The Amazon River plume—a Lagrangian view

Hydrographic data, nutrient data and bulk rates of nitrate uptake and primary production were determined in the Amazon River plume (ARP) in the Western Tropical North Atlantic (WTNA) during three cruises in May 2018, June/July 2019, with RV Endeavor and April/May 2021 with RV Meteor. Using daily quasi-geostrophic surface velocity data from satellite observations, the geographical positions of the stations of observations were transformed onto Lagrangian coordinates to obtain a dynamically coherent and consistent spatial distribution. After the transformation, the observed surface salinity and temperature fields were consistent with the flow fields, the ARP formed a coherent structure and the retroflection of the North Brazil Current became visible. By transforming other surface variables such as nitrate concentration, photosynthetically available radiation, turbidity, bulk rates of nitrate uptake, and primary production onto Lagrangian coordinates, patterns became consistent with the physical variables at the surface. The use of “synchronous” fields as done here by transformation onto Lagrangian coordinates is essential for spatially structured analyses of data collected over tens of days in a highly dynamic region characterized by complex flow fields with low persistence such as the WTNA. Therefore, the use of the Lagrangian method provides a powerful tool for exploring spatial distributions of biologically relevant factors in regions with complex and dynamic flow patterns. These spatial distributions are qualitatively in agreement with satellite images of daily sea surface temperature and composites of monthly mean Chlorophyll a distributions

Uptake of dissolved inorganic nitrogen and N2 fixation by Crocosphaera watsonii under climate change scenarios

The response of N2 fixation to projected future conditions in the ocean cannot be reliably predicted to date. We conducted a minicosm experiment with pre-acclimated cultures of the globally significant diazotroph Crocosphaera watsonii strain WH8501 (“Crocosphaera”). PH and temperature were altered simultaneously to match the RCP scenarios 4.5 and 6 and investigate a more realistic future scenario compared to studies that focus on changes of a single stressor only. The cell abundance and nitrogen metabolism of Crocosphaera was monitored over 5 days. Our results imply that Crocosphaera is able to simultaneously perform N2 fixation and assimilate dissolved inorganic nitrogen (DIN, i.e., nitrate and ammonium) under all the conditions tested and implies a competition with non-diazotrophic phytoplankton for DIN, which should be further investigated. Using NanoSIMS analysis of single cells, our results point towards a preference for DIN assimilation over N2 fixation under more acidic and warmer conditions. Overall, our results show that while the combined alteration of pH and temperature had a negative effect on the diazotroph’s growth and N2 fixation, Crocosphaera is likely to cope well with conditions in the future ocean. The high intra-population variability in nitrogen assimilation pathways may give this species the flexibility to quickly react to environmental changes

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Dissolved organic matter offsets the detrimental effects of climate change in the nitrogen‐fixing cyanobacterium Crocosphaera

Abstract Diazotrophs provide a significant reactive nitrogen source in the ocean. Increased warming and stratification may decrease nutrient availability in the future, forcing microbial communities toward using dissolved organic matter (DOM). Not depending on reactive nitrogen availability, diazotrophs may be “winners” in a nutrient‐depleted ocean. However, their ability to exploit DOM may influence this success. We exposed cultures of the widespread Crocosphaera to low (26°C, pH 8.1), moderate (28°C, pH 8.0), and extreme (30°C, pH 7.9) climate change scenarios, under control or DOM‐amended conditions. Growth was suboptimal in the low and extreme treatments and favored in the moderate treatment. DOM was preferred as a carbon source regardless of the treatment and promoted N2 fixation in extreme conditions. This was reflected in the increased expression of photosynthesis genes to obtain energy. DOM provides Crocosphaera with a key ecological advantage, possibly dictating diazotroph‐derived nitrogen inputs in the future ocean

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe