179566 research outputs found
Sort by
High performance imputation of structural and single nucleotide variants using low-coverage whole genome sequencing
No full textBACKGROUND: Whole genome sequencing (WGS), despite its advantages, is yet to replace methods for genotyping single nucleotide variants (SNVs) such as SNP arrays and targeted genotyping assays. Structural variants (SVs) have larger effects on traits than SNVs, but are more challenging to accurately genotype. Using low-coverage WGS with genotype imputation offers a cost-effective strategy to achieve genome-wide variant coverage, but is yet to be tested for SVs.METHODS: Here, we investigate combined SNV and SV imputation with low-coverage WGS data in Atlantic salmon (Salmo salar). As the reference panel, we used genotypes for high-confidence SVs and SNVs for n = 365 wild individuals sampled from diverse populations. We also generated 15 × WGS data (n = 20 samples) for a commercial population external to the reference panel, and called SVs and SNVs with gold-standard approaches. An imputation method selected for its established performance using low-coverage sequencing data (GLIMPSE) was tested at WGS depths of 1 × , 2 × , 3 × , and 4 × for samples within and external to the reference panel.RESULTS: SNVs were imputed with high accuracy and recall across all WGS depths, including for samples out-with the reference panel. For SVs, we compared imputation based purely on linkage disequilibrium (LD) with SNVs, to that supplemented with SV genotype likelihoods (GLs) from low-coverage WGS. Including SV GLs increased imputation accuracy, but as a trade-off with recall, requiring 3-4 × depth for best performance. Combining strategies allowed us to capture 84% of the reference panel deletions with 87% accuracy at 1 × depth. We also show that SV length affects imputation performance, with provision of SV GLs greatly enhancing accuracy for the longest SVs in the dataset.CONCLUSIONS: This study highlights the promise of reference panel imputation using low-coverage WGS, including novel opportunities to enhance the resolution of genome-wide association studies by capturing SVs.</p
Human-Precision Medicine Interaction:Public Perceptions of Polygenic Risk Score for Genetic Health Prediction
No full textPrecision Medicine (PM) transforms the traditional “one-drug-fits-all” paradigm by customising treatments based on individual characteristics, and is an emerging topic for HCI research on digital health. A key element of PM, the Polygenic Risk Score (PRS), uses genetic data to predict an individual’s disease risk. Despite its potential, PRS faces barriers to adoption, such as data inclusivity, psychological impact, and public trust. We conducted a mixed-methods study to explore how people perceive PRS, formed of surveys (n=254) and interviews (n=11) with UK-based participants. The interviews were supplemented by interactive storyboards with the ContraVision technique to provoke deeper reflection and discussion. We identified ten key barriers and five themes to PRS adoption and proposed design implications for a responsible PRS framework. To address the complexities of PRS and enhance broader PM practices, we introduce the term Human-Precision Medicine Interaction (HPMI), which integrates, adapts, and extends HCI approaches to better meet these challenges
Problems and solutions when quantifying nitrogen in silicate and oxide minerals and glasses using electron probe microanalysis
No full textWith growing interest in the Earth's deep nitrogen cycle, electron probe microanalysis is increasingly used to quantify nitrogen in minerals and glasses. However, measuring nitrogen by electron microprobe comes with challenges, including beam sensitivity and differences in peak and background shapes between sample and reference materials. This study provides a robust analytical protocol to addresses these issues. We gathered mineral and glass reference materials with known nitrogen mass fractions from previous work, and synthesised additional glasses with nitrogen quantified independently by gas-source mass spectrometry. Our method uses nitrides as calibration materials because of their beam stability and high nitrogen mass fraction. We assess peak shapes to implement an area-peak factor correction, and account for curved backgrounds using a four-point background correction. Importantly, we describe how to estimate uncertainties on both background and area-peak factor corrections, which is required to assess detection limits but has been largely overlooked in previous studies. Our method yields nitrogen mass fractions within uncertainty for five out of seven reference materials, with two exceptions highlighting the need for further refinement. We provide Python code for applying the corrections and calculating uncertainties, allowing our method to be implemented by any researcher with access to an electron microprobe laboratory
Compressed Sensing Digital MIMO Radar Using a Non-Uniformly Spaced SIW Sparse Receiver Array
