| 1. |
- Shi, Lin, et al.
(författare)
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Variable selection and validation in multivariate modelling
- 2019
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 35:6, s. 972-980
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Tidskriftsartikel (refereegranskat)abstract
- Motivation Validation of variable selection and predictive performance is crucial in construction of robust multivariate models that generalize well, minimize overfitting and facilitate interpretation of results. Inappropriate variable selection leads instead to selection bias, thereby increasing the risk of model overfitting and false positive discoveries. Although several algorithms exist to identify a minimal set of most informative variables (i.e. the minimal-optimal problem), few can select all variables related to the research question (i.e. the all-relevant problem). Robust algorithms combining identification of both minimal-optimal and all-relevant variables with proper cross-validation are urgently needed. Results We developed the MUVR algorithm to improve predictive performance and minimize overfitting and false positives in multivariate analysis. In the MUVR algorithm, minimal variable selection is achieved by performing recursive variable elimination in a repeated double cross-validation (rdCV) procedure. The algorithm supports partial least squares and random forest modelling, and simultaneously identifies minimal-optimal and all-relevant variable sets for regression, classification and multilevel analyses. Using three authentic omics datasets, MUVR yielded parsimonious models with minimal overfitting and improved model performance compared with state-of-the-art rdCV. Moreover, MUVR showed advantages over other variable selection algorithms, i.e. Boruta and VSURF, including simultaneous variable selection and validation scheme and wider applicability.
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| 2. |
- Kunzelmann, Marco, et al.
(författare)
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Non-targeted analysis of unexpected food contaminants using LC-HRMS
- 2018
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 410:22, s. 5593-5602
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Tidskriftsartikel (refereegranskat)abstract
- A non-target analysis method for unexpected contaminants in food is described. Many current methods referred to as non-target are capable of detecting hundreds or even thousands of contaminants. However, they will typically still miss all other possible contaminants. Instead, a metabolomics approach might be used to obtain true non-target analysis. In the present work, such a method was optimized for improved detection capability at low concentrations. The method was evaluated using 19 chemically diverse model compounds spiked into milk samples to mimic unknown contamination. Other milk samples were used as reference samples. All samples were analyzed with UHPLC-TOF-MS (ultra-high-performance liquid chromatography time-of-flight mass spectrometry), using reversed-phase chromatography and electrospray ionization in positive mode. Data evaluation was performed by the software TracMass 2. No target lists of specific compounds were used to search for the contaminants. Instead, the software was used to sort out all features only occurring in the spiked sample data, i.e., the workflow resembled a metabolomics approach. Procedures for chemical identification of peaks were outside the scope of the study. Method, study design, and settings in the software were optimized to minimize manual evaluation and faulty or irrelevant hits and to maximize hit rate of the spiked compounds. A practical detection limit was established at 25 mu g/kg. At this concentration, most compounds (17 out of 19) were detected as intact precursor ions, as fragments or as adducts. Only 2 irrelevant hits, probably natural compounds, were obtained. Limitations and possible practical use of the approach are discussed.
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| 3. |
- Rosén, Johan, et al.
(författare)
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A new method for analysis of underivatized free beta-methylamino-alanine : Validation and method comparison
- 2016
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 121, s. 105-108
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Tidskriftsartikel (refereegranskat)abstract
- A new method was developed for analysis of free beta-Methylamino-alanine (BMAA) in biological matrices. The method is based on direct analysis of the underivatized molecule, using an amide column for separation by Hydrophilic Interaction Liquid Chromatography (HILIC) and detection by tandem mass spectrometry (MS/MS) using a deuterium labeled internal standard. The use of Ultra-High Performance Liquid Chromatography (UHPLC) combined with MS/MS detection allowed for high chromatographic resolution and a low limit of detection (0.025 mu g/g wet weight (ww) in mussels). The method was validated by analyzing spiked blank mussels from the Baltic Sea (0.15-4.4 mu g/g (ww), trueness 99%-105%, RSD 2%-8%). An inter-laboratory comparative analysis of extracts of mussel was performed. The mussels were extracted according to an established protocol for analysis of free BMAA, and the extracts were then analyzed in parallel by the new method and a validated procedure based on detection of BMAA derivatized with dansyl chloride. Both methods detected BMAA in similar concentrations. Thus, derivatization with dansyl chloride did not influence the results compared to direct detection. The new method presents an alternative to the commonly applied derivatization step, and is proved through validation and method comparison to reliably identify and quantify free BMAA at low concentration levels.
