SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Savage Christopher) "

Sökning: WFRF:(Savage Christopher)

  • Resultat 1-10 av 34
  • [1]234Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Wang, Zhaoming, et al. (författare)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • Ingår i: Human Molecular Genetics. - 0964-6906. ; 23:24, s. 6616-6633
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
  •  
2.
  • Machiela, Mitchell J, et al. (författare)
  • Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
  • 2016
  • Ingår i: Nature Communications. - Nature Publishing Group. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
  •  
3.
  • Athron, Peter, et al. (författare)
  • A global fit of the MSSM with GAMBIT
  • 2017
  • Ingår i: European Physical Journal C. - 1434-6044. ; 77:12
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the seven-dimensional Minimal Super-symmetric Standard Model (MSSM7) with the new GAMBIT software framework, with all parameters defined at the weak scale. Our analysis significantly extends previous weak-scale, phenomenological MSSM fits, by adding more and newer experimental analyses, improving the accuracy and detail of theoretical predictions, including dominant uncertainties from the Standard Model, the Galactic dark matter halo and the quark content of the nucleon, and employing novel and highly-efficient statistical sampling methods to scan the parameter space. We find regions of the MSSM7 that exhibit co-annihilation of neutralinos with charginos, stops and sbottoms, as well as models that undergo resonant annihilation via both light and heavy Higgs funnels. We find high-likelihood models with light charginos, stops and sbottoms that have the potential to be within the future reach of the LHC. Large parts of our preferred parameter regions will also be accessible to the next generation of direct and indirect dark matter searches, making prospects for discovery in the near future rather good.
  •  
4.
  • Athron, Peter, et al. (författare)
  • GAMBIT : the global and modular beyond-the-standard-model inference tool
  • 2017
  • Ingår i: European Physical Journal C. - 1434-6044. ; 77:11
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the open-source global fitting package GAMBIT: the Global And Modular Beyond-the-Standard-Model Inference Tool. GAMBIT combines extensive calculations of observables and likelihoods in particle and astroparticle physics with a hierarchical model database, advanced tools for automatically building analyses of essentially any model, a flexible and powerful system for interfacing to external codes, a suite of different statistical methods and parameter scanning algorithms, and a host of other utilities designed to make scans faster, safer and more easily-extendible than in the past. Here we give a detailed description of the framework, its design and motivation, and the current models and other specific components presently implemented in GAMBIT. Accompanying papers deal with individual modules and present flrst GAMBIT results. GAMBIT can be downloaded from gambit.hepforge.org.
  •  
5.
  • Athron, Peter, et al. (författare)
  • Global fits of GUT-scale SUSY models with GAMBIT
  • 2017
  • Ingår i: European Physical Journal C. - 1434-6044. ; 77:12
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the most comprehensive global fits to date of three supersymmetric models motivated by grand unification: the Constrained Minimal Supersymmetric Standard Model (CMSSM), and its Non-Universal Higgs Mass generalisations NUHM1 and NUHM2. We include likelihoods from a number of direct and indirect dark matter searches, a large collection of electroweak precision and flavour observables, direct searches for supersymmetry at LEP and Runs I and II of the LHC, and constraints from Higgs observables. Our analysis improves on existing results not only in terms of the number of included observables, but also in the level of detail with which we treat them, our sampling techniques for scanning the parameter space, and our treatment of nuisance parameters. We show that stau co-annihilation is now ruled out in the CMSSM at more than 95% confidence. Stop co-annihilation turns out to be one of the most promising mechanisms for achieving an appropriate relic density of darkmatter in all threemodels, whilst avoiding all other constraints. We find high-likelihood regions of parameter space featuring light stops and charginos, making them potentially detectable in the near future at the LHC. We also show that tonne-scale direct detection will play a largely complementary role, probing large parts of the remaining viable parameter space, including essentially all models with multi-TeV neutralinos.
  •  
6.
  • Athron, Peter, et al. (författare)
  • Status of the scalar singlet dark matter model
  • 2017
  • Ingår i: European Physical Journal C. - 1434-6044. ; 77:8
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the simplest viable models for dark matter is an additional neutral scalar, stabilised by a symmetry. Using the GAMBIT package and combining results from four independent samplers, we present Bayesian and frequentist global fits of this model. We vary the singlet mass and coupling along with 13 nuisance parameters, including nuclear uncertainties relevant for direct detection, the local dark matter density, and selected quark masses and couplings. We include the dark matter relic density measured by Planck, direct searches with LUX, PandaX, SuperCDMS and XENON100, limits on invisible Higgs decays from the Large Hadron Collider, searches for high-energy neutrinos from dark matter annihilation in the Sun with IceCube, and searches for gamma rays from annihilation in dwarf galaxies with the Fermi-LAT. Viable solutions remain at couplings of order unity, for singlet masses between the Higgs mass and about 300 GeV, and at masses above 1 TeV. Only in the latter case can the scalar singlet constitute all of dark matter. Frequentist analysis shows that the low-mass resonance region, where the singlet is about half the mass of the Higgs, can also account for all of dark matter, and remains viable. However, Bayesian considerations show this region to be rather fine-tuned.
