| 1. |
- 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.
|
|
| 2. |
- Rodriguez-Martin, B, et al.
(författare)
-
Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
- 2020
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 52:3, s. 306-
-
Tidskriftsartikel (refereegranskat)abstract
- About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of 22 L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.
|
|
| 3. |
- Yakneen, S, et al.
(författare)
-
Butler enables rapid cloud-based analysis of thousands of human genomes
- 2020
-
Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 38:3, s. 288-
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 4. |
- Doi, Yasuo, et al.
(författare)
-
The JCMT BISTRO Survey: Magnetic Fields Associated with a Network of Filaments in NGC 1333
- 2020
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 899:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present new observations of the active star formation region NGC 1333 in the Perseus molecular cloud complex from the James Clerk Maxwell Telescope B-Fields In Star-forming Region Observations (BISTRO) survey with the POL-2 instrument. The BISTRO data cover the entire NGC 1333 complex (∼1.5 pc ? 2 pc) at 0.02 pc resolution and spatially resolve the polarized emission from individual filamentary structures for the first time. The inferred magnetic field structure is complex as a whole, with each individual filament aligned at different position angles relative to the local field orientation. We combine the BISTRO data with low- and high- resolution data derived from Planck and interferometers to study the multiscale magnetic field structure in this region. The magnetic field morphology drastically changes below a scale of ∼1 pc and remains continuous from the scales of filaments (∼0.1 pc) to that of protostellar envelopes (∼0.005 pc or ∼1000 au). Finally, we construct simple models in which we assume that the magnetic field is always perpendicular to the long axis of the filaments. We demonstrate that the observed variation of the relative orientation between the filament axes and the magnetic field angles are well reproduced by this model, taking into account the projection effects of the magnetic field and filaments relative to the plane of the sky. These projection effects may explain the apparent complexity of the magnetic field structure observed at the resolution of BISTRO data toward the filament network.
|
|
| 5. |
- Ngaosuvan, Leonard, et al.
(författare)
-
Improving Custody Dispute Negotiation: Empirical Testing of the Equality Principle
- 2020
-
Ingår i: Family Court Review. - Hoboken, NJ, United States : Wiley. - 1531-2445 .- 1744-1617. ; 58:4, s. 1049-1060
-
Tidskriftsartikel (refereegranskat)abstract
- The Equality Principle (EP) is a novel idea to motivate parents litigating in custody disputes to negotiate. The EP is designed for a special but common case in which both parents are individually fit, there are no decisive differences between the two households that the parents live in, but the conflict between the parents is so infected that the children's well-being is threatened and shared custody must be ruled out. The present paper empirically tested the Equality Principle in its higher bidder version. In this version, both parents are first told that the conditions for the EP are met. Then, both parents are asked how much visitation they would allow the other parent, assuming that they would win sole custody and living. The most generous parent is awarded custody and living, along with a dictum to facilitate the promised amount of visitation. In the present model (PM), the offered amount of visitation has no functional effect on the custody dispute because the judges and jurors award custody as well as the amount of visitation. A within-subjects vignette experiment measured 52 participants' levels of visitation generosity in the EP and the PM. Participants showed significantly higher visitation generosity in the EP compared to the PM. The results are discussed in terms of representation of the present model, an equal amount of visitation offered, ecological validity, child perspective, and appellant's rights. In conclusion, the present paper showed that the EP is a promising strategy to resolve seemingly unresolvable custody disputes. Practicioner's Keypoints The longer the custody dispute, the more children suffer. The Equality Principle encourages swift resolution which helps children. The Equality Principle is designed to resolve custody litigations where both parents are fit by making them compete in visitation generosity. The Equality Principle has at least two versions; randomization and highest bidder of visitation time wins. Highest bidder is probably more plausible for the general public. Empirical evidence shows that the Equality Principle in the highest bidder wins variant is a promising strategy to quickly resolve high conflict custody disputes with fit parents.
|
|
