27 research outputs found
Substrate Type Determines Metagenomic Profiles from Diverse Chemical Habitats
Environmental parameters drive phenotypic and genotypic frequency variations in microbial communities and thus control the extent and structure of microbial diversity. We tested the extent to which microbial community composition changes are controlled by shifting physiochemical properties within a hypersaline lagoon. We sequenced four sediment metagenomes from the Coorong, South Australia from samples which varied in salinity by 99 Practical Salinity Units (PSU), an order of magnitude in ammonia concentration and two orders of magnitude in microbial abundance. Despite the marked divergence in environmental parameters observed between samples, hierarchical clustering of taxonomic and metabolic profiles of these metagenomes showed striking similarity between the samples (>89%). Comparison of these profiles to those derived from a wide variety of publically available datasets demonstrated that the Coorong sediment metagenomes were similar to other sediment, soil, biofilm and microbial mat samples regardless of salinity (>85% similarity). Overall, clustering of solid substrate and water metagenomes into discrete similarity groups based on functional potential indicated that the dichotomy between water and solid matrices is a fundamental determinant of community microbial metabolism that is not masked by salinity, nutrient concentration or microbial abundance
Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis.
PURPOSE: This study aimed to quantify the probability of overdiagnosis of prostate cancer by polygenic risk. METHODS: We calculated the polygenic risk score based on 66 known prostate cancer susceptibility variants for 17,012 men aged 50-69 years (9,404 men identified with prostate cancer and 7,608 with no cancer) derived from three UK-based ongoing studies. We derived the probabilities of overdiagnosis by quartiles of polygenic risk considering that the observed prevalence of screen-detected prostate cancer is a combination of underlying incidence, mean sojourn time (MST), test sensitivity, and overdiagnosis. RESULTS: Polygenic risk quartiles 1 to 4 comprised 9, 18, 25, and 48% of the cases, respectively. For a prostate-specific antigen test sensitivity of 80% and MST of 9 years, 43, 30, 25, and 19% of the prevalent screen-detected cancers in quartiles 1 to 4, respectively, were likely to be overdiagnosed cancers. Overdiagnosis decreased with increasing polygenic risk, with 56% decrease between the lowest and the highest polygenic risk quartiles. CONCLUSION: Targeting screening to men at higher polygenic risk could reduce the problem of overdiagnosis and lead to a better benefit-to-harm balance in screening for prostate cancer.N.P. is a Cancer Research UK Clinician Scientist Fellow. The COGS
project was funded through a European Commission’s Seventh
Framework Programme grant (agreement number: 223175-
HEALTH-F2-2009–223175), Cancer Research UK (C490/A10124),
the UK National Institute for Health Research Biomedical Research
Centre at the University of Cambridge. The ProtecT study is supported
by the UK National Institute for Health Research (NIHR)
Health Technology Assessment (HTA) Programme, HTA 96/20/99;
ISRCTN20141297. The Comparative Arm of ProtecT (CAP) trial
is funded by Cancer Research UK and the UK Department of
Health (C11043/A4286, C18281/A8145, C18281/A11326,
and C18281/A15064). UKGPCS is funded by Cancer Research
UK and the National Cancer Research Network. The Biomedical
Research Centre at the Institute of Cancer Research and Royal
Marsden NHS Foundation Trust receive funding support from
NIHR. SEARCH is funded by Cancer Research UK. We thank all
the participants in these studies: members of the ProtecT study
research group (Anne George, Michael Davis, and Athene Lane),
Don Conroy, Craig Luccarini, Caroline Baynes, the SEARCH team,
the Eastern Cancer Registration and Information Centre, and the
general practitioners who assisted with recruitment.
This work was supported by funding from the Cancer Research
UK Clinician Scientist Fellowship.This is the final published version. It first appeared at http://www.nature.com/gim/journal/vaop/ncurrent/full/gim2014192a.html
A new expansive two-open-doors laminoplasty for multilevel cervical spondylotic myelopathy: technical report and follow-up results
Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study.
Background Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).Methods The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.Results Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.Conclusions We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.Impact The metabolome provides a promising set of biomarkers that may aid prostate cancer classification