| 1. |
- Dai, Qile, et al.
(författare)
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OTTERS: a powerful TWAS framework leveraging summary-level reference data
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.
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| 2. |
- Delgado, Luis Fernando, et al.
(författare)
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Phylogeny-based comparative genomics of Vibrio vulnificus links genetic traits to pathogenicity
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Vibrio vulnificus is a natural part of the microbiome of brackish waters worldwide. It is also an opportunistic pathogen that can cause severe infections and septicemia via consumption of seafood or through wound infections. The species possess diverse virulence factors, yet its precise disease mechanism remains undefined. Comparative genomics between clinical and environmental isolates offers a means to identify key virulence genes, but the scarcity of environmental isolates for V. vulnificus has constituted a significant limitation. Here we sequenced genomes of 82 V. vulnificus isolates from water, sediment and seagrass surface from stations along the Baltic Sea coast and complemented these with 208 and 117 previously sequenced clinical and environmental genomes, respectively, in a comparative analysis. Phylogenetic reconstruction corroborated earlier analysis with four main lineages forming within the species. Strains from the Baltic Sea region were confined to certain phylogenetic lineages (L4 and sublineages L2c and L2e) whereas clinical and environmental strains were found in all lineages, indicting that the phylogenetic structure of V. vulnificus reflects adaptations to specific environmental conditions rather than pathogenicity. Employing orthologue enrichment analysis in a phylogenetic framework using the PhyloBOTL pipeline developed in this work revealed 58 significantly enriched orthologs in clinical compared to environmental isolates. These orthologs were grouped into 18 co-localisation clusters based on the corresponding genes’ proximity in the genomes. The co-localisation clusters entailed clusters with 1 genes previously linked with pathogenicity in V. vulnificus, such as genes for capsular polysaccharide (CPS) synthesis and biofilm formation, but also clusters with genes not previously associated with virulence in the species. Examples of the latter were genes for pilus biosynthesis of the usher-chaperone (CU) pathway, for spermidine synthesis, and for effector proteins of the Type VI secretion system. Finally we leveraged on the clinically enriched genes to design PCR primers for detection and surveillance of pathogenic V. vulnificus strains.
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| 3. |
- Dwibedi, Chinmay Kumar, et al.
(författare)
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Long-range dispersal moved Francisella tularensis into Western Europe from the East
- 2016
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Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 2:12
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Tidskriftsartikel (refereegranskat)abstract
- For many infections transmitting to humans from reservoirs in nature, disease dispersal patterns over space and time are largely unknown. Here, a reversed genomics approach helped us understand disease dispersal and yielded insight into evolution and biological properties of Francisella tularensis, the bacterium causing tularemia. We whole-genome sequenced 67 strains and characterized by single-nucleotide polymorphism assays 138 strains, collected from individuals infected 1947-2012 across Western Europe. We used the data for phylogenetic, population genetic and geographical network analyses. All strains (n= 205) belonged to a monophyletic population of recent ancestry not found outside Western Europe. Most strains (n= 195) throughout the study area were assigned to a star-like phylogenetic pattern indicating that colonization of Western Europe occurred via clonal expansion. In the East of the study area, strains were more diverse, consistent with a founder population spreading from east to west. The relationship of genetic and geographic distance within the F. tularensis population was complex and indicated multiple long-distance dispersal events. Mutation rate estimates based on year of isolation indicated null rates; in outbreak hotspots only, there was a rate of 0.4 mutations/genome/year. Patterns of nucleotide substitution showed marked AT mutational bias suggestive of genetic drift. These results demonstrate that tularemia has moved from east to west in Europe and that F. tularensis has a biology characterized by long-range geographical dispersal events and mostly slow, but variable, replication rates. The results indicate that mutation-driven evolution, a resting survival phase, genetic drift and long-distance geographical dispersal events have interacted to generate genetic diversity within this species.
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| 4. |
- Huber, Birgit, et al.
(författare)
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Ochrobactrum pituitosum sp. nov., isolated from an industrial environment.
