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  • 1.
    Appelblad, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jonsson, Tobias
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Irgum, Knut
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Determination of C-21 ketosteroids in serum using trifluoromethanesulfonic acid catalyzed precolumn dansylation and 1,1’-oxalyldiimidazole postcolumn peroxyoxalate chemiluminescence detection1998In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 70, no 23, p. 5002-5009Article in journal (Refereed)
    Abstract [en]

    A new procedure for the quantitation of C-21 ketosteroids using trifluoromethanesulfonic acid-catalyzed precolumn dansylation and coupled column liquid chromatographic separation, followed by postcolumn 1,1‘-oxalyldiimidazole peroxyoxalate chemiluminescence detection is presented. In the simultaneous optimization of chromatographic resolution and chemiluminescence intensity, a coupled column chromatographic system and a stopped-flow system were used. An eluent containing 20 mM phosphate buffer at pH 6.7 accomplished an efficient separation of 3α-hydroxy-5β-pregnan-20-one from a mixture containing 10 C-21 ketosteroids. Phosphate buffer also proved to be the most advantageous, among the six buffers tested, for sensitive detection. Experimental design and multivariate data analysis were used to characterize and optimize the postcolumn reaction chemistry in the chromatographic system. A valid full factorial design with excellent predictability showed that the flow rates for both 1,1‘-oxalyldiimidazole and hydrogen peroxide were the factors most strongly affecting the sensitivity of the system. The theoretical plate numbers were above 11 000 for all 10 dansylated ketosteroids. The 3σ detection limit estimated from 3α-hydroxy-5β-pregnan-20-one calibration curve data was 1.6 pmol (n = 4, 125 μL injected) and spiked serum containing 0−74 pmol of this compound showed overall recoveries of 73 ± 9% (n = 12). Quantitation of 3α-hydroxy-5β-pregnan-20-one was finally carried out on 45 serum samples and the results compared to those from a radioimmunoassay (RIA) method. The data acquired with the procedure described in this work compare well with the results from RIA, which confirms the reliability of the new analytical procedure.

  • 2.
    Betson, Tatiana R
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Augusti, Angela
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Schleucher, Jürgen
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Quantification of deuterium isotopomers of tree-ring cellulose using nuclear magnetic resonance.2006In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 78, no 24, p. 8406-8411Article in journal (Refereed)
    Abstract [en]

    Stable isotopes in tree rings are important tools for reconstruction of past climate. Deuterium (D) is of particular interest since it may contain climate signals and report on tree physiology. Measurements of the D/H ratio of tree-ring cellulose have proven difficult to interpret, presumably because the D/H ratio of the whole molecule blends the abundances of the seven D isotopomers of cellulose. Here we present a method to measure the abundance of the D isotopomers of tree-ring cellulose by nuclear magnetic resonance spectroscopy (NMR). The method transforms tree-ring cellulose into a glucose derivative that gives highly resolved, quantifiable deuterium NMR spectra. General guidelines for measurement of D isotopomers by NMR are described. The transformation was optimized for yield and did not alter the original D isotopomer abundances, thus, conserving the original signals recorded in wood cellulose. In the tree-ring samples tested, the abundances of D isotopomers varied by approximately ±10% (2% standard error). This large variability can only be caused by biochemistry processes and shows that more information is present in D isotopomer abundances, compared to the D/H ratio. Therefore, measurements of the D isotopomer distribution of tree rings may be used to obtain information on long-term adaptations to environmental changes and past climate change.

  • 3.
    Cedergren, Anders
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nordmark, Ulrika
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Determination of water in NIST reference material for mineral oils2000In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 72, no 14, p. 3392-3395Article in journal (Refereed)
    Abstract [en]

    The accuracy of the reference concentrations of moisture in electrical insulating oil RM 8506 and lubricating oil RM 8507 (both of mineral type) and specified by the National institute of Standards and Technology (NIST) as containing 39.7 and 76.8 ppm (w/w) water, respectively, has recently been the subject of debate in this journal. To shed some further light on this controversy, we report in this correspondence results for these oils obtained by two additional methods, one based on specially designed reagents for diaphragm-free Karl Fischer (KF) coulometry and the other based on the concept of stripping at elevated temperature/continuous KF coulometry. A positive interference effect was shown to take place for RM 8506 when the direct coulometric method was used. If the results are corrected for this, the values including six different procedures varied in the range 13.5-15.6 ppm (w/w). For RM 8507, all values were between 42.5 and 47.2 ppm (w/w), which means that the values recommended by NIST for both reference oils using volumetric titration are about twice as high as those obtained with the other techniques. A possible explanation for this discrepancy is presented.

  • 4.
    Courtois, Julien
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Fischer, Gerd
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Schauff, Siri
    Albert, Klauss
    Irgum, Knut
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Interactions of bupivacaine with a molecularly imprinted polymer in a monolithic format studied by NMR2006In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 78, no 2, p. 580-584Article in journal (Refereed)
    Abstract [en]

    A trimethylolpropane trimethacrylate-based monolith of dimensions carefully chosen to fit exactly in a standard 4-mm solid-state CP/MAS NMR rotor was photopolymerized and subsequently molecularly imprinted with bupivacaine using a grafting protocol with methacrylic acid and ethylene dimethacrylate as monomers. As no crushing or grinding of the monolith was necessary, additional unspecific surface area was not created. This procedure ascertains that differences observed between imprinted and nonimprinted polymers are due only to graft imprinted surfaces and give therefore better results in NMR spectroscopy due to less unspecific interactions between analyte and monolith. This improves the comparability to chromatographic evaluations where uncrushed monolithic columns are also used. To track interactions between analyte and stationary phase, the saturation transfer difference (STD) technique was applied on the polymer in the suspended state using the same solvent as in the chromatographic evaluation. This relatively new NMR method has to our knowledge not been used on chromatographic materials before. By using STD NMR on pristine monoliths, it was possible to measure large differences between the imprinted or nonimprinted polymers and the analyte indicating significant differences in the interaction mechanisms. These could be directly correlated with retention differences observed in chromatographic evaluations.

  • 5.
    Courtois, Julien
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Szumski, Michal
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Georgsson, Fredrik
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Irgum, Knut
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Assessing the macroporous structure of monolithic columns by transmission electron microscopy2007In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 79, no 1, p. 335-344Article in journal (Refereed)
    Abstract [en]

    A set of monolithic stationary phases representing a broad span of monomers and porogens have been characterized directly in their capillary chromatographic format by computational assessment of their pore structure from transmission electron micrographs obtained after in situ embedment of the monoliths in contrast resin, followed by dissolution of the fused-silica tubing, further encasement of the resin-embedded monolith, and microtomy. This technique has been compared to mercury intrusion, a more conventional technique for macroporosity estimation. Supplementing the embedding resin by lead methacrylate gave a negative staining, and the resulting micrographs showed a good contrast between the polymeric monoliths and the embedding resin that allowed studies on the pore formation and polymer development. The technique was also applied to a commercial monolithic silica column.

