Initial Sequence and Comparative Analysis of the Cat Genome

The genome sequence (1.9-fold coverage) of an inbred Abyssinian domestic cat was assembled, mapped, and annotated with a comparative approach that involved cross-reference to annotated genome assemblies of six mammals (human, chimpanzee, mouse, rat, dog, and cow). The results resolved chromosomal positions for 663,480 contigs, 20,285 putative feline gene orthologs, and 133,499 conserved sequence blocks (CSBs). Additional annotated features include repetitive elements, endogenous retroviral sequences, nuclear mitochondrial (numt) sequences, micro-RNAs, and evolutionary breakpoints that suggest historic balancing of translocation and inversion incidences in distinct mammalian lineages. Large numbers of single nucleotide polymorphisms (SNPs), deletion insertion polymorphisms (DIPs), and short tandem repeats (STRs), suitable for linkage or association studies were characterized in the context of long stretches of chromosome homozygosity. In spite of the light coverage capturing ∼65% of euchromatin sequence from the cat genome, these comparative insights shed new light on the tempo and mode of gene/genome evolution in mammals, promise several research applications for the cat, and also illustrate that a comparative approach using more deeply covered mammals provides an informative, preliminary annotation of a light (1.9-fold) coverage mammal genome sequence

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

The influence of different deep-sea coral habitats on sediment macrofaunal community structure and function

Deep-sea corals can create a highly complex, three-dimensional structure that facilitates sediment accumulation and influences adjacent sediment environments through altered hydrodynamic regimes. Infaunal communities adjacent to different coral types, including reef-building scleractinian corals and individual colonies of octocorals, are known to exhibit higher macrofaunal densities and distinct community structure when compared to non-coral soft-sediment communities. However, the coral types have different morphologies, which may modify the adjacent sediment communities in discrete ways. Here we address: (1) how infaunal communities and their associated sediment geochemistry compare among deep-sea coral types (Lophelia pertusa, Madrepora oculata, and octocorals) and (2) do infaunal communities adjacent to coral habitats exhibit typical regional and depth-related patterns observed in the Gulf of Mexico (GOM). Sediment push cores were collected to assess diversity, composition, numerical abundance, and functional traits of macrofauna (>300 µm) across 450 kilometers in the GOM at depths ranging from 263–1,095 m. Macrofaunal density was highest in L. pertusa habitats, but similar between M. oculata and octocorals habitats. Density overall exhibited a unimodal relationship with depth, with maximum densities between 600 and 800 m. Diversity and evenness were highest in octocoral habitats; however, there was no relationship between diversity and depth. Infaunal assemblages and functional traits differed among coral habitats, with L. pertusa habitats the most distinct from both M. oculata and octocorals. These patterns could relate to differences in sediment geochemistry as L. pertusa habitats contained high organic carbon content but low proportions of mud compared to both M. oculata and octocoral habitats. Distance-based linear modeling revealed depth, mud content, and organic carbon as the primary factors in driving coral infaunal community structure, while geographic location (longitude) was the primary factor in functional trait composition, highlighting both the location and ecological differences of L. pertusa habitats from other coral habitats. Enhanced habitat structural complexity associated with L. pertusa and differences in localized hydrodynamic flow may contribute to the dissimilarities in the communities found among the coral types. Our results suggest a decoupling for infaunal coral communities from the typical depth-related density and diversity patterns present throughout soft-sediment habitats in the GOM, highlighting the importance of deep-sea corals in structuring unique communities in the nearby benthos

Examination of Bathymodiolus childressi nutritional sources, isotopic niches, and food-web linkages at two seeps in the US Atlantic margin using stable isotope analysis and mixing models

Chemosynthetic environments support distinct benthic communities capable of utilizing reduced chemical compounds for nutrition. Hundreds of methane seeps have been documented along the U.S. Atlantic margin (USAM), and detailed investigations at a few seeps have revealed distinct environments containing mussels, microbial mats, authigenic carbonates, and soft sediments. The dominant mussel, Bathymodiolus childressi, contains methanotrophic endosymbionts but is also capable of filter feeding, and stable isotope analysis (SIA) of mussel-shell periostracum suggests that these mussels are mixotrophic, assimilating multiple food resources. However, it is unknown whether mixotrophy is widespread or varies spatially and temporally. We used SIA (δ13C, δ15N, and δ34S) and an isotope mixing model (MixSIAR) to estimate resource contribution to B. childressi and characterize food webs at two seep sites (Baltimore Seep; 400 m and Norfolk Seep; 1500 m depths) along the USAM, and applied a linear mixed-effects model to explore the role of mussel population density and tissue type in influencing SIA variance. After controlling for location and temporal variation, isotopic variability was a function of proportion of live mussels present and tissue type. Isotopic differences were also spatially discrete, possibly reflecting variations in the underlying carbon source at the two sites. Low mussel δ13C values (∼−63‰) are consistent with a dependence on microbial methane. However, MixSIAR results revealed mixotrophy for mussels at both sites, implying a reliance on a mixture of methane and phytoplankton-derived particulate organic material. The mixing model results also reveal population density-driven patterns, suggesting that resource use is a function of live mussel abundance. Mussel isotopes differed by tissue type, with gill having the lowest δ15N values relative to muscle and mantle tissues. Based on mass balance equations, up to 79% of the dissolved inorganic carbon (DIC) of the pore fluids within the anaerobic oxidation of the methane zone is derived from methane and available to fuel upper slope deep-sea communities, such as fishes (Dysommina rugosa and Symphurus nebulosus), echinoderms (Odontaster robustus, Echinus wallisi, and Gracilechinus affinis), and shrimp, (Alvinocaris markensis). The presence of these seeps thereby increases the overall trophic and community diversity of the USAM continental slope. Given the presence of hundreds of seeps within the region, primary production at seeps may serve as an important, yet unquantified, energy source to the USAM deep-sea environment

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

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