Organic Cation Transporter 2 (OCT2/SLC22A2) Gene Variation in the South African Bantu-Speaking Population and Functional Promoter Variants.

OMICS. 2017 Mar;21(3):169-176

Authors: Wilson NC, Choudhury A, Carstens N, Mavri-Damelin D

Abstract
SLC22A2 facilitates the transport of endogenous and exogenous cationic compounds. Many pharmacologically significant compounds are transported by SLC22A2, including the antidiabetic drug metformin, anticancer agent cisplatin, and antiretroviral lamivudine. Genetic polymorphisms in SLC22A2 can modify the pharmacokinetic profiles of such important medicines and could therefore prove useful as precision medicine biomarkers. Since the frequency of SLC22A2 polymorphisms varies among different ethnic populations, we evaluated these in South African Bantu speakers, a majority group in the South African population, who exhibit unique genetic diversity, and we subsequently functionally characterized promoter polymorphisms. We identified 11 polymorphisms within the promoter and 9 single-nucleotide polymorphisms (SNPs) within the coding region of SLC22A2. While some polymorphisms appeared with minor allele frequencies similar to other African and non-African populations, some differed considerably; this was especially notable for three missense polymorphisms. In addition, we functionally characterized two promoter polymorphisms; rs138765638, a three base-pair deletion that bioinformatics analysis suggested could alter c-Ets-1/2, Elk1, and/or STAT4 binding, and rs59695691, an SNP that could abolish TFII-I binding. Significantly higher luciferase reporter gene expression was found for rs138765638 (increase of 37%; p = 0.001) and significantly lower expression for rs59695691 (decrease of 25%; p = 0.038), in comparison to the wild-type control. These observations highlight the importance of identifying and functionally characterizing genetic variation in genes of pharmacological significance. Finally, our data for SLC22A2 attest to the importance of considering genetic variation in different populations for drug safety, response, and global pharmacogenomics, through, for example, projects such as the Human Heredity and Health in Africa initiative.

PMID: 28253084 [PubMed - in process]

Genome Sequencing Technologies and Nursing: What Are the Roles of Nurses and Nurse Scientists?

Nurs Res. 2017 Mar/Apr;66(2):198-205

Authors: Taylor JY, Wright ML, Hickey KT, Housman DE

Abstract
BACKGROUND: Advances in DNA sequencing technology have resulted in an abundance of personalized data with challenging clinical utility and meaning for clinicians. This wealth of data has potential to dramatically impact the quality of healthcare. Nurses are at the focal point in educating patients regarding relevant healthcare needs; therefore, an understanding of sequencing technology and utilizing these data are critical.
AIM: The objective of this study was to explicate the role of nurses and nurse scientists as integral members of healthcare teams in improving understanding of DNA sequencing data and translational genomics for patients.
APPROACH: A history of the nurse role in newborn screening is used as an exemplar.
DISCUSSION: This study serves as an exemplar on how genome sequencing has been utilized in nursing science and incorporates linkages of other omics approaches used by nurses that are included in this special issue. This special issue showcased nurse scientists conducting multi-omic research from various methods, including targeted candidate genes, pharmacogenomics, proteomics, epigenomics, and the microbiome. From this vantage point, we provide an overview of the roles of nurse scientists in genome sequencing research and provide recommendations for the best utilization of nurses and nurse scientists related to genome sequencing.

PMID: 28252579 [PubMed - in process]

Longitudinal sampling of the lung microbiota in individuals with cystic fibrosis.

