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Solvent system selection is the first step toward a successful counter-current chromatography (CCC) separation. This paper introduces a systematic and practical solvent system selection strategy based on the nonrandom two-liquid segment activity coefficient (NRTL-SAC) model, which is efficient in predicting the solute partition coefficient. Firstly, the application of the NRTL-SAC method was extended to the ethyl acetate/ n -butanol/water and chloroform/methanol/water solvent system families. Moreover, the versatility and predictive capability of the NRTL-SAC method were investigated. The results indicate that the solute molecular parameters identified from hexane/ethyl acetate/methanol/water solvent system family are capable of predicting a large number of partition coefficients in several other different solvent system families. The NRTL-SAC strategy was further validated by successfully separating five components from Salvia plebeian R.Br. We therefore propose that NRTL-SAC is a promising high throughput method for rapid solvent system selection and highly adaptable to screen suitable solvent system for real-life CCC separation. [ABSTRACT FROM AUTHOR]

Abstract: Tangerine peels are herbal materials of two coupled traditional Chinese medicines, Pericarpium Citri Reticulatae (PCR) and Pericarpium Citri Reticulatae Viride (PCRV). In this paper, high-performance liquid chromatographic fingerprints of tangerine peels during growth were firstly measured for deliberately collected 34 samples from three species (Citrus reticulata ‘Chachi’, Citrus reticulata ‘Dahongpao’ and Citrus erythrosa Tanaka). After sixteen characteristic components which have similar change trends in the grown process were screened out with the help of heuristic evolving latent projection (HELP) method, score plots of principal component analysis (PCA) successfully presented the grown footprints of tangerine peels. It implied that July might be the best harvest time for PCRV, November and December were better for PCR. Furthermore, hesperidin, nobiletin and tangeretin were screened as chemical markers by loadings of PCA. The HPLC–HELP–PCA strategy has shown its potential in optimization of harvest time and chemical markers’ screening, which will have wide perspective in the analysis of “coupled TCMs”. [Copyright &y& Elsevier]

Abstract: High-performance liquid chromatographic (HPLC) fingerprints of Pericarpium Citri Reticulatae (PCR) and Pericarpium Citri Reticulatae Viride (PCRV) were firstly measured for deliberately collected 39 authentic samples and 21 commercial samples. Both correlation coefficients of similarity for chromatograms and absolute peak areas of characteristic compounds were calculated for quantitative expression of the HPLC fingerprints. After principal component analysis (PCA) successfully distinguished the ‘mixed peels’ samples from authentic samples, partial least squares-linear discrimination analysis (PLS-LDA) was then effectively applied to class separation between authentic PCR and PCRV. Furthermore, the unequivocally determined compounds, hesperidin, nobiletin and tangeretin, were screened out by loadings plots of PCA and PLS-LDA. The results indicated that they could be used as chemical markers for discrimination among different groups of samples. The proposed method shows an efficient strategy for quality control of PCR and PCRV, which cannot only distinguish the ‘mixed peels’ but also discriminate authentic PCR and PCRV. This method has potential perspective for quality control of traditional Chinese medicine (TCM). [Copyright &y& Elsevier]

Abstract: The importance of 5′AMP-activated protein kinase (AMPK) in regulating glucose and fatty acid metabolism is increasing. Thus, it is regarded as a new pharmacological target for treatment of obesity, insulin resistance and type 2 diabetes mellitus (T2DM). In order to explore the relationships between AMPK and diabetes mellitus, urines samples from four groups of C57 mice, i.e., the normal male and female C57 mice, female C57-AMPK gene knocked-out mice, and male C57-AMPK gene knocked-out mice, were studied by coupling GC/MS with a powerful machine learning method, random forest. The experimentation has been designed as two steps: firstly, the normal male and female mice were compared with male and female C57-AMPK gene knocked-out mice, respectively; then the differences between male C57-AMPK gene knocked-out mice and female C57-AMPK gene knocked-out mice were further detected. Finally, not only the differences between the normal C57 mice and C57-AMPK gene knocked-out mice were observed, but also the gender-related metabolites differences of the C57-AMPK gene knocked-out mice were obviously visualized. The results obtained with this research demonstrate that combining GC/MS profiling with random forest is a useful approach to analyze metabolites and to screen the potential biomarkers for exploring the relationships between AMPK and diabetes mellitus. [Copyright &y& Elsevier]

Abstract: Large amounts of data from high-throughput metabolomics experiments become commonly more and more complex, which brings an enormous amount of challenges to existing statistical modeling. Thus there is a need to develop statistically efficient approach for mining the underlying metabolite information contained by metabolomics data under investigation. In the work, we developed a novel kernel Fisher discriminant analysis (KFDA) algorithm by constructing an informative kernel based on decision tree ensemble. The constructed kernel can effectively encode the similarities of metabolomics samples between informative metabolites/biomarkers in specific parts of the measurement space. Simultaneously, informative metabolites or potential biomarkers can be successfully discovered by variable importance ranking in the process of building kernel. Moreover, KFDA can also deal with nonlinear relationship in the metabolomics data by such a kernel to some extent. Finally, two real metabolomics datasets together with a simulated data were used to demonstrate the performance of the proposed approach through the comparison of different approaches. [Copyright &y& Elsevier]

