| 1. |
- Campbell, PJ, et al.
(author)
-
Pan-cancer analysis of whole genomes
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Journal article (peer-reviewed)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.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Pihl, E., et al.
(author)
-
Ten new insights in climate science 2020- A horizon scan
- 2020
-
In: Global Sustainability. - : Cambridge University Press. - 2059-4798.
-
Journal article (peer-reviewed)abstract
- Non-technical summary We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments. Technical summary A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost-benefit ratio and new perspectives on the potential for green growth in the short- A nd long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations. Social media summary Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
|
|
| 5. |
|
|
| 6. |
- Weinstein, John N., et al.
(author)
-
The cancer genome atlas pan-cancer analysis project
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
-
Research review (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
|
|
| 7. |
- Yakneen, S, et al.
(author)
-
Butler enables rapid cloud-based analysis of thousands of human genomes
- 2020
-
In: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 38:3, s. 288-
-
Journal article (peer-reviewed)abstract
- We present Butler, a computational tool that facilitates large-scale genomic analyses on public and academic clouds. Butler includes innovative anomaly detection and self-healing functions that improve the efficiency of data processing and analysis by 43% compared with current approaches. Butler enabled processing of a 725-terabyte cancer genome dataset from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project in a time-efficient and uniform manner.
|
|
| 8. |
|
|
| 9. |
- Pitz-Paal, R., et al.
(author)
-
Concentrating solar power in Europe, the Middle East and North Africa: Achieving its potential
- 2012
-
In: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 33
-
Conference paper (peer-reviewed)abstract
- Concentrating solar power (CSP) is a commercially available renewable energy technology capable of harnessing the immense solar resource in Southern Europe, the Middle East and North Africa (the MENA region), and elsewhere. This paper summarises the findings of a study by the European Academies Science Advisory Council which has examined the current status and development challenges of CSP, and consequently has evaluated the potential contribution of CSP in Europe and the MENA region to 2050. It identifies the actions that will be required by scientists, engineers, policy makers, politicians, business and investors alike, to enable this vast solar resource to make a major contribution to establishing a sustainable energy system. The study concludes that cost reductions of 50-60% in CSP electricity may reasonably be expected in the next 10-15 years, enabling the technology to be cost competitive with fossil-fired power generation at some point between 2020 and 2030. Incorporation of storage delivers added value in enabling CSP to deliver dispatchable power. Incentive schemes will be needed in Europe and MENA countries to enable this point to be achieved. Such schemes should reflect the true value of electricity to the grid, effectively drive R&D, and ensure transparency of performance and cost data.
|
|
| 10. |
- Hugosson, J, et al.
(author)
-
Population-based screening for prostate cancer by measuring free and total serum prostate-specific antigen in Sweden
- 2003
-
In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 92, s. 39-43
-
Journal article (peer-reviewed)abstract
- Objectives To report the initial results from Sweden of a large population-based randomized study of screening using prostate-specific antigen (PSA) to detect prostate cancer, as the efficacy of such screening to decrease prostate cancer mortality has not yet been proven. Methods From the population registry men aged 50-66 years were randomized to screening (9973) and to future controls (9973). Men randomized to screening were invited to have their serum measured for free PSA (fPSA) and total PSA (tPSA) in serum using the Prostatus(R) f/tPSA assay (Perkin-Elmer, Turku, Finland). Men with a tPSA of <3.0 ng/mL were not further investigated, while those with a tPSA of &GE;3.0 ng/mL were investigated with a digital rectal examination (DRE), transrectal ultrasonography (TRUS) and sextant biopsies. Results Of those invited, 60% accepted PSA testing and 11.3% had a tPSA of &GE;3.0 ng/mL. Altogether 145 cancers were detected (positive predictive value, PPV, 24%); none were stage M1, two were stage N+ and 10 stage T3-4. Most (59%) cancers were impalpable and 39% were both impalpable and invisible on TRUS. At biopsy, 7% were Gleason score 2-4, 71% 5-6, 19% 7 and 2% Gleason score 8-10. A threshold tPSA of &GE;4.0 ng/mL would have detected 109 cancers in 366 biopsied men (PPV 30%) while cancer detection would have been 14% higher with a PPV of 36% using a threshold tPSA of &GE;3.0 ng/mL combined with a f/tPSA threshold of &LE;18%. Conclusion PSA screening detects early-stage low-grade prostate cancer. Both the sensitivity and specificity can be increased by incorporating f/tPSA with a tPSA threshold of <4 ng/mL.
|
|