PLoS One. 2017;12(3):e0172811

Authors: Whelan FJ, Heirali AA, Rossi L, Rabin HR, Parkins MD, Surette MG

Abstract
Cystic fibrosis (CF) manifests in the lungs resulting in chronic microbial infection. Most morbidity and mortality in CF is due to cycles of pulmonary exacerbations-episodes of acute inflammation in response to the lung microbiome-which are difficult to prevent and treat because their cause is not well understood. We hypothesized that longitudinal analyses of the bacterial component of the CF lung microbiome may elucidate causative agents within this community for pulmonary exacerbations. In this study, 6 participants were sampled thrice-weekly for up to one year. During sampling, sputum, and data (antibiotic usage, spirometry, and symptom scores) were collected. Time points were categorized based on relation to exacerbation as Stable, Intermediate, and Treatment. Retrospectively, a subset of were interrogated via 16S rRNA gene sequencing. When samples were examined categorically, a significant difference between the lung microbiota in Stable, Intermediate, and Treatment samples was observed in a subset of participants. However, when samples were examined longitudinally, no correlations between microbial composition and collected data (antibiotic usage, spirometry, and symptom scores) were observed upon exacerbation onset. In this study, we identified no universal indicator within the lung microbiome of exacerbation onset but instead showed that changes to the CF lung microbiome occur outside of acute pulmonary episodes and are patient-specific.

PMID: 28253277 [PubMed - in process]

Imaging the Abdominal Manifestations of Cystic Fibrosis.

Int J Hepatol. 2017;2017:5128760

Authors: Gillespie CD, O'Reilly MK, Allen GN, McDermott S, Chan VO, Ridge CA

Abstract
Cystic fibrosis (CF) is a multisystem disease with a range of abdominal manifestations including those involving the liver, pancreas, and kidneys. Recent advances in management of the respiratory complications of the disease has led to a greater life expectancy in patients with CF. Subsequently, there is increasing focus on the impact of abdominal disease on quality of life and survival. Liver cirrhosis is the most important extrapulmonary cause of death in CF, yet significant challenges remain in the diagnosis of CF related liver disease. The capacity to predict those patients at risk of developing cirrhosis remains a significant challenge. We review representative abdominal imaging findings in patients with CF selected from the records of two academic health centres, with a view to increasing familiarity with the abdominal manifestations of the disease. We review their presentation and expected imaging findings, with a focus on the challenges facing diagnosis of the hepatic manifestations of the disease. An increased familiarity with these abdominal manifestations will facilitate timely diagnosis and management, which is paramount to further improving outcomes for patients with cystic fibrosis.

PMID: 28250993 [PubMed - in process]

Over-the-scope-clip closure of long lasting gastrocutaneous fistula after percutaneous endoscopic gastrostomy tube removal in immunocompromised patients: A single center case series.

World J Gastrointest Endosc. 2017 Feb 16;9(2):85-90

Authors: Heinrich H, Gubler C, Valli PV

Abstract
Over-the-scope-clips (OTSC(®)) have been shown to be an effective and safe endoscopic treatment option for the closure of gastrointestinal perforations, leakages and fistulae. Indications for endoscopic OTSC(®) treatment have grown in number and also include gastro cutaneous fistula (GCF) after percutaneous endoscopic gastrostomy (PEG) tube removal. Non-healing GCF is a rare complication after removal of PEG tubes and may especially develop in immunosuppressed patients with multiple comorbidities. There is growing evidence in the literature that OTSC(®) closure of GCF after PEG tube removal is emerging as an effective, simple and safe endoscopic treatment option. However current evidence is limited to the geriatric population and short standing GCF, while information on closure of long standing GCF after PEG tube removal in a younger population with significant comorbidities is lacking. In this retrospective single-center case-series we report on five patients undergoing OTSC(®) closure of chronic GCF after PEG tube removal. Four out of five patients were afflicted with long lasting, symptomatic fistulae. All five patients suffered from chronic disease associated with a catabolic metabolism (cystic fibrosis, chemotherapy for neoplasia, liver cirrhosis). The mean patient age was 43 years. The mean dwell time of PEG tubes in all five patients was 808 d. PEG tube dwell time was shortest in patient 5 (21 d). The mean duration from PEG tube removal to fistula closure in patients 1-4 was 360 d (range 144-850 d). The intervention was well tolerated by all patients and no adverse events occured. Successful immediate and long-term fistula closure was accomplished in all five patients. This single center case series is the first to show successful endoscopic OTSC(®) closure of long lasting GCF in five consecutive middle-aged patients with significant comorbidities. Endoscopic closure of chronic persistent GCF after PEG tube removal using an OTSC(®) was achieved in all patients with no immediate or long-term complications. OTSC(®) is a promising endoscopic treatment option for this condition with a potentially high immediate and long term success rate in patients with multiple comorbidities.

