23 research outputs found

    Integrated genomic characterization of pancreatic ductal adenocarcinoma

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    We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

    Length and sex effects on the spatial structure of catches of Pacific halibut (Hippoglossus stenolepis) on longline gear

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    Field experiments were conducted to test the hypotheses that Pacific halibut (Hippoglossus stenolepis) display small-scale spatial structure within longline catches, relative to other species and empty hooks, or within-species based on sex or length. Sequential hook-by-hook inventories, along with length and sex data, were taken at thirty-one survey stations. Two-dimensional spatial statistics were used to test for 1) aggregation, defined as the clustering of individuals within a given demographic of size or sex over small intervals of distance; and 2) segregation, defined as the sequential occurrence of individuals within a given demographic of size or sex, uninterrupted by other observations, irrespective of the distance between individuals. Statistically significant structure was detected within catches that is more commonly associated with fish length than sex. Significant spatial structuring occurred at 60% of all stations tested. Significant aggregation of halibut of legal length for commercial retention (≥82 cm) was detected at 44% of stations and aggregation of sublegal-size halibut was detected at 11%. Maleand female-based aggregations were observed at 22% and 11% of stations, respectively. Significant segregation of females was observed at 20% of stations, male segregation occurred at 8% of stations, and segregation by size at 16% of stations. Understanding small-scale spatial structure within longline catches may help us interpret changes in survey and commercial catch data. If structure is generated by behavior, then observed size-at-age or relative sex-ratios may be biased relative to underlying distributions. Although physical processes such as gape limitation should remain stable over the time, dynamic processes may be spatially and temporally variab

    A test of the detection range of acoustic transmitters and receivers deployed in deep waters of Southeast Alaska, USA

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    Abstract Background Movement data represent important inputs to both numerical and conceptual models that contribute to the assessment and management of sablefish (Anoplopoma fimbria) and Pacific halibut (Hippoglossus stenolepis) in the eastern North Pacific. While conventional mark-recovery data have greatly increased our understanding of these populations, tagging methods that produce only endpoint data (i.e., locations at tagging and recapture) cannot address dynamics such as the timing, frequency, and recurrence of movements. As a preliminary step in evaluating the feasibility of using acoustic biotelemetry for addressing management-relevant questions for relatively deepwater (≤ 600 m depth) species, we conducted tests of the detection range between VEMCO V16-5H transmitters and VR2W receivers. Six range-test stations were established that varied from a relatively shallow (154 m), narrow (3.8 km) ocean pass; through the mouth of a wide (20 km), deep (600 + m) fjord; and over the continental shelf. Each station consisted of one receiver mooring and five transmitter moorings deployed at regular distances from 200 to 1200 m from the base of the receiver mooring. Bottom depth varied from 195 to 588 m. Transmitters were suspended 0.5 and 5 m off bottom, and receivers at 145–400 m below the sea surface depend on bottom depth. Receivers were deployed for 162–595 days; however, maximum transmission time was 365 days. Results The rate at which acoustic transmissions were detected by the receivers decreased with distance from the transmitters, mostly monotonically; at first gradually, from transmitters at distances of 400–800 m from the receivers, and then more steeply at distances beyond 800 m. Considerable variability in detection rates was observed, including low detection rates from individual locations and distances. Temporal changes in detection rates were observed that included convergence/divergence between detection of transmitters at a given distance from receivers but that were suspended at different elevations above bottom; stepwise seasonal shifts in mean detection; diurnal periodicity that was likely due to diurnal winds; and tidally mediated detection cycles. We determined that a linear “gate” of receivers spaced 1000 m apart would have a very high probability (≥ 0.99) under most conditions of detecting an acoustically tagged Pacific halibut transiting the gate, and that tagged-halibut identification rates using 2400-m receiver spacing could approach or exceed 90%. However, during episodic periods of relatively poor tag detection, these rates are likely to decline to ~ 60–80%; and to below 10% under extreme conditions. Conclusions Acoustic telemetry is a feasible technique for monitoring the movement of deepwater epibenthic fishes. However, temporal and spatial variability in detection rates, especially in seasonally stratified waters, has a strong potential to impart biases on study results and generate spurious patterns unrelated to tagged-fish behavior. The nature of such biases should be carefully considered during array placement and data interpretation. Range testing should be conducted at all geographic locations at which arrays are to be established, rather than extrapolating from a few test locations. Arrays should always contain sentinel tags to monitor detection rates and account for transient features that affect those rates. We also note the necessity of placing at least two gates at any given location in order to substantiate movement of tagged animals past any desired point of reference

    Data from: Identification of genomic regions associated with sex in Pacific halibut

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    Understanding and identifying the genetic mechanisms responsible for sex-determination are important for species management, particularly in exploited fishes where sex biased harvest could have implications on population dynamics and long-term persistence. The Pacific halibut (Hippoglossus stenolepis) supports important fisheries in the North Pacific Ocean. The proportion of each sex in the annual harvest is currently estimated using growth curves, but genetic techniques may provide a more accurate method. We used restriction-site associated DNA (RAD) sequencing to identify RAD-tags that were linked to genetic sex, based on differentiation (FST) between the sexes. Identified RAD-tags were aligned to the Atlantic halibut (Hippoglossus hippoglossus) linkage map, the turbot (Scophthalmus maximus) genome, and the half-smooth tongue sole (Cynoglossus semilaevis) genome to identify genomic regions that may be involved in sex determination. In total, 56 RAD-tags (70 single nucleotide polymorphisms) were linked to sex, and three RAD-tags were identified in only females. Sex-linked loci aligned to three linkage groups in the Atlantic halibut (LG07: 7 loci, LG15: 1 locus, and LG24: 1 locus), three chromosomes in the turbot (LG12: 13 loci, LG01: 1 locus, and LG05: 1 locus), and one chromosome in the half-smooth tongue sole (ChrZ: 9 loci). Results add support to the hypothesis that Pacific halibut genetic sex is determined in a ZW system. Two sex-linked loci were further developed into sex identification assays, and their efficacy was tested on individuals that had been morphologically sexed. The accuracy of each assay on its own was 97.5% compared to morphological sex

    supplemental_materials_alignments

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    Alignments between Pacific halibut loci and 1) Atlantic halibut linkage map, 2) turbot genome, and 3) half-smooth tongue sole genome

    halibut_genepop

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    File containing all genotypes. File in Genepop format. Locus names are formatted with an underscore between the RADtag name and SNP position
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