  • 6.
    Dumarey, Melanie
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Vander Heyden, Yvan
    Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel, Belgium.
    Rutan, Sarah C
    Department of Chemistry, Virginia Commonwealth University, Richmond, VA.
    Evaluation of the identification power of RPLC analyses in the screening for drug compounds2010In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 82, no 14, p. 6056-65Article in journal (Refereed)
    Abstract [en]

    The identification of drugs of abuse is an important issue in forensic science. The main goal is to trace and identify as many drugs as possible in the shortest possible time preferably with a simple analysis method. One possibility is to screen samples using a Liquid Chromatography-Diode Array Detection (LC-DAD) system. However, when simultaneously performing another analysis on a chromatographic column exhibiting selectivity differences from the first one, that is, orthogonal or dissimilar columns, a greater number of drugs can be possibly identified without investing a lot of extra time or money. The primary difficulty is then selecting the most appropriate columns. In this paper, it is demonstrated that selecting the most dissimilar columns based on measures such as correlation or Snyder's F(s) value is not optimal, because these measures do not take into account the identification power of the individual systems. This implies that a large number of drugs may not necessarily be identified on the systems selected using these criteria. Therefore, three other measures are tested to evaluate the identification power obtained by parallel screening on two columns or by comprehensive two-dimensional LC (LC x LC). The simplest approach is counting the number of compounds separable with a difference in retention time greater than a predefined critical value. However, this measure does not reflect the coelution pattern of the unidentified drugs nor the separation degree of all compounds. The second tested measure, information, enables differentiation between systems identifying the same number of compounds but resulting in a different coelution pattern. Multivariate selectivity, the third tested parameter, takes into account the degree of separation of all compounds and has the advantage that it reflects the gain in identification power achieved by introducing DAD data. All three proposed measures also enable evaluation of whether the corresponding LC x LC method will result in a greater identification power.

  • 7.
    Eliasson, Mattias
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Rännar, Stefan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Madsen, Rasmus
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Donten, Magdalena A
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Marsden-Edwards, Emma
    Waters Corp, Milford, MA 01757 USA .
    Moritz, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Shockcor, John P
    Waters Corp, Milford, MA 01757 USA .
    Johansson, Erik
    Umetr AB, Umeå, Sweden.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Strategy for optimizing LC-MS data processing in Metabolomics: A design of experiments approach2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 15, p. 6869-6876Article in journal (Refereed)
    Abstract [en]

    A strategy for optimizing LC-MS metabolomics data processing is proposed. We applied this strategy on the XCMS open source package written in R on both human and plant biology data. The strategy is a sequential design of experiments (DoE) based on a dilution series from a pooled sample and a measure of correlation between diluted concentrations and integrated peak areas. The reliability index metric, used to define peak quality, simultaneously favors reliable peaks and disfavors unreliable peaks using a weighted ratio between peaks with high and low response linearity. DoE optimization resulted in the case studies in more than 57% improvement in the reliability index compared to the use of the default settings. The proposed strategy can be applied to any other data processing software involving parameters to be tuned, e.g., MZmine 2. It can also be fully automated and used as a module in a complete metabolomics data processing pipeline.

  • 8. Fei, Y Y
    et al.
    Schmidt, Alexej
    Helicure AB, Umeå Biotech Incubator, Umeå.
    Bylund, Göran
    Helicure AB, Umeå Biotech Incubator, Umeå.
    Johansson, D X
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Henriksson, Sara
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Lebrilla, C
    Solnick, J V
    Borén, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Helicure AB, Umeå Biotech Incubator, Umeå.
    Zhu, X D
    Use of real-time, label-free analysis in revealing low-affinity binding to blood group antigens by Helicobacter pylori2011In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 83, no 16, p. 6336-6341Article in journal (Refereed)
    Abstract [en]

    Infectious diseases are often initiated by microbial adherence that is mediated by the binding of attachment molecules, termed adhesins, to cell surface receptors on host cells. We present an experimental system, oblique-incidence reflectivity difference (OI-RD) microscopy, which allows the detection of novel, low-affinity microbial attachment mechanisms that may be essential for infectious processes. OI-RD microscopy was used to analyze direct binding of the oncopathogen, Helicobacter pylori ( H. pylori ) to immobilized glycoconjugates in real time with no need for labeling tags. The results suggest the presence of additional Lewis b blood group antigen (Le(b)) binding adhesins that have not been detected previously. OI-RD microscopy also confirmed the high-affinity binding of H. pylori outer-membrane protein BabA to Le(b). The OI-RD microscopy method is broadly applicable to real-time characterization of intact microbial binding to host receptors and offers new strategies to elucidate the molecular interactions of infectious agents with human host cells.

  • 9.
    Gouveia-Figueira, Sandra
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nording, Malin L.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Development and Validation of a Sensitive UPLC-ESI-MS/MS Method for the Simultaneous Quantification of 15 Endocannabinoids and Related Compounds in Milk and Other Biofluids2014In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 86, no 2, p. 1186-1195Article in journal (Refereed)
    Abstract [en]

    The endocannabinoid (eCB) system has gained an increasing interest over the past decades since the discovery of anandamide and 2-arachidonoyl glycerol (2-AG). These, and structurally related compounds, are associated with a wide variety of physiological processes. For instance, eCB levels in milk have been associated with infants' feeding and sleeping behavior. A method based on ultraperformance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) was developed and validated for the simultaneous quantification of 15 eCBs and related compounds, including both fatty acid amides and glycerols. Linearity (0.9845 < R-2 < 1), limit of detection and quantification (0.52-293 pg on column), inter- and intraday accuracy (>70%) and precision (CV < 15%), stability, and recovery (in milk and plasma) were established in accordance to the U.S. Food and Drug Administration guidelines. The method was successfully applied to bovine and elk milk revealing species-specific eCB profiles, with significant different levels of 2-AG, 2-linoleoyl glycerol, docosahexaenoyl ethanolamide, palmitoyl ethanolamide, and oleoyl ethanolamide. Furthermore, stearoyl ethanolamide and docosatetraenoyl ethanolamide were only detected in elk milk. In summary, our UPLC-ESI-MS/MS method may be used for quantification of eCBs and related compounds in different biofluids and applied to investigations of the role of these emerging compounds in various physiological processes.

  • 10. Gustafsson, Magnus
    et al.
    Hirschberg, Daniel
    Palmberg, Carina
    Jörnvall, Hans
    Bergman, Tomas
    Integrated sample preparation and MALDI mass spectrometry on a microfluidic compact disk.2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 2Article in journal (Refereed)
    Abstract [en]

    High-throughput microfluidic processing of protein digests integrated with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry on a compact disk (CD) is described. Centrifugal force moves liquid through multiple microstructures, each containing a 10-nL reversed-phase chromatography column. The CD enables parallel preparation of 96 samples with volumes ranging from one to several microliters. The peptides in the digests are concentrated, desalted, and subsequently eluted from the columns directly into MALDI target areas (200 x 400 microm) on the CD using a solvent containing the MALDI matrix. After crystallization, the CD is inserted into the MALDI instrument for peptide mass fingerprinting and database identification at a routine sensitivity down to the 200-amol level. Detection of proteolytic peptides down to the 50-amol level is demonstrated. The success rate of the CD technology in protein identification is about twice that of the C(18) ZipTips and standard MALDI steel targets. The CDs are operated using robotics to transfer samples and reagents from microcontainers to the processing inlets on the disposable CD and spinning to control the movement of liquid through the microstructures.

  • 11.
    Hemström, Petrus
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Szumski, Michal
    Umeå University, Faculty of Science and Technology, Chemistry.
    Irgum, Knut
    Umeå University, Faculty of Science and Technology, Chemistry.
    Atom-transfer radical graft polymerization initiated directly from silica applied to functionalization of stationary phases for high-performance liquid chromatography in the hydrophilic interaction chromatography mode.2006In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 78, no 20, p. 7098-7103Article in journal (Refereed)
    Abstract [en]

    Initiation of atom-transfer radical polymerization of a number of monomers (styrene, methyl acrylate, 3-[N,N-dimethyl-N-(methacryloyloxyethyl)ammonium] propanesulfonate, butyl methacrylate, 2,3-epoxypropyl methacrylate) directly from chlorinated porous silica particles has been performed. The grafting has been confirmed and evaluated by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. This initiation technique results in a hydrolytically stable initial Si-C bond, tethering the polymer to the silica substrate. The resulting grafted particles have been used as separation materials for both reversed-phase and hydrophilic interaction chromatography.

