| 1. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 2. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 6. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 7. |
- Pöntinen, M., et al.
(författare)
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Euclid: Identification of asteroid streaks in simulated images using deep learning
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 679
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Tidskriftsartikel (refereegranskat)abstract
- The material composition of asteroids is an essential piece of knowledge in the quest to understand the formation and evolution of the Solar System. Visual to near-infrared spectra or multiband photometry is required to constrain the material composition of asteroids, but we currently have such data, especially in the near-infrared wavelengths, for only a limited number of asteroids. This is a significant limitation considering the complex orbital structures of the asteroid populations. Up to 150 000 asteroids will be visible in the images of the upcoming ESA Euclid space telescope, and the instruments of Euclid will offer multiband visual to near-infrared photometry and slitless near-infrared spectra of these objects. Most of the asteroids will appear as streaks in the images. Due to the large number of images and asteroids, automated detection methods are needed. A non-machine-learning approach based on the Streak Det software was previously tested, but the results were not optimal for short and/or faint streaks. We set out to improve the capability to detect asteroid streaks in Euclid images by using deep learning. We built, trained, and tested a three-step machine-learning pipeline with simulated Euclid images. First, a convolutional neural network (CNN) detected streaks and their coordinates in full images, aiming to maximize the completeness (recall) of detections. Then, a recurrent neural network (RNN) merged snippets of long streaks detected in several parts by the CNN. Lastly, gradient-boosted trees (XGBoost) linked detected streaks between different Euclid exposures to reduce the number of false positives and improve the purity (precision) of the sample. The deep-learning pipeline surpasses the completeness and reaches a similar level of purity of a non-machine-learning pipeline based on the StreakDet software. Additionally, the deep-learning pipeline can detect asteroids 0.25–0.5 magnitudes fainter than StreakDet. The deep-learning pipeline could result in a 50% increase in the number of detected asteroids compared to the StreakDet software. There is still scope for further refinement, particularly in improving the accuracy of streak coordinates and enhancing the completeness of the final stage of the pipeline, which involves linking detections across multiple exposures.
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| 8. |
- Cole, Lorna J., et al.
(författare)
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A critical analysis of the potential for EU Common Agricultural Policy measures to support wild pollinators on farmland
- 2020
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Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 57:4, s. 681-694
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Tidskriftsartikel (refereegranskat)abstract
- Agricultural intensification and associated loss of high-quality habitats are key drivers of insect pollinator declines. With the aim of decreasing the environmental impact of agriculture, the 2014 EU Common Agricultural Policy (CAP) defined a set of habitat and landscape features (Ecological Focus Areas: EFAs) farmers could select from as a requirement to receive basic farm payments. To inform the post-2020 CAP, we performed a European-scale evaluation to determine how different EFA options vary in their potential to support insect pollinators under standard and pollinator-friendly management, as well as the extent of farmer uptake. A structured Delphi elicitation process engaged 22 experts from 18 European countries to evaluate EFAs options. By considering life cycle requirements of key pollinating taxa (i.e. bumble bees, solitary bees and hoverflies), each option was evaluated for its potential to provide forage, bee nesting sites and hoverfly larval resources. EFA options varied substantially in the resources they were perceived to provide and their effectiveness varied geographically and temporally. For example, field margins provide relatively good forage throughout the season in Southern and Eastern Europe but lacked early-season forage in Northern and Western Europe. Under standard management, no single EFA option achieved high scores across resource categories and a scarcity of late season forage was perceived. Experts identified substantial opportunities to improve habitat quality by adopting pollinator-friendly management. Improving management alone was, however, unlikely to ensure that all pollinator resource requirements were met. Our analyses suggest that a combination of poor management, differences in the inherent pollinator habitat quality and uptake bias towards catch crops and nitrogen-fixing crops severely limit the potential of EFAs to support pollinators in European agricultural landscapes. Policy Implications. To conserve pollinators and help protect pollination services, our expert elicitation highlights the need to create a variety of interconnected, well-managed habitats that complement each other in the resources they offer. To achieve this the Common Agricultural Policy post-2020 should take a holistic view to implementation that integrates the different delivery vehicles aimed at protecting biodiversity (e.g. enhanced conditionality, eco-schemes and agri-environment and climate measures). To improve habitat quality we recommend an effective monitoring framework with target-orientated indicators and to facilitate the spatial targeting of options collaboration between land managers should be incentivised.
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| 9. |
- Reiner, A. T., et al.
(författare)
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Concise Review: Developing Best-Practice Models for the Therapeutic Use of Extracellular Vesicles
- 2017
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Ingår i: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 6:8
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Forskningsöversikt (refereegranskat)abstract
- Growing interest in extracellular vesicles (EVs, including exosomes and microvesicles) as therapeutic entities, particularly in stem cell-related approaches, has underlined the need for standardization and coordination of development efforts. Members of the International Society for Extracellular Vesicles and the Society for Clinical Research and Translation of Extracellular Vesicles Singapore convened a Workshop on this topic to discuss the opportunities and challenges associated with development of EV-based therapeutics at the preclinical and clinical levels. This review outlines topic-specific action items that, if addressed, will enhance the development of best-practice models for EV therapies.
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| 10. |
- Eeraerts, Maxime, et al.
(författare)
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Synthesis of highbush blueberry pollination research reveals region-specific differences in the contributions of honeybees and wild bees
- 2023
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Ingår i: Journal of Applied Ecology. - 0021-8901. ; 60:12, s. 2528-2539
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Forskningsöversikt (refereegranskat)abstract
- Highbush blueberry production has expanded worldwide in recent decades. To safeguard future yields, it is essential to understand if insect pollination is limiting current blueberry production and which insects contribute to pollination in different production regions. We present a systematic review including a set of meta-analyses on insect-mediated pollination in highbush blueberry. We summarize the geographic distribution of research, the abundance of different pollinator taxa and their relative pollination contributions. Using raw data from 21 studies, totalling 496 site replicates, we determine the degree of pollination service and pollen limitation (i.e. combining open pollination levels with experimental bagged and/or hand pollination treatments), as well as the contribution of honeybees and wild bees to pollination (i.e. observational, open pollination). Most studies originate from North America, focusing on only a few cultivars. Honeybees are the dominant pollinator, and wild bees are occasionally abundant. Wild bees are more efficient pollinators on a single-visit basis compared to honeybees, which increases their relative pollination contribution compared to their relative abundance. Insect-mediated pollination services increased blueberry fruit set, berry weight and seed set (R2 values: 64.8%, 75.9% and 75.2% respectively). We often detected pollen limitation, indicated by an increase in fruit set, berry weight and seed set (R2: 10.1%, 18.2% and 21.5%, respectively), with additional hand pollination. Increasing visitation of honeybees and wild bees contributed to blueberry pollination by increasing fruit set (R2: 5.4% and 3.5%), berry weight (R2: 6.5% and 2.8%) and seed set (R2: 6.4% and 3.8%) respectively. Bee contributions to fruit set and berry weight were variable across regions. Synthesis and application: A diverse community of insects, primarily bees, contributes to highbush blueberry pollination and yield. However, pollination deficits are common. The finding that both honeybees and wild bees enhance pollination highlights the possibility of adopting different management strategies that utilize honeybees, wild bees or both depending on the specific context and region. This further emphasizes the general importance of conserving pollinator health and diversity. Our synthesis highlights data gaps and areas for future research to better understand the pollination contribution of different pollinators to crops that are expanding globally.
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