Publications
305 results found
Annamalay A, James P, Lanaspa M, et al., 2016, Microbial diversity and abundance in respiratory disease and HIV in children from Mozambique, Thoracic Society of Australia & New Zealand and the Australian & New Zealand Society of Respiratory Science, Annual Scientific Meeting, Publisher: Wiley, Pages: 57-57, ISSN: 1440-1843
Annamalay A, James P, Lanaspa M, et al., 2016, Microbial Diversity And Abundance In Respiratory Disease And Hiv In Children From Mozambique, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Singanayagam A, Glanville N, Pearson R, et al., 2015, FLUTICASONE PROPIONATE ALTERS THE RESIDENT AIRWAY MICROBIOTA AND IMPAIRS ANTI-VIRAL AND ANTI-BACTERIAL IMMUNE RESPONSES IN THE AIRWAYS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A1-A1, ISSN: 0040-6376
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- Citations: 2
Vukcevic D, Traherne JA, Naess S, et al., 2015, Imputation of KIR Types from SNP Variation Data, American Journal of Human Genetics, Vol: 97, Pages: 593-607, ISSN: 1537-6605
Large population studies of immune system genes are essential for characterizing their role in diseases, including autoimmune conditions. Of key interest are a group of genes encoding the killer cell immunoglobulin-like receptors (KIRs), which have known and hypothesized roles in autoimmune diseases, resistance to viruses, reproductive conditions, and cancer. These genes are highly polymorphic, which makes typing expensive and time consuming. Consequently, despite their importance, KIRs have been little studied in large cohorts. Statistical imputation methods developed for other complex loci (e.g., human leukocyte antigen [HLA]) on the basis of SNP data provide an inexpensive high-throughput alternative to direct laboratory typing of these loci and have enabled important findings and insights for many diseases. We present KIR∗IMP, a method for imputation of KIR copy number. We show that KIR∗IMP is highly accurate and thus allows the study of KIRs in large cohorts and enables detailed investigation of the role of KIRs in human disease.
Holt RJ, Vandiedonck C, Willis-Owen SA, et al., 2015, A functional AT/G polymorphism in the 5'-untranslated region (UTR) of SETDB2 in the IgE locus on human chromosome 13q14, Genes and Immunity, Vol: 16, Pages: 488-494, ISSN: 1476-5470
The IgE associated locus on human chromosome 13q14 influencing asthma related traits contains the genes PHF11 and SETDB2. SETDB2 is located in the same linkage disequilibrium region as PHF11 and polymorphisms within SETDB2 have been shown to associate with total serum IgE levels. In this report, we sequenced the 15 exons of SETDB2 and identified a single previously un-genotyped mutation (AT/G, rs386770867) in the 5’ untranslated region (UTR) of the gene. The polymorphism was found to be significantly associated with serum IgE levels in our asthma cohort (P = 0.0012). Electrophoretic mobility shift assays (EMSA) revealed that the transcription factor YY1 binds to the AT allele whilst SRY binds to the G allele. Allele-specific transcription analysis (allelotyping) was performed in 35 individuals heterozygous for rs386770867 from a panel of 200 British families ascertained through probands with severe Stage 3 asthma. The AT allele was found to be significantly over expressed in these individuals (P = 1.26 x 10-21). A dual luciferase assay with the pGL3 Luciferase report gene showed that the AT allele significantly affects transcriptional activities. Our results indicate the IgE-associated AT/G polymorphism (rs386770867) regulates transcription of SETDB2.