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| 4. |
- Jiang, Liying, et al.
(författare)
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Quantification of neurotoxin BMAA (beta-N-methylamino-L-alanine) in seafood from Swedish markets
- 2014
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The neurotoxin beta-N-methylamino-L-alanine (BMAA) produced naturally by cyanobacteria, diatoms and dinoflagellates can be transferred and accumulated up the food chain, and may be a risk factor for neurodegenerative diseases. This study provides the first systematic screening of BMAA exposure of a large population through the consumption of seafood sold in metropolitan markets. BMAA was distinguished from known isomers by liquid chromatography tandem mass spectrometry after acidic hydrolysis and derivatization. Using deuterium-labeled internal standard, BMAA was quantified as 0.01-0.90 mu g/g wet weight of tissues in blue mussel, oyster, shrimp, plaice, char and herring, but was undetectable (<0.01 mu g/g) in other samples (salmon, cod, perch and crayfish). Provided that the content of BMAA detected is relevant for intake calculations, the data presented may be used for a first estimation of BMAA exposure through seafood from Swedish markets, and to refine the design of future toxicological experiments and assessments.
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| 5. |
- Tengstrand, Erik, et al.
(författare)
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A concept study on non-targeted screening for chemical contaminants in food using liquid chromatography–mass spectrometry in combination with a metabolomics approach
- 2013
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 405:4, s. 1237-1243
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Tidskriftsartikel (refereegranskat)abstract
- A generic method to screen for new or unexpected contaminants at ppm levels in food has been developed. The method comprises an acidic acetonitrile extraction, detection with ultra-high-pressure liquid chromatography coupled to electrospray ionisation time-of-flight mass spectrometry and statistical evaluation using a metabolomics approach comparing suspected contaminated food with uncontaminated foods. The method was tested for 26 model contaminants from 100 μg/g down to 0.4 μg/g in three brands of fresh orange juice. Blinded statistical evaluation revealed signals from all added contaminants detectable by liquid chromatography –electrospray ionisation using positive ionisation mode, while only two false-positive signals were reported. The method is primarily intended to be used for investigation of food samples suspected to be contaminated with unknown substances. Additionally it could be used to continuously monitor for appearance of new food contaminants as a complement to the specific targeted analysis that is today’s foundation of food safety analysis.
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| 6. |
- Gyllenhammar, Irina, et al.
(författare)
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Tidstrend 1996-2011: Bisfenol A (BPA) och andrafenolära ämnen i blod från förstföderskor i Uppsala
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Under perioden 1996 till 2011 har Livsmedelsverket samlat in blodserum från förstföderskor i Uppsalalän. Ett av syftena med studierna är att undersöka hur halterna av vissa persistenta organiska miljögifter(POP) förändras med tiden. I denna rapport utvärderas blodserumnivåer för fem fenolära ämnen,bisfenol A (BPA), bisfenol S (BPS), bisfenol F (BPF), 4-nonylfenol (4-NP) och bensofenon-3 (BP-3).Den fria formen av ämnena analyserades med hjälp av UPLC-MS/MS.Resultaten tyder på att halterna av alla dessa ämnen är låga och ligger under kvantifieringsgränsen(LOQ = 0,1 ng/ml). Nivåer av fritt BPA som uppmättes i vissa prover kommer troligtvis frånkontamination under provhanteringens gång och inte från faktiska nivåer i blodet. Slutsatsen är atthalterna av fritt BPA, BPS, BPF, 4-NP och BP-3 har varit låga hos ammande kvinnor från Uppsalaregionenmellan åren 1996-2011. Studien antyder att det är tveksamt att använda biobankadeblodprover för analys av BPA-exponering i befolkningen, om inte provtagning och provhanteringgenomförts på ett sätt som gör att BPA-kontamination av proverna kan uteslutas.