  • 12. Hirschberg, Daniel
    et al.
    Jägerbrink, Theres
    Samskog, Jenny
    Gustafsson, Magnus
    Ståhlberg, Marie
    Alvelius, Gunvor
    Husman, Bolette
    Carlquist, Mats
    Jörnvall, Hans
    Bergman, Tomas
    Detection of phosphorylated peptides in proteomic analyses using microfluidic compact disk technology.2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 19Article in journal (Refereed)
    Abstract [en]

    A compact disk (CD)-based microfluidic method for selective detection of phosphopeptides by mass spectrometry is described. It combines immobilized metal affinity chromatography (IMAC) and enzymatic dephosphorylation. Phosphoproteins are digested with trypsin and processed on the CD using nanoliter scale IMAC with and without subsequent in situ alkaline phosphatase treatment. This is followed by on-CD matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Dephosphorylation of the IMAC-enriched peptides allows selective phosphopeptide detection based on the differential mass maps generated (mass shifts of 80 Da or multiples of 80 Da). The CD contains 96 microstructures, each with a 16 nL IMAC microfluidic column. Movement of liquid is controlled by differential spinning of the disk. Up to 48 samples are distributed onto the CD in two equal sets. One set is for phosphopeptide enrichment only, the other for identical phosphopeptide enrichment but combined with in situ dephosphorylation. Peptides are eluted from the columns directly into MALDI target areas, still on the CD, using a solvent containing the MALDI matrix. After crystallization, the CD is inserted into a MALDI mass spectrometer for analysis down to the femtomole level. The average success rate in phosphopeptide detection is over 90%. Applied to noncharacterized samples, the method identified two novel phosphorylation sites, Thr 735 and Ser 737, in the ligand-binding domain of the human mineralocorticoid receptor.

  • 13.
    Jiang, Wen
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Irgum, Knut
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Synthesis and Evaluation of Polymer-Based Zwitterionic Stationary Phases for Separation of Ionic Species2001In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 73, no 9, p. 1993-2003Article in journal (Refereed)
    Abstract [en]

    Three different zwitterionic functional stationary phases for chromatography were synthesized on the basis of 2-hydroxyethyl methacrylate (HEMA) polymeric particles. Two synthesis routes, producing materials designated S300-ECH-DMA-PS or S300-TC-DMA-PS, involved activation of the hydroxyl groups of the HEMA material with epichlorohydrin or thionyl chloride, respectively, followed by dimethylamination and quaternizing 3-sulfopropylation with 1,3-propane sultone. The third route was accomplished by attaching methacrylate moieties to the HEMA through a reaction with methacrylic anhydride, followed by graft photopolymerization of the zwitterionic monomer 3-[N,N-dimethyl-N-(methacryloyloxyethyl)ammonium] propanesulfonate, initiated by benzoin methyl ether under 365-nm light. According to elemental analyses, both the S300-ECH-DMA-PS and S300-TC-DMA-PS materials appeared to have overall charge stoichometries close to unity, whereas the grafted material, S300-MAA-SPE, seemed to carry an excess of anion exchange sites in addition to the zwitterionic groups. Yet all three zwitterionic stationary phases were capable of separating inorganic anions and cations simultaneously and independently using aqueous solutions of perchloric acid or perchlorate salts as eluent, albeit with markedly different selectivities. On the S300-TC-DMA-PS and S300-MAA-SPE materials, the retention times increased for cations and decreased for anions with increasing eluent concentration, whereas with the S300-ECH-DMA-PS material, the retention times of both anions and cations decreased with increasing eluent concentration. These results demonstrate the importance of choosing appropriate synthesis conditions in order to prepare covalently bonded zwitterionic separation materials with an acceptable charge balance.

  • 14.
    Jonsson, Pär
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gullberg, Jonas
    Nordström, Anders
    Kusano, Miyako
    Kowalczyk, Mauriusz
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Moritz, Thomas
    A strategy for identifying differences in large series of metabolomic samples analyzed by GC/MS2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 6, p. 1738-1745Article in journal (Refereed)
    Abstract [en]

    In metabolomics, the purpose is to identify and quantify all the metabolites in a biological system. Combined gas chromatography and mass spectrometry (GC/MS) is one of the most commonly used techniques in metabolomics together with 1H NMR, and it has been shown that more than 300 compounds can be distinguished with GC/MS after deconvolution of overlapping peaks. To avoid having to deconvolute all analyzed samples prior to multivariate analysis of the data, we have developed a strategy for rapid comparison of nonprocessed MS data files. The method includes baseline correction, alignment, time window determinations, alternating regression, PLS-DA, and identification of retention time windows in the chromatograms that explain the differences between the samples. Use of alternating regression also gives interpretable loadings, which retain the information provided by m/z values that vary between the samples in each retention time window. The method has been applied to plant extracts derived from leaves of different developmental stages and plants subjected to small changes in day length. The data show that the new method can detect differences between the samples and that it gives results comparable to those obtained when deconvolution is applied prior to the multivariate analysis. We suggest that this method can be used for rapid comparison of large sets of GC/MS data, thereby applying time-consuming deconvolution only to parts of the chromatograms that contribute to explain the differences between the samples.

  • 15.
    Jonsson, Pär
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Johansson, Annika I.
    Gullberg, Jonas
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jiye, A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Grung, Björn
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    High-throughput data analysis for detecting and identifying differences between samples in GC/MS-based metabolomic analyses2005In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 77, no 17, p. 5635-5642Article in journal (Refereed)
    Abstract [en]

    In metabolomics, the objective is to identify differences in metabolite profiles between samples. A widely used tool in metabolomics investigations is gas chromatography-mass spectrometry (GC/MS). More than 400 compounds can be detected in a single analysis, if overlapping GC/ MS peaks are deconvoluted. However, the deconvolution process is time-consuming and difficult to automate, and additional processing is needed in order to compare samples. Therefore, there is a need to improve and automate the data processing strategy for data generated in GC/MS-based metabolomics; if not, the processing step will be a major bottleneck for high-throughput analyses. Here we describe a new semiautomated strategy using a hierarchical multivariate curve resolution approach that processes all samples simultaneously. The presented strategy generates (after appropriate treatment, e.g., multivariate analysis) tables of all the detected metabolites that differ in relative concentrations between samples. The processing of 70 samples took similar time to that of the GC/TOFMS analyses of the samples. The strategy has been validated using two different sets of samples: a complex mixture of standard compounds and Arabidopsis samples.

