Olav Martin Kvalheim

University of Bergen | UiB · Department of Chemistry

Mass spectrometry metabolomics has become increasingly popular as an integral aspect of studies to identify active compounds from natural product mixtures. Classical metabolomics data analysis approaches do not consider the possibility that interactions (such as synergy) could occur between mixture components. With this study, we developed "interac...

Introduction Comprehensive lipoprotein profiling using proton nuclear magnetic resonance (NMR) spectroscopy of serum represents an alternative to the homeostatic model assessment of insulin resistance (HOMA-IR). Both adiposity and physical (in)activity associate to insulin resistance, but quantification of the influence of these two lifestyle relat...

Accelerometers provide detailed data about physical activity (PA) across the full intensity spectrum. However, when examining associations with health, results are often aggregated to only a few summary measures [e.g. time spent “sedentary” or “moderate-to-vigorous” intensity PA]. Using multivariate pattern analysis, which can handle collinear expo...

Background Our understanding of the mechanisms through which physical activity might benefit lipoprotein metabolism is inadequate. Here we characterise the continuous associations between physical activity of different intensities, sedentary time, and a comprehensive lipoprotein particle profile. Methods Our cohort included 762 fifth grade (mean [...

Aerobic fitness (AF) and lipoprotein subclasses associate to each other and to cardiovascular health. Adiposity and physical activity (PA) influence the association pattern of AF to lipoproteins almost inversely making it difficult to assess their independent and joint influence on the association pattern. This study, including 841 children (50% bo...

Aim Aerobic fitness is associated with cardiometabolic risk factors in children. Associations with traditional measures of lipid metabolism are uncertain. We investigated whether higher levels of fitness benefit lipid metabolism by exploring cross-sectional and prospective associations between aerobic fitness and a comprehensive lipoprotein profile...

Lipoprotein subclasses possess crucial cardiometabolic information. Due to strong multicollinearity among variables, little is known about the strength of influence of physical activity (PA) and adiposity upon this cardiometabolic pattern. Using a novel approach to adjust for covariates, we aimed at determining the “net” patterns and strength for P...

The inter-relationship between physical activity, sedentary behaviour and sleep (collectively defined as physical behaviours) is of interest to researchers from different fields. Each of these physical behaviours has been investigated in epidemiological studies, yet their codependency and interactions need to be further explored and accounted for i...

Chemical ecology has been suggested as a less time-consuming and more cost-efficient monitoring tool of seagrass ecosystems than traditional methods. Phenolic chemistry in Zostera marina samples was analyzed against latitude, sea depth, sample position within a seagrass meadow (periphery or center) and wave exposure. Multivariate data analysis show...

Background and aims The associations between aerobic fitness and traditional measures of lipid metabolism in children are uncertain. We investigated whether higher levels of aerobic fitness benefit lipoprotein metabolism by exploring associations with a comprehensive lipoprotein particle profile. Methods In our prospective cohort study, we used ta...

There is solid evidence for an association between physical activity and metabolic health outcomes in children and youth, but for methodological reasons most studies describe the intensity spectrum using only a few summary measures. We aimed to determine the multivariate physical activity intensity signature associated with metabolic health in a la...

The use of high-resolution physical activity intensity spectra obtained from accelerometry can improve knowledge of associations with health and development beyond the use of traditional summary measures of intensity. The aim of the present study was to compare three different approaches for determining associations for spectrum descriptors of phys...

It is discussed whether associations between accelerometer-derived physical activity intensities and outcomes should be analysed as absolute or relative data. The aim of the present study was to compare interpretation of association patterns of spectrum physical activity descriptions with outcome using raw, normalized, log-transformed, or compositi...

This work examines the performance of significance multivariate correlation (sMC) and selectivity ratio (SR) for ranking variables according to their importance in latent‐variable regressions (LVRs) models. Both indices are based on target projection (TP) of a validated LVR model obtained by partial least squares (PLS). The matrix of explanatory x‐...

