LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 14

Search options

  1. Article ; Online: Exploring the overlap between rheumatoid arthritis susceptibility loci and long non-coding RNA annotations.

    James Ding / Chenfu Shi / John Bowes / Stephen Eyre / Gisela Orozco

    PLoS ONE, Vol 15, Iss 3, p e

    2020  Volume 0223939

    Abstract: Whilst susceptibility variants for many complex diseases, such as rheumatoid arthritis (RA), have been well characterised, the mechanism by which risk is mediated is still unclear for many loci. This is especially true for the majority of variants that ... ...

    Abstract Whilst susceptibility variants for many complex diseases, such as rheumatoid arthritis (RA), have been well characterised, the mechanism by which risk is mediated is still unclear for many loci. This is especially true for the majority of variants that do not affect protein-coding regions. lncRNA represent a group of molecules that have been shown to be enriched amongst variants associated with RA and other complex diseases, compared to random variants. In order to establish to what degree direct disruption of lncRNA may represent a potential mechanism for mediating RA susceptibility, we chose to further explore this overlap. By testing the ability of annotated features to improve a model of disease susceptibility, we were able to demonstrate a local enrichment of enhancers from immune-relevant cell types amongst RA susceptibility variants (log2 enrichment 3.40). This was not possible for lncRNA annotations in general, however a small, but significant enrichment was observed for immune-enriched lncRNA (log2 enrichment 0.867002). This enrichment was no longer apparent when the model was conditioned on immune-relevant enhancers (log2 enrichment -0.372734), suggesting that direct disruption of lncRNA sequence, independent of enhancer disruption, does not represent a major mechanism by which susceptibility to complex diseases is mediated. Furthermore, we demonstrated that, in keeping with general lncRNA characteristics, immune-enriched lncRNA are expressed at low levels that may not be amenable to functional characterisation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs

    Wouter J. Venema / Sanne Hiddingh / Jorg van Loosdregt / John Bowes / Brunilda Balliu / Joke H. de Boer / Jeannette Ossewaarde-van Norel / Susan D. Thompson / Carl D. Langefeld / Aafke de Ligt / Lars T. van der Veken / Peter H.L. Krijger / Wouter de Laat / Jonas J.W. Kuiper

    Cell Genomics, Vol 4, Iss 1, Pp 100460- (2024)

    2024  

    Abstract: Summary: Single-nucleotide polymorphisms (SNPs) near the ERAP2 gene are associated with various autoimmune conditions, as well as protection against lethal infections. Due to high linkage disequilibrium, numerous trait-associated SNPs are correlated with ...

    Abstract Summary: Single-nucleotide polymorphisms (SNPs) near the ERAP2 gene are associated with various autoimmune conditions, as well as protection against lethal infections. Due to high linkage disequilibrium, numerous trait-associated SNPs are correlated with ERAP2 expression; however, their functional mechanisms remain unidentified. We show by reciprocal allelic replacement that ERAP2 expression is directly controlled by the splice region variant rs2248374. However, disease-associated variants in the downstream LNPEP gene promoter are independently associated with ERAP2 expression. Allele-specific conformation capture assays revealed long-range chromatin contacts between the gene promoters of LNPEP and ERAP2 and showed that interactions were stronger in patients carrying the alleles that increase susceptibility to autoimmune diseases. Replacing the SNPs in the LNPEP promoter by reference sequences lowered ERAP2 expression. These findings show that multiple SNPs act in concert to regulate ERAP2 expression and that disease-associated variants can convert a gene promoter region into a potent enhancer of a distal gene.
    Keywords ERAP2 ; GWAS ; autoimmunity ; SNP ; eQTL ; rs2248374 ; Genetics ; QH426-470 ; Internal medicine ; RC31-1245
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Towards stratified treatment of JIA

    Stephanie J.W. Shoop-Worrall / Saskia Lawson-Tovey / Lucy R. Wedderburn / Kimme L. Hyrich / Nophar Geifman / Aline Kimonyo / Alyssia McNeece / Andrew Dick / Andrew Morris / Annie Yarwood / Athimalaipet Ramanan / Bethany R. Jebson / Chris Wallace / Daniela Dastros-Pitei / Damian Tarasek / Elizabeth Ralph / Emil Carlsson / Emily Robinson / Emma Sumner /
    Fatema Merali / Fatjon Dekaj / Helen Neale / Hussein Al-Mossawi / Jacqui Roberts / Jenna F. Gritzfeld / Joanna Fairlie / John Bowes / John Ioannou / Melissa Kartawinata / Melissa Tordoff / Michael Barnes / Michael W. Beresford / Michael Stadler / Paul Martin / Rami Kallala / Sandra Ng / Samantha Smith / Sarah Clarke / Soumya Raychaudhuri / Stephen Eyre / Sumanta Mukherjee / Teresa Duerr / Thierry Sornasse / Vasiliki Alexiou / Victoria J. Burton / Wei-Yu Lin / Wendy Thomson / Zoe Wanstall

    EBioMedicine, Vol 100, Iss , Pp 104946- (2024)

    machine learning identifies subtypes in response to methotrexate from four UK cohortsResearch in context

    2024  

    Abstract: Summary: Background: Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To ... ...