    KeyWords Plus: CHROMATOGRAPHY MASS-SPECTROMETRY; PRINCIPAL COMPONENT ANALYSIS; SYSTEMS BIOLOGY; ARABIDOPSIS-THALIANA; CHEMOMETRIC ANALYSIS; 2-WAY DATA; MS; REGRESSION; RESOLUTION; ALIGNMENT

  • 16. Kirwan, Gemma M
    et al.
    Johansson, Erik
    Kleemann, Robert
    Verheij, Elwin R
    Wheelock, Asa M
    Goto, Susumu
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wheelock, Craig E
    Building Multivariate Systems Biology Models2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 16, p. 7064-7071Article in journal (Refereed)
    Abstract [en]

    Systems biology methods using large-scale "omics" data sets face unique challenges: integrating and analyzing near limitless data space, while recognizing and removing systematic variation or noise. Herein we propose a complementary multivariate analysis workflow to both integrate "omics" data from disparate sources and analyze the results for specific and unique sample correlations. This workflow combines principal component analysis (PCA), orthogonal projections to latent structures discriminate analysis (OPLS-DA), orthogonal 2 projections to latent structures (O2PLS), and shared and unique structures (SUS) plots. The workflow is demonstrated using data from a study in which ApoE3Leiden mice were fed an atherogenic diet consisting of increasing cholesterol levels followed by therapeutic intervention (fenofibrate, rosuvastatin, and LXR activator T-0901317). The levels of structural lipids (lipidomics) and free fatty acids in liver were quantified via liquid chromatography-mass spectrometry (LC-MS). The complementary workflow identified diglycerides as key hepatic metabolites affected by dietary cholesterol and drug intervention. Modeling of the three therapeutics for mice fed a high-cholesterol diet further highlighted diglycerides as metabolites of interest in atherogenesis, suggesting a role in eliciting chronic liver inflammation. In particular, O2PLS-based SUS2 plots showed that treatment with T-0901317 or rosuvastatin returned the diglyceride profile in high-cholesterol-fed mice to that of control animals.

  • 17.
    Larsson, Tom
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Frech, Wolfgang
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Species-specific isotope dilution with permeation tubes for determination of gaseous mercury species2003In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 75, no 20, p. 5584-5591Article in journal (Refereed)
    Abstract [en]

    Instrumentation and methodology for determination of the gaseous mercury species Hg0, (CH3)2Hg, and CH3Hg+ has been developed. The method is based on continuous addition of gaseous isotopically enriched Hg species (tracers) at the point of sample acquisition, in combination with reduced pressure sampling on Carbotrap adsorbent tubes. Permeation tubes are used for generation of the tracers. Collected species are thermally desorbed and purged through an aqueous sodium tetraethylborate solution for derivatization of CH3Hg+. The purged gas is dried with a Nafion membrane, and the Hg species are subsequently collected on a smaller Tenax TA adsorbent tube. Species are then thermally desorbed from the Tenax TA and introduced into a gas chromatograph connected to an inductively coupled plasma mass spectrometer for separation and detection. To be able to add tracers during field sampling, we developed a portable device, supplying the permeation tubes with a thermostated and mass flow-controlled air stream of 5.0 ± 0.1 C and 50.0 mL min-1, respectively. Typical permeation rates obtained during a period of more than 6 weeks were 12.93 ± 0.56, 0.42 ± 0.01, and 0.49 ± 0.03 (mean ± standard deviation) pg of Hg min-1 for a set of 199Hg0, (CH3)2198Hg, and CH3200Hg+ tubes, respectively. Methodological detection limits (3) were determined to 700 pg of Hg m-3 for Hg0 and 50 pg of Hg m-3 for (CH3)2Hg and CH3Hg+. The collection efficiencies for sampled volumes of 400 L of synthetic air on the Carbotrap tubes used in this study were 13 ± 2, 102 ± 2, and 99 ± 4% for Hg0, (CH3)2Hg, and CH3Hg+, respectively. Desorption efficiencies for the above species and tubes were 98 ± 2, 98 ± 1, and 90 ± 4%, respectively. Fractions (20-40%) of the added (CH3)2198Hg and CH3200Hg+ tracers were found to be transformed during the analytical processing of collected air samples. Determined concentrations in the research laboratory air, corrected for species transformations, were 3-53, 8-11, and 1-2 ng of Hg m-3 for Hg0, (CH3)2Hg, and CH3Hg+, respectively. Concentrations in the ambient air were determined to be 2.1-2.6 ng m-3 for Hg0 and below the detection limit for (CH3)2Hg and CH3Hg+.

  • 18.
    Larsson, William
    et al.
    Umeå University, Faculty of Science and Technology, Chemistry.
    Jalbert, Jocelyn
    Gilbert, Roland
    Cedergren, Anders
    Umeå University, Faculty of Science and Technology, Chemistry.
    Efficiency of methods for Karl Fischer determination of water in oils based on oven evaporation and azeotropic distillation2003In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 75, no 6, p. 1227-32Article in journal (Refereed)
    Abstract [en]

    The efficiency of azeotropic distillation and oven evaporation techniques for trace determination of water in oils has recently been questioned by the National Institute of Standards and Technology (NIST), on the basis of measurements of the residual water found after the extraction step. The results were obtained by volumetric Karl Fischer (KF) titration in a medium containing a large excess of chloroform (> or = 65%), a proposed prerequisite to ensure complete release of water from the oil matrix. In this work, the extent of this residual water was studied by means of a direct zero-current potentiometric technique using a KF medium containing more than 80% chloroform, which is well above the concentration recommended by NIST. A procedure is described that makes it possible to correct the results for dilution errors as well as for chemical interference effects caused by the oil matrix. The corrected values were found to be in the range of 0.6-1.5 ppm, which should be compared with the 12-34 ppm (uncorrected values) reported by NIST for the same oils. From this, it is concluded that the volumetric KF method used by NIST gives results that are much too high.

  • 19.
    Liem-Nguyen, Van
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bouchet, Sylvain
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Björn, Erik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Determination of Sub-Nanomolar Levels of Low Molecular Mass Thiols in Natural Waters by Liquid Chromatography Tandem Mass Spectrometry after Derivatization with p‑(Hydroxymercuri) Benzoate and Online Preconcentration2015In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 2, p. 1089-1096Article in journal (Refereed)
    Abstract [en]

    Low molecular mass (LMM) thiols is a diverse group of compounds, which play several important roles in aquatic ecosystems, even though they typically occur at low concentrations. Comprehensive studies of LMM thiols in natural waters have so far been hampered by selectivity and limit of detection constraints of previous analytical methods. Here, we describe a selective and robust method for the quantification of 16 LMM thiols in natural waters. Thiols were derivatized with 4-(hydroxymercuri)benzoate (PHMB) and preconcentrated online by solid-phase extraction (SPE) before separation by liquid chromatography and determination by electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Their quantification was performed by selective reaction monitoring (SRM), while the presence of a product ion atm/z 355, specific for thiols and common for the investigated compounds, also allows to screen samples for unknown thiols by a precursor ion scan approach. The robustness of the method was validated for aqueous matrices with different pH, sulfide, and dissolved organic carbon (DOC) concentrations. The limits of detection for the thiols were in the sub-nanomolar range (0.06–0.5 nM) and the methodology allowed determination of both reduced and total thiol concentrations (using tris(2-carboxyethyl)phosphine (TCEP) as reducing agent). Six thiols (mercaptoacetic acid, cysteine, homocysteine, N-acetyl-cysteine, mercaptoethane-sulfonate, and glutathione) were detected with total concentrations of 7–153 nM in boreal lake or wetland pore waters while four thiols (mercaptoacetic acid, cysteine, homocysteine, and N-acetyl-cysteine) were detected in their reduced form at concentrations of 5–80 nM.