When analysing physical activity (PA) levels using accelerometry, the epoch setting is critical to capture intensity-specific PA correctly. The aim of the present study was to investigate the PA intensity signatures related to metabolic health in children using different epoch settings. A sample of 841 Norwegian children (age 10.2 ± 0.3 years; BMI...

Background: The analysis of associations between accelerometer-derived physical activity (PA) intensities and cardiometabolic health is a major challenge due to multicollinearity between the explanatory variables. This challenge has facilitated the application of different analytic approaches within the field. The aim of the present study was to c...

Associations between multicollinear accelerometry-derived physical activity (PA) data and cardiometabolic health in children needs to be analyzed using an approach that can handle collinearity among the explanatory variables. The aim of this paper is to provide readers a tutorial overview of interpretation of multivariate pattern analysis models us...

Background and aims: Physical activity is favourably associated with certain markers of lipid metabolism. The relationship of physical activity with lipoprotein particle profiles in children is not known. Here we examine cross-sectional associations between objectively measured physical activity and sedentary time with serum markers of lipoprotein...

Purpose: The use of uniaxial summary measures from accelerometry (i.e., counts per minute or minutes spent in moderate-to-vigorous intensity) substantially restricts information about physical activity (PA), and is probably a result of reliance on analytic approaches that cannot handle collinear variables. In the present study, we aimed to determi...

Compounds derived from natural sources represent the majority of small-molecule drugs utilized today. Plants, owing to their complex biosynthetic pathways, are poised to synthesize diverse secondary metabolites that selectively target biological macromolecules. Despite the vast chemical landscape of botanicals, drug discovery programs from these so...

Using a metabolomics data set with 1057 serum samples, we designed and assessed different procedures based on Monte Carlo resampling schemes to determine the optimal number of components to be included in partial least squares (PLS) regression models. Corresponding estimates of prediction error were calculated and compared in a single algorithm com...

Background: Physical activity is a cornerstone for promoting good metabolic health in children, but it is heavily debated which intensities (including sedentary time) are most influential. A fundamental limitation to current evidence for this relationship is the reliance on analytic approaches that cannot handle collinear variables. The aim of the...

Physical activity (PA) favorably affects metabolic health in children, but it is unclear how total volumes versus patterns (bouts and breaks) of PA relate to health. By means of multivariate pattern analysis that can handle collinear variables, we determined the associations of PA volumes and patterns with children's metabolic health using differen...

Botanical medicines have been utilized for centuries, but it remains challenging to identify bioactive constituents from complex botanical extracts. Bioassay-guided fractionation is often biased toward abundant or easily isolatable compounds. To comprehensively evaluate active botanical mixtures, methods that allow for the prioritization of active...

Mass spectral data sets often contain experimental artefacts, and data filtering prior to statistical analysis is crucial to extract reliable information. This is particularly true in untargeted metabolomics analyses, where the analyte(s) of interest are not known a priori. It is often assumed that chemical interferents (i.e. solvent contaminants s...

Monte Carlo resampling is utilized to determine the number of components in partial least squares (PLS) regression. The data are randomly and repeatedly divided into calibration and validation samples. For each repetition, the root‐mean‐squared error (RMSE) is determined for the validation samples for a = 1, 2, … , A PLS components to provide a dis...

A critical challenge in the study of botanical natural products is the difficulty of identifying multiple compounds that may contribute additively, synergistically, or antagonistically to biological activity. Herein, it is demonstrated how combining untargeted metabolomics with synergy-directed fractionation can be effective toward accomplishing th...

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High aerobic fitness is consistently associated with a favorable metabolic risk profile in children. However, measurement of oxygen uptake, regarded as the gold standard for evaluating aerobic fitness, is often not feasible. Thus, the aim of the present study was to perform a clinical validation of three measures of aerobic fitness (peak oxygen con...

A challenge that must be addressed when conducting studies with complex natural products is how to evaluate their complexity and variability. Traditional methods of quantifying a single or a small range of metabolites may not capture the full chemical complexity of multiple samples. Different metabolomics approaches were evaluated to discern how th...