The peak shifts may lead to an incorrect statistical result for nontargeted metabolomics profiling, such as classification and discrimination in pattern recognition. In the paper, a more accurate alignment algorithm is developed based on Subwindow Factor Analysis and Mass Spectral information (SFA-MS). Compared with other methods, this new algorithm aligns the peaks more accurately without changing their shapes, especially for the overlapping peak clusters. To begin, the Continuous Wavelet Transform with Haar wavelet as the mother wavelet (Haar CWT) is used to determine the position and width of peaks. On this basis, the candidate drift points are confirmed by Fast Fourier Transform (FFT) cross correlation. Furthermore, the MS fitting degree of the common components between the reference chromatogram and the raw chromatogram is determined by the Subwindow Factor Analysis (SFA). When the MS information between reference and raw peaks is identical, the corresponding moving points are the optimum shifts. It is remarkable that all the peaks are moved through linear interpolation in the non-peak parts, so that the aligned chromatograms remain unchanged. The SFA-MS algorithm was implemented in the Matlab language and is available as an open source package. [ABSTRACT FROM AUTHOR]

Screening important variables for class-imbalanced data is still a challenging task. In this study, we propose an algorithm for stably selecting key variables on class-imbalanced data based on the precision-recall curve (PRC), where the PRC is utilized as the assessment criterion in the model building stage, and sparse regularized logistic regression combined with subsampling (SRLRS) is designed to perform stable variable selection. Considering the characteristic of class-imbalanced data, we also proposed classification-based partition for cross validation, as well as leaving half of majority observations out and leaving one minority observation out (LHO-LOO) for subsampling. Simulation results and real data showed that our algorithm is highly suitable for handling class-imbalanced data, and that the PRC can be an alternative evaluation criterion for model selection when handling class-imbalanced data. [ABSTRACT FROM AUTHOR]

The partial least squares-discriminant analysis (PLS-DA) is the most widely used statistical tool to perform classification and biomarker screening in metabolomics. However, the PLS-DA tends to overfit the data, and the selection of biomarkers is often unstable because of the disturbance of uninformative variables in principal components. In this paper, we propose an algorithm for performing stable biomarker screening and for seeking the optimal generalization performance, in which the biomarker identification is based on sparse regularization variable selection in combination with subsampling (SRS), and the classification is subsequently performed by a linear support vector machine (SVM) classifier in the selected-variable space to obtain the maximum classification accuracy. Two metabolomics datasets measured by gas chromatography-mass spectrometry are employed to evaluate the performance of the proposed SRS-SVM algorithm, and the comparison with existing related algorithms is given. The result shows that the SRS-SVM algorithm outperforms the PLS-DA and is competitive with other related algorithms in terms of prediction classification accuracy measured by both internal and external validation. Furthermore, the selection of candidate biomarkers is quite stable by the SRS-SVM algorithm, and it can be an alternative and competitive method for the analysis of metabolomics data. The R code for implementing the SRS-SVM algorithm is available in the Electronic supplementary material . [ABSTRACT FROM AUTHOR]

Partial least squares (PLS) is one of the most widely used methods for chemical modeling. However, like many other parameter tunable methods, it has strong tendency of over-fitting. Thus, a crucial step in PLS model building is to select the optimal number of latent variables (nLVs). Cross-validation (CV) is the most popular method for PLS model selection because it selects a model from the perspective of prediction ability. However, a clear minimum of prediction errors may not be obtained in CV which makes the model selection difficult. To solve the problem, we proposed a new strategy for PLS model selection which combines the cross-validated coefficient of determination ( Q c v 2 ) and model stability ( S ). S is defined as the stability of PLS regression vectors which is obtained using model population analysis (MPA). The results show that, when a clear maximum of Q c v 2 is not obtained, S can provide additional information of over-fitting and it helps in finding the optimal nLVs. Compared with other regression vector based indictors such as the Euclidean 2-norm ( B2 ), the Durbin Watson statistic ( DW ) and the jaggedness ( J ), S is more sensitive to over-fitting. The model selected by our method has both good prediction ability and stability. [ABSTRACT FROM AUTHOR]

Bioactive component identification is a crucial issue in search for new drug leads. We provide a new strategy to search for bioactive components based on Sure Independence Screening (SIS) and interval PLS (iPLS). The method, which is termed as SIS–iPLS, is not only able to find out the chief bioactive components, but also able to judge how many components should be there responsible for the total bioactivity. The method is totally “data-driven” with no need for prior knowledge about the unknown mixture analyzed, therefore especially suitable for effect-directed work like bioassay-guided fractionation. Two data sets, a synthetic mixture system of twelve components and a suite of Radix Puerariae Lobatae extracts samples, are used to test the identification ability of the SIS–iPLS method. [ABSTRACT FROM AUTHOR]

