237 research outputs found

    Semi-automatic selection of summary statistics for ABC model choice

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    A central statistical goal is to choose between alternative explanatory models of data. In many modern applications, such as population genetics, it is not possible to apply standard methods based on evaluating the likelihood functions of the models, as these are numerically intractable. Approximate Bayesian computation (ABC) is a commonly used alternative for such situations. ABC simulates data x for many parameter values under each model, which is compared to the observed data xobs. More weight is placed on models under which S(x) is close to S(xobs), where S maps data to a vector of summary statistics. Previous work has shown the choice of S is crucial to the efficiency and accuracy of ABC. This paper provides a method to select good summary statistics for model choice. It uses a preliminary step, simulating many x values from all models and fitting regressions to this with the model as response. The resulting model weight estimators are used as S in an ABC analysis. Theoretical results are given to justify this as approximating low dimensional sufficient statistics. A substantive application is presented: choosing between competing coalescent models of demographic growth for Campylobacter jejuni in New Zealand using multi-locus sequence typing data

    De novo sequence assembly and characterisation of a partial transcriptome for an evolutionarily distinct reptile, the tuatara (Sphenodon punctatus)

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    BACKGROUND: The tuatara (Sphenodon punctatus) is a species of extraordinary zoological interest, being the only surviving member of an entire order of reptiles which diverged early in amniote evolution. In addition to their unique phylogenetic placement, many aspects of tuatara biology, including temperature-dependent sex determination, cold adaptation and extreme longevity have the potential to inform studies of genome evolution and development. Despite increasing interest in the tuatara genome, genomic resources for the species are still very limited. We aimed to address this by assembling a transcriptome for tuatara from an early-stage embryo, which will provide a resource for genome annotation, molecular marker development and studies of development and adaptation in tuatara. RESULTS: We obtained 30 million paired-end 50 bp reads from an Illumina Genome Analyzer and assembled them with Velvet and Oases using a range of kmers. After removing redundancy and filtering out low quality transcripts, our transcriptome dataset contained 32911 transcripts, with an N50 of 675 and a mean length of 451 bp. Almost 50% (15965) of these transcripts could be annotated by comparison with the NCBI non-redundant (NR) protein database or the chicken, green anole and zebrafish UniGene sets. A scan of candidate genes and repetitive elements revealed genes involved in immune function, sex differentiation and temperature-sensitivity, as well as over 200 microsatellite markers. CONCLUSIONS: This dataset represents a major increase in genomic resources for the tuatara, increasing the number of annotated gene sequences from just 60 to almost 16,000. This will facilitate future research in sex determination, genome evolution, local adaptation and population genetics of tuatara, as well as inform studies on amniote evolution

    A systems-based approach to parameterise seismic hazard in regions with little historical or instrumental seismicity:Active fault and seismogenic source databases for southern Malawi

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    Seismic hazard is commonly characterised using instrumental seismic records. However, these records are short relative to earthquake repeat times, and extrapolating to estimate seismic hazard can misrepresent the probable location, magnitude, and frequency of future large earthquakes. Although paleoseismology can address this challenge, this approach requires certain geomorphic setting, is resource intensive, and can carry large inherent uncertainties. Here, we outline how fault slip rates and recurrence intervals can be estimated by combining fault geometry, earthquake-scaling relationships, geodetically derived regional strain rates, and geological constraints of regional strain distribution. We apply this approach to southern Malawi, near the southern end of the East African Rift, and where, although no on-fault slip rate measurements exist, there are constraints on strain partitioning between border and intra-basin faults. This has led to the development of the South Malawi Active Fault Database (SMAFD), a geographical database of 23 active fault traces, and the South Malawi Seismogenic Source Database (SMSSD), in which we apply our systems-based approach to estimate earthquake magnitudes and recurrence intervals for the faults compiled in the SMAFD. We estimate earthquake magnitudes of MW 5.4–7.2 for individual fault sections in the SMSSD and MW 5.6–7.8 for whole-fault ruptures. However, low fault slip rates (intermediate estimates ∼ 0.05–0.8 mm/yr) imply long recurrence intervals between events: 102–105 years for border faults and 103–106 years for intra-basin faults. Sensitivity analysis indicates that the large range of these estimates can best be reduced with improved geodetic constraints in southern Malawi. The SMAFD and SMSSD provide a framework for using geological and geodetic information to characterise seismic hazard in regions with few on-fault slip rate measurements, and they could be adapted for use elsewhere in the East African Rift and globally

