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Normark, Johan
Publications (10 of 14) Show all publications
Surowiec, I., Skotare, T., Sjögren, R., Gouveia-Figueira, S. C., Orikiiriza, J. T., Bergström, S., . . . Trygg, J. (2019). Joint and unique multiblock analysis of biological data: multiomics malaria study. Paper presented at Conference on Challenges in Analysis of Complex Natural Mixtures, Univ Edinburgh, Edinburgh, MAY 13-15, 2019. Faraday discussions (Online), 218, 268-283
Open this publication in new window or tab >>Joint and unique multiblock analysis of biological data: multiomics malaria study
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2019 (English)In: Faraday discussions (Online), ISSN 1359-6640, E-ISSN 1364-5498, Vol. 218, p. 268-283Article in journal (Refereed) Published
Abstract [en]

Modern profiling technologies enable obtaining large amounts of data which can be later used for comprehensive understanding of the studied system. Proper evaluation of such data is challenging, and cannot be faced by bare analysis of separate datasets. Integrated approaches are necessary, because only data integration allows finding correlation trends common for all studied data sets and revealing hidden structures not known a priori. This improves understanding and interpretation of the complex systems. Joint and Unique MultiBlock Analysis (JUMBA) is an analysis method based on the OnPLS-algorithm that decomposes a set of matrices into joint parts containing variation shared with other connected matrices and variation that is unique for each single matrix. Mapping unique variation is important from a data integration perspective, since it certainly cannot be expected that all variation co-varies. In this work we used JUMBA for integrated analysis of lipidomic, metabolomic and oxylipin datasets obtained from profiling of plasma samples from children infected with P. falciparum malaria. P. falciparum is one of the primary contributors to childhood mortality and obstetric complications in the developing world, what makes development of the new diagnostic and prognostic tools, as well as better understanding of the disease, of utmost importance. In presented work JUMBA made it possible to detect already known trends related to disease progression, but also to discover new structures in the data connected to food intake and personal differences in metabolism. By separating the variation in each data set into joint and unique, JUMBA reduced complexity of the analysis, facilitated detection of samples and variables corresponding to specific structures across multiple datasets and by doing this enabled fast interpretation of the studied system. All this makes JUMBA a perfect choice for multiblock analysis of systems biology data.

Place, publisher, year, edition, pages
Cambridge: Royal Society of Chemistry, 2019
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:umu:diva-156705 (URN)10.1039/C8FD00243F (DOI)000481497900014 ()
Conference
Conference on Challenges in Analysis of Complex Natural Mixtures, Univ Edinburgh, Edinburgh, MAY 13-15, 2019
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-11-14Bibliographically approved
Reuterswärd, P., Bergström, S., Orikiiriza, J., Lindquist, E., Bergström, S., Svahn, H. A., . . . Nilsson, P. (2018). Levels of human proteins in plasma associated with acute paediatric malaria. Malaria Journal, 17, Article ID 426.
Open this publication in new window or tab >>Levels of human proteins in plasma associated with acute paediatric malaria
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2018 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 17, article id 426Article in journal (Refereed) Published
Abstract [en]

Background: The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts.

Results: An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values < 0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values < 10−14) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values < 0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria.

Conclusion: In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis.

Place, publisher, year, edition, pages
BMC, 2018
Keywords
Affinity proteomics, Human plasma profiling, Malaria, Plasmodium falciparum, suspension bead arrays, Sequestration, Cytoadhesion
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-154943 (URN)10.1186/s12936-018-2576-y (DOI)000450509700002 ()30442134 (PubMedID)
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-05-29Bibliographically approved
Bergström, S. & Normark, J. (2018). Microbiological features distinguishing Lyme disease and relapsing fever spirochetes. Wiener Klinische Wochenschrift, 130(15-16), 484-490
Open this publication in new window or tab >>Microbiological features distinguishing Lyme disease and relapsing fever spirochetes
2018 (English)In: Wiener Klinische Wochenschrift, ISSN 0043-5325, E-ISSN 1613-7671, Vol. 130, no 15-16, p. 484-490Article in journal (Refereed) Published
Abstract [en]

