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

Dynamic stability of a nonlinear multiple-nanobeam system

We use the incremental harmonic balance (IHB) method to analyse the dynamic stability problem of a nonlinear multiple-nanobeam system (MNBS) within the framework of Eringen’s nonlocal elasticity theory. The nonlinear dynamic system under consideration includes MNBS embedded in a viscoelastic medium as clamped chain system, where every nanobeam in the system is subjected to time-dependent axial loads. By assuming the von Karman type of geometric nonlinearity, a system of m nonlinear partial differential equations of motion is derived based on the Euler–Bernoulli beam theory and D’ Alembert’s principle. All nanobeams in MNBS are considered with simply supported boundary conditions. Semi-analytical solutions for time response functions of the nonlinear MNBS are obtained by using the single-mode Galerkin discretization and IHB method, which are then validated by using the numerical integration method. Moreover, Floquet theory is employed to determine the stability of obtained periodic solutions for different configurations of the nonlinear MNBS. Using the IHB method, we obtain an incremental relationship with the frequency and amplitude of time-varying axial load, which defines stability boundaries. Numerical examples show the effects of different physical and material parameters such as the nonlocal parameter, stiffness of viscoelastic medium and number of nanobeams on Floquet multipliers, instability regions and nonlinear amplitude–frequency response curves of MNBS. The presented results can be useful as a first step in the study and design of complex micro/nanoelectromechanical systems