No full textA compressed sensing (CS) digital radar system based on a sparse array design is proposed for use in automotive collision-avoidance applications. The proof-of-concept radar system offers an enlarged antenna aperture, employing fewer elements and can distinguish targets at an angular separation of only 2 degrees for a bandwidth of 6.25%. This resolution is made possible using a multiple-input multiple-output (MIMO) configuration from the original sparse array which was implemented and tested using substrate integrated waveguide (SIW) technology. More specifically, the total aperture size (of the effective virtual receiver array) is 23.5λ which is equivalent to a uniform-linear array (ULA) having 48 elements spaced at 0.5λ apart. However, the total number of elements is 32. This defines a cost-effective setup offering a reduction of 16 elements which accounts for a 33% reduction in the number of required channels for the SIW array. Also, the radar exploits sparse-reconstruction techniques for target detection. Results of the simulations and measurements show that the performance of the proposed SIW antenna and experimentally verified radar system can offer competitive high-resolution detection when compared to other findings in the literature and to the best knowledge of the authors, no similar antenna and radar system implementation has been designed and experimentally verified
Genetic Diversity in the Diminazene Resistance-Associated P2 Adenosine Transporter-1 (AT-1) Gene of Trypanosoma evansi
No full textTrypanosomes are parasitic protozoa that cause severe diseases in humans and animals. The most important species of Trypanosmes include Trypanosoma evansi and Trypanosoma brucei gambiense. The most well-known human diseases are sleeping sickness in Africa and Chagas disease in South America. The most identified animal diseases include Nagana in the African tsetse fly belt and Surra in South Asia, North Africa, and the Middle East. Surra is caused by Trypanosoma evansi. Diminazene resistance is an emerging threat caused by T. evansi infecting animals. The underlying mechanism of diminazene resistance is poorly understood. Trypanosoma brucei gambiense causes African sleeping sickness. The development of diminazene resistance in Trypanosoma brucei gambiense is associated with the alterations in the corresponding P2 adenosine transporter-1 ( AT-1) gene. In the present study, by extrapolating the findings from Trypanosoma brucei gambiense, we analyzed genetic diversity in the P2 adenosine transporter-1 gene ( AT-1) from T. evansi to explore a potential link between the presence of mutations in this locus and diminazene treatment in ruminants. We examined T. evansi-infected blood samples collected from goats, sheep, camels, buffalo, and cattle in seven known endemic regions of the Punjab province of Pakistan. Heterozygosity (H e) indices indicated a high level of genetic diversity between seven T. evansi field isolates that had resistance-type mutations at codons 178E/S, 239Y/A/E, and 286S/H/I/D/T of the P2 adenosine transporter-1 ( AT-1) locus. A low level of genetic diversity was observed in 19 T. evansi field isolates with susceptible-type mutations at codons A178, G181, D239, and N286 of the P2 adenosine transporter-1 ( AT-1) locus. Our results on T. evansi warrant further functional studies to explore the relationship between diminazene resistance and the mutations in AT-1. </p
A lymphostatin homologue from Chlamydia pecorum inhibits mitogen-activated bovine T cell proliferation and IFNγ production
Get PDFPathogens frequently produce proteins to evade or inhibit host immune responses. One such protein is lymphostatin from attaching and effacing Escherichia coli (also known as lymphocyte inhibitory factor A; LifA), which influences intestinal colonization and inhibits mitogen- and antigen-activated proliferation of T lymphocytes and pro-inflammatory cytokine synthesis. Here, we report the cloning, purification and characterization of a LifA homologue from Chlamydia pecorum. The predicted 382 KDa protein (CPE2_0552) exhibited 36% identity and 55% similarity over 3171 amino acids to lymphostatin from enteropathogenic E. coli strain E2348/69. CPE2_0552 shares glycosyltransferase and cysteine protease motifs required for lymphostatin activity, including similarity in the tertiary structure of these domains predicted by AlphaFold 3. Purified CPE2_0552 did not share the L-shaped globular structure of lymphostatin when analyzed by transmission electron microscopy. CPE2_0552 inhibited concanavalin A-stimulated proliferation of bovine T cells in a concentration-dependent manner, with an inhibitory dose 50 (ID 50) of 812 pg/mL. This was 38-fold higher than the ID 50 of E. coli E2348/69 lymphostatin tested in parallel on T cells from the same donors (21 pg/mL), but was similar to another LifA homologue from E. coli O157:H7 (ToxB). Moreover, CPE2_0552 inhibited the secretion of interferon gamma (IFNγ), a key cytokine that influences the outcome of Chlamydia infections. At the concentrations at which CPE2_0552 inhibited T lymphocyte proliferation and IFNγ secretion, negligible cytotoxicity was observed after 72 h of stimulation. Our study indicates that E. coli lymphostatin belongs to a wider family of lymphocyte-inhibitory molecules that exist in distantly related bacterial pathogens. </p
Global evolution of inflammatory bowel disease across epidemiologic stages
Get PDFDuring the twentieth century, inflammatory bowel disease (IBD) was considered a disease of early industrialized regions in North America, Europe and Oceania 1. At the turn of the twenty-first century, IBD incidence increased in newly industrialized and emerging regions in Africa, Asia and Latin America, while the prevalence in early industrialized regions continued to grow steadily 2, 3–4. Changes in the incidence and prevalence denote the evolution of IBD across four epidemiologic stages: stage 1 (emergence), characterized by low incidence and prevalence; stage 2 (acceleration in incidence), marked by rapidly rising incidence and low prevalence; and stage 3 (compounding prevalence), where the incidence decelerates, plateaus or declines while the prevalence steadily increases. A fourth stage (prevalence equilibrium) has been proposed in which the prevalence slope plateaus due to demographic shifts in an ageing IBD population, but it has not yet been evidenced. To date, these stages have remained theoretical, lacking specific numerical indicators to define transition points. Here, using real-world data from 522 population-based studies encompassing 82 global regions and spanning more than a century (1920–2024), we show spatiotemporal transitions across stages 1–3 and model stage 4 progression. Understanding the evolution of IBD across epidemiologic stages enables healthcare systems to better anticipate the future worldwide burden of IBD.</p
