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

Supporting Literacy and Digital Literacy Development in Early Childhood Education Using Storytelling Activities

Educators have increasingly adopted formalized approaches for teaching literacy skills in early childhood education. In line with an emergent critique of this approach, the present study investigated the design and effectiveness of a literacy intervention that blended Gagné’s nine events of instructional design with storytelling. Three classes in a public preschool in Indonesia participated in an experimental study involving 45 children, aged 5–6 years. Across 3 weeks, one experimental condition received storytelling activities and a second experimental condition received digital storytelling activities. The control condition received regular literacy classroom activities. Before, and after, the 3-week storytelling intervention, measures of literacy and digital literacy skills were administered to all groups. In the digital storytelling condition, children’s literacy skills increased significantly compared to children in the control condition. Other exploratory data analyses suggested that both types of storytelling activities enhanced digital literacy skills. The findings need to be replicated with an extended series of storytelling activities that involve larger groups of participants

Robot Programming to Empower Higher Cognitive Functions in Early Childhood

This chapter describes a new approach of educational robotics (ER) aimed at empowering higher cognitive functions in school. As robot programming requires mentally planning complex action sequences before the motor act, ER may promote several crucial cognitive processes underlying learning. During robot programming, the child has to first set the target, second sequentially think through the steps needed to achieve that target, then verify the goal, and eventually reset the plan. All these mental acts involve executive functions (EFs), which are complex higher cognitive processes, crucial in early development because they are the base for abstraction and logical reasoning, decision-making, sequential thinking, and maintaining and updating information in memory and problem-solving. Robot programming may empower EFs not only by improving top-down cognitive control, working memory, and inhibition skills but also by placing the child, more than other passive thought technologies, in front of “objects to think with” in a group setting that stimulates the use of EFs for social and emotional purposes. Recent studies demonstrating, through a rigorous and scientific approach, the effect of ER on EFs in typical and atypical development will be discussed