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Pharmacogenomics databases

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https://www.readbyqxmd.com/read/28900181/heterogeneity-aware-random-forest-for-drug-sensitivity-prediction
#1
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
#2
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
#3
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
#4
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
#5
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...
July 26, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28704821/application-of-the-drugevar-database-in-cancer-genomics-and-pharmacogenomics
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28271979/toward-a-taxonomy-for-multi-omics-science-terminology-development-for-whole-genome-study-approaches-by-omics-technology-and-hierarchy
#14
Nina Pirih, Tanja Kunej
Omics is a form of high-throughput systems science. However, taxonomies for omics studies are limited, inviting us to rethink new ways in which we classify, prioritize, and rank various omics systems science studies. In this overarching context, the genome-wide study approaches have proliferated in number and popularity over the past decade. However, their hierarchy is not well organized and the development of attendant terminology is not controlled. In the present study, we searched the literature in PubMed and the Web of Science databases published from March 1999 to September 2016 using the keywords, including genome-wide, association, whole genome, transcriptome-wide, metabolome, epigenome, and phenome...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28271248/network-reconstruction-reveals-that-valproic-acid-activates-neurogenic-transcriptional-programs-in-adult-brain-following-traumatic-injury
#15
Gerald A Higgins, Patrick Georgoff, Vahagn Nikolian, Ari Allyn-Feuer, Brian Pauls, Richard Higgins, Brian D Athey, Hasan E Alam
OBJECTIVES: To determine the mechanism of action of valproic acid (VPA) in the adult central nervous system (CNS) following traumatic brain injury (TBI) and hemorrhagic shock (HS). METHODS: Data were analyzed from different sources, including experiments in a porcine model, data from postmortem human brain, published studies, public and commercial databases. RESULTS: The transcriptional program in the CNS following TBI, HS, and VPA treatment includes activation of regulatory pathways that enhance neurogenesis and suppress gliogenesis...
August 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28270929/changing-paradigms-in-the-management-of-rejection-in-kidney-transplantation-evolving-from-protocol-based-care-to-the-era-of-p4-medicine
#16
Mirela Maier, Tomoko Takano, Ruth Sapir-Pichhadze
PURPOSE OF REVIEW: P4 medicine denotes an evolving field of medicine encompassing predictive, preventive, personalized, and participatory medicine. Using the example of kidney allograft rejection because of donor-recipient incompatibility in human leukocyte antigens, this review outlines P4 medicine's relevance to the various stages of the kidney transplant cycle. SOURCES OF INFORMATION: A search for English articles was conducted in Medline via OvidSP (up to August 18, 2016) using a combination of subject headings (MeSH) and free text in titles, abstracts, and author keywords for the concepts kidney transplantation and P4 medicine...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28249909/morphoproteomics-identifies-sirt1-and-ezh2-pathways-as-commonalities-in-b-cell-acute-lymphoblastic-leukemia-pathogenetic-implications-and-opportunities-for-therapeutic-intervention
#17
Robert E Brown, Kristine E Konopka, Priya Weerasinghe, Vanya Jaitly, Amitava Dasgupta, Mary F McGuire, Nghia D Nguyen
B-cell acute lymphoblastic leukemia (ALL) represents a malignant process in which bone marrow-derived lymphoblasts retain their undifferentiated state. Genetic testing has revealed either no identifiable cytogenetic and genomic abnormalities in such patients or a wide range of aberrations that may or may not contribute to the block in differentiation and the associated proliferation of the malignant lymphoblasts in cases of B-cell ALL. In this study, we applied morphoproteomics to a representative spectrum of cases of newly diagnosed B-cell ALL in order to identify pathways that are known to be associated with the maintenance of the undifferentiated state while promoting proliferation...
January 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28241745/drug-voyager-a-computational-platform-for-exploring-unintended-drug-action
#18
Min Oh, Jaegyoon Ahn, Taekeon Lee, Giup Jang, Chihyun Park, Youngmi Yoon
BACKGROUND: The dominant paradigm in understanding drug action focuses on the intended therapeutic effects and frequent adverse reactions. However, this approach may limit opportunities to grasp unintended drug actions, which can open up channels to repurpose existing drugs and identify rare adverse drug reactions. Advances in systems biology can be exploited to comprehensively understand pharmacodynamic actions, although proper frameworks to represent drug actions are still lacking. RESULTS: We suggest a novel platform to construct a drug-specific pathway in which a molecular-level mechanism of action is formulated based on pharmacologic, pharmacogenomic, transcriptomic, and phenotypic data related to drug response ( http://databio...
February 28, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28176638/personalized-medicine-and-adverse-drug-reactions-the-experience-of-an-italian-teaching-hospital
#19
Raffaele La Russa, Vittorio Fineschi, Mariantonia Di Sanzo, Vittorio Gatto, Alessandro Santurro, Gabriella Martini, Matteo Scopetti, Paola Frati
The personalized medicine is a model of medicine based on inherent difference given by the genetic heritage that characterizes us, diversity that can affect also our response to administered therapy. Nowadays, the term "adverse drug reaction" is identified with any harmful effect involuntary resulting from the use of a medicinal product; pharmacogenomics, in this field, has the aim to improve the drug response and to reduce the adverse reaction. We analyzed all reports of adverse reaction collected in the Pharmacovigilance Centre database of an Italian University Hospital, at the Sant'Andrea Hospital Sapienza University of Rome, in a period of two years...
February 7, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28139890/pharmacogenomics-of-17-alpha-hydroxyprogesterone-caproate-for-recurrent-preterm-birth-a-case-control-study
#20
T A Manuck, W S Watkins, M S Esplin, J Biggio, R Bukowski, S Parry, H Zhan, H Huang, W Andrews, G Saade, Y Sadovsky, U M Reddy, J Ilekis, M Yandell, M W Varner, L B Jorde
OBJECTIVE: To compare maternal genotypes between women with and without significant prolongation of pregnancy in the setting of 17-alpha hydroxyprogesterone caproate (17-P) administration for the prevention of recurrent preterm birth (PTB). DESIGN: Case-control. SETTING: Three tertiary-care centres across the USA. POPULATION: Women (n = 99) with ≥ 1 prior singleton spontaneous PTB, receiving 17-P. METHODS: Women were classified as having successful prolongation of pregnancy during the 17-P treated pregnancy, in two ways: (1) Definition A: success/non-success based on difference in gestational age at delivery between 17-P-treated and untreated pregnancies (success: delivered ≥ 3 weeks later with 17-P) and (2) Definition B: success/non-success based on reaching term (success: delivered at term with 17-P)...
January 31, 2017: BJOG: An International Journal of Obstetrics and Gynaecology
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