- 2010
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Ingår i: International journal of systematic and evolutionary microbiology. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 60:Pt 2, s. 321-6
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Tidskriftsartikel (refereegranskat)abstract
- Strain CCUG 50899, a Gram-negative, rod-shaped, non-spore-forming, motile bacterium isolated from industrial environment in Sweden and tentatively assigned to the species Ochrobactrum anthropi, was studied in order to clarify its taxonomic status. 16S rRNA gene sequence similarities placed the strain in the genus Ochrobactrum, sharing highest similarity with the type strains of Ochrobactrum rhizosphaerae (99.3 %), Ochrobactrum thiophenivorans (98.7 %), Ochrobactrum pseudogrignonense (98.6 %) and Ochrobactrum grignonense (98.5 %). The fatty acid profile of [O. anthropi] CCUG 50899 (major fatty acids C(18 : 1)omega7c and C(19 : 0) cyclo omega8c and presence of C(18 : 1) 2-OH), the polar lipid profile (diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, two unknown aminolipids and an unknown phospholipid), the presence of the quinone system ubiquinone Q-10 and a polyamine pattern with the major compounds putrescine and spermidine and moderate amounts of sym-homospermidine supported its affiliation to the genus Ochrobactrum. DNA-DNA reassociation experiments with the type strains of its closest relatives O. rhizosphaerae, O. pseudogrignonense, O. thiophenivorans and O. grignonense demonstrated that [O. anthropi] CCUG 50899 should be placed in a novel species, which is distinguishable from related species by a set of biochemical traits. Based on these data, reclassification of [O. anthropi] CCUG 50899 as the type strain of a novel species appears to be justified. Hence, we describe a novel species to accommodate this strain, for which we propose the name Ochrobactrum pituitosum sp. nov. The type strain is CCUG 50899(T) (=DSM 22207(T)).
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| 5. |
- Prasciolu, Mauro, et al.
(författare)
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On the use of multilayer Laue lenses with X-ray free electron lasers
- 2021
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Ingår i: International Conference on X-Ray Lasers 2020. - : SPIE. - 0277-786X .- 1996-756X. - 9781510646186 ; 11886
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Konferensbidrag (refereegranskat)abstract
- We report on the use of multilayer Laue lenses to focus the intense X-ray Free Electron Laser (XFEL) beam at the European XFEL to a spot size of a few tens of nanometers. We present the procedure to align and characterize these lenses and discuss challenges working with the pulse trains from this unique X-ray source.
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| 6. |
- Scholz, Gunthard, et al.
(författare)
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Migration of blue stain hyphae within wax treated wood
- 2011
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Ingår i: IAWA Journal. - : Brill. - 0928-1541 .- 2294-1932. ; 32:1, s. 88-96
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Tidskriftsartikel (refereegranskat)abstract
- The colonization of wax impregnated pine sapwood (Pinus sylvestris L.) and beech (Fagus sylvatica L.) by blue stain fungi and their hyphal migration within the treated wood was investigated. Neither the hydrophobation effect nor the physical presence of the congealed wax deposits could impede fungal growth on the surface. However, in contrast to the untreated controls, there was a lower occurrence of hyphae in wax-treated wood. Blue stain fungi grew mainly near the cross cut as well as in empty spaces such as micro-capillaries, parenchyma tissue or other wax free zones of treated wood.
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| 7. |
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| 10. |
- Tönjes, Anke, et al.
(författare)
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Genome Wide Meta-analysis Highlights the Role of Genetic Variation in RARRES2 in the Regulation of Circulating Serum Chemerin.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue. Genetic factors determining chemerin release from adipose tissue are yet unknown. We conducted a meta-analysis of genome-wide association studies (GWAS) for serum chemerin in three independent cohorts from Europe: Sorbs and KORA from Germany and PPP-Botnia from Finland (total N = 2,791). In addition, we measured mRNA expression of genes within the associated loci in peripheral mononuclear cells by micro-arrays, and within adipose tissue by quantitative RT-PCR and performed mRNA expression quantitative trait and expression-chemerin association studies to functionally substantiate our loci. Heritability estimate of circulating chemerin levels was 16.2% in the Sorbs cohort. Thirty single nucleotide polymorphisms (SNPs) at chromosome 7 within the retinoic acid receptor responder 2 (RARRES2)/Leucine Rich Repeat Containing (LRRC61) locus reached genome-wide significance (p<5.0×10-8) in the meta-analysis (the strongest evidence for association at rs7806429 with p = 7.8×10-14, beta = -0.067, explained variance 2.0%). All other SNPs within the cluster were in linkage disequilibrium with rs7806429 (minimum r2 = 0.43 in the Sorbs cohort). The results of the subgroup analyses of males and females were consistent with the results found in the total cohort. No significant SNP-sex interaction was observed. rs7806429 was associated with mRNA expression of RARRES2 in visceral adipose tissue in women (p<0.05 after adjusting for age and body mass index). In conclusion, the present meta-GWAS combined with mRNA expression studies highlights the role of genetic variation in the RARRES2 locus in the regulation of circulating chemerin concentrations.
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