Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). 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 promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Representing the road infrastructure in open traffic

In this paper we focus on the design of network objects for all types of assignment methods, varying from macroscopic assignments to micro simulation models. The basic idea is that the model environment should allow the simulation of traffic at multiple scales, based on standardized data formats. We derive the data requirements from an analysis of driving behaviour. Apart from the functional requirements, we propose a data format that aligns with to an existing international standard for geoinformation, i.e. CityGML (Geographical Markup Language for city and landscape models). Based on the requirement analysis we present a shortlist of objects and their characteristics that should be part of the description of the road infrastructure in simulation models. These objects have been implemented in the Open Source traffic and transportation model environment “Open Traffic”. Open Traffic offers the utility to transform the road infrastructure into logical networks for traffic simulation and assignment at various scales.Transport & PlanningCivil Engineering and Geoscience

CIA-2: Deelonderzoek CAPSMAL: Implementatie van een model voor smalle stroken in FOSIM

Onderzoek uitgevoerd door het Laboratorium voor Verkeerskunde van de Technische Universiteit Delft in opdracht van de Adviesdienst Verkeer en Vervoer van Rijkswaterstaat. De Adviesdienst Verkeer en Vervoer van Rijkswaterstaat voert de studie 'Capaciteitswaarden Infrastructuur Autosnelwegen - deel 2' (CIA-2) uit om de capaciteit van verschillende typen wegelementen te bepalen. Eén van de deelstudies van CIA-2, 'CAPSMAL', betreft de capaciteit van dwarsprofielen met smalle rijstroken. Als onderdeel van de CAPSMAL-studie is een eerder door TNO opgesteld model voor bestuurdersgedrag op smalle stroken toegepast in het microsimulatiemodel FOSIM. Hiertoe is allereerst het TNO-model beschreven in relatie tot de werking van FOSIM. Op basis hiervan is het model in FOSIM geïmplementeerd. Verificatie van het model in FOSIM geeft aan dat de implementatie overeenkomstig de specificaties van het TNO-model is, zodat het gebruikt kan worden voor de volgende fase van het CAPSMAL-onderzoek waarin het model voor smalle stroken geanalyseerd wordt om te bepalen hoe het verder ontwikkeld kan worden tot een valide model.Transport & PlanningCivil Engineering and Geoscience

Open traffic: A toolbox for traffic research

Open Traffic is an open source software project that provides a transport modeling software environment. While most transport model packages offer ready-to-use modules for end-users, Open Traffic provides open access to a modelling environment for the (further) development of methods and algorithms and enables the sharing, distribution and further development of the implied knowledge. The Open Traffic platform is designed as a modular system which enables users to utilize existing modules and extend the system with new ones. The system supports the development of multi modal and multi scale models by providing a collection of objects that enable the creation of a transport infrastructure and its environment at multiple levels of detail. The definition of the geographical objects aligns to the principles of CityGML, an open standard for geo data that is internationally accepted by the Open Geospatial Consortium. Additional utilities such as a graphical editor and visualizer, in addition with facilities to import data from external sources like Open Streetmap and Esri shape files, enable users to quickly create and demonstrate their use-cases. In this article we present the high level architecture of Open Traffic, its current status, and a first application with the implementation of the micro simulation model MOTUS. Also, the possibilities and requirements to adhere Open Traffic to agent based modelling approaches are explored.Transport and PlanningCivil Engineering and Geoscience

Impact of radio channel characteristics on the longitudinal behaviour of truck platoons in critical car-following situations

Truck platooning is an application of cooperative adaptive cruise control (CACC) which relies on vehicle-to-vehicle communications facilitated by vehicle ad-hoc networks. Communication uncertainties can affect the performance of a CACC controller. Previous research has not considered the full spectrum of possible car-following scenarios needed to understand how the longitudinal behaviour of truck platoons would be affected by changes in the communication network. In this paper, we investigate the impact of radio channel parameters on the string stability and collision avoidance capabilities of a CACC controller governing the longitudinal behaviour of truck platoons in a majority of critical car-following situations. We develop and use a novel, sophisticated and open-source VANET simulator OTS-Artery, which brings microscopic traffic simulation, network simulation, and psychological concepts in a single environment, for our investigations. Our results indicate that string stability and safety of truck platoons are mostly affected in car-following situations where truck platoons accelerate from the standstill to the maximum speed and decelerate from the maximum speed down to the standstill. The findings suggest that string stability can be improved by increasing transmission power and lowering receiver sensitivity. However, the safety of truck platoons seems to be sensitive to the choice of the path loos model.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Transport and PlanningPolicy Analysi