  • 20. Lindahl, Anna
    et al.
    Saaf, Siv
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Lehtio, Janne
    Nordström, Anders
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Karolinska Inst, Sci Life Lab, Dept Oncol Pathol, Stockholm, Sweden.
    Tuning Metabolome Coverage in Reversed Phase LC-MS Metabolomics of MeOH Extracted Samples Using the Reconstitution Solvent Composition2017In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 89, no 14, p. 7356-7364Article in journal (Refereed)
    Abstract [en]

    Considering the physicochemical diversity of the metabolome, untargeted metabolomics will inevitably discriminate against certain compound classes. Efforts are nevertheless made to maximize the metabolome coverage. Contrary to the main steps of a typical liquid chromatography-mass spectrometry (LC-MS) metabolomics workflow, such as metabolite extraction, the sample reconstitution step has not been optimized for maximal metabolome coverage. This sample concentration step typically occurs after metabolite extraction, when dried samples are reconstituted in a solvent for injection on column. The aim of this study was to evaluate the impact of the sample reconstitution solvent composition on metabolome coverage in untargeted LCMS metabolomics. Lysogeny Broth medium samples reconstituted in MeOH/H2O ratios ranging from 0 to 100% MeOH and analyzed with untargeted reversed phase LC-MS showed that the highest number of metabolite features (n = 1500) was detected in samples reconstituted in 100% H2O. As compared to a commonly used reconstitution solvent mixture of 50/50 MeOH/H2O, our results indicate that the small fraction of compounds increasing in peak area response by the addition of MeOH to H2O, 5%, is outweighed by the fraction of compounds with decreased response, 57%. We evaluated our results on human serum samples from lymphoma patients and healthy control subjects. Reconstitution in 100% H2O resulted in a higher number of significant metabolites discriminating between these two groups than both 50% and 100% MeOH. These findings show that the sample reconstitution step has a clear impact on the metabolome coverage of MeOH extracted biological samples, highlighting the importance of the reconstitution solvent composition for untargeted discovery metabolomics.

  • 21.
    Liu, Mingquan
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Torsetnes, Silje Bøen
    Wierzbicka, Celina
    Jensen, Ole Nørregaard
    Sellergren, Börje
    Irgum, Knut
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Selective Enrichment of Phosphorylated Peptides by Monolithic Polymers Surface Imprinted with bis-Imidazolium Moieties by UV-Initiated Cryopolymerization2019In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 91, no 15, p. 10188-10196Article in journal (Refereed)
    Abstract [en]

    Reversible protein phosphorylation on serine, threonine, and tyrosine residues is essential for fast, specific, and accurate signal transduction in cells. Up to now, the identification and quantification of phosphorylated amino acids, peptides, and proteins continue to be one of the significant challenges in contemporary bioanalytical research. In this paper, a series of surface grafted monoliths in the capillary format targeting phosphorylated serine has been prepared by first synthesizing a monolithic core substrate material based on trimethylolpropane trimethacrylate, onto which a thin surface-imprinted layer was established by oriented photografting of a variety of mono- and bis-imidazolium host monomers at subzero temperature, using six different continuous or pulsed UV light sources. The imprinted monolith capillaries were evaluated in a capillary liquid chromatographic system connected to a mass spectrometer in order to test the specific retention of phosphorylated peptides. Site-specific recognition selectivity and specificity for phosphorylated serine was demonstrated when separating amino acids and peptides, proving that the optimized materials could be used as novel trapping media in affinity-based phosphoproteomic analysis.

  • 22.
    Liu, Mingquan
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Tran, Tri Minh
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Elhaj, Ahmed Awad Abbas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Torsetnes, Silje Boen
    Jensen, Ole N.
    Sellergren, Borje
    Irgum, Knut
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Molecularly Imprinted Porous Monolithic Materials from Melamine-Formaldehyde for Selective Trapping of Phosphopeptides2017In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 89, no 17, p. 9491-9501Article in journal (Refereed)
    Abstract [en]

    Thirty-five melamine formaldehyde (MF) monolithic materials with bimodal pore distributions were synthesized in fused silica capillaries by catalyst-free polycondensation, starting with an aqueous MF precondensate, using acetonitrile as the macroporogen and a variety of aliphatic polyethers and triblock copolymeric surfactants as porogens and mesoporogens, respectively. By varying the prepolymer composition and the type and molecular weight of the polymeric porogen components, a library of porous monolithic materials was produced, covering a range of meso- and macroporous properties. A multivariate evaluation revealed that the amount of surfactant was the strongest contributor to specific surface area and pore volume and to the inversely related mesopore size, whereas the macropore dimensions were controlled mainly by the amount of aliphatic polyether porogen. One of these capillary monoliths, chosen based on the combination of meso- and macropores providing optimal percolative flow and accessible surface area, was synthesized in the presence of N-Fmoc and O-Et protected phosphoserine and phosphotyrosine to prepare molecularly imprinted monoliths with surface layers selective for phosphopeptides. These imprinted monoliths were characterized alongside nonimprinted monoliths by a variety of techniques and finally evaluated by liquid chromatography mass spectrometry in the capillary format to assess their abilities to trap and release phosphorylated amino acids and peptides from partly aqueous media. Selective enrichment of phosphorylated targets was demonstrated, suggesting that these materials could be useful as trapping media in-affinity-based phosphoproteomics.

  • 23.
    Nordmark, Ulrika
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Cedergren, Anders
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Conditions for Accurate Karl Fischer Coulometry Using Diaphragm-Free Cells2000In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 72, no 1, p. 172-179Article in journal (Refereed)
    Abstract [en]

    Factors influencing the extent of formation of oxidizable reduction products in coulometric cells used for Karl Fischer (KF) determination of water were investigated. For methanolic KF reagents buffered with imidazole (Im) or diethanolamine (DEA) (separately or in combination), three parameters were found to be of outmost importance: the cathodic current density, the pH, and the concentration of protonated base (ImH+ or DEAH+). For reagents buffered with only Im, the relative formation of oxidizable reduction products varied in the range 2-40%; i.e., 51-70 g of water was found for a 50 g water sample, depending on the above-mentioned parameters. The lowest values were observed for reagents having a pH around 10 in combination with cathodic current densities in the range 2000-5000 mA cm-2. For all the Im-buffered reagents investigated, the addition of modifiers such as chloroform, hexanol, and carbon tetrachloride was found to decrease the formation of oxidizable reduction products significantly. For example, a reagent buffered at pH 10 containing 1 M hexanol gave less than 0.3% formation in the current density interval from 200 to 4000 mA cm-2. The best reagents based on the above-mentioned modifiers were tested in the continuous coulometric mode with errors typically in the interval 0-0.5% using optimum conditions. One prerequisite for obtaining such small errors with diaphragm-free continuous coulometry is to use a cathode area no larger than 0.002 cm2. For some of the reagents based on both Im and DEA, the formation of oxidizable reduction products was close to zero at certain current densities, although the analytical performance was not as good as for the reagents buffered solely by Im due to longer conditioning and titration times.

  • 24.
    Nordström, Anders
    et al.
    Department of Molecular Biology, The Scripps Center for Mass Spectrometry, The Scripps Research Institute.
    Apon, Junefredo V
    Uritboonthai, Wilasinee
    Go, Eden P
    Siuzdak, Gary
    Surfactant-enhanced desorption/ionization on silicon mass spectrometry.2006In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 78, no 1, p. 272-8Article in journal (Refereed)
    Abstract [en]

    Perfluorinated surfactants are demonstrated to dramatically enhance desorption/ionization on fluorinated silicon (DIOS) mass spectrometry. Perfluorooctanesulfonic acid improved the signal-to-noise ratio of tryptic digests and gave a 3-fold increase in the number of peptides identified. Similar results were also obtained using perfluoroundecanoic acid; yet among the seven different surfactants tested, controls such as nonfluorinated sodium dodecyl sulfate or fluorinated molecules with minimal surfactant activity did not enhance the signal. The same surfactants also enhanced the DIOS-MS signal of amino acids, carbohydrates, and other small organic compounds. The signal enhancement may be facilitated by the high surface activity of the perfluorinated surfactants on the fluorinated silicon surfaces allowing for a higher concentration of analyte to be absorbed.