PMID: 28250901 [PubMed - in process]

Current knowledge of metabolomic approach in infectious fish disease studies.

J Fish Dis. 2017 Mar 02;:

Authors: Low CF, Rozaini MZ, Musa N, Syarul Nataqain B

Abstract
The approaches of transcriptomic and proteomic have been widely used to study host-pathogen interactions in fish diseases, and this is comparable to the recently emerging application of metabolomic in elucidating disease-resistant mechanisms in fish that gives new insight into potential therapeutic strategies to improve fish health. Metabolomic is defined as the large-scale study of all metabolites within an organism and represents the frontline in the 'omics' approaches, providing direct information on the metabolic responses and perturbations in metabolic pathways. In this review, the current research in infectious fish diseases using metabolomic approach will be summarized. The metabolomic approach in economically important fish infected with viruses, bacteria and nematodes will also be discussed. The potential of the metabolomic approach for management of these infectious diseases as well as the challenges and the limitations of metabolomic in fish disease studies will be explored. Current review highlights the impacts of metabolomic studies in infectious fish diseases, which proposed the potential of new therapeutic strategies to enhance disease resistance in fish.

PMID: 28252175 [PubMed - as supplied by publisher]

PRODIGEN: visualizing the probability landscape of stochastic gene regulatory networks in state and time space.

BMC Bioinformatics. 2017 Feb 15;18(Suppl 2):24

Authors: Ma C, Luciani T, Terebus A, Liang J, Marai GE

Abstract
BACKGROUND: Visualizing the complex probability landscape of stochastic gene regulatory networks can further biologists' understanding of phenotypic behavior associated with specific genes.
RESULTS: We present PRODIGEN (PRObability DIstribution of GEne Networks), a web-based visual analysis tool for the systematic exploration of probability distributions over simulation time and state space in such networks. PRODIGEN was designed in collaboration with bioinformaticians who research stochastic gene networks. The analysis tool combines in a novel way existing, expanded, and new visual encodings to capture the time-varying characteristics of probability distributions: spaghetti plots over one dimensional projection, heatmaps of distributions over 2D projections, enhanced with overlaid time curves to display temporal changes, and novel individual glyphs of state information corresponding to particular peaks.
CONCLUSIONS: We demonstrate the effectiveness of the tool through two case studies on the computed probabilistic landscape of a gene regulatory network and of a toggle-switch network. Domain expert feedback indicates that our visual approach can help biologists: 1) visualize probabilities of stable states, 2) explore the temporal probability distributions, and 3) discover small peaks in the probability landscape that have potential relation to specific diseases.

PMID: 28251874 [PubMed - in process]

Unboxing cluster heatmaps.

BMC Bioinformatics. 2017 Feb 15;18(Suppl 2):63

Authors: Engle S, Whalen S, Joshi A, Pollard KS

Abstract
BACKGROUND: Cluster heatmaps are commonly used in biology and related fields to reveal hierarchical clusters in data matrices. This visualization technique has high data density and reveal clusters better than unordered heatmaps alone. However, cluster heatmaps have known issues making them both time consuming to use and prone to error. We hypothesize that visualization techniques without the rigid grid constraint of cluster heatmaps will perform better at clustering-related tasks.
RESULTS: We developed an approach to "unbox" the heatmap values and embed them directly in the hierarchical clustering results, allowing us to use standard hierarchical visualization techniques as alternatives to cluster heatmaps. We then tested our hypothesis by conducting a survey of 45 practitioners to determine how cluster heatmaps are used, prototyping alternatives to cluster heatmaps using pair analytics with a computational biologist, and evaluating those alternatives with hour-long interviews of 5 practitioners and an Amazon Mechanical Turk user study with approximately 200 participants. We found statistically significant performance differences for most clustering-related tasks, and in the number of perceived visual clusters. Visit git.io/vw0t3 for our results.
CONCLUSIONS: The optimal technique varied by task. However, gapmaps were preferred by the interviewed practitioners and outperformed or performed as well as cluster heatmaps for clustering-related tasks. Gapmaps are similar to cluster heatmaps, but relax the heatmap grid constraints by introducing gaps between rows and/or columns that are not closely clustered. Based on these results, we recommend users adopt gapmaps as an alternative to cluster heatmaps.