Brill S, James P, Cuthbertson L, et al., 2015, LATE-BREAKING ABSTRACT: Haemophilus dominance of the stable COPD microbiome is associated with greater bacterial load and inflammation and is modulated by prophylactic antibiotic therapy, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Molyneaux P, Cookson W, Moffatt M, et al., 2015, LSC Abstract - Changes in the respiratory microbiome during acute exacerbations of Idiopathic Pulmonary Fibrosis, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Brill SE, James P, Cookson WOC, et al., 2015, Relationship between COPD characteristics and airway bacterial load measured using 16S qPCR, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Lu SK, Anbunathan H, Popat S, et al., 2015, Molecular Landscape of Malignant Mesothelioma from Whole Exome Sequencing, Publisher: ELSEVIER SCIENCE INC, Pages: S253-S253, ISSN: 1556-0864
Cox MJ, Moffatt MF, Cookson WOC, 2015, Outside In: Sequencing the Lung Microbiome, American Journal of Respiratory and Critical Care Medicine, Vol: 192, Pages: 403-404, ISSN: 1535-4970
Brill S, Law M, El-Emir E, et al., 2015, Effects of different antibiotic classes on airwaybacteria in stable COPD using culture and molecularQ1 techniques: a randomised controlled trial, Thorax, Vol: 70, Pages: 930-938, ISSN: 1468-3296
BackgroundLong term antibiotic therapy is used to prevent exacerbations of chronic obstructive pulmonary disease (COPD) but there is uncertainty over whether this reduces airway bacteria. The optimum antibiotic choice remains unknown. We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo. MethodsThis was a single-centre, single-blind, randomised placebo-controlled trial (clinicaltrials.gov number NCT01398072). Patients ≥45 years with COPD, FEV1<80% predicted and chronic productive cough were randomised to receive either moxifloxacin 400mg daily for 5 days/4 weeks, doxycycline 100mg/day, azithromycin 250mg 3x/week or one placebo tablet daily for 13 weeks. The primary outcome was the change in total cultured bacterial load in sputum from baseline; secondary outcomes included bacterial load by 16S qPCR, sputum inflammation and antibiotic resistance. Results99 patients were randomised; 86 completed follow-up, were able to expectorate sputum and were analysed. After adjustment, there was a mean reduction in bacterial load of 0.42 log10 cfu/ml (95% CI -0.08, 0.91, p=0.10) with moxifloxacin, 0.11 (-0.33, 0.55, p=0.62) with doxycycline, and 0.08 (-0.38, 0.54, p=0.73) with azithromycin from placebo, respectively. There were also no significant changes in bacterial load measured by 16S qPCR or in airway inflammation. More treatment-related adverse events occurred with moxifloxacin. Of note, mean inhibitory concentrations of cultured isolates increased by at least 3 times over placebo in all treatment arms.ConclusionsTotal airway bacterial load did not decrease significantly after three months of antibiotic therapy. Large increases in antibiotic resistance were seen in all treatment groups and this has important implications for future studies.
Shaw AG, Sim K, Randell P, et al., 2015, Late-onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants, PLOS One, Vol: 10, ISSN: 1932-6203
Huang Y-T, Liang L, Moffatt MF, et al., 2015, iGWAS: Integrative Genome-Wide Association Studies of Genetic and Genomic Data for Disease Susceptibility Using Mediation Analysis, GENETIC EPIDEMIOLOGY, Vol: 39, Pages: 347-356, ISSN: 0741-0395
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- Citations: 30
Huang J, Chen J, Esparza J, et al., 2015, eQTL mapping identifies insertion- and deletion-specific eQTLs in multiple tissues, NATURE COMMUNICATIONS, Vol: 6
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- Citations: 11
Liang L, Willis-Owen SA, Laprise C, et al., 2015, An epigenome-wide association study of total serum immunoglobulin E concentration, Nature, Vol: 520, Pages: 670-674, ISSN: 0028-0836
Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE can alleviate hay fever and allergic asthma. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation. We therefore surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genome wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes. We validated positive results in additional families and in subjects from the general population. Here we show replicated associations-with a meta-analysis false discovery rate less than 10(-4)-between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors and mitochondrial proteins. We confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without asthma and high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining the tenfold higher variance found compared with that derived from large single-nucleotide polymorphism genome-wide association studies. This study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases.