    Abstract Summary: Background: Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment of early JIA, novel methods in machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; and iii) compare clusters to existing treatment response measures. Methods: Discovery and verification cohorts included CYP who first initiated MTX before January 2018 in one of four UK multicentre prospective cohorts of JIA within the CLUSTER consortium. JADAS components (active joint count, physician (PGA) and parental (PGE) global assessments, ESR) were recorded at MTX start and over the following year.Clusters of MTX ‘response’ were uncovered using multivariate group-based trajectory modelling separately in discovery and verification cohorts. Clusters were compared descriptively to ACR Pedi 30/90 scores, and multivariate logistic regression models predicted cluster-group assignment. Findings: The discovery cohorts included 657 CYP and verification cohorts 1241 CYP. Six clusters were identified: Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%), Persistent PGA (8%) and Persistent PGE (13%), the latter two characterised by improvement in all features except one. Factors associated with clusters included ethnicity, ILAR category, age, PGE, and ESR scores at MTX start, with predictive model area under the curve values of 0.65–0.71. Singular ACR Pedi 30/90 scores at 6 and 12 months could not capture speeds of improvement, relapsing courses or diverging disease patterns. Interpretation: Six distinct patterns following initiation of MTX have been identified using methods in artificial intelligence. These clusters demonstrate the limitations in traditional yes/no treatment response assessment (e.g., ACRPedi30) and can form the basis ...
    Keywords Juvenile idiopathic arthritis ; Machine learning ; Treatment outcome ; Epidemiology ; Methotrexate ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 310
    Language English
    Publishing date 2024-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Application of information theoretic feature selection and machine learning methods for the development of genetic risk prediction models

    Farideh Jalali-najafabadi / Michael Stadler / Nick Dand / Deepak Jadon / Mehreen Soomro / Pauline Ho / Helen Marzo-Ortega / Philip Helliwell / Eleanor Korendowych / Michael A. Simpson / Jonathan Packham / Catherine H. Smith / Jonathan N. Barker / Neil McHugh / Richard B. Warren / Anne Barton / John Bowes / BADBIR Study Group / BSTOP Study Group

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 14

    Abstract: Abstract In view of the growth of clinical risk prediction models using genetic data, there is an increasing need for studies that use appropriate methods to select the optimum number of features from a large number of genetic variants with a high degree ...

    Abstract Abstract In view of the growth of clinical risk prediction models using genetic data, there is an increasing need for studies that use appropriate methods to select the optimum number of features from a large number of genetic variants with a high degree of redundancy between features due to linkage disequilibrium (LD). Filter feature selection methods based on information theoretic criteria, are well suited to this challenge and will identify a subset of the original variables that should result in more accurate prediction. However, data collected from cohort studies are often high-dimensional genetic data with potential confounders presenting challenges to feature selection and risk prediction machine learning models. Patients with psoriasis are at high risk of developing a chronic arthritis known as psoriatic arthritis (PsA). The prevalence of PsA in this patient group can be up to 30% and the identification of high risk patients represents an important clinical research which would allow early intervention and a reduction of disability. This also provides us with an ideal scenario for the development of clinical risk prediction models and an opportunity to explore the application of information theoretic criteria methods. In this study, we developed the feature selection and psoriatic arthritis (PsA) risk prediction models that were applied to a cross-sectional genetic dataset of 1462 PsA cases and 1132 cutaneous-only psoriasis (PsC) cases using 2-digit HLA alleles imputed using the SNP2HLA algorithm. We also developed stratification method to mitigate the impact of potential confounder features and illustrate that confounding features impact the feature selection. The mitigated dataset was used in training of seven supervised algorithms. 80% of data was randomly used for training of seven supervised machine learning methods using stratified nested cross validation and 20% was selected randomly as a holdout set for internal validation. The risk prediction models were then further validated in UK Biobank ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 006
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Molecular insights into genome-wide association studies of chronic kidney disease-defining traits

    Xiaoguang Xu / James M. Eales / Artur Akbarov / Hui Guo / Lorenz Becker / David Talavera / Fehzan Ashraf / Jabran Nawaz / Sanjeev Pramanik / John Bowes / Xiao Jiang / John Dormer / Matthew Denniff / Andrzej Antczak / Monika Szulinska / Ingrid Wise / Priscilla R. Prestes / Maciej Glyda / Pawel Bogdanski /
    Ewa Zukowska-Szczechowska / Carlo Berzuini / Adrian S. Woolf / Nilesh J. Samani / Fadi J. Charchar / Maciej Tomaszewski

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 12

    Abstract: The molecular mechanisms that underlie associations in GWAS, incl. chronic kidney disease (CKD), are largely unknown. Here, the authors perform an integrative analysis of genetic, transcriptomic and epigenomic data from human kidney to pinpoint plausible ...

