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

Catchment classification: Empirical analysis of hydrologic similarity based on catchment function in the eastern USA

Hydrologic similarity between catchments, derived from similarity in how catchments respond to precipitation input, is the basis for catchment classification, for transferability of information, for generalization of our hydrologic understanding and also for understanding the potential impacts of environmental change. An important question in this context is, how far can widely available hydrologic information (precipitation-temperature-streamflow data and generally available physical descriptors) be used to create a first order grouping of hydrologically similar catchments? We utilize a heterogeneous dataset of 280 catchments located in the Eastern US to understand hydrologic similarity in a 6-dimensional signature space across a region with strong environmental gradients. Signatures are defined as hydrologic response characteristics that provide insight into the hydrologic function of catchments. A Bayesian clustering scheme is used to separate the catchments into 9 homogeneous classes, which enable us to interpret hydrologic similarity with respect to similarity in climatic and landscape attributes across this region. We finally derive several hypotheses regarding controls on individual signatures from the analysis performed here.Civil Engineering and Geoscience

The future of hydrology: An evolving science for a changing world

Human activities exert global-scale impacts on our environment with significant implications for freshwater-driven services and hazards for humans and nature. Our approach to the science of hydrology needs to significantly change so that we can understand and predict these implications. Such an adjustment is a necessary prerequisite for the development of sustainable water resource management strategies and to achieve long-term water security for people and the environment. Hydrology requires a paradigm shift in which predictions of system behavior that are beyond the range of previously observed variability or that result from significant alterations of physical (structural) system characteristics become the new norm. To achieve this shift, hydrologists must become both synthesists, observing and analyzing the system as a holistic entity, and analysts, understanding the functioning of individual system components, while operating firmly within a well-designed hypothesis testing framework. Cross-disciplinary integration must become a primary characteristic of hydrologic research, catalyzing new research and nurturing new educational models. The test of our quantitative understanding across atmosphere, hydrosphere, lithosphere, biosphere, and anthroposphere will necessarily lie in new approaches to benchmark our ability to predict the regional hydrologic and connected implications of environmental change. To address these challenges and to serve as a catalyst to bring about the necessary changes to hydrologic science, we call for a long-term initiative to address the regional implications of environmental change.Water ManagementCivil Engineering and Geoscience

Advancing catchment hydrology to deal with predictions under change

Throughout its historical development, hydrology as an earth science, but especially as a problem-centred engineering discipline has largely relied (quite successfully) on the assumption of stationarity. This includes assuming time invariance of boundary conditions such as climate, system configurations such as land use, topography and morphology, and dynamics such as flow regimes and flood recurrence at different spatio-temporal aggregation scales. The justification for this assumption was often that when compared with the temporal, spatial, or topical extent of the questions posed to hydrology, such conditions could indeed be considered stationary, and therefore the neglect of certain long-term non-stationarities or feedback effects (even if they were known) would not introduce a large error.Water ManagementCivil Engineering and Geoscience