| 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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| 3. |
- Bennaceur, A., et al.
(författare)
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Mechanisms for leveraging models at runtime in self-adaptive software
- 2014
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Ingår i: Lecture Notes in Computer Science: Dagstuhl Seminar 11481 on Models@run.time; ; 27 November 2011 through 2 December 2011. - Cham : Springer. - 9783319089140
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Konferensbidrag (refereegranskat)abstract
- Modern software systems are often required to adapt their behavior at runtime in order to maintain or enhance their utility in dynamic environments. Models at runtime research aims to provide suitable abstractions, techniques, and tools to manage the complexity of adapting software systems at runtime. In this chapter, we discuss challenges associated with developing mechanisms that leverage models at runtime to support runtime software adaptation. Specifically, we discuss challenges associated with developing effective mechanisms for supervising running systems, reasoning about and planning adaptations, maintaining consistency among multiple runtime models, and maintaining fidelity of runtime models with respect to the running system and its environment. We discuss related problems and state-of-the-art mechanisms, and identify open research challenges.
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| 8. |
- Woll, Petter S, et al.
(författare)
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Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo.
- 2014
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 25:6, s. 794-808
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Tidskriftsartikel (refereegranskat)abstract
- Evidence for distinct human cancer stem cells (CSCs) remains contentious and the degree to which different cancer cells contribute to propagating malignancies in patients remains unexplored. In low- to intermediate-risk myelodysplastic syndromes (MDS), we establish the existence of rare multipotent MDS stem cells (MDS-SCs), and their hierarchical relationship to lineage-restricted MDS progenitors. All identified somatically acquired genetic lesions were backtracked to distinct MDS-SCs, establishing their distinct MDS-propagating function in vivo. In isolated del(5q)-MDS, acquisition of del(5q) preceded diverse recurrent driver mutations. Sequential analysis in del(5q)-MDS revealed genetic evolution in MDS-SCs and MDS-progenitors prior to leukemic transformation. These findings provide definitive evidence for rare human MDS-SCs in vivo, with extensive implications for the targeting of the cells required and sufficient for MDS-propagation.
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| 9. |
- Zhou, M., et al.
(författare)
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Coalescence of Macroscopic Flux Ropes at the Subsolar Magnetopause : Magnetospheric Multiscale Observations
- 2017
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 119:5
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Tidskriftsartikel (refereegranskat)abstract
- We report unambiguous in situ observation of the coalescence of macroscopic flux ropes by the magnetospheric multiscale (MMS) mission. Two coalescing flux ropes with sizes of similar to 1 R-E were identified at the subsolar magnetopause by the occurrence of an asymmetric quadrupolar signature in the normal component of the magnetic field measured by the MMS spacecraft. An electron diffusion region (EDR) with a width of four local electron inertial lengths was embedded within the merging current sheet. The EDR was characterized by an intense parallel electric field, significant energy dissipation, and suprathermal electrons. Although the electrons were organized by a large guide field, the small observed electron pressure nongyrotropy may be sufficient to support a significant fraction of the parallel electric field within the EDR. Since the flux ropes are observed in the exhaust region, we suggest that secondary EDRs are formed further downstream of the primary reconnection line between the magnetosheath and magnetospheric fields.
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