Chemometrics in Metabolomics, Systems biology and Process Analytical Technologies

METABOLOMICS Metabolomics studies generate increasingly complex data tables, which are hard to summarize and visualize without appropriate tools. The use of chemometrics tools, e.g., principal component analysis (PCA), partial least-squares o latent structures (PLS), and orthogonal PLS (OPLS), is therefore of great importance as these include efficient, validated, and robust methods for modeling informationrich chemical and biological data. SYSTEMS BIOLOGY Within Systems biology, we work alongside UPSC and FuncFiber Excellence centres at Umeå University, to unravel the function of genes in transgenic poplar trees. We are developing data driven tools and strategies on how to combine, model and predict biological information based on transgenic trees generated from multiple profiling platforms (e.g. NIR, FTIR-imaging, PyMS, metabolomics, enzymology and transcriptomics). PROCESS ANALYTICAL TECHNOLOGIES Within PAT, the Food and Drug Administration (FDA) in the US has reconsidered its procedures for regulatory approval of new drugs. They recognize the need for design of experiments and multivariate techniques to find and evaluate critical parameters. As a result, this will ensure process stability and reduced batch variability and enable prediction of final product quality and safety.

KIDNEY TRANSPLANT MONITORING OF RENAL FUNCTION
Histological examination of a renal biopsy specimen remains the golden standard in differentiating allograft rejection (kidney tranplant rejection) from CyA nephrotoxicity. CyA nephrotoxicity is inevitable when CyA levels exceed 1000ng/L but can and does occur based on individual sensitivity or additional renal damage. Histologically, CyA nephrotoxicity is characterised by a tubular toxicity that produces region specific abnormalities such as inclusion bodies (giant mitochondria) in cortical tubular epithelial cells of the convoluted part of the proximal tubule, or isometric vacuolization and microcalcification in the thick descending limb of the loop of Henle. In this project, a metabolomics approach is used to provide a means to monitor graft failure at an early stage so as to optimise post-transplantation therapy and maximise the chances of transplantation success. One of the outcomes is the identification of novel urinary markers of graft dysfunction and be able to monitor the dynamic (real-time) biochemical changes following transplantation (this is not possible histopathologically).

FUNCTIONAL FOODS
Nutrition-associated chronic diseases, such as the metabolic syndrome, have increased at an alarming rate in affluent nations over the last decades. Several epidemiology studies supports that even moderate overweight significantly elevates the risk of contracting cardiovascular disease (CVD). Apart from non-regulated foodstuffs, a number of products with specific health claims have been placed on the international market, over the last decade. They are commonly referred to as Functional Foods. In consultation with the NFA and the National Board for Consumer Policies, the Swedish food industry has prepared a program of action where claims of health claim between foodstuffs and health must consist of two parts: details on an established diet-health relationship entailed to product compositional information and a scientific documentation of product-specific physiological health claims. Traditionally, health effects of specific diets are assessed by epidemiology, whereas clinical trial studies are most important for the understanding of impacts resulting from pharmacological intervention.
The objective with this project is to develop a holistic response method using metabolomics including NMR and MS spectroscopy to detect and understand the chemical, biological and physiological effect of different foodstuffs.

NEURODEGENERATIVE DISEASE DIAGNOSIS AND PROGNOSOS
Huntington’s disease (HD) is a genetic neurodegenerative illness for which there is no cure. The origin of HD lies in an increase in the length of a glutamine repeat in the huntingtin protein; patients with longer repeats develop HD at younger ages. A “fingerprint” or metabolic profile of biomarkers could provide insight into the mechanism of this disease and a means to evaluate the efficacy of potential treatments. Metabolite profiling of biofluids and tissues using spectroscopic techniques such as nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) can be used to obtain a characteristic “fingerprint pattern” for a range of biologically important endogenous metabolites. Successful application of this technology has achieved identification of biomarkers for a wide range of pathologies including inborn errors of metabolism, liver and kidney disease, cardiovascular disease, insulin resistance, and neurodegenerative disorders among others.

In the present project, high-resolution NMR and GC-MS spectroscopic techniques have been used in conjunction with multivariate statistics to characterize the metabolic profiles of biofluids with the aim of further understanding the mechanism of pathogenesis
in this model and uncovering potential biomarkers of disease progression.

Publications

Author

Title

Year sorteringsordning

Fulltext

Surowiec, Izabella
Johansson, Erik
Torell, Frida; et al.

Multivariate strategy for the sample selection and integration of multi-batch data in metabolomics
Metabolomics, 13(10)

2017

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Torell, Frida
Bennett, Kate
Rännar, Stefan; et al.

The effects of thawing on the plasma metabolome: evaluating differences between thawed plasma and multi-organ samples
Metabolomics, 13(6)

2017

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Orikiiriza, Judy
Surowiec, Izabella
Lindquist, Elisabeth; et al.

Lipid response patterns in acute phase paediatric Plasmodium falciparum malaria
Metabolomics, 13(4)

2017

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Surowiec, Izabella
Vikström, Ludvig
Hector, Gustaf; et al.

Generalized Subset Designs in Analytical Chemistry
Analytical Chemistry, 89(12): 6491-6497

2017

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Checa, A.
Idborg, H.
Zandian, A.; et al.

Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study
Lupus, 26(10): 1023-1033

2017

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Surowiec, Izabella
Gouveia-Figueira, Sandra
Orikiiriza, Judy; et al.

The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children
Malaria Journal, 16

2017

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Brynolfsson, Patrik
Nilsson, David
Torheim, Turid; et al.

Haralick texture features from apparent diffusion coefficient (ADC) MRI images depend on imaging and pre-processing parameters
Scientific Reports, 7

2017

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Bygdell, Joakim
Srivastava, Vaibhav
Obudulu, Ogonna; et al.

Protein expression in tension wood formation monitored at high tissue resolution in Populus
Journal of Experimental Botany, 68(13): 3405-3417

2017

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Peolsson, Anneli
Peterson, Gunnel
Trygg, Johan; et al.

Multivariate analysis of ultrasound-recorded dorsal strain sequences: Investigation of dynamic neck extensions in women with chronic whiplash associated disorders
Scientific Reports, 6

2016

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Rentoft, Matilda
Lindell, Kristoffer
Tran, Phong; et al.

Heterozygous colon cancer-associated mutations of SAMHD1 have functional significance
Proceedings of the National Academy of Sciences of the United States of America, 113(17): 4723-4728

2016

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