Aim: To reveal the lipoprotein subclass pattern associated to cardiorespiratory fitness (CRF) in healthy children. Methods: Serum concentrations of lipoprotein subclasses and concentrations and average particle size of their main classes were quantified in 94 ethnic Norwegian children using high performance liquid chromatography (HPLC). Twenty-f...

Objective: To investigate the effect of a seven-month, school-based cluster-randomized controlled trial on academic performance in 10-year-old children. Methods: In total, 1129 fifth-grade children from 57 elementary schools in Sogn og Fjordane County, Norway, were cluster-randomized by school either to the intervention group or to the control g...

Background: We have assessed the effects of laparoscopic sleeve gastrectomy (LSG) and biliopancratic diversion with a duodenal switch (BPDDS) on fatty acid (FA) levels in serum. In particular, we examine the impact of surgery on the ratio of the FAs eicosapentaenoic acid (EPA) to arachidonic acid (AA) which impacts, e.g., cardiovascular health. Ou...

Serum fatty acid (FA) levels were monitored in women with severe obesity during intensive lifestyle intervention. At baseline, total FA levels and most individual FAs were elevated compared to a matching cohort of normal and overweight women (healthy controls). After 3 weeks of intensive lifestyle intervention, total level was only 11-12% higher th...

Introduction The lipid metabolism is one of the most important and complex processes in the body. Serum concentrations of 18 fatty acids (FAs) and 24 lipoprotein features, i.e. concentrations of lipoprotein main and subclasses and average particle size in main classes, in 195 ethnic Norwegian children from the rural Fjord region were quantified by...

Concentrations in serum were determined for 18 fatty acids (FAs) and 21 lipoprotein main and subclasses by chromatographic analyses and the average size was calculated for very low density (VLDL), low density (LDL) and high density (HDL) particles. 283 ethnic Norwegian children and adults from the rural Fjord region of Western Norway were compared...

A central challenge of natural products research is assigning bioactive compounds from complex mixtures. The gold standard approach to address this challenge, bioassay-guided fractionation, is often biased toward abundant, rather than bioactive, mixture components. This study evaluated the combination of bioassay-guided fractionation with untargete...

A battery of methods for multivariate data analysis has been used to assess the associations between concentrations of fatty acids (FAs) and lipoprotein subclasses and particle size in serum for a normolipidemic population of ethnic Norwegians living in the rural Fjord region. Significant gender differences were found in the lipoprotein and FA patt...

##Assembly-Data-START## Assembly Method :: Sequencher v. 5.3 Sequencing Technology :: Sanger dideoxy sequencing ##Assembly-Data-END##

##Assembly-Data-START## Assembly Method :: Sequencher v. 5.3 Sequencing Technology :: Sanger dideoxy sequencing ##Assembly-Data-END##

The Moffatt-Swern oxidation (MSO) is a multistep, versatile, metal-free reaction by which alcohols are transformed into aldehydes and ketones. Batch MSO requires low temperatures (-70 degrees C) due to a highly exothermic reaction step that generates intermediates. This work shows that a rigorous investigation of the MSO in batch can be used as a s...

Evidence is emerging from school-based studies that physical activity might favorably affect children's academic performance. However, there is a need for high-quality studies to support this. Therefore, the main objective of the Active Smarter Kids (ASK) study is to investigate the effect of daily physical activity on children's academic performan...

The quality and practical usefulness of a regression model are a function of both interpretability and prediction performance. This work presents some new graphical tools for improved interpretation of latent variable regression models that can also assist in improved algorithms for variable selection. Thus, these graphs provide visualization of th...

Physical activity (PA) and sedentary behavior (SED) may have independent effects on health and disease. This might be due to PA and SED having distinct effects on lipoprotein metabolism. The aim of this study was to determine associations between lipoprotein subclass particle concentrations (-P) and accelerometer-measured SED and moderate-to-vigoro...

