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

Artificial intelligence models for suspended river sediment prediction : state-of-the art, modeling framework appraisal, and proposed future research directions

202303 bcwwVersion of RecordSelf-fundedPublishe

A Computational Simulation of Steady Natural Convection in an H-form Cavity

15 pages, 5 figures, 1 table, 34 references. Other papers can be downloaded at http://www.denys-dutykh.com/International audienceThe simulation of natural convection problem based on the Galerkin finite-element method, with the penalty finite-element formulation of the momentum balance equation, is exploited for accurate solutions of equations describing the problem of H-Form cavity differentially heated side walls. The cavity is occupied by the air whose Prandtl number is Pr=0.71, the fluid is assumed to be steady, viscous and incompressible within thermal convection. A numerical investigation has been made for Rayleigh numbers ranging from 10 to 10^6 for three cases of total internal height aspects of H-Form cavity: 0%, 50%, and 85%. Firstly, the goal is to validate the numerical code used to resolve the equations governing the problem of this work. For that, we present a comparison between the profiles at the point (0.5, 0) for the u-component, and u-component obtained in previous work for simple square cavity. Further, a comparison of the averaged Nusselt number with previous works for simple square cavity is realized in order to ensure the numerical accuracy, and the validity of our considered numerical tool. Secondly, the objective is to investigate on the hydrodynamic effects of Rayleigh number for different total internal height aspects of H-Form cavity on the dynamics of natural convection. Shortly after, the ambition is to assess the heat transfer rate for different Rayleigh number for three cases of internal height aspects