  • 25.
    Nordström, Anders
    et al.
    Department of Molecular Biology, Scripps Center for Mass Spectrometry, The Scripps Research Institute.
    O'Maille, Grace
    Qin, Chuan
    Siuzdak, Gary
    Nonlinear data alignment for UPLC-MS and HPLC-MS based metabolomics: quantitative analysis of endogenous and exogenous metabolites in human serum.2006In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 78, no 10, p. 3289-95Article in journal (Refereed)
    Abstract [en]

    A nonlinear alignment strategy was examined for the quantitative analysis of serum metabolites. Two small-molecule mixtures with a difference in relative concentration of 20-100% for 10 of the compounds were added to human serum. The metabolomics protocol using UPLC and XCMS for LC-MS data alignment could readily identify 8 of 10 spiked differences among more than 2700 features detected. Normalization of data against a single factor obtained through averaging the XCMS integrated response areas of spiked standards increased the number of identified differences. The original data structure was well preserved using XCMS, but reintegration of identified differences in the original data reduced the number of false positives. Using UPLC for separation resulted in 20% more detected components compared to HPLC. The length of the chromatographic separation also proved to be a crucial parameter for a number of detected features. Moreover, UPLC displayed better retention time reproducibility and signal-to-noise ratios for spiked compounds over HPLC, making this technology more suitable for nontargeted metabolomics applications.

  • 26.
    Nordström, Anders
    et al.
    Swedish University of Agricultural Sciences.
    Tarkowski, Petr
    Tarkowska, Danuse
    Dolezal, Karel
    Astot, Crister
    Sandberg, Göran
    Moritz, Thomas
    Derivatization for LC-electrospray ionization-MS: a tool for improving reversed-phase separation and ESI responses of bases, ribosides, and intact nucleotides.2004In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 10, p. 2869-77Article in journal (Refereed)
    Abstract [en]

    We have developed a method for analyzing polar compounds by reversed-phase LC-ESI-MS following esterification of the analytes' free hydroxyl groups with propionyl or benzoyl acid anhydride. The method was applied to members of the plant hormone group cytokinins, which includes adenine bases, ribosides/glycosides, and nucleotides substituted at N-6 with an isoprenoid side chain, spanning a wide range of polarity. It was also used to analyze other compounds of biological importance, e.g., the nucleotides AMP, ADP, and ATP. The formation of more hydrophobic derivatives had a significant impact on two aspects of the analysis. The retention on a reversed-phase material was greatly increased without the use of any acetate/formate buffer or ion pairing reagent, and the ESI response was enhanced, due to the higher surface activities of the derivatives. Detection limits of propionylated cytokinins were in the high-attomole to low-femtomole range, an improvement by factors of 10-100 compared to previously reported figures. Using an automated SPE-based purification method, 12 endogenous cytokinins were quantified in extracts from 20- to 100-mg samples of leaves (from the plant Arabidopsis thaliana) with high accuracy and precision. Furthermore, the chromatographic properties of the benzoylated AMP, ADP, and ATP in the reversed-phase LC-MS system were much better in terms of retention, separation, and sensitivity than those of their underivatized counterparts, even without the use of any ion pairing reagent. Our data show that derivatization followed by LC-ESI-MS is an effective strategy for analyzing low molecular weight compounds, enabling compounds with a wide range of polarity to be determined in a single-injection LC-MS analysis.

  • 27.
    Nordström, Anders
    et al.
    The Scripps Research Institute; Karolinska Institutet and Karolinska University Hospital.
    Want, Elizabeth
    Northen, Trent
    Lehtiö, Janne
    Siuzdak, Gary
    Multiple ionization mass spectrometry strategy used to reveal the complexity of metabolomics.2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 2, p. 421-9Article in journal (Refereed)
    Abstract [en]

    A multiple ionization mass spectrometry strategy is presented based on the analysis of human serum extracts. Chromatographic separation was interfaced inline with the atmospheric pressure ionization techniques electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) in both positive (+) and negative (-) ionization modes. Furthermore, surface-based matrix-assisted laser desorption/ionization (MALDI) and desorption ionization on silicon (DIOS) mass spectrometry were also integrated with the separation through fraction collection and offline mass spectrometry. Processing of raw data using the XCMS software resulted in time-aligned ion features, which are defined as a unique m/z at a unique retention time. The ion feature lists obtained through LC-MS with ESI and APCI interfaces in both +/- ionization modes were compared, and unique ion tables were generated. Nonredundant, unique ion features, were defined as mass numbers for which no mass numbers corresponding to [M + H](+), [M - H](-), or [M + Na](+) were observed in the other ionization methods at the same retention time. Analysis of the extracted serum using ESI for both (+) and (-) ions resulted in >90% additional unique ions being detected in the (-) ESI mode. Complementing the ESI analysis with APCI resulted in an additional approximately 20% increase in unique ions. Finally, ESI/APCI ionization was combined with fraction collection and offline-MALDI and DIOS mass spectrometry. The parts of the total ion current chromatograms in the LC-MS acquired data corresponding to collected fractions were summed, and m/z lists were compiled and compared to the m/z lists obtained from the DIOS/MALDI spectra. It was observed that, for each fraction, DIOS accounted for approximately 50% of the unique ions detected. These results suggest that true global metabolomics will require multiple ionization technologies to address the inherent metabolite diversity and therefore the complexity in and of metabolomics studies.

  • 28.
    Ohlsson, K. E. Anders
    Department of Forest Ecology and Management, Swedish University of Agricultural Sciences, SE-90183 Umeå , Sweden.
    Uncertainty of Blank Correction in Isotope Ratio Measurement2013In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 85, no 11, p. 5326-5329Article in journal (Refereed)
    Abstract [en]

    Blank correction for isotope ratio measurement on small amounts of substances is often limited by presence of a blank, with an apparent isotopic composition different from that of the sample. For isotope ratios, blank correction is commonly performed either by the regression method, which works without the need for estimation of the blank, or by the subtraction method. With the subtraction method, estimation of the amount and isotope delta of the blank is required, and these estimates could be obtained either by direct, semi-indirect, or indirect measurement. Previously given expressions for the standard uncertainties of indirectly measured blank amounts and blank isotope deltas did not account for covariance between input quantities. In the present work, a previously published data set was re-evaluated, with covariance terms properly included in the calculation of uncertainties. It was shown that covariance effects may yield a significant reduction in uncertainty estimates, both for blank quantities and for blank corrected results. For series measurements on a standard material, it was also shown that the distribution of individual corrected isotope delta values around the average value was approximately normal, with its standard deviation equal to the estimated standard uncertainty of the corrected values. In most cases, it was observed that the regression and subtraction methods yield approximately the same blank corrected average values and uncertainties, regardless of method selected for estimation of blank quantities.

  • 29.
    Pinto, Rui Climaco
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gerber, Lorenz
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Eliasson, Mattias
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sundberg, Björn
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Strategy for minimizing between-study variation of large-scale phenotypic experiments using multivariate analysis2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 20, p. 8675-8681Article in journal (Refereed)
    Abstract [en]

    We have developed a multistep strategy that integrates data from several large-scale experiments that suffer from systematic between-experiment variation. This strategy removes such variation that would otherwise mask differences of interest. It was applied to the evaluation of wood chemical analysis of 736 hybrid aspen trees: wild-type controls and transgenic trees potentially involved in wood formation. The trees were grown in four different greenhouse experiments imposing significant variation between experiments. Pyrolysis coupled to gas chromatography/mass spectrometry (Py-GC/MS) was used as a high throughput-screening platform for fingerprinting of wood chemotype. Our proposed strategy includes quality control, outlier detection, gene specific classification, and consensus analysis. The orthogonal projections to latent structures discriminant analysis (OPLS-DA) method was used to generate the consensus chemotype profiles for each transgenic line. These were thereafter compiled to generate a global dataset. Multivariate analysis and cluster analysis techniques revealed a drastic reduction in between-experiment variation that enabled a global analysis of all transgenic lines from the four independent experiments. Information from in-depth analysis of specific transgenic lines and independent peak identification validated our proposed strategy.

