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

High Cationic Dispersity Boosted Oxygen Reduction Reactivity in Multi-Element Doped Perovskites

Oxygen-ion conducting perovskite oxides are important functional materials for solid oxide fuel cells and oxygen-permeable membranes operating at high temperatures (>500 °C). Co-doped perovskites have recently shown their potential to boost oxygen-related kinetics, but challenges remain in understanding the underlying mechanisms. This study unveils the local cation arrangement as a new key factor controlling oxygen kinetics in perovskite oxides. By single- and co-doping Nb5+ and Ta5+ into SrCoO3-δ, dominant factors affecting oxygen kinetics, such as lattice geometry, cobalt states, and oxygen vacancies, which are confirmed by neutron and synchrotron X-ray diffraction as well as high-temperature X-ray absorption spectroscopy, are controlled. The combined experimental and theoretical study unveils that co-doping likely leads to higher cation dispersion at the B-site compared to single-doping. Consequently, a high-entropy configuration enhances oxygen ion migration in the lattice, translating to improved oxygen reduction activity.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.ChemE/Materials for Energy Conversion and Storag