    Abstract The molecular mechanisms that underlie associations in GWAS, incl. chronic kidney disease (CKD), are largely unknown. Here, the authors perform an integrative analysis of genetic, transcriptomic and epigenomic data from human kidney to pinpoint plausible molecular pathways of CKD genetic associations.
    Keywords Science ; Q
    Language English
    Publishing date 2018-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Molecular insights into genome-wide association studies of chronic kidney disease-defining traits

    Xiaoguang Xu / James M. Eales / Artur Akbarov / Hui Guo / Lorenz Becker / David Talavera / Fehzan Ashraf / Jabran Nawaz / Sanjeev Pramanik / John Bowes / Xiao Jiang / John Dormer / Matthew Denniff / Andrzej Antczak / Monika Szulinska / Ingrid Wise / Priscilla R. Prestes / Maciej Glyda / Pawel Bogdanski /
    Ewa Zukowska-Szczechowska / Carlo Berzuini / Adrian S. Woolf / Nilesh J. Samani / Fadi J. Charchar / Maciej Tomaszewski

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 12

    Abstract: The molecular mechanisms that underlie associations in GWAS, incl. chronic kidney disease (CKD), are largely unknown. Here, the authors perform an integrative analysis of genetic, transcriptomic and epigenomic data from human kidney to pinpoint plausible ...

    Abstract The molecular mechanisms that underlie associations in GWAS, incl. chronic kidney disease (CKD), are largely unknown. Here, the authors perform an integrative analysis of genetic, transcriptomic and epigenomic data from human kidney to pinpoint plausible molecular pathways of CKD genetic associations.
    Keywords Science ; Q
    Language English
    Publishing date 2018-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Book: The City of our dreams

    Morrell, John Bowes

    1955  

    Author's details By J[ohn] B[owes] Morrell
    Size 150 S, 4
    Edition (2. ed.)
    Publisher St. Anthony
    Publishing place London
    Document type Book
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  8. Article ; Online: TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits.

    Dorothée Diogo / Lisa Bastarache / Katherine P Liao / Robert R Graham / Robert S Fulton / Jeffrey D Greenberg / Steve Eyre / John Bowes / Jing Cui / Annette Lee / Dimitrios A Pappas / Joel M Kremer / Anne Barton / Marieke J H Coenen / Barbara Franke / Lambertus A Kiemeney / Xavier Mariette / Corrine Richard-Miceli / Helena Canhão /
    João E Fonseca / Niek de Vries / Paul P Tak / J Bart A Crusius / Michael T Nurmohamed / Fina Kurreeman / Ted R Mikuls / Yukinori Okada / Eli A Stahl / David E Larson / Tracie L Deluca / Michelle O'Laughlin / Catrina C Fronick / Lucinda L Fulton / Roman Kosoy / Michael Ransom / Tushar R Bhangale / Ward Ortmann / Andrew Cagan / Vivian Gainer / Elizabeth W Karlson / Isaac Kohane / Shawn N Murphy / Javier Martin / Alexandra Zhernakova / Lars Klareskog / Leonid Padyukov / Jane Worthington / Elaine R Mardis / Michael F Seldin / Peter K Gregersen

    PLoS ONE, Vol 10, Iss 4, p e

    2015  Volume 0122271

    Abstract: Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to ... ...

    Abstract Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3 x 10(-21)), A928V (rs35018800, OR = 0.53, P = 1.2 x 10(-9)), and I684S (rs12720356, OR = 0.86, P = 4.6 x 10(-7)). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6 x 10(-18)), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; P(omnibus) = 0.005). Finally, in a phenome-wide association study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR) in >29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  9. Book: Tuberculosis; a global study in social pathology

    McDougall, John Bowes

    1949  

    Keywords Tuberculosis / Epidemiology and statistics
    Language English
    Size viii, 455 p., ill.
    Publisher Williams & Wilkins
    Publishing place Baltimore
    Document type Book
    Database Catalogue of the US National Library of Medicine (NLM)

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  10. Book: The tuberculosis control programme in Italy

    McDougall, John Bowes

    1949  

    Institution World Health Organization,
    Author's details investigator, Dr. J.B. McDougall
    MeSH term(s) Tuberculosis/epidemiology ; Tuberculosis/therapy ; National Health Programs/statistics & numerical data ; Epidemiologic Studies ; Program Evaluation
    Keywords Italy
    Language English
    Size 39 pages
    Document type Book
    Note Cover title. ; WHO/TBC/9. ; "25 July 1949." ; "Original: English." ; "Period of investigation: June 1949 (following previous visits in 1945, 1946, and 1948)."
    Database Catalogue of the US National Library of Medicine (NLM)

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top