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- 2019
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Tidskriftsartikel (refereegranskat)
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- Österlund, Tobias, 1984, et al.
(författare)
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HirBin: high-resolution identification of differentially abundant functions in metagenomes
- 2017
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gene-centric analysis of metagenomics data provides information about the biochemical functions present in a microbiome under a certain condition. The ability to identify significant differences in functions between metagenomes is dependent on accurate classification and quantification of the sequence reads (binning). However, biological effects acting on specific functions may be overlooked if the classes are too general. Methods: Here we introduce High-Resolution Binning (HirBin), a new method for gene-centric analysis of metagenomes. HirBin combines supervised annotation with unsupervised clustering to bin sequence reads at a higher resolution. The supervised annotation is performed by matching sequence fragments to genes using well-established protein domains, such as TIGRFAM, PFAM or COGs, followed by unsupervised clustering where each functional domain is further divided into sub-bins based on sequence similarity. Finally, differential abundance of the sub-bins is statistically assessed. Results: We show that HirBin is able to identify biological effects that are only present at more specific functional levels. Furthermore we show that changes affecting more specific functional levels are often diluted at the more general level and therefore overlooked when analyzed using standard binning approaches. Conclusions: HirBin improves the resolution of the gene-centric analysis of metagenomes and facilitates the biological interpretation of the results.
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- Österbrand, Marcus, 1976, et al.
(författare)
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A method to predict the metabolic effects of changes in insulin treatment in subgroups of a large population based patient cohort.
- 2007
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 22:3, s. 151-7
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Tidskriftsartikel (refereegranskat)abstract
- This case-control study was designed to analyse predictors of the effects on HbA1c levels in 4001 type 1 and type 2 diabetic patients after changing their insulin treatment. Patients from 15 outpatient diabetic clinics were treated with basal insulin and multiple injections of short-acting insulin. The effects on HbA1c of changing from NPH insulin to insulin glargine as basal insulin were studied, compared to patients continuing with NPH insulin. The following possible predictors were examined with multiple regression analysis: age, sex, type and duration of diabetes, smoking, metformin use, insulin requirement, number of basal doses per day, BMI and HbA1c at baseline. The difference between the two regression functions yielded the effect of switching treatment to insulin glargine compared to continuing with NPH insulin. Male gender, low BMI and high baseline HbA1c levels were significant predictors for a greater decrease in HbA1c when changing to insulin glargine. For example, for men with a BMI of 25 and an HbA1c of 8.0%, there was a calculated mean benefit in HbA1c of 0.26 percentage points by changing to insulin glargine, whereas women with a BMI 30 had no benefit of such a change. Thus, changing to insulin glargine had best effect in male patients with low BMI. This is one of the first studies designed to find responders to insulin treatment. Analyses of predictors may prove useful in order to tailor insulin treatment in diabetic patients in clinical practice. The clinical effects need to be confirmed in other studies and randomised controlled trials.
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- Österberg, Linnea, 1992, et al.
(författare)
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A novel yeast hybrid modeling framework integrating Boolean and enzyme-constrained networks enables exploration of the interplay between signaling and metabolism
- 2021
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 17:4
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Tidskriftsartikel (refereegranskat)abstract
- The interplay between nutrient-induced signaling and metabolism plays an important role in maintaining homeostasis and its malfunction has been implicated in many different human diseases such as obesity, type 2 diabetes, cancer, and neurological disorders. Therefore, unraveling the role of nutrients as signaling molecules and metabolites together with their interconnectivity may provide a deeper understanding of how these conditions occur. Both signaling and metabolism have been extensively studied using various systems biology approaches. However, they are mainly studied individually and in addition, current models lack both the complexity of the dynamics and the effects of the crosstalk in the signaling system. To gain a better understanding of the interconnectivity between nutrient signaling and metabolism in yeast cells, we developed a hybrid model, combining a Boolean module, describing the main pathways of glucose and nitrogen signaling, and an enzyme-constrained model accounting for the central carbon metabolism of Saccharomyces cerevisiae, using a regulatory network as a link. The resulting hybrid model was able to capture a diverse utalization of isoenzymes and to our knowledge outperforms constraint-based models in the prediction of individual enzymes for both respiratory and mixed metabolism. The model showed that during fermentation, enzyme utilization has a major contribution in governing protein allocation, while in low glucose conditions robustness and control are prioritized. In addition, the model was capable of reproducing the regulatory effects that are associated with the Crabtree effect and glucose repression, as well as regulatory effects associated with lifespan increase during caloric restriction. Overall, we show that our hybrid model provides a comprehensive framework for the study of the non-trivial effects of the interplay between signaling and metabolism, suggesting connections between the Snf1 signaling pathways and processes that have been related to chronological lifespan of yeast cells.