PMID: 28251868 [PubMed - in process]

Systems biology combining human- and animal-data miRNA and mRNA data identifies new targets in ureteropelvic junction obstruction.

BMC Syst Biol. 2017 Mar 01;11(1):31

Authors: Papadopoulos T, Casemayou A, Neau E, Breuil B, Caubet C, Calise D, Thornhill BA, Bachvarova M, Belliere J, Chevalier RL, Moulos P, Bachvarov D, Buffin-Meyer B, Decramer S, Auriol FC, Bascands JL, Schanstra JP, Klein J

Abstract
BACKGROUND: Although renal fibrosis and inflammation have shown to be involved in the pathophysiology of obstructive nephropathies, molecular mechanisms underlying evolution of these processes remain undetermined. In an attempt towards improved understanding of obstructive nephropathy and improved translatability of the results to clinical practice we have developed a systems biology approach combining omics data of both human and mouse obstructive nephropathy.
RESULTS: We have studied in parallel the urinary miRNome of infants with ureteropelvic junction obstruction and the kidney tissue miRNome and transcriptome of the corresponding neonatal partial unilateral ureteral obstruction (UUO) mouse model. Several hundreds of miRNAs and mRNAs displayed changed abundance during disease. Combination of miRNAs in both species and associated mRNAs let to the prioritization of five miRNAs and 35 mRNAs associated to disease. In vitro and in vivo validation identified consistent dysregulation of let-7a-5p and miR-29-3p and new potential targets, E3 ubiquitin-protein ligase (DTX4) and neuron navigator 1 (NAV1), potentially involved in fibrotic processes, in obstructive nephropathy in both human and mice that would not be identified otherwise.
CONCLUSIONS: Our study is the first to correlate a mouse model of neonatal partial UUO with human UPJ obstruction in a comprehensive systems biology analysis. Our data revealed let-7a and miR-29b as molecules potentially involved in the development of fibrosis in UPJ obstruction via the control of DTX4 in both man and mice that would not be identified otherwise.

PMID: 28249581 [PubMed - in process]

Reactome pathway analysis: a high-performance in-memory approach.

BMC Bioinformatics. 2017 Mar 02;18(1):142

Authors: Fabregat A, Sidiropoulos K, Viteri G, Forner O, Marin-Garcia P, Arnau V, D'Eustachio P, Stein L, Hermjakob H

Abstract
BACKGROUND: Reactome aims to provide bioinformatics tools for visualisation, interpretation and analysis of pathway knowledge to support basic research, genome analysis, modelling, systems biology and education. Pathway analysis methods have a broad range of applications in physiological and biomedical research; one of the main problems, from the analysis methods performance point of view, is the constantly increasing size of the data samples.
RESULTS: Here, we present a new high-performance in-memory implementation of the well-established over-representation analysis method. To achieve the target, the over-representation analysis method is divided in four different steps and, for each of them, specific data structures are used to improve performance and minimise the memory footprint. The first step, finding out whether an identifier in the user's sample corresponds to an entity in Reactome, is addressed using a radix tree as a lookup table. The second step, modelling the proteins, chemicals, their orthologous in other species and their composition in complexes and sets, is addressed with a graph. The third and fourth steps, that aggregate the results and calculate the statistics, are solved with a double-linked tree.
CONCLUSION: Through the use of highly optimised, in-memory data structures and algorithms, Reactome has achieved a stable, high performance pathway analysis service, enabling the analysis of genome-wide datasets within seconds, allowing interactive exploration and analysis of high throughput data. The proposed pathway analysis approach is available in the Reactome production web site either via the AnalysisService for programmatic access or the user submission interface integrated into the PathwayBrowser. Reactome is an open data and open source project and all of its source code, including the one described here, is available in the AnalysisTools repository in the Reactome GitHub ( https://github.com/reactome/ ).