Highlights: [•] An effective approach has been developed for analysis complex metabolomics data. [•] Random forest provides useful tools for data visualization and interpretation. [•] Metabolic perturbations in metabolic syndrome patients were discovered. [ABSTRACT FROM AUTHOR]

Abstract: One of the main goals of metabolomics studies is to discover informative metabolites or biomarkers, which may be used to diagnose diseases and to find out pathology. Sophisticated feature selection approaches are required to extract the information hidden in such complex ‘omics’ data. In this study, it is proposed a new and robust selective method by combining random forests (RF) with model population analysis (MPA), for selecting informative metabolites from three metabolomic datasets. According to the contribution to the classification accuracy, the metabolites were classified into three kinds: informative, no-informative, and interfering metabolites. Based on the proposed method, some informative metabolites were selected for three datasets; further analyses of these metabolites between healthy and diseased groups were then performed, showing by T-test that the P values for all these selected metabolites were lower than 0.05. Moreover, the informative metabolites identified by the current method were demonstrated to be correlated with the clinical outcome under investigation. The source codes of MPA-RF in Matlab can be freely downloaded from http://code.google.com/p/my-research-list/downloads/list [Copyright &y& Elsevier]

Abstract: The volatile components between stems and roots and also among five Clematis species from China were studied and analyzed by gas chromatography–mass spectrometry (GC–MS) combined with alternative moving window factor analysis (AMWFA), a new chemometric resolution method. Identification of the compounds was also assisted by comparison of temperature-programmed retention indices (PTRIs) on HP-5MS with authentic samples included in our own laboratory database under construction. A total of 153 different compounds accounting for 86.6–96.5% were identified and significant qualitative and quantitative differences were observed among the samples. The major volatile components in different essential oils from Clematis species were n-hexadecanoic acid and (Z,Z)-9,12-octadecadienoic acid. Our work further demonstrated chemometric resolution techniques upon the two-dimensional data and PTRIs can provide a complementary and convenient method for fast and accurate analysis of complex essential oils. [Copyright &y& Elsevier]

Abstract: A sensitive liquid chromatography–electrospray ionization mass spectrometry (LC–ESI-MS) method is developed and validated for rapid determination of amantadine in human plasma. Desloratadine was used as the internal standard (I.S.). Human plasma (0.2mL) was first alkalified with 100μL of sodium hydroxide (3M) and then extracted with 1mL of n-hexane containing 1% isopropanol (v/v) and 10% dichloromethane (v/v) by vortex-mixer for 3min. The mixture was centrifuged at 14,000rpm for 5min. The supernatant was evaporated to dryness and the residue was dissolved in mobile phase. Samples were separated using a Thermo Hypersil-HyPURITYC18 reversed-phase column (150mm×2.1mm i.d., 5μm). Mobile phase consisted of methanol–acetonitrile–20mM ammonium acetate (45:10:45, v/v/v) containing 1% acetic acid with pH 4.0. Amantadine and I.S. were measured by electrospray ion source in positive selective ion monitoring mode. The good linearity ranged from 3.9 to 1000ng/mL and the lowest limit of quantification was 3.9ng/mL. The extraction efficiencies were approximately 70% and recoveries of method ranged from 98.53 to 103.24%. The intra-day relative standard deviations (R.S.D.) were less than 8.43% and inter-day R.S.D. below 10.59%. The quality control samples were stable when kept at room temperature for 12h, at −20°C for 30 days and after four freeze/thaw cycles. The method has been successfully used to evaluation of the pharmacokinetics and bioequivalence of amantadine in 20 healthy volunteers after an oral dose of 100mg amantadine. [Copyright &y& Elsevier]

Learning from class-imbalanced data has gained increasing attention in recent years due to the massive growth of skewed data across many scientific fields such as metabolomics. Some researches show that it is not the imbalance itself which hinders the classification performance, but class overlapping do play an important role in the performance degradation when associated to class-imbalance. So alleviating the overlapping of the imbalanced data might be an effective way to improve the performance in class-imbalance learning. In this study, we propose two feature selection algorithms that aim to minimize the overlap degree between the majority and the minority, which is based on a simple assumption that decreasing overlap degree of a data set makes it more separable. The proposed MOSNS and MOSS methods are built via sparse regularization techniques. Simulation results indicate that our algorithms is effective in recognizing key features and control false discoveries for class-imbalance learning. Four class-imbalanced metabolomics data sets are also employed to test the performance of our algorithm, and a comparison with accuracy (ACC)-based and ROC-based selection procedures is performed. The result shows that our algorithms are highly competitive and can be an alternative feature selection strategy in class-imbalance learning. ● Two feature selection algorithms are proposed by minimizing the overlap of a data set. ● Sparse feature selection strategy are used in class-imbalance learning. ● The classification performance of metabolomics data can be improved by sparse feature selection and re-balance preprocessing. [ABSTRACT FROM AUTHOR]