Modern pedigree dogs in the United Kingdom Kennel Club: a journey through shifting population landscapes and demography
Get PDFBackgroundThe limited genetic diversity in pedigree dog populations and the associated increased burden of inherited disease have led to calls for the development and implementation of effective population management strategies. Such strategies must be rooted in a thorough understanding of the genetic reserves and demographics of each population to be managed. Although numerous studies have examined the genetic diversity within various dog breeds, information on the structure of breeding populations and the characteristics of the dogs used for breeding is scarce. Furthermore, the few existing estimates typically represent the most common breeds, which may not be directly relevant for many of the numerically smaller breeds. We examined the demographic parameters of all 222 pedigree breeds recognised by The Kennel Club (KC) in the UK between 1990 and 2021. A meta-analysis was used to test whether all breeds can be represented by a single pedigree dog population, establish reference values for that population and determine the presence of significant variability between breeds.ResultsOverall, the KC-registered pedigree dog population is declining in size, and the percentage of dogs used in breeding is low. Dogs which have been successful in activities such as conformation shows and field trials have been popular in breeding. However, their use in breeding is in decline, partly in favour of imported dogs. The number of imported dogs, and their use in breeding have increased over time, particularly following amendments to the Pet Travel Scheme (PETS) in 2012. Across analyses, the within-breed estimates varied significantly, with the proportion of variation attributed to true variability between breeds exceeding 90% for the majority of estimates.ConclusionThe results of this study provide reference values which can be used to describe the demographics of the KC-registered pedigree dog population and its changes over the last three decades. However, the significantly high variability observed between breeds does not support the hypothesis of a single pedigree dog population and underlines that population management strategies must be tailored to the unique circumstances of each breed
Ligand-modified nickel nitride for natural seawater H<sub>2</sub>O<sub>2</sub> synthesis
Get PDFHydrogen peroxide (H2O2) is a clean and versatile oxidant with significant applications in marine pollution treatment. Direct electrosynthesis of H2O2 via the two-electron oxygen reduction reaction (2e- ORR) from seawater offers a sustainable and efficient alternative by eliminating the need for H2O2 transport and storage. Herein, we report a 2-bromothiophene-modified nickel nitride (D-Ni3N) catalyst that optimizes oxygen adsorption to selectively enhance the 2e- ORR pathway while mitigating halide-induced corrosion and alkaline earth salt precipitation. D-Ni3N achieves a remarkable H2O2 yield rate of 4.69 mol·h−1·g−1 with a Faradaic efficiency of 94.6 %, sustaining continuous operation for over 120 hours in natural seawater. Notably, the capital cost of 70 wt% H2O2 is remarkably low at just $0.20 kg−1. This work highlights the transformative potential of ligand-modified metal nitrides as stable and efficient 2e- ORR catalysts for sustainable H2O2 production in seawater purification applications.</p
Future of money and HCI
Get PDFMoney and financial activities reflect social connections and societal norms. Collaborative financial activities and decision-making are highly common in our day-to-day activities. However, existing financial technologies (fintech) are often limited to individual-centric approaches and goals. Recent HCI work has repeatedly noted the need for creating new interaction strategies and design paradigms to better support our financial behaviors, habits, and goals. However, there has not been much concrete work yet, specifically when it comes to supporting collaborative behaviors and social norms that underpin much of our daily financial activities. In this in-person workshop, we will bring together an interdisciplinary group of researchers interested in reshaping the current landscape of digital money and fintech with a focus on social and collaborative interactions. Specifically, we will identify limitations of existing fintech approaches and potential strategies to address these limitations. We will also discuss key challenges for fintech design and development, including collaboration, privacy, agency, trust, and accessibility. The workshop will lead to identifying novel HCI research and implementation directions focusing on the future of financial technologies.</p
Access Repository Dashboard
Do you manage Edinburgh Research Explorer? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!