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Sökning: WFRF:(Mikkelsen T)

  • Resultat 1-10 av 68
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  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • Campbell, PJ, et al. (författare)
  • Pan-cancer analysis of whole genomes
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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  • Timotijevic, L., et al. (författare)
  • Designing a research infrastructure (RI) on food behaviour and health : Balancing user needs, business model, governance mechanisms and technology
  • 2021
  • Ingår i: Trends in Food Science & Technology. - : Elsevier Ltd. - 0924-2244 .- 1879-3053. ; 116, s. 405-414
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A better understanding of food-related behaviour and its determinants can be achieved through harmonisation and linking of the various data-sources and knowledge platforms. Scope: We describe the key decision-making in the development of a prototype of the Determinants and Intake Platform (DI Platform), a data platform that aims to harmonise and link data on consumer food behaviour. It will be part of the Food Nutrition Health Research Infrastructure (FNH-RI) that will facilitate health, social and food sciences. Approach: The decision-making was based on the evidence of user needs and data characteristics that guided the specification of the key building blocks of the DI Platform. Eight studies were carried out, including consumer online survey; interview studies of key DI Platform stakeholders; desk research and workshops. Key findings: Consumers were most willing to share data with universities, then industry and government. Trust, risk perception and altruism predicted willingness to share. For most other stakeholders non-proprietary data was most likely to be shared. Lack of data standards, and incentives for sharing were the main barriers for sharing data among the key stakeholders. The value of various data types would hugely increase if linked with other sources. Finding the right balance between optimizing data sharing and minimizing ethical and legal risks was considered a key challenge. Conclusions: The development of DI Platform is based on careful balancing of the user, technical, business, legal and ethical requirements, following the FAIR principles and the need for financial sustainability, technical flexibility, transparency and multi-layered organisational governance.
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  • Mikkelsen, T N, et al. (författare)
  • Experimental design of multifactor climate change experiments with elevated CO2, warming and drought: the CLIMAITE project
  • 2008
  • Ingår i: Functional Ecology. - : Wiley. - 1365-2435 .- 0269-8463. ; 22:1, s. 185-195
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent findings indicate that the interactions among CO2, temperature and water can be substantial, and that the combined effects on the biological systems of several factors may not be predicted from experiments with one or a few factors. Therefore realistic multifactorial experiments involving a larger set of main factors are needed. We describe a new Danish climate change-related field scale experiment, CLIMAITE, in a heath/grassland ecosystem. CLIMAITE is a full factorial combination of elevated CO2, elevated temperature and prolonged summer drought. The manipulations are intended to mimic anticipated major environmental changes at the site by year 2075 as closely as possible. The impacts on ecosystem processes and functioning (at ecophysiological levels, through responses by individuals and communities to ecosystem-level responses) are investigated simultaneously. The increase of [CO2] closely corresponds with the scenarios for year 2075, while the warming treatment is at the lower end of the predictions and seems to be the most difficult treatment to increase without unwanted side effects on the other variables. The drought treatment follows predictions of increased frequency of drought periods in summer. The combination of the treatments does not create new unwanted side effects on the treatments relative to the treatments alone.
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  • Resultat 1-10 av 68

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