| 1. |
- Bengtsson, Anders A., et al.
(författare)
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Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren’s Syndrome and Systemic Sclerosis
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diag- nose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway.
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| 2. |
- Madsen, Rasmus Kirkegaard, 1979-, et al.
(författare)
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Diagnostic properties of metabolic perturbations in rheumatoid arthritis
- 2011
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 13:1, s. R19-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of the study was to assess the feasibility of diagnosing early rheumatoid arthritis (RA) by measuring selected metabolic biomarkers. METHODS: We compared the metabolic profile of patients with RA with those of healthy controls and patients with psoriatic arthritis (PsoA). The metabolites were measured using two different chromatography-mass spectrometry platforms, thereby giving a broad overview of serum metabolites. The metabolic profiles of patient and control groups were compared using multivariate statistical analysis. The findings were validated in a follow-up study of RA patients and healthy volunteers. RESULTS: RA patients were diagnosed with a sensitivity of 93 % and a specificity of 70 % in a validation study using detection of 52 metabolites. Patients with RA or PsoA could be distinguished with a sensitivity of 90 % and a specificity of 94 %. Glyceric acid, D-ribofuranoise and hypoxanthine were increased in RA patients, whereas histidine, threonic acid, methionine, cholesterol, asparagine and threonine were all decreased when compared with healthy controls. CONCLUSIONS: Metabolite profiling (metabolomics) is a potentially useful technique for diagnosing RA. The predictive value was irrespective of the presence of antibodies against cyclic citrullinated peptides (ACPA).
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| 3. |
- Bygdell, Joakim, et al.
(författare)
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Protein expression in tension wood formation monitored at high tissue resolution in Populus
- 2017
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Ingår i: Journal of Experimental Botany. - : Oxford University Press. - 0022-0957 .- 1460-2431. ; 68:13, s. 3405-3417
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Tidskriftsartikel (refereegranskat)abstract
- Tension wood (TW) is a specialized tissue with contractile properties that is formed by the vascular cambium in response to gravitational stimuli. We quantitatively analysed the proteomes of Populus tremula cambium and its xylem cell derivatives in stems forming normal wood (NW) and TW to reveal the mechanisms underlying TW formation. Phloem-, cambium-, and wood-forming tissues were sampled by tangential cryosectioning and pooled into nine independent samples. The proteomes of TW and NW samples were similar in the phloem and cambium samples, but diverged early during xylogenesis, demonstrating that reprogramming is an integral part of TW formation. For example, 14-3-3, reactive oxygen species, ribosomal and ATPase complex proteins were found to be up-regulated at early stages of xylem differentiation during TW formation. At later stages of xylem differentiation, proteins involved in the biosynthesis of cellulose and enzymes involved in the biosynthesis of rhamnogalacturonan-I, rhamnogalacturonan-II, arabinogalactan-II and fasciclin-like arabinogalactan proteins were up-regulated in TW. Surprisingly, two isoforms of exostosin family proteins with putative xylan xylosyl transferase function and several lignin biosynthesis proteins were also up-regulated, even though xylan and lignin are known to be less abundant in TW than in NW. These data provided new insight into the processes behind TW formation.
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| 4. |
- Bylesjö, Max, et al.
(författare)
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Integrated analysis of transcript, protein and metabolite data to study lignin biosynthesis in hybrid aspen
- 2009
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 8:1, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- Tree biotechnology will soon reach a mature state where it will influence the overall supply of fiber, energy and wood products. We are now ready to make the transition from identifying candidate genes, controlling important biological processes, to discovering the detailed molecular function of these genes on a broader, more holistic, systems biology level. In this paper, a strategy is outlined for informative data generation and integrated modeling of systematic changes in transcript, protein and metabolite profiles measured from hybrid aspen samples. The aim is to study characteristics of common changes in relation to genotype-specific perturbations affecting the lignin biosynthesis and growth. We show that a considerable part of the systematic effects in the system can be tracked across all platforms and that the approach has a high potential value in functional characterization of candidate genes.
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| 5. |
- Eliasson, Mattias, et al.