PMID: 28249561 [PubMed - in process]

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"cystic fibrosis"

These pubmed results were generated on 2017/03/02

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Mechanisms of Groucho-mediated repression revealed by genome-wide analysis of Groucho binding and activity.

BMC Genomics. 2017 Feb 28;18(1):215

Authors: Chambers M, Turki-Judeh W, Kim MW, Chen K, Gallaher SD, Courey AJ

Abstract
BACKGROUND: The transcriptional corepressor Groucho (Gro) is required for the function of many developmentally regulated DNA binding repressors, thus helping to define the gene expression profile of each cell during development. The ability of Gro to repress transcription at a distance together with its ability to oligomerize and bind to histones has led to the suggestion that Gro may spread along chromatin. However, much is unknown about the mechanism of Gro-mediated repression and about the dynamics of Gro targeting.
RESULTS: Our chromatin immunoprecipitation sequencing analysis of temporally staged Drosophila embryos shows that Gro binds in a highly dynamic manner primarily to clusters of discrete (<1 kb) segments. Consistent with the idea that Gro may facilitate communication between silencers and promoters, Gro binding is enriched at both cis-regulatory modules, as well as within the promotors of potential target genes. While this Gro-recruitment is required for repression, our data show that it is not sufficient for repression. Integration of Gro binding data with transcriptomic analysis suggests that, contrary to what has been observed for another Gro family member, Drosophila Gro is probably a dedicated repressor. This analysis also allows us to define a set of high confidence Gro repression targets. Using publically available data regarding the physical and genetic interactions between these targets, we are able to place them in the regulatory network controlling development. Through analysis of chromatin associated pre-mRNA levels at these targets, we find that genes regulated by Gro in the embryo are enriched for characteristics of promoter proximal paused RNA polymerase II.
CONCLUSIONS: Our findings are inconsistent with a one-dimensional spreading model for long-range repression and suggest that Gro-mediated repression must be regulated at a post-recruitment step. They also show that Gro is likely a dedicated repressor that sits at a prominent highly interconnected regulatory hub in the developmental network. Furthermore, our findings suggest a role for RNA polymerase II pausing in Gro-mediated repression.

PMID: 28245789 [PubMed - in process]

Systematic Identification and Assessment of Therapeutic Targets for Breast Cancer Based on Genome-Wide RNA Interference Transcriptomes.

Genes (Basel). 2017 Feb 24;8(3):

Authors: Liu Y, Yin X, Zhong J, Guan N, Luo Z, Min L, Yao X, Bo X, Dai L, Bai H

Abstract
With accumulating public omics data, great efforts have been made to characterize the genetic heterogeneity of breast cancer. However, identifying novel targets and selecting the best from the sizeable lists of candidate targets is still a key challenge for targeted therapy, largely owing to the lack of economical, efficient and systematic discovery and assessment to prioritize potential therapeutic targets. Here, we describe an approach that combines the computational evaluation and objective, multifaceted assessment to systematically identify and prioritize targets for biological validation and therapeutic exploration. We first establish the reference gene expression profiles from breast cancer cell line MCF7 upon genome-wide RNA interference (RNAi) of a total of 3689 genes, and the breast cancer query signatures using RNA-seq data generated from tissue samples of clinical breast cancer patients in the Cancer Genome Atlas (TCGA). Based on gene set enrichment analysis, we identified a set of 510 genes that when knocked down could significantly reverse the transcriptome of breast cancer state. We then perform multifaceted assessment to analyze the gene set to prioritize potential targets for gene therapy. We also propose drug repurposing opportunities and identify potentially druggable proteins that have been poorly explored with regard to the discovery of small-molecule modulators. Finally, we obtained a small list of candidate therapeutic targets for four major breast cancer subtypes, i.e., luminal A, luminal B, HER2+ and triple negative breast cancer. This RNAi transcriptome-based approach can be a helpful paradigm for relevant researches to identify and prioritize candidate targets for experimental validation.

PMID: 28245581 [PubMed - in process]

Management of thrombosis in paroxysmal nocturnal hemoglobinuria: a clinician's guide.

