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Pharmacogenomics databases

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https://www.readbyqxmd.com/read/29337087/genetic-polymorphisms-of-pharmacogenomic-vip-variants-in-the-yi-population-from-china
#1
Mengdan Yan, Dianzhen Li, Guige Zhao, Jing Li, Fanglin Niu, Bin Li, Peng Chen, Tianbo Jin
INTRODUCTION: Drug response and target therapeutic dosage are different among individuals. The variability is largely genetically determined. With the development of pharmacogenetics and pharmacogenomics, widespread research have provided us a wealth of information on drug-related genetic polymorphisms, and the very important pharmacogenetic (VIP) variants have been identified for the major populations around the world whereas less is known regarding minorities in China, including the Yi ethnic group...
January 11, 2018: Gene
https://www.readbyqxmd.com/read/29315502/a-genome-wide-association-study-identifies-a-candidate-gene-associated-with-atazanavir-exposure-measured-in-hair
#2
Bani Tamraz, Yong Huang, Audrey L French, Seble Kassaye, Kathryn Anastos, Marek J Nowicki, Stephen Gange, Deborah R Gustafson, Peter Bacchetti, Ruth M Greenblatt, Pirro G Hysi, Bradley E Aouizerat
Hair provides a direct measure of long-term exposure of atazanavir (ATV). We report the results of the first genome-wide association study (GWAS) of ATV exposure measured in hair in an observational cohort representative of U.S. women living with HIV; the Women's Interagency HIV Study. Approximately 14.1 million SNPs were analyzed in linear regression-based GWAS, with replication, adjusted for non-genetic predictors collected under conditions of actual use of ATV in 398 participants. Lastly, the PharmGKB database was used to identify pharmacogene associations with ATV exposure...
January 9, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29197117/addition-of-allopurinol-for-altering-thiopurine-metabolism-to-optimize-therapy-in-patients-with-inflammatory-bowel-disease
#3
Geoffrey C Wall, Hamid Muktar, Cassandra Effken, Pramod B Mahajan
Thiopurine drugs, including azathioprine and 6-mercaptopurine, are used commonly in patients with inflammatory bowel disease for maintenance of remission. Although generally well tolerated, adverse effects lead to discontinuation in a significant minority of patients. Pharmacogenomic studies have suggested that metabolic breakdown of azathioprine in an individual is genetically determined. Coupled with the fact that certain thiopurine metabolites, notably 6-thioguanine nucleotide and 6-methylmercaptopurine, are associated with antiinflammatory effects and adverse effects, respectively, some investigators have examined intentionally shunting the metabolism of azathioprine toward increasing 6-thioguanine nucleotide levels by using low doses of the xanthine oxidoreductase inhibitor allopurinol to improve efficacy and decrease toxicity of azathioprine in patients with inflammatory bowel disease...
December 1, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29186349/gdsctools-for-mining-pharmacogenomic-interactions-in-cancer
#4
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/29099060/clinical-pharmacogenetics-of-cytochrome-p450-associated-drugs-in-children
#5
Ida Aka, Christiana J Bernal, Robert Carroll, Angela Maxwell-Horn, Kazeem A Oshikoya, Sara L Van Driest
Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug-CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs...
November 2, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/28963061/simplifying-the-use-of-pharmacogenomics-in-clinical-practice-building-the-genomic-prescribing-system
#6
Keith Danahey, Brittany A Borden, Brian Furner, Patrick Yukman, Sheena Hussain, Donald Saner, Samuel L Volchenboum, Mark J Ratain, Peter H O'Donnell
BACKGROUND: A barrier to the use of genomic information during prescribing is the limited number of software solutions that combine a user-friendly interface with complex medical data. We built and designed an online, secure, electronic custom interface termed the Genomic Prescribing System (GPS). METHODS: Actionable pharmacogenomic (PGx) information was reviewed, collected, and stored in the back-end of GPS to enable creation of customized drug- and variant-specific clinical decision support (CDS) summaries...
September 26, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28961771/cloud-based-interactive-analytics-for-terabytes-of-genomic-variants-data
#7
Cuiping Pan, Gregory McInnes, Nicole Deflaux, Michael Snyder, Jonathan Bingham, Somalee Datta, Philip S Tsao
Motivation: Large scale genomic sequencing is now widely used to decipher questions in diverse realms such as biological function, human diseases, evolution, ecosystems, and agriculture. With the quantity and diversity these data harbor, a robust and scalable data handling and analysis solution is desired. Results: We present interactive analytics using a cloud-based columnar database built on Dremel to perform information compression, comprehensive quality controls, and biological information retrieval in large volumes of genomic data...