The recent proposal of splitting the genus Borrelia into two genera in the newly formed family of Borreliaceae, i.aEuro<overline>e. Borrelia and Borreliella has motivated us to reflect upon how these organisms has been characterized and differentiated. This article therefore aims to take a closer look on the biology and virulence attributes of the two suggested genera, i.aEuro<overline>e. those causing Lyme borreliosis and relapsing fever borreliosis. Both genera have much in common with similar infection biological features. They are both characterized as bacterial zoonoses, transmitted by hematophagous arthropods with almost identical microbiological appearance. Nevertheless, a closer look at the genotypic and phenotypic characteristics clearly reveals several differences that might motivate the suggested split. On the other hand, a change of this well-established classification within the genus Borrelia might impose an economical burden as well as a great confusion in society, including medical and scientific societies as well as the general population.

Place, publisher, year, edition, pages
SPRINGER WIEN, 2018
Keywords
Borrelia, Borreliella, Lyme borreliosis, Relapsing fever, Taxonomy
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-151059 (URN)10.1007/s00508-018-1368-2 (DOI)000441195100005 ()30074091 (PubMedID)
Available from: 2018-09-04 Created: 2018-09-04 Last updated: 2018-09-04Bibliographically approved
Surowiec, I., Johansson, E., Stenlund, H., Rantapää-Dahlqvist, S., Bergström, S., Normark, J. & Trygg, J. (2018). Quantification of run order effect on chromatography: mass spectrometry profiling data. Journal of Chromatography A, 1568, 229-234
Open this publication in new window or tab >>Quantification of run order effect on chromatography: mass spectrometry profiling data
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2018 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1568, p. 229-234Article in journal (Refereed) Published
Abstract [en]

Chromatographic systems coupled with mass spectrometry detection are widely used in biological studies investigating how levels of biomolecules respond to different internal and external stimuli. Such changes are normally expected to be of low magnitude and therefore all experimental factors that can influence the analysis need to be understood and minimized. Run order effect is commonly observed and constitutes a major challenge in chromatography-mass spectrometry based profiling studies that needs to be addressed before the biological evaluation of measured data is made. So far there is no established consensus, metric or method that quickly estimates the size of this effect. In this paper we demonstrate how orthogonal projections to latent structures (OPLS®) can be used for objective quantification of the run order effect in profiling studies. The quantification metric is expressed as the amount of variation in the experimental data that is correlated to the run order. One of the primary advantages with this approach is that it provides a fast way of quantifying run-order effect for all detected features, not only internal standards. Results obtained from quantification of run order effect as provided by the OPLS can be used in the evaluation of data normalization, support the optimization of analytical protocols and identification of compounds highly influenced by instrumental drift. The application of OPLS for quantification of run order is demonstrated on experimental data from plasma profiling performed on three analytical platforms: GCMS metabolomics, LCMS metabolomics and LCMS lipidomics.

Keywords
Run order effect quantification, Mass spectrometry profiling, OPLS, Instrumental drift
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-150428 (URN)10.1016/j.chroma.2018.07.019 (DOI)000443669600025 ()2-s2.0-85049727571 (Scopus ID)
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2019-05-29Bibliographically approved
Orikiiriza, J., Surowiec, I., Lindquist, E., Bonde, M., Magambo, J., Muhinda, C., . . . Normark, J. (2017). Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria. Metabolomics, 13(4), Article ID 41.
Open this publication in new window or tab >>Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria
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2017 (English)In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 13, no 4, article id 41Article in journal (Refereed) Published
Abstract [en]

Introduction: Several studies have observed serum lipid changes during malaria infection in humans. All of them were focused at analysis of lipoproteins, not specific lipid molecules. The aim of our study was to identify novel patterns of lipid species in malaria infected patients using lipidomics profiling, to enhance diagnosis of malaria and to evaluate biochemical pathways activated during parasite infection.

