| 1. |
- Opitz, Rachel, et al.
(författare)
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A Lockpick's Guide to dataARC: Designing Infrastructures and Building Communities to Enable Transdisciplinary Research
- 2021
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Ingår i: Internet Archaeology. - : Council for British Archaeology. - 1363-5387. ; 56
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Tidskriftsartikel (refereegranskat)abstract
- The North Atlantic Biocultural Organization (NABO) community initiated dataARC to develop digital research infrastructures to support their work on long-term human-ecodynamics in the North Atlantic. These infrastructures were designed to address the challenges of sharing research data, the connections between those data and high-level interpretations, and the interpretations themselves. In parallel, they were also designed to support the reuse of diverse data that underpin transdisciplinary synthesis research and to contextualise materials disseminated widely to the public more firmly in their evidence base. This article outlines the research infrastructure produced by the project and reflects on its design and development. We outline the core motivations for dataARC's work and introduce the tools, platforms and (meta)data products developed. We then undertake a critical review of the project's workflow. This review focuses on our understanding of the needs of stakeholder groups, the principles that guided the design of the infrastructure, and the extent to which these principles are successfully promoted in the current implementation. Drawing on this assessment, we consider how the infrastructure, in whole or in part, might be reused by other transdisciplinary research communities. Finally, we highlight key socio-technical gaps that may emerge as structural barriers to transdisciplinary, engaged, and open research if left unaddressed.
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| 2. |
- Ellinghaus, David, et al.
(författare)
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Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci
- 2016
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Ingår i: Nature Genetics. - New York, USA : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 48:5, s. 510-518
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Tidskriftsartikel (refereegranskat)abstract
- We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.
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| 3. |
- Frantz, Laurent A. F., et al.
(författare)
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Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:35, s. 17231-17238
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Tidskriftsartikel (refereegranskat)abstract
- Archaeological evidence indicates that pig domestication had begun by similar to 10,500 y before the present ( BP) in the Near East, and mitochondrial DNA ( mtDNA) suggests that pigs arrived in Europe alongside farmers similar to 8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
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| 4. |
- Goyette, Philippe, et al.
(författare)
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High-density mapping of the MHC identifies a shared role for HLA-DRB1*01 : 03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis
- 2015
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Ingår i: Nature Genetics. - New York, USA : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:2, s. 172-179
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.
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| 5. |
- Koens, Lisette H, et al.
(författare)
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A Screening Tool to Quickly Identify Movement Disorders in Patients with Inborn Errors of Metabolism
- 2023
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 38:4, s. 646-653
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Movement disorders are frequent in patients with inborn errors of metabolism (IEMs) but poorly recognized, particularly by nonmovement disorder specialists. We propose an easy-to-use clinical screening tool to help recognize movement disorders.OBJECTIVE: The aim is to develop a user-friendly rapid screening tool for nonmovement disorder specialists to detect moderate and severe movement disorders in patients aged ≥4 years with IEMs.METHODS: Videos of 55 patients with different IEMs were scored by experienced movement disorder specialists (n = 12). Inter-rater agreements were determined on the presence and subtype of the movement disorder. Based on ranking and consensus, items were chosen to be incorporated into the screening tool.RESULTS: A movement disorder was rated as present in 80% of the patients, with a moderate inter-rater agreement (κ =0.420, P < 0.001) on the presence of a movement disorder. When considering only moderate and severe movement disorders, the inter-rater agreement increased to almost perfect (κ = 0.900, P < 0.001). Dystonia was most frequently scored (27.3%) as the dominant phenotype. Treatment was mainly suggested for patients with moderate or severe movement disorders. Walking, observations of the arms, and drawing a spiral were found to be the most informative tasks and were included in the screening tool.CONCLUSIONS: We designed a screening tool to recognize movement disorders in patients with IEMs. We propose that this screening tool can contribute to select patients who should be referred to a movement disorder specialist for further evaluation and, if necessary, treatment of the movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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