(författare)
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Strategy for optimizing LC-MS data processing in Metabolomics : A design of experiments approach
- 2012
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 84:15, s. 6869-6876
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Tidskriftsartikel (refereegranskat)abstract
- A strategy for optimizing LC-MS metabolomics data processing is proposed. We applied this strategy on the XCMS open source package written in R on both human and plant biology data. The strategy is a sequential design of experiments (DoE) based on a dilution series from a pooled sample and a measure of correlation between diluted concentrations and integrated peak areas. The reliability index metric, used to define peak quality, simultaneously favors reliable peaks and disfavors unreliable peaks using a weighted ratio between peaks with high and low response linearity. DoE optimization resulted in the case studies in more than 57% improvement in the reliability index compared to the use of the default settings. The proposed strategy can be applied to any other data processing software involving parameters to be tuned, e.g., MZmine 2. It can also be fully automated and used as a module in a complete metabolomics data processing pipeline.
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| 6. |
- Galindo-Prieto, Beatriz, et al.
(författare)
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A new approach for variable influence on projection (VIP) in O2PLS models
- 2017
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Ingår i: Chemometrics and Intelligent Laboratory Systems. - : Elsevier. - 0169-7439 .- 1873-3239. ; 160, s. 110-124
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Tidskriftsartikel (refereegranskat)abstract
- A novel variable influence on projection approach for O2PLS® models, named VIPO2PLS, is presented in this paper. VIPO2PLS is a model-based method for judging the importance of variables. Its cornerstone is the 2-way formalism of the O2PLS models; i.e. the use of both predictive and orthogonal normalized loadings of the two modelled data matrices, and also a new weighting system based on the sum of squares of both data blocks (X, Y). The VIPO2PLS algorithm has been tested in one synthetic data set and two real cases, and the outcomes have been compared to the PLS-VIP, VIPOPLS, and i-PLS methods. The purpose is to achieve a sharper and enhanced model interpretation of O2PLS models by using the new VIPO2PLS method for assessing the importance of both X- and Y- variables.
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| 7. |
- Galindo-Prieto, Beatriz, et al.
(författare)
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Multiblock variable influence on orthogonal projections (MB-VIOP) for enhanced interpretation of total, global, local and unique variations in OnPLS models
- 2021
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Ingår i: BMC Bioinformatics. - : BioMed Central. - 1471-2105. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: For multivariate data analysis involving only two input matrices (e.g., X and Y), the previously published methods for variable influence on projection (e.g., VIPOPLS or VIPO2PLS) are widely used for variable selection purposes, including (i) variable importance assessment, (ii) dimensionality reduction of big data and (iii) interpretation enhancement of PLS, OPLS and O2PLS models. For multiblock analysis, the OnPLS models find relationships among multiple data matrices (more than two blocks) by calculating latent variables; however, a method for improving the interpretation of these latent variables (model components) by assessing the importance of the input variables was not available up to now.Results: A method for variable selection in multiblock analysis, called multiblock variable influence on orthogonal projections (MB-VIOP) is explained in this paper. MB-VIOP is a model based variable selection method that uses the data matrices, the scores and the normalized loadings of an OnPLS model in order to sort the input variables of more than two data matrices according to their importance for both simplification and interpretation of the total multiblock model, and also of the unique, local and global model components separately. MB-VIOP has been tested using three datasets: a synthetic four-block dataset, a real three-block omics dataset related to plant sciences, and a real six-block dataset related to the food industry.Conclusions: We provide evidence for the usefulness and reliability of MB-VIOP by means of three examples (one synthetic and two real-world cases). MB-VIOP assesses in a trustable and efficient way the importance of both isolated and ranges of variables in any type of data. MB-VIOP connects the input variables of different data matrices according to their relevance for the interpretation of each latent variable, yielding enhanced interpretability for each OnPLS model component. Besides, MB-VIOP can deal with strong overlapping of types of variation, as well as with many data blocks with very different dimensionality. The ability of MB-VIOP for generating dimensionality reduced models with high interpretability makes this method ideal for big data mining, multi-omics data integration and any study that requires exploration and interpretation of large streams of data.
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| 8. |
- Gandla, Madhavi Latha, et al.