  •  
7.
  • Brownstein, Catherine A., et al. (författare)
  • An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
  • 2014
  • Ingår i: Genome Biology. - 1465-6906. ; 15:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
  •  
8.
  • Brownstein, Catherine A., et al. (författare)
  • An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
  • 2014
  • Ingår i: Genome Biology. - 1465-6906 .- 1474-760X. ; 15:3, s. R53
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
  •  
9.
  • Gilbert, Benjamin, et al. (författare)
  • A bioenergetic framework for the temperature dependence of trophic interactions
  • 2014
  • Ingår i: Ecology Letters. - 1461-023X. ; 17:8, s. 902-914
  • Tidskriftsartikel (refereegranskat)abstract
    • Changing temperature can substantially shift ecological communities by altering the strength and stability of trophic interactions. Because many ecological rates are constrained by temperature, new approaches are required to understand how simultaneous changes in multiple rates alter the relative performance of species and their trophic interactions. We develop an energetic approach to identify the relationship between biomass fluxes and standing biomass across trophic levels. Our approach links ecological rates and trophic dynamics to measure temperature-dependent changes to the strength of trophic interactions and determine how these changes alter food web stability. It accomplishes this by using biomass as a common energetic currency and isolating three temperature-dependent processes that are common to all consumer-resource interactions: biomass accumulation of the resource, resource consumption and consumer mortality. Using this framework, we clarify when and how temperature alters consumer to resource biomass ratios, equilibrium resilience, consumer variability, extinction risk and transient vs. equilibrium dynamics. Finally, we characterise key asymmetries in species responses to temperature that produce these distinct dynamic behaviours and identify when they are likely to emerge. Overall, our framework provides a mechanistic and more unified understanding of the temperature dependence of trophic dynamics in terms of ecological rates, biomass ratios and stability.
  •  
10.
  • Jacobs, Kevin B, et al. (författare)
  • Detectable clonal mosaicism and its relationship to aging and cancer.
  • 2012
  • Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036. ; 44:6, s. 651-658
  • Tidskriftsartikel (refereegranskat)abstract
    • In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 34
  • [1]234Nästa
Typ av publikation
tidskriftsartikel (33)
konferensbidrag (1)
Typ av innehåll
refereegranskat (34)
Författare/redaktör
Savage, Christopher, (21)
Edsjö, Joakim, (9)
Gapstur, Susan M (8)
Stevens, Victoria L (8)
Severi, Gianluca (8)
Yeager, Meredith (8)
visa fler...
Scott, Pat, (8)
Duell, Eric J. (8)
Black, Amanda (8)
Conrad, Jan, (7)
Chanock, Stephen J (7)
Albanes, Demetrius (7)
Canzian, Federico (7)
Lissowska, Jolanta (7)
Kraft, Peter (7)
Gaziano, J Michael (7)
Freese, Katherine, (6)
Bueno-de-Mesquita, H ... (6)
Weniger, Christoph (6)
Krogh, Vittorio (5)
Khaw, Kay-Tee (5)
Riboli, Elio (5)
Wolk, Alicja (5)
Haiman, Christopher ... (5)
Berndt, Sonja I (5)
Cancel-Tassin, Geral ... (5)
Giles, Graham G (5)
Johansen, Christoffe ... (5)
Jenab, Mazda (5)
Garcia-Closas, Monts ... (5)
Hoover, Robert N. (5)
Kolonel, Laurence N (5)
Olson, Sara H. (5)
Davis, Faith G. (5)
Melin, Beatrice S., (5)
Bracci, Paige M (5)
Holly, Elizabeth A (5)
Hutchinson, Amy (5)
Kooperberg, Charles (5)
Kurtz, Robert C (5)
Li, Donghui (5)
Risch, Harvey A (5)
Shu, Xiao-Ou (5)
Henriksson, Roger, (5)
Bringmann, Torsten (5)
Cornell, Jonathan M. (5)
Dal, Lars A. (5)
Farmer, Ben, (5)
Kvellestad, Anders (5)
Putze, Antje (5)
visa färre...
Lärosäte
Stockholms universitet (23)
Kungliga Tekniska Högskolan (7)
Umeå universitet (6)
Karolinska Institutet (6)
Uppsala universitet (4)
Lunds universitet (1)
Språk
Engelska (34)
Forskningsämne (UKÄ/SCB)
Naturvetenskap (24)
Medicin och hälsovetenskap (10)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy