| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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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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| 2. |
- Geoffroy, Gaspard, 1991-, et al.
(författare)
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Validating the spatial variability in the semidiurnal internal tide in a realistic global ocean simulation with Argo and mooring data
- 2023
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Ingår i: Ocean Science. - 1812-0784 .- 1812-0792. ; 19:3, s. 811-835
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Tidskriftsartikel (refereegranskat)abstract
- The autocovariance of the semidiurnal internal tide (IT) is examined in a 32 d segment of a global run of the HYbrid Coordinate Ocean Model (HYCOM). This numerical simulation, with 41 vertical layers and ∘ horizontal resolution, includes tidal and atmospheric forcing, allowing for the generation and propagation of ITs to take place within a realistic eddying general circulation. The HYCOM data are in turn compared with global observations of the IT around 1000 dbar, from Argo float park-phase data and mooring records. HYCOM is found to be globally biased low in terms of the IT variance and decay of the IT autocovariance over timescales shorter than 32 d. Except in the Southern Ocean, where limitations in the model cause the discrepancy with in situ measurements to grow poleward, the spatial correlation between the Argo and HYCOM tidal variance suggests that the generation of low-mode semidiurnal ITs is globally well captured by the model.
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