KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

This study compares the application of two variable selection methods in partial least squares regression (PLSR), the variable importance in projection (VIP) method and the selectivity ratio (SR) method. For this purpose, three different data sets were analysed: (a) physiochemical water quality parameters related to sensorial data, (b) gas chromatography–mass spectrometry (GC-MS) chemical (organic compound) profiles from fossil sea sediment samples related to sea surface temperature (SST) changes, and (c) exposed genes of Daphnia magna female samples related to their total offspring production. Correlation coefficients (r), levels of significance (p-value) and interpretation of the underlying experimental phenomena allowed the discussion about the best approach for variable selection in each case. The comparison of the two variable selection methods in the first water quality data set showed that the SR method is more accurate for sensorial prediction. For the climate data set, when raw total ion current (TIC) GC-MS chromatograms were considered, variables selected using the VIP method were easier to interpret compared with those selected by the SR method. However, when only some chromatographic peak areas (concentrations) were considered, the SR method was more efficient for prediction, and the VIP method selected the most relevant variables for the interpretation of SST changes. Finally, for the transcriptomic data set, the SR method was found again to be more reliable for prediction purposes. Copyright © 2015 John Wiley & Sons, Ltd.

Comparison of the variable importance in projection (VIP) and of the selectivity ratio (SR) methods for variable selection and interpretation

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances (PFASs) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFASs: PFOA, PFNA, PFHxS and PFOS. These made up half of the lower bound (LB) exposure to those PFASs with available occurrence data, the remaining contribution being primarily from PFASs with short half‐lives. Equal potencies were assumed for the four PFASs included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/mL for the sum of the four PFASs in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake (TWI) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI, which is of concern.

Risk to human health related to the presence of perfluoroalkyl substances in food

Acknowledgements: The Panel wishes to thank the hearing experts: Tony Fletcher, Philippe Adam Grandjean and Marco Zeilmaker, and EFSA staff members: Davide Arcella for the support provided to this scientific output. The Panel acknowledges all European Competent Authorities that provided occurrence data on perfluoroalkylated substances in food, and supported the data collection for the Comprehensive European Food Consumption Database. The Panel would also like to thank the following authors and co‐authors for providing additional data in relation to their respective studies: Esben Budtz‐Jorgensen, Jerry Campbell, Jessie A Gleason, Berit Granum, Mette Sorenson, Kyle Steenland and Kristina W Whitworth.

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation

A new liquid chromatography mass spectrometry (LC–MS) metabolomics strategy coupled to chemometric evaluation, including variable and biomarker selection, has been assessed as a tool to discriminate between control and stressed Saccharomyces cerevisiae yeast samples. Metabolic changes occurring during yeast culture at different temperatures (30 and 42 °C) were analysed and the complex data generated in profiling experiments were evaluated by different chemometric multivariate approaches. Multivariate curve resolution alternating least squares (MCR-ALS) was applied to full spectral scan LC–MS preprocessed data multisets arranged in augmented column-wise data matrices. The results showed that sectioning the MS-chromatograms in different windows and analysing them by MCR-ALS enabled the proper resolution of very complex coeluted chromatographic peaks. The investigation of possible relationships between MCR-ALS resolved chromatographic peak areas and culture temperature was then investigated by partial least squares discriminant analysis (PLS-DA). Selection of most relevant resolved chromatographic peaks associated to yeast culture temperature changes was achieved according to PLS-DA-Variable Importance in Projection scores. A metabolite identification workflow was developed utilizing MCR-ALS resolved pure MS spectra and high-resolution accurate mass measurements to confirm assigned structures based on entries in metabolite databases. A total of 65 metabolites were identified. A preliminary interpretation of these results indicates that the strategy described in this study can be proposed as a general tool to facilitate biomarker identification and modelling in similar untargeted metabolomic studies.

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Chemometric evaluation of Saccharomyces cerevisiae metabolic profiles using LC–MS

Copper containing fungicides are used to protect vineyards from fungal infections. Higher residues of copper in grapes at toxic concentrations are potentially toxic and affect the microorganisms living in vineyards, such as Saccharomyces cerevisiae. In this study, the response of the metabolic profiles of S. cerevisiae at different concentrations of copper sulphate (control, 1 mM, 3 mM and 6 mM) was analysed by liquid chromatography coupled to mass spectrometry (LC-MS) and multivariate curve resolution-alternating least squares (MCR-ALS) using an untargeted metabolomics approach. Peak areas of the MCR-ALS resolved elution profiles in control and in Cu(II)-treated samples were compared using partial least squares regression (PLSR) and PLS-discriminant analysis (PLS-DA), and the intracellular metabolites best contributing to sample discrimination were selected and identified. Fourteen metabolites showed significant concentration changes upon Cu(II) exposure, following a dose–response effect. The observed changes were consistent with the expected effects of Cu(II) toxicity, including oxidative stress and DNA damage. This research confirmed that LC-MS based metabolomics coupled to chemometric methods are a powerful approach for discerning metabolomics changes in S. cerevisiae and for elucidating modes of toxicity of environmental stressors, including heavy metals like Cu(II).

LC-MS based metabolomics and chemometrics study of the toxic effects of copper on Saccharomyces cerevisiae.

The aim of this study is to evaluate the presence of perfluoroalkyl substances (PFASs) in the blood of 46 residents from Barcelona and to study the factors that affect exposure. Compounds analysed included perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorobutane sulfonate (PFBS), perfluorooctanoate acid (PFOA) and perfluorononanoate acid (PFNA). Blood was liquid–liquid extracted and PFASs were determined by liquid chromatography coupled to tandem mass spectrometry. Good recoveries (between 97 ± 14 and 105 ± 13 %) were obtained and method detection limits were from 0.03 to 0.07 ng mL−1. ΣPFASs ranged from 0.11 to 4.37 ng mL−1. PFOS was the main compound detected at 0.09–3.35 ng mL−1, followed by PFOA and PFHxS. PFBS and PFNA were seldom detected. Working conditions, smoking and gender did not cause any significant differences among ΣPFASs levels in the blood while age and parity produced decreased concentrations. On the other hand, laboratory working conditions produced significant higher PFOA levels compared to the general population. Compared to other studies, the PFASs levels in blood from Barcelona residents is low (mean ΣPFASs of 1.67 ± 0.88 ng mL−1) and with little variation among the studied population.

Factors affecting the accumulation of perfluoroalkyl substances in human blood

Chemometric evaluation of different experimental conditions on wheat (Triticum aestivum L.) development using liquid chromatography mass spectrometry (LC-MS) profiles of benzoxazinone derivatives.

Mireia Farrés

Papers

Comparison of the variable importance in projection (VIP) and of the selectivity ratio (SR) methods for variable selection and interpretation

Chemometric evaluation of Saccharomyces cerevisiae metabolic profiles using LC–MS

LC-MS based metabolomics and chemometrics study of the toxic effects of copper on Saccharomyces cerevisiae.

Factors affecting the accumulation of perfluoroalkyl substances in human blood

Chemometric evaluation of different experimental conditions on wheat (Triticum aestivum L.) development using liquid chromatography mass spectrometry (LC-MS) profiles of benzoxazinone derivatives.