Methods: Using a multivariate characterization approach, 60 samples were representatively selected, 20 from each category (mild, severe and controls) of the 690 study participants between age of 0.5–6 years. Lipids from patient’s plasma were extracted with chloroform/methanol mixture and subjected to lipid profiling with application of the LCMS-QTOF method.

Results: We observed a structured plasma lipid response among the malaria-infected patients as compared to healthy controls, demonstrated by higher levels of a majority of plasma lipids with the exception of even-chain length lysophosphatidylcholines and triglycerides with lower mass and higher saturation of the fatty acid chains. An inverse lipid profile relationship was observed when plasma lipids were correlated to parasitaemia.

Conclusions: This study demonstrates how mapping the full physiological lipid response in plasma from malaria-infected individuals can be used to understand biochemical processes during infection. It also gives insights to how the levels of these molecules relate to acute immune responses.

Keywords
Lipidomics profiling, Malaria, Plasmodium falciparum, Triacylglycerides, Lysophosphatidylcholines
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-133729 (URN)10.1007/s11306-017-1174-2 (DOI)000394544900010 ()28286460 (PubMedID)
Available from: 2017-05-05 Created: 2017-05-05 Last updated: 2018-06-09Bibliographically approved
Surowiec, I., Gouveia-Figueira, S., Orikiiriza, J., Lindquist, E., Bonde, M., Magambo, J., . . . Trygg, J. (2017). The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children. Malaria Journal, 16, Article ID 358.
Open this publication in new window or tab >>The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children
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2017 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 16, article id 358Article in journal (Refereed) Published
Abstract [en]

Background: Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism.

Methods: Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA (R)) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis).

Results: Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls.

Conclusions: It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keywords
Oxylipins, Endocannabinoids, Malaria infection, Plasmodium falciparum
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-140041 (URN)10.1186/s12936-017-2001-y (DOI)000410218400001 ()28886714 (PubMedID)
Funder
Swedish Research CouncilSwedish Society of Medicine
Note

Ytterligare finansiär: Jeansson Foundation

Available from: 2017-10-05 Created: 2017-10-05 Last updated: 2018-06-09Bibliographically approved
Orikiiriza, J., Nakawesi, J., Kikaire, B., Turitwenka, D., Schlech, W., Kambugu, A., . . . Achan, J. (2017). Unmet needs persist in pediatric HIV programs: lessons from selected case studies in Uganda [Letter to the editor]. AIDS (London), 31(8), 1196-1199
Open this publication in new window or tab >>Unmet needs persist in pediatric HIV programs: lessons from selected case studies in Uganda
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2017 (English)In: AIDS (London), ISSN 0269-9370, E-ISSN 1473-5571, Vol. 31, no 8, p. 1196-1199Article in journal, Letter (Refereed) Published
National Category
Immunology
Identifiers
urn:nbn:se:umu:diva-134696 (URN)10.1097/QAD.0000000000001436 (DOI)000401195800018 ()28441178 (PubMedID)
Available from: 2017-06-01 Created: 2017-06-01 Last updated: 2018-06-09Bibliographically approved
Engström, P., Krishnan, K. S., Ngyuen, B. D., Chorell, E., Normark, J., Silver, J., . . . Bergström, S. (2015). A 2-Pyridone-Amide Inhibitor Targets the Glucose Metabolism Pathway of Chlamydia trachomatis. mBio, 6(1), Article ID e02304-14.
Open this publication in new window or tab >>A 2-Pyridone-Amide Inhibitor Targets the Glucose Metabolism Pathway of Chlamydia trachomatis
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2015 (English)In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 6, no 1, article id e02304-14Article in journal (Refereed) Published
Abstract [en]