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| 6. |
- Östensson, Malin, 1984
(författare)
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Statistical Methods for Genome Wide Association Studies
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis focus on various statistical methods for analyzing Genome Wide Association data. The thesis include four papers, three of them considers the analysis of complex traits, and the last one a method for analyzing mendelian traits. Although GWAS have identified many associated regions in the genome for many com- plex diseases, there is still much of the genetic heritability that remains unexplained. The power of detecting new genetic risk variants can be improved by considering several genes in the same model. A genetic variant in the HLA region on chromosome 6 is necessary but not sufficient to develop Celiac Disease. In the first two papers we utilize this information to discover additional genetic variants. In Paper I this is done by a method which use the ’Cochran Armitage trend test’, to find a trend in allele frequencies. Simulations are used to evaluate the power of this test compared with the commonly used Pearson 1 df chisquare test and the test is then applied to a previously published Celiac Disease case-control material. In paper II the HLA information is utilized by a stratified TDT, conditioning on the HLA variants. In addition, an imputation-based version of the TDT is presented, as well as a likelihood ratio test searching for two-locus interactions by comparing the heterogeneity and epistasis models. Here the candidates for interaction analysis are chosen by a two-step approach, combining the results from the TDT and prior information from previous studies. In contrast to the approach used in paper II for identifying interactions between genes, in paper 3 we instead consider the method of performing a full Genome Wide Interaction Analysis. By examining how commonly we will find interactions without marginal effects in a GWIA we discuss what conclusions can be drawn from such findings. In the final paper we develop a program locating a region containing a causal gene for rare monogenic traits. This program can be used in large pedigrees with multiple affected cases, and discerns the causal region by coloring them according to how common they are in the population.
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| 8. |
- Östensson, Malin, 1984, et al.
(författare)
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A Possible Mechanism behind Autoimmune Disorders Discovered By Genome-Wide Linkage and Association Analysis in Celiac Disease
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Celiac disease is a common autoimmune disorder characterized by an intestinal inflammation triggered by gluten, a storage protein found in wheat, rye and barley. Similar to other autoimmune diseases such as type 1 diabetes, psoriasis and rheumatoid arthritis, celiac disease is the result of an immune response to self-antigens leading to tissue destruction and production of autoantibodies. Common diseases like celiac disease have a complex pattern of inheritance with inputs from both environmental as well as additive and non-additive genetic factors. In the past few years, Genome Wide Association Studies (GWAS) have been successful in finding genetic risk variants behind many common diseases and traits. To complement and add to the previous findings, we performed a GWAS including 206 trios from 97 nuclear Swedish and Norwegian families affected with celiac disease. By stratifying for HLA-DQ, we identified a new genome-wide significant risk locus covering the DUSP10 gene. To further investigate the associations from the GWAS we performed pathway analyses and two-locus interaction analyses. These analyses showed an over-representation of genes involved in type 2 diabetes and identified a set of candidate mechanisms and genes of which some were selected for mRNA expression analysis using small intestinal biopsies from 98 patients. Several genes were expressed differently in the small intestinal mucosa from patients with celiac autoimmunity compared to intestinal mucosa from control patients. From top-scoring regions we identified susceptibility genes in several categories: 1) polarity and epithelial cell functionality; 2) intestinal smooth muscle; 3) growth and energy homeostasis, including proline and glutamine metabolism; and finally 4) innate and adaptive immune system. These genes and pathways, including specific functions of DUSP10, together reveal a new potential biological mechanism that could influence the genesis of celiac disease, and possibly also other chronic disorders with an inflammatory component.
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| 9. |
- Örtengren, Ulf, 1959, et al.
(författare)
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Influence of pH and time on organic substance release from a model dental composite: a fluorescence spectrophotometry and gas chromatography/mass spectrometry analysis.
- 2004
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Ingår i: European journal of oral sciences. - : Wiley. - 0909-8836 .- 1600-0722. ; 112:6, s. 530-7
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Tidskriftsartikel (refereegranskat)abstract
- In this study we assessed the influence of pH and time on the degradation and elution of organic substances from the composite resin material, Z-100. To accomplish this, fluorescence spectrophotometry was evaluated as an appropriate technique for the identification of six organic substances (methacrylic acid, methyl methacrylate, hydroquinone, ethylene glycol dimethacrylate, triethylene glycol dimethacrylate and 4,4'-isopropylidenediphenol) that were eluted from resin composite material stored for 24 h or 6 months at pH 4.0, 6.0 or 8.0. In addition, complementary analyses (solid-phase microextraction/gas chromatography/mass spectrometry) were carried out to identify and quantify the substances. The main substances leached from the resin composite were methacrylic acid, triethylene glycol dimethacrylate and hydroquinone. It was concluded that fluorescence spectrophotometry seems to be a suitable, non-destructive technique for the qualitative analysis of eluted organic components. Critical combinations of time and pH allowed the elution of several organic substances, predominantly methacrylic acid, triethylene glycol dimethacrylate and hydroquinone, from the model resin composite, Z-100.
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| 10. |
- Örtengren, Tore, et al.
(författare)
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Membrane leakage in spinal ganglion nerve cells induced by experimental whiplash extension motion: a study in pigs
- 1996
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 13:3, s. 171-180
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Tidskriftsartikel (refereegranskat)abstract
- Nerve cells in the cervical and upper thoracic spinal ganglia were examined for possible plasma membrane leakage, as revealed by their ability to exclude a dye-protein complex, after experimentally induced whiplash in a pig model system. The rationale for this approach is found in the fact that the interstitium of spinal ganglia differs from most other parts of the nervous system in that it lacks a barrier, allowing blood constituents to gain access. The dye Evans blue, which rapidly conjugates with blood proteins, is found in the interstitium of normal spinal ganglia after intravenous injection, but it is excluded from the nerve cells and their enveloping satellite cells. In contrast, after a simulated whiplash extension trauma many of the nerve cells were stained, reflecting the inability of their plasma membranes to exclude the dye-protein complex. Morphometric measurements revealed that the highest frequency of cellular dye uptake was observed in the C4-C7 spinal ganglia (mean 16 - 18%; range 5-27%). The blood-nerve barrier of the adjacent nerve fascicles remained intact, with rare exception. Several factors are considered to contribute to the induction of these cell abnormalities in the spinal ganglia after an experimentally induced, simulated whiplash trauma in this pig model system.
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