Ther Adv Hematol. 2017 Mar;8(3):119-126

Authors: Griffin M, Munir T

Abstract
Paroxysmal nocturnal haemoglobinuria (PNH), an ultra-orphan disease with a prevalence of 15.9 per million in Europe, is a life-threatening disorder, characterized by haemolysis, bone marrow failure and thrombosis. Patients with PNH prior to the availability of eculizumab had a median survival of between 10 and 22 years, with thrombosis accounting for 22-67% of deaths. 29-44% of patients had at least one thrombosis. This paper provides a clinician's guide to the diagnosis, management and complications of PNH, with an emphasis on thrombosis.

PMID: 28246555 [PubMed - in process]

Varying Intolerance of Gene Pathways to Mutational Classes Explain Genetic Convergence across Neuropsychiatric Disorders.

Cell Rep. 2017 Feb 28;18(9):2217-2227

Authors: Shohat S, Ben-David E, Shifman S

Abstract
Genetic susceptibility to intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ) often arises from mutations in the same genes, suggesting that they share common mechanisms. We studied genes with de novo mutations in the three disorders and genes implicated in SCZ by genome-wide association study (GWAS). Using biological annotations and brain gene expression, we show that mutation class explains enrichment patterns more than specific disorder. Genes with loss-of-function mutations and genes with missense mutations were associated with different pathways across disorders. Conversely, gene expression patterns were specific for each disorder. ID genes were preferentially expressed in the cortex; ASD genes were expressed in the fetal cortex, cerebellum, and striatum; and genes associated with SCZ were expressed in the adolescent cortex. Our study suggests that convergence across neuropsychiatric disorders stems from common pathways that are consistently vulnerable to genetic variations but that spatiotemporal activity of genes contributes to specific phenotypes.

PMID: 28249166 [PubMed - in process]

"Omics"-Informed Drug and Biomarker Discovery: Opportunities, Challenges and Future Perspectives.

Proteomes. 2016 Sep 12;4(3):

Authors: Matthews H, Hanison J, Nirmalan N

Abstract
The pharmaceutical industry faces unsustainable program failure despite significant increases in investment. Dwindling discovery pipelines, rapidly expanding R&amp;D budgets and increasing regulatory control, predict significant gaps in the future drug markets. The cumulative duration of discovery from concept to commercialisation is unacceptably lengthy, and adds to the deepening crisis. Existing animal models predicting clinical translations are simplistic, highly reductionist and, therefore, not fit for purpose. The catastrophic consequences of ever-increasing attrition rates are most likely to be felt in the developing world, where resistance acquisition by killer diseases like malaria, tuberculosis and HIV have paced far ahead of new drug discovery. The coming of age of Omics-based applications makes available a formidable technological resource to further expand our knowledge of the complexities of human disease. The standardisation, analysis and comprehensive collation of the "data-heavy" outputs of these sciences are indeed challenging. A renewed focus on increasing reproducibility by understanding inherent biological, methodological, technical and analytical variables is crucial if reliable and useful inferences with potential for translation are to be achieved. The individual Omics sciences-genomics, transcriptomics, proteomics and metabolomics-have the singular advantage of being complimentary for cross validation, and together could potentially enable a much-needed systems biology perspective of the perturbations underlying disease processes. If current adverse trends are to be reversed, it is imperative that a shift in the R&amp;D focus from speed to quality is achieved. In this review, we discuss the potential implications of recent Omics-based advances for the drug development process.

PMID: 28248238 [PubMed - in process]

Distinct Antigen Delivery Systems Induce Dendritic Cells' Divergent Transcriptional Response: New Insights from a Comparative and Reproducible Computational Analysis.

Int J Mol Sci. 2017 Feb 25;18(3):