    Comparison of the Pathogenic Potential of Campylobacter jejuni, C. upsaliensis and C. helveticus and Limitations of Using Larvae of Galleria mellonella as an Infection Model

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    Campylobacter enteritis in humans is primarily associated with C. jejuni/coli infection. Other species cause campylobacteriosis relatively infrequently; while this could be attributed to bias in diagnostic methods, the pathogenicity of non-jejuni/coli Campylobacter spp. such as C. upsaliensis and C. helveticus (isolated from dogs and cats) is uncertain. Galleria mellonella larvae are suitable models of the mammalian innate immune system and have been applied to C. jejuni studies. This study compared the pathogenicity of C. jejuni, C. upsaliensis, and C. helveticus isolates. Larvae inoculated with either C. upsaliensis or C. helveticus showed significantly higher survival than those inoculated with C. jejuni. All three Campylobacter species induced indistinguishable histopathological changes in the larvae. C. jejuni could be isolated from inoculated larvae up to eight days post-inoculation whereas C. upsaliensis and C. helveticus could only be isolated in the first two days. There was a significant variation in the hazard rate between batches of larvae, in Campylobacter strains, and in biological replicates as random effects, and in species and bacterial dose as fixed effects. The Galleria model is applicable to other Campylobacter spp. as well as C. jejuni, but may be subject to significant variation with all Campylobacter species. While C. upsaliensis and C. helveticus cannot be considered non-pathogenic, they are significantly less pathogenic than C. jejuni

    Geodetic constraints on cratonic microplates and broad strain during rifting of thick Southern African lithosphere

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    Southern Africa is typically considered to belong to a single tectonic plate, Nubia, despite active faulting along the southwestern branch of the East African Rift System. We analyze regional Global Navigation Satellite System (GNSS) measurements, and find that the “San” microplate, situated south of the southwestern branch of the East African Rift, is statistically distinct from Nubia, with 0.4–0.7 mm/yr of extension across the boundary. Adding nine new campaign GNSS sites, we show that the extension rate across the southern Malawi Rift is 2.2 ± 0.3 mm/yr, with 75% of the relative velocity occurring over 890 km, despite the surface expression of faulting being <150 km wide. Thus, for the first time, we use geodetic measurements to describe the accommodation of strain in broad zones between Archean cratons in southern Africa's thick continental lithosphere

    Aligning assessment with the needs of work-integrated learning: the challenges of authentic assessment in a complex context

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    Work-integrated learning (WIL) is a feature of university courses, both in professional areas, where it is commonplace, but also across many different disciplines. Assessment of WIL can be complex as it involves parties and settings external to the university, and it can be problematic because of difficulties in aligning learning activities during placements with what is or can be assessed by the university. This paper explores the relationship between students’ placement experiences and accompanying assessments in contexts where activities are tightly coupled with the curriculum, and in those where it is not. It draws on a qualitative analysis of student interviews and drawings by the interviewees of their WIL experiences, supplemented with analysis of unit guides. Our findings highlight that students’ perceptions of authenticity of assessment were undermined by misalignments between the student, university and industry. Assessment authenticity was perceived by students as based on alignment between their current and future selves in the assessment process, involvement of industry supervisors and relevance of placement activities to assessment activities. The paper discusses the complexity of coordination of educational activities with external partners, especially when one party drives assessment. It then suggests a reframing of WIL assessment to promote alignment and authenticity

    Whole-Genome Comparison of Two Campylobacter jejuni Isolates of the Same Sequence Type Reveals Multiple Loci of Different Ancestral Lineage