  • 30.
    Qu, Zhechao
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Steinvall, Erik
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Ghorbani, Ramin
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Schmidt, Florian M.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Tunable Diode Laser Atomic Absorption Spectroscopy for Detection of Potassium under Optically Thick Conditions2016In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 88, no 7, p. 3754-3760Article in journal (Refereed)
    Abstract [en]

    Potassium (K) is an important element related to ash and fine-particle formation in biomass combustion processes. In situ measurements of gaseous atomic potassium, K(g), using robust optical absorption techniques can provide valuable insight into the K chemistry. However, for typical parts per billion K(g) concentrations in biomass flames and reactor gases, the product of atomic line strength and absorption path length can give rise to such high absorbance that the sample becomes opaque around the transition line center. We present a tunable diode laser atomic absorption spectroscopy (TDLAAS) methodology that enables accurate, calibration-free species quantification even under optically thick conditions, given that Beer−Lambert’s law is valid. Analyte concentration and collisional line shape broadening are simultaneously determined by a least-squares fit of simulated to measured absorption profiles. Method validation measurements of K(g) concentrations in saturated potassium hydroxide vapor in the temperature range 950−1200 K showed excellent agreement with equilibrium calculations, and a dynamic range from 40 pptv cm to 40 ppmv cm. The applicability of the compact TDLAAS sensor is demonstrated by real-time detection of K(g) concentrations close to biomass pellets during atmospheric combustion in a laboratory reactor. 

  • 31. Redestig, Henning
    et al.
    Fukushima, Atsushi
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Moritz, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Masanori, Arita
    Saito, Kazuki
    Kusano, Miyako
    Compensation for systematic cross-contribution improves normalization of mass spectrometry based metabolomics data2009In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 81, no 19, p. 7974-7980Article in journal (Refereed)
    Abstract [en]

    Most mass spectrometry based metabolomics studies are semiquantitative and depend on efficient normalization techniques to suppress systematic error. A common approach is to include isotope-labeled internal standards (ISs) and then express the estimated metabolite abundances relative to the IS. Because of problems such as insufficient chromatographic resolution, however, the analytes may directly influence estimates of the IS, a phenomenon known as cross-contribution (CC). Normalization using ISs that suffer from CC effects will cause significant loss of information if the interfering analytes are associated with the studied factors. We present a novel normalization algorithm, which compensates for systematic CC effects that can be traced back to a linear association with the experimental design. The proposed method was found to be superior at purifying the signal of interest compared to current normalization methods when applied to two biological data sets and a multicomponent dilution mixture. Our method is applicable to data from randomized and designed experiments that use ISs to monitor the systematic error.

  • 32. Reichel, Annett
    et al.
    Schaible, Dirk
    Al Furoukh, Natalie
    Institute of Biochemistry, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
    Cohen, Mati
    Schreiber, Gideon
    Piehler, Jacob
    Noncovalent, site-specific biotinylation of histidine-tagged proteins.2007In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 79, no 22Article in journal (Refereed)
    Abstract [en]

    Site-specific conjugation of proteins to surfaces, spectroscopic probes, or other functional units is a key task for implementing biochemical assays. The streptavidin-biotin interaction has proven a highly versatile tool for detection, quantification, and functional analysis of proteins. We have developed an approach for site-specific reversible biotinylation of recombinant proteins through their histidine tag using biotin conjugated to the multivalent chelator trisnitrilotriacetic acid (BTtris-NTA). Stable binding of BTtris-NTA to His-tagged proteins was demonstrated, which is readily reversed by addition of imidazole, enabling versatile conjugation schemes in solution as well as at interfaces. Gel filtration experiments revealed that His-tagged proteins bind to streptavidin doped with BTtris-NTA in a 2:1 stoichiometry. Furthermore, an increased binding affinity toward His-tagged proteins was observed for BTtris-NTA linked to streptavidin compared to tris-NTA in solution and on surfaces. These results indicate an efficient cooperative interaction of two adjacent tris-NTA moieties with a single His-tag, yielding an extremely tight complex with a lifetime of several days. We demonstrate several applications of BTtris-NTA including multiplexed capturing of proteins to biosensor surfaces, cell surface labeling, and Western blot detection. The remarkable selectivity of the His-tag-specific biotinylation, as well as the highly stable, yet reversible complex provides the basis for numerous further applications for functional protein analysis.

  • 33. Reinke, Stacey N.
    et al.
    Galindo-Prieto, Beatriz
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Skotare, Tomas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Broadhurst, David I.
    Singhania, Akul
    Horowitz, Daniel
    Djukanovic, Ratko
    Hinks, Timothy S. C.
    Geladi, Paul
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wheelock, Craig E.
    OnPLS-Based Multi-Block Data Integration: A Multivariate Approach to Interrogating Biological Interactions in Asthma2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 22, p. 13400-13408Article in journal (Refereed)
    Abstract [en]

    Integration of multiomics data remains a key challenge in fulfilling the potential of comprehensive systems biology. Multiple-block orthogonal projections to latent structures (OnPLS) is a Multi projection method that simultaneously models multiple data matrices, reducing feature space without relying on a priori biological knowledge. In order to improve the interpretability of OnPLS models, the associated multi-block variable influence on orthogonal projections (MB-VIOP) method is used to identify variables with the highest contribution to the model. This study combined OnPLS and MB-VIOP with interactive visualization methods to interrogate an exemplar multiomics study, using a subset of 22 individuals from an asthma cohort. Joint data structure in six data blocks was assessed: transcriptomics; metabolomics; targeted assays for sphingolipids, oxylipins, and fatty acids; and a clinical block including lung function, immune cell differentials, and cytokines. The model identified seven components, two of which had contributions from all blocks (globally joint structure) and five that had contributions from two to five blocks (locally joint structure). Components 1 and 2 were the most informative, identifying differences between healthy controls and asthmatics and a disease sex interaction, respectively. The interactions between features selected by MB-VIOP were visualized using chord plots, yielding putative novel insights into asthma disease pathogenesis, the effects of asthma treatment, and biological roles of uncharacterized genes. For example, the gene ATP6 V1G1, which has been implicated in osteoporosis, correlated with metabolites that are dysregulated by inhaled corticoid steroids (ICS), providing insight into the mechanisms underlying bone density loss in asthma patients taking ICS. These results show the potential for OnPLS, combined with MB-VIOP variable selection and interaction visualization techniques, to generate hypotheses from multiomics studies and inform biology.