Authors: Costa V, Righelli D, Russo F, De Berardinis P, Angelini C, D'Apice L

Abstract
Vaccination is the most successful and cost-effective method to prevent infectious diseases. However, many vaccine antigens have poor in vivo immunogenic potential and need adjuvants to enhance immune response. The application of systems biology to immunity and vaccinology has yielded crucial insights about how vaccines and adjuvants work. We have previously characterized two safe and powerful delivery systems derived from non-pathogenic prokaryotic organisms: E2 and fd filamentous bacteriophage systems. They elicit an in vivo immune response inducing CD8+ T-cell responses, even in absence of adjuvants or stimuli for dendritic cells' maturation. Nonetheless, a systematic and comparative analysis of the complex gene expression network underlying such activation is missing. Therefore, we compared the transcriptomes of ex vivo isolated bone marrow-derived dendritic cells exposed to these antigen delivery systems. Significant differences emerged, especially for genes involved in innate immunity, co-stimulation, and cytokine production. Results indicate that E2 drives polarization toward the Th2 phenotype, mainly mediated by Irf4, Ccl17, and Ccr4 over-expression. Conversely, fd-scαDEC-205 triggers Th1 T cells' polarization through the induction of Il12b, Il12rb, Il6, and other molecules involved in its signal transduction. The data analysis was performed using RNASeqGUI, hence, addressing the increasing need of transparency and reproducibility of computational analysis.

PMID: 28245601 [PubMed - in process]

10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"cystic fibrosis"

These pubmed results were generated on 2017/03/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Pharmacogenomics of autism spectrum disorder.

Pharmacogenomics. 2017 Mar;18(4):403-414

Authors: Brown JT, Eum S, Cook EH, Bishop JR

Abstract
Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and interactions as well as restricted, repetitive behaviors and interests. Pharmacologic interventions are often needed to manage irritability, aggressive behaviors and hyperactivity. Pharmacogenomic studies have investigated genetic associations with treatment response and side effects in an attempt to better understand drug mechanisms in hopes of optimizing the balance of symptom improvement versus side effects. The majority of pharmacogenomic studies to date have focused on antipsychotics, antidepressants and stimulants that are the most commonly utilized medication classes for ASD. This review is a comprehensive examination of the existing pharmacogenomic studies in ASD highlighting the current state of knowledge regarding genetic variation influencing pharmacokinetics and pharmacodynamics, and associated clinical outcomes.

PMID: 28244813 [PubMed - in process]

Increased risk of hospitalization for ultrarapid metabolizers of cytochrome P450 2D6.

Pharmgenomics Pers Med. 2017;10:39-47

Authors: Takahashi PY, Ryu E, Pathak J, Jenkins GD, Batzler A, Hathcock MA, Black JL, Olson JE, Cerhan JR, Bielinski SJ

Abstract
BACKGROUND: Cytochrome P450 2D6 (CYP2D6) is responsible for the metabolism of clinically used drugs and other environmental exposures, but it is unclear whether the CYP2D6 phenotype is associated with adverse health outcomes. The aim was to determine the association of CYP2D6 phenotype with the risk of hospitalization or an emergency department (ED) visit among a group of primary care patients.
METHODS: In this study, 929 adult patients underwent CYP2D6 testing. The primary outcome was risk of hospitalization or an ED visit from January 2005 through September 2014. CYP2D6 genotypes were interpreted as 1 of 7 clinical phenotypes, from ultrarapid to poor metabolizer, and patients with the extensive metabolizer phenotype were used as the reference group. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for finding the association of CYP2D6 phenotypes with the risk of hospitalization or an ED visit by using Cox proportional hazard models and adjusting for age and sex.
RESULTS: The median age was 49 years (interquartile range, 46-52 years); 74% of patients had 3 or fewer chronic conditions, 285 had at least 1 hospitalization, and 496 had at least 1 ED visit. The risk of hospitalization was higher among patients who were ultrarapid metabolizers compared to extensive metabolizers (47% vs 30%; HR, 1.69; 95% CI, 1.11-2.57), as was the risk of an ED visit (62% vs 49%; HR, 1.50; 95% CI, 1.05-2.14). For poor metabolizers compared to extensive metabolizers, there was no difference in the risk of hospitalization (HR, 0.95; 95% CI, 0.58-1.56), but there was an increase in the risk of an ED visit (HR, 1.38; 95% CI, 0.96-1.98) (the difference was not statistically significant).
CONCLUSION: We found an increased risk of hospitalization or an ED visit among ultrarapid compared to extensive CYP2D6 metabolizers. Further research identifying the mechanisms of the association and ultimate clinical utility is warranted.

PMID: 28243137 [PubMed - in process]