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| 7. |
- Petersson, Erik V., 1979-
(författare)
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Analysis of Acrylamide and Anthocyanins in Foods : Extraction Optimization for Challenging Analytes
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, the main concern has been to improve the reliability of different parts of the analytical workflow (Paper I, II, IV &V). Additionally, one of the resulting optimized methods was used in a real application (Paper III). Paper I-II concerned the extraction of acrylamide (AA) from foods. In Paper I different parameters such as sample particle size, extraction solvent, extraction time and extraction temperature were optimized, leading to a method that showed good agreement with the assigned AA levels of several proficiency test samples. Later, after the publication of the paper, the method showed good performance in a collaborative trial validation, in terms of trueness, repeatability and reproducibility figures. It was labeled “undoubtedly fit for the purpose”. In Paper II, it was shown that the ‘extra’ amounts of AA obtained during extraction of foods with an alkaline aqueous solution was not due to improved extractability of AA from the food matrix. Strongly alkaline conditions seemed to rather induce net formation of AA from water-soluble precursors formed during thermolysis. This phenomenon should therefore be regarded as an extraction artifact. Paper III was an application of the optimized method from Paper I, where it was used to study the reduction of AA in potato chips (crisps) by using pre-treatments and frying at reduced pressure. There were significant reductions in AA, down to below the limit of quantification (5 µg/kg) for the method. Paper IV-V concerned analysis of anthocyanins (AC) in red onion. In Paper IV, a new separation method using capillary electrophoresis was developed, and its rapidness combined with an acidic background electrolyte helped in preventing AC degradation. Furthermore, its alternative separation mechanism is a complement to that of the more commonly used liquid chromatography technique. In Paper V, simultaneous extraction and degradation of anthocyanins from red onion was studied in a static batch reactor at 110ºC. The extraction and degradation kinetics were successfully separated, and an ideal theoretical extraction curve was constructed by compensating mathematically for degradation effects, showing that more anthocyanins, 21 to 36% depending on different species, could be extracted if no degradation occurred. The results give important information about the different kinetics competing during an extraction procedure, and also show that quantitative extraction is not to recommend in the batch system used in the study.
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| 8. |
- Wilson, Kathryn M., et al.
(författare)
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Validation of a food frequency questionnaire measurement of dietary acrylamide intake using hemoglobin adducts of acrylamide and glycidamide
- 2009
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 20:3, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Acrylamide, a probable human carcinogen, is formed during high-heat cooking of many common foods. The validity of food frequency questionnaire (FFQ) measures of acrylamide intake has not been established. We assessed the validity of acrylamide intake calculated from an FFQ using a biomarker of acrylamide exposure. METHODS: We calculated acrylamide intake from an FFQ in the Nurses' Health Study II. We measured hemoglobin adducts of acrylamide and its metabolite, glycidamide, in a random sample of 342 women. Correlation and regression analyses were used to assess the relationship between acrylamide intakes and adducts. RESULTS: The correlation between acrylamide intake and the sum of acrylamide and glycidamide adducts was 0.31 (95% CI: 0.20-0.41), adjusted for laboratory batch, energy intake, and age. Further adjustment for BMI, alcohol intake, and correction for random within-person measurement error in adducts gave a correlation of 0.34 (CI: 0.23-0.45). The intraclass correlation coefficient for the sum of adducts was 0.77 in blood samples collected 1-3 years apart in a subset of 45 women. Intake of several foods significantly predicted adducts in multiple regression. CONCLUSIONS: Acrylamide intake and hemoglobin adducts of acrylamide and glycidamide were moderately correlated. Within-person consistency in adducts was high over time.
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| 9. |
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| 10. |
- Rosén, Johan, 1726-1773
(författare)
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Quæstionis academicæ, de genio lingvæ Svecanæ, pars tertia, ... auctore et præside, Johanne Rosén, ... itemque respondente Michaele Grönlund, Helsingo, in auditorio Carol. maj ad d. XI. Decemb. ann. MDCCLI, in controversiam vocanda.
- 1751
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
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