July 26, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28900181/heterogeneity-aware-random-forest-for-drug-sensitivity-prediction
#8
Raziur Rahman, Kevin Matlock, Souparno Ghosh, Ranadip Pal
Samples collected in pharmacogenomics databases typically belong to various cancer types. For designing a drug sensitivity predictive model from such a database, a natural question arises whether a model trained on diverse inter-tumor heterogeneous samples will perform similar to a predictive model that takes into consideration the heterogeneity of the samples in model training and prediction. We explore this hypothesis and observe that ensemble model predictions obtained when cancer type is known out-perform predictions when that information is withheld even when the samples sizes for the former is considerably lower than the combined sample size...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28884473/pharmacotherapy-for-smoking-cessation-effects-by-subgroup-defined-by-genetically-informed-biomarkers
#9
REVIEW
Ewoud Schuit, Orestis A Panagiotou, Marcus R Munafò, Derrick A Bennett, Andrew W Bergen, Sean P David
BACKGROUND: Smoking cessation therapies are not effective for all smokers, and researchers are interested in identifying those subgroups of individuals (e.g. based on genotype) who respond best to specific treatments. OBJECTIVES: To assess whether quit rates vary by genetically informed biomarkers within pharmacotherapy treatment arms and as compared with placebo. To assess the effects of pharmacotherapies for smoking cessation in subgroups of smokers defined by genotype for identified genome-wide significant polymorphisms...
September 8, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28871186/analysis-of-population-specific-pharmacogenomic-variants-using-next-generation-sequencing-data
#10
Eunyong Ahn, Taesung Park
Functional rare variants in drug-related genes are believed to be highly differentiated between ethnic- or racial populations. However, knowledge of population differentiation (PD) of rare single-nucleotide variants (SNVs), remains widely lacking, with the highest fixation indices, (Fst values), from both rare and common variants annotated to specific genes, having only been marginally used to understand PD at the gene level. In this study, we suggest a new, gene-based PD method, PD of Rare and Common variants (PDRC), for analyzing rare variants, as inspired by Generalized Cochran-Mantel-Haenszel (GCMH) statistics, to identify highly population-differentiated drug response-related genes ("pharmacogenes")...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28816643/pharmacometabolomics-informs-quantitative-radiomics-for-glioblastoma-diagnostic-innovation
#11
Theodora Katsila, Minos-Timotheos Matsoukas, George P Patrinos, Dimitrios Kardamakis
Applications of omics systems biology technologies have enormous promise for radiology and diagnostics in surgical fields. In this context, the emerging fields of radiomics (a systems scale approach to radiology using a host of technologies, including omics) and pharmacometabolomics (use of metabolomics for patient and disease stratification and guiding precision medicine) offer much synergy for diagnostic innovation in surgery, particularly in neurosurgery. This synthesis of omics fields and applications is timely because diagnostic accuracy in central nervous system tumors still challenges decision-making...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28748348/impact-of-genetic-polymorphisms-on-phenytoin-pharmacokinetics-and-clinical-outcomes-in-the-middle-east-and-north-africa-region
#12
REVIEW
Renée Dagenais, Kyle John Wilby, Hazem Elewa, Mary H H Ensom
BACKGROUND: Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood. OBJECTIVES: The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed...
September 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28704821/application-of-the-drugevar-database-in-cancer-genomics-and-pharmacogenomics
#13
Konstantinos Sarris, Angeliki Komianou, George P Patrinos, Theodora Katsila
In the post-genomic era, there is an increasing and urgent need for managing and visualizing big data. Data complexity and size will turn information growth into knowledge growth only if presented in a comprehensive and user-friendly way. In such a context, the information technology community collaborates in a multidisciplinary manner with other scientific fields searching for and/or developing tools and services for data management and visualization. We have previously developed DruGeVar, a comprehensive database that triangulates drugs with genes and pharmacogenomic biomarkers to serve clinical pharmacogenomics...
2017: Public Health Genomics
https://www.readbyqxmd.com/read/28686320/the-emerging-science-of-precision-medicine-and-pharmacogenomics-for-parkinson-s-disease
#14
Haydeh Payami
Current therapies for Parkinson's disease are problematic because they are symptomatic and have adverse effects. New drugs have failed in clinical trials because of inadequate efficacy. At the core of the problem is trying to make one drug work for all Parkinson's disease patients, when we know this premise is wrong because (1) Parkinson's disease is not a single disease, and (2) no two individuals have the same biological makeup. Precision medicine is the goal to strive for, but we are only at the beginning stages of building the infrastructure for one of the most complex projects in the history of science, and it will be a long time before Parkinson's disease reaps the benefits...
