| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
- 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. |
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| 4. |
- Allaria, E., et al.
(författare)
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Highly coherent and stable pulses from the FERMI seeded free-electron laser in the extreme ultraviolet
- 2012
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Ingår i: Nature Photonics. - 1749-4885. ; 6:10, s. 699-704
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Tidskriftsartikel (refereegranskat)abstract
- Free-electron lasers (FELs) are promising devices for generating light with laser-like properties in the extreme ultraviolet and X-ray spectral regions. Recently, FELs based on the self-amplified spontaneous emission (SASE) mechanism have allowed major breakthroughs in diffraction and spectroscopy applications, despite the relatively large shot-to-shot intensity and photon-energy fluctuations and the limited longitudinal coherence inherent in the SASE mechanism. Here, we report results on the initial performance of the FERMI seeded FEL, based on the high-gain harmonic generation configuration, in which an external laser is used to initiate the emission process. Emission from the FERMI FEL-1 source occurs in the form of pulses carrying energy of several tens of microjoules per pulse and tunable throughout the 65 to 20 nm wavelength range, with unprecedented shot-to-shot wavelength stability, low-intensity fluctuations, close to transform-limited bandwidth, transverse and longitudinal coherence and full control of polarization.
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| 5. |
- Rheinbay, E, et al.
(författare)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 6. |
- Carlevaro-Fita, J, et al.
(författare)
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Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
- 2020
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
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Tidskriftsartikel (refereegranskat)abstract
- Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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| 7. |
- Dearing, JA, et al.
(författare)
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Social-ecological systems in the Anthropocene : The need for integrating social and biophysical records at regional scales.
- 2015
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Ingår i: The Anthropocene Review. - : SAGE Publications. - 2053-0196 .- 2053-020X. ; 2:3, s. 220-246
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Tidskriftsartikel (refereegranskat)abstract
- Understanding social-ecological system dynamics is a major research priority for sustainable management of landscapes, ecosystems and resources. But the lack of multi-decadal records represents an important gap in information that hinders the development of the research agenda. Without improved information on the long-term and complex interactions between causal factors and responses, it will be difficult to answer key questions about trends, rates of change, tipping points, safe operating spaces and pre-impact conditions. Where available long-term monitored records are too short or lacking, palaeoenvironmental sciences may provide continuous multi-decadal records for an array of ecosystem states, processes and services. Combining these records with conventional sources of historical information from instrumental monitoring records, official statistics and enumerations, remote sensing, archival documents, cartography and archaeology produces an evolutionary framework for reconstructing integrated regional histories. We demonstrate the integrated approach with published case studies from Australia, China, Europe and North America.
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| 8. |
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| 9. |
- Herbst, SA, et al.
(författare)
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Proteogenomics refines the molecular classification of chronic lymphocytic leukemia
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 6226-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic-based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterize the proteome and transcriptome alongside genetic and ex-vivo drug response profiling in a clinically annotated CLL discovery cohort (n = 68). Unsupervised clustering of the proteome data reveals six subgroups. Five of these proteomic groups are associated with genetic features, while one group is only detectable at the proteome level. This new group is characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). Classifiers developed to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n = 165, n = 169) confirm that ASB-CLL comprises about 20% of CLL patients. The inferior overall survival in ASB-CLL is also independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling.
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| 10. |
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