What is already known about this subject: Physical activity and high aerobic fitness protects against cardiovascular disease and early death, besides having a very modest impact on lipoprotein-cholesterol in obese subjects. Physical activity has been shown to favourably alter lipoprotein particle concentrations and apolipoprotein B with minimal we...

Classical scrapie in sheep is a fatal neurodegenerative disease associated with the conversion PrPC to PrPSc. Much is known about genetic susceptibility, uptake and dissemination of PrPSc in the body, but many aspects of prion diseases are still unknown. Different proteomic techniques have been used during the last decade to investigate differences...

This work reviews some of the major developments in the latent variable (LV) approach to exploratory and predictive modeling. Furthermore, it explores the nature and various aspects of the LV methodology and its role in science and technology. The immense potential of the LV approach to the analysis of complex systems is proven through its applicat...

The initialization of concentration vector for iterative target transformation factor analysis (ITTFA) and identification of pure or key variables are the important issue in MCR. In this study, dissimilarity analysis and evolving factor analysis (EFA) are combined to find the selective or key variables and subsequently obtain initial estimates of t...

A new approach for assigning bioactivity to individual components in extracts from natural products is presented and validated. 60 mixtures were created according to a uniform design from 12 chemical components of which 7 possessed antioxidant activity. The synthetic mixtures were characterized by chromatographic profiling and their antioxidant pow...

We provide an overview of latent variable methods used in pharmaceutics and integrated with advanced characterization techniques such as vibrational spectroscopy. The basics of the most common latent variable methods, principal component analysis (PCA), principal component regression (PCR) and partial least-squares (PLS) regression, are presented....

A robust method for reduction of instrument differences, the vector of calibration ratios, was developed to eliminate differences in unit resolution mass spectra of fatty acid methyl esters (FAME) caused by experimental conditions. Mass spectra of FAMEs were analyzed by two different mass spectrometers and after application of different tune proced...

Mass spectral profiles from cerebrospinal fluid (CSF) are used as input to a novel multivariate approach to select features responsible for the separation of patients with multiple sclerosis (MS) from control groups. Our targeted statistical approach makes it possible to systematically remove features in the spectral fingerprints masking the compon...

Displays of latent variable regression models in variable and object space are provided to reveal model parameters useful for interpretation and to reveal the most influential x-variables with respect to the predicted response. Although the target projected (TP) component obtained from a standard partial least square, or equivalently, the predictiv...

The characteristic of discreteness in mass spectral direction distinguishes GC/MS from other spectral techniques. Based on this feature, we propose a new method to construct the initial concentration vectors for iterative target transformation factor analysis (ITTFA). For each chemical component, a search for a selective ion with good signal-to-noi...

Using whole chromatographic profiles and measurements of total bioactivity as input, a quantitative pattern-activity relationship (QPAR) approach is proposed as a general method for providing two pieces of crucial information about complex bioactive mixtures available: (i) a model for predicting total bioactivity from the chromatographic fingerprin...

The discriminating variable (DIVA) test and the selectivity ratio (SR) plot are developed as quantitative tools for revealing the variables in spectral or chromatographic profiles discriminating best between two groups of samples. The SR plot is visually similar to a spectrum or a chromatogram, but with the most intense regions corresponding to the...

This work presents a new method for variable selection in complex spectral profiles. The method is validated by comparing samples from cerebrospinal fluid (CSF) with the same samples spiked with peptide and protein standards at different concentration levels. Partial least squares discriminant analysis (PLS-DA) attempts to separate two groups of sa...

Target projection (TP) also called target rotation (TR) was introduced to facilitate interpretation of latent-variable regression models. Orthogonal partial least squares (OPLS) regression and PLS post-processing by similarity transform (PLS + ST) represent two alternative algorithms for the same purpose. In addition, OPLS and PLS + ST provide comp...

The theory together with an algorithm for uncorrelated linear discriminant analysis (ULDA) is introduced and applied to explore metabolomics data. ULDA is a supervised method for feature extraction (FE), discriminant analysis (DA) and biomarker screening based on the Fisher criterion function. While principal component analysis (PCA) searches for d...