transplantation Reports
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