Real-life metabolomics data analysis: how to deal with complex data?

Door de grote datasets die gegenereerd worden in metabolomics studies, in combinatie met de ingewikkelde studiedesigns die vaak nodig zijn om subtiele verschillen in metabolietprofielen te kunnen detecteren, zijn standaard multivariate technieken niet meer afdoende. Dit geldt voor alle fasen van de data-analyse in metabolomics studies: voor zowel de verkennende fase, als de modelfase, als de validatiefase, toont Carina Rubingh aan. Doordat ze in haar onderzoek data uit de praktijk (real life data) gebruikte, zijn de problemen die aan de orde komen herkenbaar voor vele onderzoekers. Rubinghs oplossingen zijn direct toepasbaar en beperken zich niet alleen tot metabolomics studies, maar zijn van toepassing voor alle onderzoeksgebieden waar soortgelijke data gegenereerd wordt

Food Consumption and Nutrient Intake by Children Aged 10 to 48 Months Attending Day Care in The Netherlands

The diet of young children is an important determinant of long-term health effects, such as overweight and obesity. We analyzed two-day food consumption records from 1526 young children (10–48 months old) attending 199 daycare centers across The Netherlands. Data were observed and recorded in diaries by caregivers at the day nursery and by parents at home on days that the children attended the daycare center. According to national and European reference values, the children had an adequate nutrient intake with exception of low intakes of total fat, n-3 fatty acids from fish and possibly iron. Intakes of energy and protein were substantially higher than recommended and part of the population exceeded the tolerable upper intake levels for sodium, zinc and retinol. Consumption of fruit, fats, fish, and fluids was substantially less than recommended. The children used mostly (semi-)skimmed milk products and non-refined bread and cereals, as recommended. Two thirds of the consumed beverages, however, contained sugar and contributed substantially to energy intake. In young children, low intakes of n-3 fatty acids and iron are a potential matter of concern, as are the high intakes of energy, protein, sugared beverages, and milk, since these may increase the risk of becoming overweight

The costs of complex model optimization

Each data-driven action in data modelling consumes degrees of freedom, whether it concerns estimation of parameters, estimation of meta-parameters or selecting variables. By using a double cross validation approach for degrees of freedom calculation the costs for meta-parameter estimation and variable selection can be determined explicitly. The only assumptions are independent and identically distributed errors, which make the approach applicable to many predictive modelling technique

Matrix correlations for high-dimensional data: The modified RV-coefficient

Motivation: Modern functional genomics generates high-dimensional datasets. It is often convenient to have a single simple number characterizing the relationship between pairs of such high-dimensional datasets in a comprehensive way. Matrix correlations are such numbers and are appealing since they can be interpreted in the same way as Pearson's correlations familiar to biologists. The high-dimensionality of functional genomics data is, however, problematic for existing matrix correlations. The motivation of this article is 2-fold: (i) we introduce the idea of matrix correlations to the bioinformatics community and (ii) we give an improvement of the most promising matrix correlation coefficient (the RV-coefficient) circumventing the problems of high-dimensional data. Results: The modified RV-coefficient can be usedin high-dimensional data analysis studies as an easy measure of common information of two datasets. This is shown by theoretical arguments, simulations and applications to two real-life examples from functional genomics, i.e. a transcriptomics and metabolomics example. © The Author 2008. Published by Oxford University Press. All rights reserved

Assessing food allergy risks from residual peanut protein in highly refined vegetable oil

Refined vegetable oils including refined peanut oil are widely used in foods. Due to shared production processes, refined non-peanut vegetable oils can contain residual peanut proteins. We estimated the predicted number of allergic reactions to residual peanut proteins using probabilistic risk assessment applied to several scenarios involving food products made with vegetable oils. Variables considered were: a) the estimated production scale of refined peanut oil, b) estimated cross-contact between refined vegetable oils during production, c) the proportion of fat in representative food products and d) the peanut protein concentration in refined peanut oil. For all products examined the predicted risk of objective allergic reactions in peanut-allergic users of the food products was extremely low. The number of predicted reactions ranged depending on the model from a high of 3 per 1000 eating occasions (Weibull) to no reactions (LogNormal). Significantly, all reactions were predicted for allergen intakes well below the amounts reported for the most sensitive individual described in the clinical literature. We conclude that the health risk from cross-contact between vegetable oils and refined peanut oil is negligible. None of the food products would warrant precautionary labelling for peanut according to the VITAL® programme of the Allergen Bureau. © 2017 Elsevier Lt

Time-dependent effect of in vivo inflammation on eicosanoid and endocannabinoid levels in plasma, liver, ileum and adipose tissue in C57BL/6 mice fed a fish-oil diet

Eicosanoids and endocannabinoids/N-acylethanolamines (NAEs) are fatty acid derived compounds with a regulatory role in inflammation. Considering their complex metabolism, it is likely that inflammation affects multiple compounds at the same time, but how lipid profiles change in plasma and other tissues after an inflammatory stimulus has not been described in detail. In addition, dietary fish oil increases levels of several n-3 fatty acid derived eicosanoids and endocannabinoids, and this may lead to a broader change in the profiles of bioactive lipids. In the present study mice were fed a diet containing 3% w/w fish oil for 6 weeks before receiving i.p. saline or 3 mg/kg lipopolysaccharide (LPS) to induce an inflammatory response. Eicosanoid and endocannabinoid/NAE levels (in total 61 metabolites) in plasma, liver, ileum, and adipose tissue were quantified using targeted lipidomics after 2, 4, 8, and 24 h, respectively. Tissue- and time-dependent effects of LPS on bioactive lipid profiles were observed. For example, levels of CYP derived eicosanoids in the ileum were markedly affected by LPS, whereas this was less pronounced in the plasma and adipose tissue. For some compounds, such as 9,10-DiHOME, opposing effects of LPS were seen in the plasma compared to the other tissues, suggesting differential regulation of bioactive lipid levels after an inflammatory stimulus. Taken together, our results show that plasma levels do not always correlate with the effects found in the tissues, which underlines the need to measure profiles and pathways of mediators involved in inflammation, including endocannabinoid-like structures, in both plasma and tissue

Fish oil and inflammatory status alter the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes in mouse plasma and tissues

It is well established that dietary intake of n-3 fatty acids is associated with anti-inflammatory effects, and this has been linked to modulation of the oxylipin and endocannabinoid metabolomes. However, the amount of data on specific tissue effects is limited, and it is not known how inflammation affects this relation. In the present study we systematically explored the combined effects of n-3 fatty acid diets and inflammation on the in vivo endocannabinoid and oxylipin metabolomes using a multicompartment, detailed targeted lipidomics approach. Male C57BL/6 mice received diets containing 0, 1, or 3 % w/w fish oil (FO) for 6 weeks, after which 2 mg/kg LPS or saline was administered i.p. Levels of endocannabinoids/N-acylethanolamines (NAEs) and oxylipins, covering n-3 and n-6 fatty acid derived compounds, were determined in plasma, liver, ileum and adipose tissue using LC–MS/MS. FO generally increased ‘n-3’ NAEs and oxylipins at the expense of compounds derived from other fatty acids, affecting all branches of the oxylipin metabolome. LPS generally increased levels of endocannabinoids/NAEs and oxylipins, with opposing effects across plasma and tissues. Multivariate data analysis revealed that separation between diet groups in the saline treated groups was primarily explained by decreases in other than n-3 derived compounds. In the LPS treated groups, the separation was primarily explained by increases in n-3 derived compounds. In conclusion, FO caused marked changes in the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes, with specific effects depending on inflammatory status