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    Campylobacter jejuni ST-474 is the most important human enteric pathogen in New Zealand, and yet this genotype is rarely found elsewhere in the world. Insight into the evolution of this organism was gained by a whole genome comparison of two ST-474, flaA SVR-14 isolates and other available C. jejuni isolates and genomes. The two isolates were collected from different sources, human (H22082) and retail poultry (P110b), at the same time and from the same geographical location. Solexa sequencing of each isolate resulted in 1.659 Mb (H22082) and 1.656 Mb (P110b) of assembled sequences within 28 (H22082) and 29 (P110b) contigs. We analysed 1502 genes for which we had sequences within both ST-474 isolates and within at least one of 11 C. jejuni reference genomes. Although 94.5% of genes were identical between the two ST-474 isolates, we identified 83 genes that differed by at least one nucleotide, including 55 genes with non-synonymous substitutions. These covered 101 kb and contained 672 point differences. We inferred that 22 (3.3%) of these differences were due to mutation and 650 (96.7%) were imported via recombination. Our analysis estimated 38 recombinant breakpoints within these 83 genes, which correspond to recombination events affecting at least 19 loci regions and gives a tract length estimate of 2 kb. This includes a 12 kb region displaying non-homologous recombination in one of the ST-474 genomes, with the insertion of two genes, including ykgC, a putative oxidoreductase, and a conserved hypothetical protein of unknown function. Furthermore, our analysis indicates that the source of this recombined DNA is more likely to have come from C. jejuni strains that are more closely related to ST-474. This suggests that the rates of recombination and mutation are similar in order of magnitude, but that recombination has been much more important for generating divergence between the two ST-474 isolates

    SolexaQA: At-a-glance quality assessment of Illumina second-generation sequencing data

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    <p>Abstract</p> <p>Background</p> <p>Illumina's second-generation sequencing platform is playing an increasingly prominent role in modern DNA and RNA sequencing efforts. However, rapid, simple, standardized and independent measures of run quality are currently lacking, as are tools to process sequences for use in downstream applications based on read-level quality data.</p> <p>Results</p> <p>We present SolexaQA, a user-friendly software package designed to generate detailed statistics and at-a-glance graphics of sequence data quality both quickly and in an automated fashion. This package contains associated software to trim sequences dynamically using the quality scores of bases within individual reads.</p> <p>Conclusion</p> <p>The SolexaQA package produces standardized outputs within minutes, thus facilitating ready comparison between flow cell lanes and machine runs, as well as providing immediate diagnostic information to guide the manipulation of sequence data for downstream analyses.</p

    Comparison of the Pathogenic Potential of Campylobacter jejuni, C. upsaliensis and C. helveticus and Limitations of Using Larvae of Galleria mellonella as an Infection Model

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    Campylobacter enteritis in humans is primarily associated with C. jejuni/coli infection. Other species cause campylobacteriosis relatively infrequently ; while this could be attributed to bias in diagnostic methods, the pathogenicity of non-jejuni/coli Campylobacter spp. such as C. upsaliensis and C. helveticus (isolated from dogs and cats) is uncertain. Galleria mellonella larvae are suitable models of the mammalian innate immune system and have been applied to C. jejuni studies. This study compared the pathogenicity of C. jejuni, C. upsaliensis, and C. helveticus isolates. Larvae inoculated with either C. upsaliensis or C. helveticus showed significantly higher survival than those inoculated with C. jejuni. All three Campylobacter species induced indistinguishable histopathological changes in the larvae. C. jejuni could be isolated from inoculated larvae up to eight days post-inoculation whereas C. upsaliensis and C. helveticus could only be isolated in the first two days. There was a significant variation in the hazard rate between batches of larvae, in Campylobacter strains, and in biological replicates as random effects, and in species and bacterial dose as fixed effects. The Galleria model is applicable to other Campylobacter spp. as well as C. jejuni, but may be subject to significant variation with all Campylobacter species. While C. upsaliensis and C. helveticus cannot be considered non-pathogenic, they are significantly less pathogenic than C. jejuni
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