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

DMS cycle in the marine ocean-atmosphere system - A global model study

A global coupled ocean-atmosphere modeling system is established to study the production of dimethylsulfide (DMS) in the ocean, the DMS flux to the atmosphere, and the resulting sulfur concentrations in the atmosphere. The DMS production and consumption processes in the ocean are simulated in the marine biogeochemistry model HAMOCC5, embedded in a ocean general circulation model (MPI-OM). The atmospheric model ECHAM5 is extended by the microphysical aerosol model HAM, treating the sulfur chemistry in the atmosphere and the evolution of the microphysically interacting internally- and externally mixed aerosol populations. We simulate a global annual mean DMS sea surface concentration of 1.8 nmol 1-1, a DMS emission of 28 Tg(S) yr-1, a DMS burden in the atmosphere of 0.077 Tg(S), and a DMS lifetime of 1.0 days. To quantify the role of DMS in the atmospheric sulfur cycle we simulate the relative contribution of DMS-derived SO2 and SO42- to the total atmospheric sulfur concentrations. DMS contributes 25% to the global annually averaged SO2 column burden. For SO 42- the contribution is 27%. The coupled model setup allows the evaluation of the simulated DMS quantities with measurements taken in the ocean and in the atmosphere. The simulated global distribution of DMS sea surface concentrations compares reasonably well with measurements. The comparison to SO42- surface concentration measurements in regions with a high DMS contribution to SU42- shows an overestimation by the model. This overestimation is most pronounced in the biologically active season with high DMS emissions and most likely caused by a too high simulated SO42- yield from DMS oxidation

The Role of Phytopathogenicity in Bark Beetle–Fungus Symbioses: A Challenge to the Classic Paradigm

The idea that phytopathogenic fungi associated with tree-killing bark beetles are critical for overwhelming tree defenses and incurring host tree mortality, herein called the classic paradigm (CP), has driven research on bark beetle–fungus symbiosis for decades. It has also strongly influenced our views of bark beetle ecology. We discuss fundamental flaws in the CP, including the lack of consistency of virulent fungal associates with tree-killing bark beetles, the lack of correspondence between fungal growth in the host tree and the development of symptoms associated with a successful attack, and the ubiquity of similar associations of fungi with bark beetles that do not kill trees. We suggest that, rather than playing a supporting role for the host beetle (tree killing), phytopathogenicity performs an important role for the fungi. In particular, phytopathogenicity may mediate competitive interactions among fungi and support survival and efficient resource capture in living, defensive trees.DST/NRF Centre of Excellence in Tree Health Biotechnology (CTHB), South Afric

Response of dimethylsulfide (DMS) in the ocean and atmosphere to global warming

A global coupled ocean-atmosphere modeling system is applied in a transient climate simulation to study the response to global warming of Dimethylsulfide (DMS) in the ocean, the DMS flux to the atmosphere, and the resulting DMS concentrations in the atmosphere. The DMS production and consumption processes in the ocean are linked to plankton dynamics simulated in the marine biogeochemistry model HAMOCC5.1, embedded in an ocean general circulation model (MPI-OM). The atmospheric model ECHAM5 is extended by the microphysical aerosol model HAM, treating the sulfur chemistry in the atmosphere and the evolution of microphysically interacting internally and externally mixed aerosol populations. For future conditions (2000-2100) we assume greenhouse gas concentrations, aerosol and aerosol precursor emissions according to the SRES A1B scenario. We analyzed the results in terms of simulated changes between the period 1861-1890 and 2061-2090. For the global annual mean DMS sea surface concentration and the DMS flux we found a reduction by 10%. The DMS burden in the atmosphere is reduced by only 3%, owing to a longer lifetime of DMS in the atmosphere in a warmer climate (+7%). Regionally the response and the underlying mechanisms are quite inhomogeneous. The largest reduction in the DMS sea surface concentration is simulated in the Southern Ocean (-40%) caused by an increase in the summer mixed layer depth, leading to less favorable light conditions for phytoplankton growth. In the mid and low latitudes DMS sea surface concentrations are predominantly reduced due to nutrient limitation of the phytoplankton growth through higher ocean stratification and less transport of nutrients into the surface layers. Copyright 2007 by the American Geophysical Union