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

Development and evaluation of rocket blast and rain erosion resistant composite coatings produced by flame spray techniques /

"February 1959."Includes bibliographical references (pages 33-56).Report prepared by the Research and Development Section, Plastics Group, Technical Staff - Engineering Process Unit, Boeing Airplane Company, Wichita Division, Wichita, Kanas, under U.S.A.F Contract No.Mode of access: Internet

SPORT : a system for processing reactor transient data on the IBM-7040 computer /

To facilitate the processing and analysis of data recorded during transient tests in the Spert reactors, a system of programs for the IBM-7040 computer has been developed to (a) smooth and store data so they are readily accessible, (b) calculate from the power history the reactivity and energy release as functions of time, and (c) provide a means by which frequency response analyses of data can be made. This report describes the mathematics employed in the various programs in the system and the procedures necessary to process data with the system. Test and sample problems are presented, and a complete listing of the source program is included."National Reactor Testing Station"--Cover."Phillips Petroleum Company, Atomic Energy Division, Contract AT(10-1)-205.""Reactor Technology ; TID-4500, (41st Ed.).""Issued: July 1965."Includes bibliographical references (p. 116).To facilitate the processing and analysis of data recorded during transient tests in the Spert reactors, a system of programs for the IBM-7040 computer has been developed to (a) smooth and store data so they are readily accessible, (b) calculate from the power history the reactivity and energy release as functions of time, and (c) provide a means by which frequency response analyses of data can be made. This report describes the mathematics employed in the various programs in the system and the procedures necessary to process data with the system. Test and sample problems are presented, and a complete listing of the source program is included.Mode of access: Internet