(författare)
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Overexpression of vesicle-associated membrane protein PttVAP27-17 as a tool to improve biomass production and the overall saccharification yields in Populus trees
- 2021
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Ingår i: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Bioconversion of wood into bioproducts and biofuels is hindered by the recalcitrance of woody raw material to bioprocesses such as enzymatic saccharification. Targeted modification of the chemical composition of the feedstock can improve saccharification but this gain is often abrogated by concomitant reduction in tree growth. Results In this study, we report on transgenic hybrid aspen (Populus tremula x tremuloides) lines that showed potential to increase biomass production both in the greenhouse and after 5 years of growth in the field. The transgenic lines carried an overexpression construct for Populus tremula x tremuloides vesicle-associated membrane protein (VAMP)-associated protein PttVAP27-17 that was selected from a gene-mining program for novel regulators of wood formation. Analytical-scale enzymatic saccharification without any pretreatment revealed for all greenhouse-grown transgenic lines, compared to the wild type, a 20-44% increase in the glucose yield per dry weight after enzymatic saccharification, even though it was statistically significant only for one line. The glucose yield after enzymatic saccharification with a prior hydrothermal pretreatment step with sulfuric acid was not increased in the greenhouse-grown transgenic trees on a dry-weight basis, but increased by 26-50% when calculated on a whole biomass basis in comparison to the wild-type control. Tendencies to increased glucose yields by up to 24% were present on a whole tree biomass basis after acidic pretreatment and enzymatic saccharification also in the transgenic trees grown for 5 years on the field when compared to the wild-type control. Conclusions The results demonstrate the usefulness of gene-mining programs to identify novel genes with the potential to improve biofuel production in tree biotechnology programs. Furthermore, multi-omic analyses, including transcriptomic, proteomic and metabolomic analyses, performed here provide a toolbox for future studies on the function of VAP27 proteins in plants.
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| 9. |
- Gerber, Lorenz, et al.
(författare)
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Multivariate curve resolution provides a high-throughput data processing pipeline for pyrolysis-gas chromatography/mass spectrometry
- 2012
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Ingår i: Journal of Analytical and Applied Pyrolysis. - : Elsevier BV. - 0165-2370 .- 1873-250X. ; 95, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- We present a data processing pipeline for Pyrolysis-Gas Chromatography/Mass Spectrometry (Py-GC/MS) data that is suitable for high-throughput analysis of lignocellulosic samples. The aproach applies multivariate curve resolution by alternate regression (MCR-AR) and automated peak assignment. MCR-AR employs parallel processing of multiple chromatograms, as opposed to sequential processing used in prevailing applications. Parallel processing provides a global peak list that is consistent for all chromatograms, and therefore does not require tedious manual curation. We evaluated this approach on wood samples from aspen and Norway spruce, and found that parallel processing results in an overall higher precision of peak area from integrated peaks. To further increase the speed of data processing we evaluated automated peak assignment solely based on basepeak mass. This approach gave estimates of the proportion of lignin (as syringyl-, guaiacyl and p-hydroxyphenyl-type lignin) and carbohydrate polymers in the wood samples that were in high agreement with those where peak assignments were based on full spectra. This method establishes Py-GC/MS as a sensitive, robust and versatile high-throughput screening platform well suited to a non-specialist operator.
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| 10. |
- Henriksson, Anna, et al.
(författare)
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Strong invaders are strong defenders : implications for the resistance of invaded communities
- 2016
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 19:4, s. 487-494
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Tidskriftsartikel (refereegranskat)abstract
- Many ecosystems receive a steady stream of non-native species. How biotic resistance develops over time in these ecosystems will depend on how established invaders contribute to subsequent resistance. If invasion success and defence capacity (i.e. contribution to resistance) are correlated, then community resistance should increase as species accumulate. If successful invaders also cause most impact (through replacing native species with low defence capacity) then the effect will be even stronger. If successful invaders instead have weak defence capacity or even facilitative attributes, then resistance should decrease with time, as proposed by the invasional meltdown hypothesis. We analysed 1157 introductions of freshwater fish in Swedish lakes and found that species' invasion success was positively correlated with their defence capacity and impact, suggesting that these communities will develop stronger resistance over time. These insights can be used to identify scenarios where invading species are expected to cause large impact.
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