August 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28616427/specific-genes-associated-with-adverse-events-of-methylphenidate-use-in-the-pediatric-population-a-systematic-literature-review
#15
REVIEW
Beinta Joensen, Morten Meyer, Lise Aagaard
The aim of this study was to review empirical studies examining associations between candidate genes and adverse events (AEs) from methylphenidate (MPH) use in children and adolescents. The PubMed, EMBASE, CINAHL, and Web of Science databases were searched from their inception until March 2017. We included empirically based articles on pharmacogenetic studies in 0-17-year-old patients that investigated associations between specific candidate genes, their polymorphisms, and reported AEs. We extracted information about study design, setting, type of AE reporter, studied genes and their polymorphisms, age and gender, administered doses, method of genotyping, outcome measures, and main findings...
April 2017: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/28557243/the-use-of-electronic-health-records-for-psychiatric-phenotyping-and-genomics
#16
REVIEW
Jordan W Smoller
The widespread adoption of electronic health record (EHRs) in healthcare systems has created a vast and continuously growing resource of clinical data and provides new opportunities for population-based research. In particular, the linking of EHRs to biospecimens and genomic data in biobanks may help address what has become a rate-limiting study for genetic research: the need for large sample sizes. The principal roadblock to capitalizing on these resources is the need to establish the validity of phenotypes extracted from the EHR...
May 30, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28398356/snp-based-hla-allele-tagging-imputation-and-association-with-antiepileptic-drug-induced-cutaneous-reactions-in-hong-kong-han-chinese
#17
H Gui, M Kwok, L Baum, P C Sham, P Kwan, S S Cherny
Human leukocyte antigen (HLA) genes control the regulation of the human immune system and are involved in immune-related diseases. Population surveys on relationships between single nucleotide polymorphisms (SNP) and HLA alleles are essential to conduct genetic association between HLA variants and diseases. Samples were obtained from our in-house database for epilepsy genetics and pharmacogenetics research. Using 184 epilepsy patients with both genome-wide SNP array and HLA-A/B candidate gene sequencing data, we sought tagging SNPs that completely represent sixHLA risk alleles; in addition, a Hong Kong population-specific reference panel was constructed for SNP-based HLA imputation...
April 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28350803/pharmacogenomic-identification-of-small-molecules-for-lineage-specific-manipulation-of-subventricular-zone-germinal-activity
#18
Kasum Azim, Diane Angonin, Guillaume Marcy, Francesca Pieropan, Andrea Rivera, Vanessa Donega, Claudio Cantù, Gareth Williams, Benedikt Berninger, Arthur M Butt, Olivier Raineteau
Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ) is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performed a bioinformatics analysis of the transcriptome of dorsal and lateral SVZ in early postnatal mice, including neural stem cells (NSCs) and their immediate progenies, which generate distinct neural lineages...
March 2017: PLoS Biology
https://www.readbyqxmd.com/read/28339912/pharmacogenomics-and-patient-treatment-parameters-to-opioid-treatment-in-chronic-pain-a-focus-on-morphine-oxycodone-tramadol-and-fentanyl
#19
Renae A Lloyd, Elizabeth Hotham, Catherine Hall, Marie Williams, Vijayaprakash Suppiah
Objective. : Opioids are one of the most commonly prescribed medicines for chronic pain. However, their use for chronic pain has been controversial. The objective of this literature review was to identify the role of genetic polymorphisms on patient treatment parameters (opioid dose requirements, response, and adverse effects) for opioids used in malignant and nonmalignant chronic pain. The opioids that this review focuses on are codeine, morphine, oxycodone, tramadol, and fentanyl...
February 24, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28327186/clinical-behavioural-and-pharmacogenomic-factors-influencing-the-response-to-levothyroxine-therapy-in-patients-with-primary-hypothyroidism-protocol-for-a-systematic-review
#20
Rosie Dew, Onyebuchi Okosieme, Colin Dayan, Vinay Eligar, Ishrat Khan, Salman Razvi, Simon Pearce, Scott Wilkes
BACKGROUND: Suboptimal thyroid hormone therapy including under-replacement and over-replacement is common amongst patients with hypothyroidism. This is a significant health concern as affected patients are at risk of adverse cardiovascular or metabolic consequences. Despite a growing body of evidence on the effects of various factors on thyroid hormone replacement, a systematic appraisal of the evidence is lacking. This review aims to appraise and quantify the extent to which clinical, behavioural and pharmacogenomic factors affect levothyroxine therapy in patients with primary hypothyroidism...
March 21, 2017: Systematic Reviews
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