| 1. |
- Almlöf, Jonas Carlsson, et al.
(author)
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Powerful Identification of Cis-regulatory SNPs in Human Primary Monocytes Using Allele-Specific Gene Expression
- 2012
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12, s. e52260-
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Journal article (peer-reviewed)abstract
- A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL) analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE) analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs) by genome-wide allele-specific gene expression (ASE) analysis with that of traditional expression quantitative trait locus (eQTL) mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.
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| 2. |
- Almlöf, Jonas, et al.
(author)
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Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7, s. e102612-
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Journal article (peer-reviewed)abstract
- We applied genome-wide allele-specific expression analysis of monocytes from 188 samples. Monocytes were purified from white blood cells of healthy blood donors to detect cis-acting genetic variation that regulates the expression of long non-coding RNAs. We analysed 8929 regions harboring genes for potential long non-coding RNA that were retrieved from data from the ENCODE project. Of these regions, 60% were annotated as intergenic, which implies that they do not overlap with protein-coding genes. Focusing on the intergenic regions, and using stringent analysis of the allele-specific expression data, we detected robust cis-regulatory SNPs in 258 out of 489 informative intergenic regions included in the analysis. The cis-regulatory SNPs that were significantly associated with allele-specific expression of long non-coding RNAs were enriched to enhancer regions marked for active or bivalent, poised chromatin by histone modifications. Out of the lncRNA regions regulated by cis-acting regulatory SNPs, 20% (n = 52) were co-regulated with the closest protein coding gene. We compared the identified cis-regulatory SNPs with those in the catalog of SNPs identified by genome-wide association studies of human diseases and traits. This comparison identified 32 SNPs in loci from genome-wide association studies that displayed a strong association signal with allele-specific expression of non-coding RNAs in monocytes, with p-values ranging from 6.7×10-7 to 9.5×10-89. The identified cis-regulatory SNPs are associated with diseases of the immune system, like multiple sclerosis and rheumatoid arthritis.
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| 3. |
- Calles, Britt-Marie, et al.
(author)
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Grunddatadomän transportsystem: Kompletterande underlag till den utforskande förstudien
- 2022
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Reports (other academic/artistic)abstract
- I mars 2022 levererade Trafikverket och samverkande myndigheter (Transportstyrelsen, Sjöfartsverket, Luftfartsverket, Trafikanalys och VTI, Statens väg- och transportforskningsinstitut) en rapport som sammanfattade den utforskande utvecklingen att utreda en grunddatadomän för transportsystemet. Föreliggande rapport är en komplettering till den ursprungliga rapporten och utgör Trafikverkets inklusive samverkande myndigheters sammantagna underlag (utforskande utveckling) för etablering av en grunddatadomän för transportsystemet. Arbetet har bedrivits under ledning av Myndigheten för digital förvaltning (DIGG) med Trafikverket som ansvarig för den utforskande utvecklingen. Till rapporten hör en bilaga, se länk till höger.Ursprunglig rapport: Grunddatadomän transportsystem: Samverkansuppdrag mellan transportmyndigheterna för att bedriva en utforskande utveckling att utreda en grunddatadomän för information kopplat till transportsystemet
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| 4. |
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| 5. |
- Lindqvist, C. Mårten, et al.
(author)
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Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:39, s. 64071-64088
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Journal article (peer-reviewed)abstract
- To characterize the mutational patterns of acute lymphoblastic leukemia (ALL) we performed deep next generation sequencing of 872 cancer genes in 172 diagnostic and 24 relapse samples from 172 pediatric ALL patients. We found an overall greater mutational burden and more driver mutations in T-cell ALL (T-ALL) patients compared to B-cell precursor ALL (BCP-ALL) patients. In addition, the majority of the mutations in T-ALL had occurred in the original leukemic clone, while most of the mutations in BCP-ALL were subclonal. BCP-ALL patients carrying any of the recurrent translocations ETV6-RUNX1, BCR-ABL or TCF3-PBX1 harbored few mutations in driver genes compared to other BCP-ALL patients. Specifically in BCP-ALL, we identified ATRX as a novel putative driver gene and uncovered an association between somatic mutations in the Notch signaling pathway at ALL diagnosis and increased risk of relapse. Furthermore, we identified EP300, ARID1A and SH2B3 as relapse-associated genes. The genes highlighted in our study were frequently involved in epigenetic regulation, associated with germline susceptibility to ALL, and present in minor subclones at diagnosis that became dominant at relapse. We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency.
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| 6. |
- Adoue, Veronique, et al.
(author)
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Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs
- 2014
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In: Molecular Systems Biology. - : EMBO. - 1744-4292 .- 1744-4292. ; 10:10, s. 754-
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Journal article (peer-reviewed)abstract
- Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases.
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| 7. |
- Andreasson, Mattias, et al.
(author)
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Project Avatar Developing a Distributed Mobile Phone Game
- 2006
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Reports (other academic/artistic)abstract
- Team Avatar, as the members of Project Avatar have come to be known by, is a group of 4th year computer science students at Uppsala University that have been developing a distributed mobile phone game during the fall of 2005. In this paper we describe the general design and environment of the result of Project Avatar - the game Three Crowns.
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| 9. |
- Dimkovski, Zlate, 1974-, et al.
(author)
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Optimization of the Triboconditioning Process on External Cylindrical Surfaces
- 2015
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In: Proceedings of the 15th International Conference on Metrology and Properties of Engineering Surfaces. - Raleigh, NC : American Society for Precision Engineering (ASPE).
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Conference paper (peer-reviewed)abstract
- The use of tungsten disulfide in tribofilms on functional surfaces has been a proven way to reduce the frictional losses in rolling and sliding contacts, especially in lubricated contacts at boundary and mixed regime. A suitable and cost-effective process to deposit tungsten disulfide is by ANS Triboconditioning, the mechano-chemical surface finishing process for improving the tribological properties of mechanical components made of steel or cast iron. However, it is not known what are the optimal process parameters, speeds and pressures, to achieve an optimal surface treatment. In this paper, the modifications of the work-piece surfaces under Triboconditioning have been tracked to optimize the process parameters. To closely control the conditions, a commercial tribometer with a block-on-ring configuration was used. Cylindrical tungsten carbide samples (representing the tool) were rubbed against steel rings (representing the work-piece) under two different loads and speeds. The ring surfaces of two different finishes (ground and honed) were measured on the same place before and after treatment to track the surface modifications. At last, the treated rings were rubbed against a flat steel surface in start-stop sequences that resemble pin-roller operating conditions of a truck valve train and the friction behavior was screened. The results show a reduction of the core roughness of the ring surfaces with the lowest friction for the ground rings treated by low load and low speed.
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