64 research outputs found
Integrating Science and Policy Through Stakeholder-Engaged Scenarios
Scenario development for integrated analysis focuses on adopting an interdisciplinary approach covering key elements of the biophysical environment as well as changes in livelihoods, education, economics and governance both locally and internationally. Most importantly, the development of these scenarios generates a dialogue across institutions, stakeholders and sectors, with the use of common data and agreement on shared qualitative and quantitative futures. The scenarios adopted combine three alternative future climates and three socio-economic development pathways. Quantification of these issues included estimation based on published data, expert knowledge and stakeholder engagement, particularly where data are most uncertain or unknown. This chapter demonstrates this approach for coastal Bangladesh
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Advances in reconstructing the AMOC using sea surface observations of salinity
The Atlantic meridional overturning circulation (AMOC) is one of the main drivers of climate variability at decadal and longer time scales. As there are no direct multi-decadal observations of this key circulation, the reconstruction of past AMOC variations is essential. This work presents a step forward in reconstructing the AMOC using climate models and time-varying surface nudging of salinity and temperature data, for which independent multi-decadal observed series are available. A number of nudging protocols are explored in a perfect model framework to best reproduce the AMOC variability accommodating to the characteristics of SST and SSS available products. As reference SST products with sufficient space and time coverage are available, we here choose to focus on the limitations associated to SSS products with the goal of providing protocols using independent salinity products. We consider a global gridded dataset and, additionally, a coarser SSS dataset restricted to the Atlantic and with a quite low spatial resolution (order of 10 degrees vs. 2 for the model grid). We show how, using the latter, we can improve the efficiency of the nudging on the AMOC reconstruction by adding a high-resolution annual cycle to the coarse resolution SSS product as well as a spatial downscaling to account for SSS gradient. The final protocol retained for the coarse SSS data is able to reconstruct a 100-year long AMOC period (average of 10.18 Sv and a standard deviation of 1.39 Sv), with a correlation of 0.76 to the target and a RMSE of 0.99 Sv. These values can be respectively compared to 0.85 and 0.75 Sv when using the global salinity surface observations. This work provides a first step towards understanding the limitations and prospects of historical AMOC reconstructions using different sea surface salinity datasets for the surface nudging
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
Comprehensive molecular characterization of the hippo signaling pathway in cancer
Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era
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