In a screen for compounds that inhibit infectivity of the obligate intracellular pathogen Chlamydia trachomatis, we identified the 2-pyridone amide KSK120. A fluorescent KSK120 analogue was synthesized and observed to be associated with the C. trachomatis surface, suggesting that its target is bacterial. We isolated KSK120-resistant strains and determined that several resistance mutations are in genes that affect the uptake and use of glucose-6-phosphate (G-6P). Consistent with an effect on G-6P metabolism, treatment with KSK120 blocked glycogen accumulation. Interestingly, KSK120 did not affect Escherichia coli or the host cell. Thus, 2-pyridone amides may represent a class of drugs that can specifically inhibit C. trachomatis infection. IMPORTANCE Chlamydia trachomatis is a bacterial pathogen of humans that causes a common sexually transmitted disease as well as eye infections. It grows only inside cells of its host organism, within a parasitophorous vacuole termed the inclusion. Little is known, however, about what bacterial components and processes are important for C. trachomatis cellular infectivity. Here, by using a visual screen for compounds that affect bacterial distribution within the chlamydial inclusion, we identified the inhibitor KSK120. As hypothesized, the altered bacterial distribution induced by KSK120 correlated with a block in C. trachomatis infectivity. Our data suggest that the compound targets the glucose-6-phosphate (G-6P) metabolism pathway of C. trachomatis, supporting previous indications that G-6P metabolism is critical for C. trachomatis infectivity. Thus, KSK120 may be a useful tool to study chlamydial glucose metabolism and has the potential to be used in the treatment of C. trachomatis infections.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-102254 (URN)10.1128/mBio.02304-14 (DOI)000350631900021 ()25550323 (PubMedID)
Available from: 2015-04-22 Created: 2015-04-22 Last updated: 2018-06-07Bibliographically approved
Surowiec, I., Orikiiriza, J., Karlsson, E., Nelson, M., Bonde, M., Kyamanwa, P., . . . Normark, J. (2015). Metabolic signature profiling as a diagnostic and prognostic tool in paediatric Plasmodium falciparum malaria. Open Forum Infectious Diseases, 2(2)
Open this publication in new window or tab >>Metabolic signature profiling as a diagnostic and prognostic tool in paediatric Plasmodium falciparum malaria
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2015 (English)In: Open Forum Infectious Diseases, ISSN 2328-8957, Vol. 2, no 2Article in journal (Refereed) Published
Abstract [en]

Background: Accuracy in malaria diagnosis and staging is vital in order to reduce mortality and post infectious sequelae. Herein we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children. Methods: A group of 421 patients between six months and six years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192 and 122 individuals respectively. A multivariate design was used as basis for representative selection of twenty patients in each category. Patient plasma was subjected to Gas Chromatography-Mass Spectrometry analysis and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in-vivo model where metabolic profiles were discernible over time of infection. Results: A two-component principal component analysis (PCA) revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, two sub-groups could be identified in the mild malaria cohort who we believe represent patients with divergent prognoses. Conclusion: Metabolite signature profiling could be used both for decision support in disease staging and prognostication.

Place, publisher, year, edition, pages
Oxford University Press, 2015
Keywords
disease staging, malaria, metabolomics
National Category
Bioinformatics (Computational Biology) Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-102800 (URN)10.1093/ofid/ofv062 (DOI)000365786200047 ()
Available from: 2015-05-05 Created: 2015-05-05 Last updated: 2018-06-07Bibliographically approved
Elbir, H., Larsson, P., Normark, J., Upreti, M., Korenberg, E., Larsson, C. & Bergström, S. (2014). Genome Sequence of the Asiatic Species Borrelia persica. Genome Announcements, 2(1), Article ID e01127-13.
Open this publication in new window or tab >>Genome Sequence of the Asiatic Species Borrelia persica
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2014 (English)In: Genome Announcements, ISSN 2169-8287, E-ISSN 2169-8287, Vol. 2, no 1, article id e01127-13Article in journal (Refereed) Published
Abstract [en]

We report the complete genome sequence of Borrelia persica, the causative agent of tick-borne relapsing fever borreliosis on the Asian continent. Its genome of 1,784,979 bp contains 1,850 open reading frames, three ribosomal RNAs, and 32 tRNAs. One clustered regularly interspaced short palindromic repeat (CRISPR) was detected.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-93716 (URN)10.1128/genomeA.01127-13 (DOI)24407639 (PubMedID)
Available from: 2014-09-30 Created: 2014-09-30 Last updated: 2018-06-07Bibliographically approved
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