Shungin D, Winkler TW, Croteau-Chonka DC, et al., 2015, New genetic loci link adipose and insulin biology to body fat distribution, NATURE, Vol: 518, Pages: 187-U378, ISSN: 0028-0836
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- Citations: 989
Locke AE, Kahali B, Berndt SI, et al., 2015, Genetic studies of body mass index yield new insights for obesity biology, Nature, Vol: 518, Pages: 197-206, ISSN: 0028-0836
O'Neal WK, Gallins P, Pace RG, et al., 2015, Gene Expression in Transformed Lymphocytes Reveals Variation in Endomembrane and HLA Pathways Modifying Cystic Fibrosis Pulmonary Phenotypes, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 96, Pages: 318-328, ISSN: 0002-9297
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- Citations: 23
Sim K, Shaw AG, Randell P, et al., 2015, Dysbiosis anticipating necrotizing enterocolitis in very premature infants, Clinical Infectious Diseases, Vol: 60, Pages: 389-397, ISSN: 1537-6591
Background. Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel disease of premature infants speculatively associated with infection. Suspected NEC can be indistinguishable from sepsis, and in established cases an infant may die within hours of diagnosis. Present treatment is supportive. A means of presymptomatic diagnosis is urgently needed. We aimed to identify microbial signatures in the gastrointestinal microbiota preceding NEC diagnosis in premature infants.Methods. Fecal samples and clinical data were collected from a 2-year cohort of 369 premature neonates. Next-generation sequencing of 16S ribosomal RNA gene regions was used to characterize the microbiota of prediagnosis fecal samples from 12 neonates with NEC, 8 with suspected NEC, and 44 controls. Logistic regression was used to determine clinical characteristics and operational taxonomic units (OTUs) discriminating cases from controls. Samples were cultured and isolates identified using matrix-assisted laser desorption/ionization–time of flight. Clostridial isolates were typed and toxin genes detected.Results. A clostridial OTU was overabundant in prediagnosis samples from infants with established NEC (P = .006). Culture confirmed the presence of Clostridium perfringens type A. Fluorescent amplified fragment-length polymorphism typing established that no isolates were identical. Prediagnosis samples from NEC infants not carrying profuse C. perfringens revealed an overabundance of a Klebsiella OTU (P = .049). Prolonged continuous positive airway pressure (CPAP) therapy with supplemental oxygen was also associated with increased NEC risk.Conclusions. Two fecal microbiota signatures (Clostridium and Klebsiella OTUs) and need for prolonged CPAP oxygen signal increased risk of NEC in presymptomatic infants. These biomarkers will assist development of a screening tool to allow very early diagnosis of NEC.Clinical Trials Registration. NCT01102738.
James PL, Cannon J, Crawford L, et al., 2015, Molecular Detection Of Mycobacterium Avium In Aerosolised Metal Working Fluid Is Linked To A Localised Outbreak Of Extrinsic Allergic Alveolitis In Factory Workers, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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- Citations: 1
Cox MJ, Salter SJ, Turek EM, et al., 2015, Contamination Of Reagents Can Critically Impact Sequence-Based Microbiome Studies, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Molyneaux PL, Cox MJ, Cookson WO, et al., 2015, Changes In The Respiratory Microbiome During Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Annamalay AA, James P, Cowman S, et al., 2015, Nontuberculous Mycobacteria In Young South African Children With Acute Lower Respiratory Infections, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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- Citations: 1
Molyneaux PL, Willis-Owen SA, Blanchard A, et al., 2015, The Longitudinal Peripheral Whole Blood Transcriptome In Idiopathic Pulmonary Fibrosis, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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- Citations: 1
Cox MJ, Turek EM, Mirza GK, et al., 2015, Longitudinal Analysis Of The Non-Cystic Fibrosis Bronchiectasis Microbiome, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Brill SE, James P, Cookson WOC, et al., 2015, Comparison Of Quantitative Culture And 16s Qpcr For Quantification Of Total Airway Bacterial Load In Chronic Obstructive Pulmonary Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Wootton DG, Cox MJ, Hickey GL, et al., 2015, The Genus Haemophilus Was Dominant In A Cohort With Community Acquired Pneumonia And Low Species Diversity Was Related To Age And Prior Pulmonary Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
CFelton I, Benson I, Nicholson A, et al., 2014, PRELIMINARY EVALUATION OF THE FUNGAL AIRWAY MICROBIOME IN ADULT CYSTIC FIBROSIS BY NEXT-GENERATION SEQUENCING, CULTURE AND STAINING TECHNIQUES, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A164-A164, ISSN: 0040-6376
Ahmed B, Cox MJ, Cookson WOC, et al., 2014, COMPARISON OF THE UPPER AND LOWER AIRWAY MICROBIOTA IN CHILDREN, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A123-A123, ISSN: 0040-6376
Moffatt MF, 2014, The lung microbiome in health and disease, IMMUNOLOGY, Vol: 143, Pages: 39-39, ISSN: 0019-2805
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