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

Nitrogen loading alters seagrass ecosystem structure and support of higher trophic levels

1.Anthropogenic-derived nutrient inputs to coastal environments have increased dramatically worldwide in the latter half of the 20th century and are altering coastal ecosystems. We evaluated the effects of nitrogen loading on changes in macrophyte community structure and the associated fauna of a north temperate estuary. We found that a shift in primary producers from eelgrass to macroalgae in response to increased nutrient loading alters habitat physical and chemical structure and food webs. As nitrogen load increased we found increased macroalgal biomass, decreased eelgrass shoot density and biomass, decreased fish and decapod abundance and biomass, and decreased fish diversity. 2.The central importance of macroalgae in altering eelgrass ecosystem support of higher trophic levels is evident in the response of the ecosystem when this component was manipulated. Removal of macroalgae increased eelgrass abundance and water column and benthic boundary layer O2 concentrations. These changes in the physical and chemical structure of the ecosystem with lower macroalgal biomass resulted in higher fish and decapod abundance and biomass. 3.Both a 15N tracer experiment and the growth of fishes indicated that little of the macroalgal production was immediately transferred to secondary consumers. δ15N values indicated that the most abundant fishes were not using a grazing food web based on macroalgae. Fish tended to grow better and have a greater survivorship in eelgrass compared to macroalgal habitats. 4.Watershed-derived nutrient loading has caused increased macroalgal biomass and degradation and loss of eelgrass habitat, thus reducing the capacity of estuaries to support nekton

Movement of bonnetheads, Sphyrna tiburo, as a response to salinity change in a Florida estuary

The movement of bonnetheads, Sphyrna tiburo, within an estuarine system on the Gulf of Mexico coast of Florida was examined to define response to salinity change. Shark presence and movements were evaluated by acoustic monitoring and gillnet sampling. Acoustic monitoring data were used to investigate active selection of different zones within the estuary based on differences in salinity among zones. Sharks were monitored for 187 days in 2003 and 217 days in 2004 in salinities ranging from 11.0 to 31.0 ppt in 2003 and 15.8 to 34.6 ppt in 2004. Monitoring data supported the hypothesis that salinity played a role in the distribution and movement of S. tiburo. Catch per unit effort (CPUE) data obtained from gillnet sampling from 1995 to 2004 were examined to determine affinity or avoidance of specific salinities within the study site as calculated using an electivity index. Electivity analysis showed almost no affinity or avoidance for specific salinity values. The difference in results between the CPUE and acoustic monitoring in relation to the potential effects of salinity likely relate to the nature of the data, with acoustic monitoring providing continuous data and CPUE providing snapshot location data. The results of this study suggest that although S. tiburo are collected within a wide range of salinity levels, salinity may affect movement and distribution. Salinity effects may be more pronounced during periods of prolonged and/or large changes in salinity as detected by long-term monitoring

Cholera in Oceania

For approximately 200 years, cholera has been feared globally as a disease that can cause rapid-onset epidemics. The causative organisms, Vibrio cholerae O1 and O139 serogroups, are endemic to Southern Asia, but appear to spread globally in waves resulting in seven recognised pandemics to date. The current seventh pandemic has seen the introduction of V. cholerae O1 El Tor into the Oceania region. Since 1962 there have been five large outbreaks at a frequency of approximately one per decade. There have also been regular small outbreaks and clusters of disease throughout the region during the seventh pandemic. The most recent outbreak of cholera in the region occurred in Papua New Guinea in 2009–2011, and this was the largest outbreak to occur in the region to date. In Oceania the majority of people live in high-income settings (Australia and New Zealand) so the risk of cholera transmission is low. Despite this, an estimated 6.5 million people living in the region are at risk of cholera. The most important risk factors are inadequate access to safe water and lack of appropriate sanitation and hygiene measures. However, many other factors may contribute to cholera transmission risk, and people living in Pacific Island countries may be at increased risk in the future due to climate change. Strengthening health delivery services in the region will ensure countries are better equipped to handle future cholera outbreaks; and further understanding the epidemiology of cholera and the causative agent in the region could help prevent future transmission

Population expansion and genetic structure in Carcharhinus brevipinna in the southern Indo-Pacific

Background: Quantifying genetic diversity and metapopulation structure provides insights into the evolutionary history of a species and helps develop appropriate management strategies. We provide the first assessment of genetic structure in spinner sharks (Carcharhinus brevipinna), a large cosmopolitan carcharhinid, sampled from eastern and northern Australia and South Africa.\ud \ud Methods and Findings: Sequencing of the mitochondrial DNA NADH dehydrogenase subunit 4 gene for 430 individuals revealed 37 haplotypes and moderately high haplotype diversity (h = 0.6770 ±0.025). While two metrics of genetic divergence (Φ(ST) and F(ST)) revealed somewhat different results, subdivision was detected between South Africa and all Australian locations (pairwise Φ(ST), range 0.02717–0.03508, p values ≤ 0.0013; pairwise F(ST) South Africa vs New South Wales = 0.04056, p = 0.0008). Evidence for fine-scale genetic structuring was also detected along Australia's east coast (pairwise Φ(ST) = 0.01328, p < 0.015), and between south-eastern and northern locations (pairwise Φ(ST) = 0.00669, p < 0.04).\ud \ud Conclusions: The Indian Ocean represents a robust barrier to contemporary gene flow in C. brevipinna between Australia and South Africa. Gene flow also appears restricted along a continuous continental margin in this species, with data tentatively suggesting the delineation of two management units within Australian waters. Further sampling, however, is required for a more robust evaluation of the latter finding. Evidence indicates that all sampled populations were shaped by a substantial demographic expansion event, with the resultant high genetic diversity being cause for optimism when considering conservation of this commercially-targeted species in the southern Indo-Pacific