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- 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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| 4. |
- Rohde, Mitchell M., et al.
(författare)
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An Interactive, physics-based unmanned ground vehicle simulator leveraging open source gaming technology : Progress in the development and application of the virtual autonomous navigation environment (VANE) desktop
- 2009
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Ingår i: Unmanned Systems Technology XI. - Bellingham, WA : SPIE - International Society for Optical Engineering. - 9780819475985 ; , s. Article number 73321C-
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Konferensbidrag (refereegranskat)abstract
- It is widely recognized that simulation is pivotal to vehicle development, whether manned or unmanned. There are few dedicated choices, however, for those wishing to perform realistic, end-to-end simulations of unmanned ground vehicles (UGVs). The Virtual Autonomous Navigation Environment (VANE), under development by US Army Engineer Research and Development Center (ERDC), provides such capabilities but utilizes a High Performance Computing (HPC) Computational Testbed (CTB) and is not intended for on-line, real-time performance. A product of the VANE HPC research is a real-time desktop simulation application under development by the authors that provides a portal into the HPC environment as well as interaction with wider-scope semi-automated force simulations (e.g. OneSAF). This VANE desktop application, dubbed the Autonomous Navigation Virtual Environment Laboratory (ANVEL), enables analysis and testing of autonomous vehicle dynamics and terrain/obstacle interaction in real-time with the capability to interact within the HPC constructive geo-environmental CTB for high fidelity sensor evaluations. ANVEL leverages rigorous physics-based vehicle and vehicle-terrain interaction models in conjunction with high-quality, multimedia visualization techniques to form an intuitive, accurate engineering tool. The system provides an adaptable and customizable simulation platform that allows developers a controlled, repeatable testbed for advanced simulations. ANVEL leverages several key technologies not common to traditional engineering simulators, including techniques from the commercial video-game industry. These enable ANVEL to run on inexpensive commercial, off-the-shelf (COTS) hardware. In this paper, the authors d escribe key aspects of ANVEL and its development, as well as several initial applications of the system. © 2009 SPIE.
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