  • 34.
    Skotare, Tomas
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nilsson, David
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Xiong, Shaojun
    Geladi, Paul
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Corporate Research, Sartorius AG, 37079 Göttingen, Germany.
    Joint and unique multiblock analysis for integration and calibration transfer of NIR instruments2019In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 91, no 5, p. 3516-3524Article in journal (Refereed)
    Abstract [en]

    In the present paper, we introduce an end-to-end workflow called joint and unique multiblock analysis (JUMBA), which allows multiple sources of data to be analyzed simultaneously to better understand how they complement each other. In near-infrared (NIR) spectroscopy, calibration models between NIR spectra and responses are used to replace wet-chemistry methods, and the models tend to be instrument-specific. Calibration-transfer techniques are used for standardization of NIR-instrumentation, enabling the use of one model on several instruments. The current paper investigates both the similarities and differences among a variety of NIR instruments using JUMBA. We demonstrate JUMBA on both a previously unpublished data set in which five NIR instruments measured mushroom substrate and a publicly available data set measured on corn samples. We found that NIR spectra from different instrumentation largely shared the same underlying structures, an insight we took advantage of to perform calibration transfer. The proposed JUMBA transfer displayed excellent calibration-transfer performance across the two analyzed data sets and outperformed existing methods in terms of both prediction accuracy and stability. When applied to a multi-instrument environment, JUMBA transfer can integrate all instruments in the same model and will ensure higher consistency among them compared with existing calibration-transfer methods.

  • 35. Spahr, Stephanie
    et al.
    Bolotin, Jakov
    Schleucher, Jürgen
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Ehlers, Ina
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    von Gunten, Urs
    Hofstetter, Thomas B
    Compound-specific carbon, nitrogen, and hydrogen isotope analysis of N-nitrosodimethylamine in aqueous solutions2015In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 5, p. 2916-2924Article in journal (Refereed)
    Abstract [en]

    Mitigation of N-nitrosodimethylamine (NDMA) and other hazardous water disinfection byproducts (DBP) is currently hampered by a limited understanding of DBP formation mechanisms. Because variations of the stable isotope composition of NDMA can potentially reveal reaction pathways and precursor compounds, we developed a method for the compound-specific isotope analysis (CSIA) of (13)C/(12)C, (15)N/(14)N, and (2)H/(1)H ratios of NDMA by gas chromatography coupled to isotope ratio mass spectrometry (GC/IRMS). Method quantification limits for the accurate isotope analysis of NDMA, N-nitrosodiethyl-, -dipropyl-, and -dibutylamine as well as N-nitrosopyrrolidine were between 0.18 to 0.60 nmol C, 0.40 to 0.80 nmol N, and 2.2 to 5.8 nmol H injected on column. Coupling solid phase extraction (SPE) to GC/IRMS enabled the precise quantification of C, N, and H isotope ratios of NDMA in aqueous samples at concentrations of 0.6 μM (45 μg L(-1)). We validated the proposed method with a laboratory experiment, in which NDMA was formed with stoichiometric yield (97 ± 4%) through chloramination of the pharmaceutical ranitidine (3 μM). δ(13)C and δ(2)H values of NDMA remained constant during NDMA formation while its δ(15)N increased due to a reaction at a N atom in the rate-limiting step of NDMA formation. The δ(2)H value of NDMA determined by SPE-GC/IRMS also corresponded well to the δ(2)H value of the N(CH3)2-group of ranitidine measured by quantitative deuterium nuclear magnetic resonance spectroscopy. This observation implies that the N(CH3)2-moiety of ranitidine is transferred to NDMA without being chemically altered and illustrates the accuracy of the proposed method.

  • 36.
    Subramaniam, Raja
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Åstot, Crister
    The Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Juhlin, Lars
    The Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Nilsson, Calle
    The Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Östin, Anders
    The Swedish Defence Research Agency, FOI CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Direct derivatization and rapid GC-MS screening of nerve agent markers in aqueous samples2010In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 82, no 17, p. 7452-7459Article in journal (Refereed)
    Abstract [en]

    A rapid screening and identification method based on derivatization and gas chromatography mass spectrometry (GC-MS) has been developed for the detection of alkylphosphonic acids (APAs), the degradation products of organophosphorus nerve agents. The novel method described involves rapid (5 min) and direct derivatization of 25 muL aqueous sample using highly fluorinated phenyldiazomethane reagents (e.g., 1-(diazomethyl)-3,5-bis(trifluoromethyl)benzene). The APA derivatives are then screened by GC-MS negative ion chemical ionization (NICI) and identified by electron ionization (EI) mode. The conditions for the derivatization were optimized using statistical experimental design and multivariate data analysis. Method robustness was evaluated using aqueous samples from an official OPCW Proficiency Test and all APAs present in the sample were conclusively identified. Limits of detection for rapid screening using SIM NICI were between 5 and 10 ng/mL APA in aqueous sample, and for identification using full scan EI 100 ng/mL.

  • 37.
    Surowiec, Izabella
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Vikström, Ludvig
    Hector, Gustaf
    Johansson, Erik
    Vikström, Conny
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Generalized Subset Designs in Analytical Chemistry2017In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 89, no 12, p. 6491-6497Article in journal (Refereed)
    Abstract [en]

    Design of experiments (DOE) is an established methodology in research, development, manufacturing, and production for screening, optimization, and robustness testing. Two-level fractional factorial designs remain the preferred approach due to high information content while keeping the number of experiments low. These types of designs, however, have never been extended to a generalized multilevel reduced design type that would be capable to include both qualitative and quantitative factors. In this Article we describe a novel generalized fractional factorial design. In addition, it also provides complementary and balanced subdesigns analogous to a fold-over in two-level reduced factorial designs. We demonstrate how this design type can be applied with good results in three different applications in analytical chemistry including (a) multivariate calibration using microwave resonance spectroscopy for the determination of water in tablets, (b) stability study in drug product development, and (c) representative sample selection in clinical studies. This demonstrates the potential of generalized fractional factorial designs to be applied in many other areas of analytical chemistry where representative, balanced, and complementary subsets are required, especially when a combination of quantitative and qualitative factors at multiple levels exists.

  • 38.
    Virel, Ana
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Saa, Laura
    Pavlov, Valeri
    CIC biomaGUNE, Parque Tecnológico de San Sebastián, San Sebastián, Spain.
    Quantification of prothrombin in human plasma amplified by autocatalytic reaction2012In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 84, no 5, p. 2380-2387Article in journal (Refereed)
    Abstract [en]

    By site directed mutagenesis, we have produced recombinant mutants of human and mouse prethrombin-2 which are able to convert themselves autocatalytically into α-thrombin. We also have created a new method to amplify the signal of bioanalytical assays based on the autocatalytic activation of these mutated proenzymes. The activation of the mutants by active α-thrombin triggers an autocatalytic reaction which leads to more active thrombin resulting in the amplification of the readout signal. Addition of mutated mouse prethrombin-2 into the conventional assay for prothrombin level in human plasma, employing ecarin and the fluorogenic substrate, resulted in improvement of the detection limit by 2 orders of magnitude.

  • 39. Wang, Shijun
    et al.
    Milam, Jenifer
    Ohlin, C. Andre
    Rambaran, Varma H.
    Clark, Eva
    Ward, Woodrow
    Seymour, Luke
    Casey, William H.
    Holder, Alvin A.
    Miao, Wujian
    Electrochemical and Electrogenerated Chemiluminescent Studies of a Trinuclear Complex, [((phen)2Ru(dpp))2RhCl2]5+, and Its Interactions with Calf Thymus DNA2009In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 81, no 10, p. 4068-4075Article in journal (Refereed)
    Abstract [en]

    The electrochemical behavior of a trinuclear ruthenium(II)-containing complex, [((phen)2Ru(dpp))2RhCl2]5+ (where phen = 1,10-phenanthroline, dpp = 2,3-bis(2-pyridyl)pyrazine), was studied in acetonitrile (MeCN) and aqueous solutions. In MeCN containing 0.10 M tetra-n-butylammonium perchlorate (TBAP), the complex displayed a reversible, overlapping RuII/III redox process with E1/2 = +1.21 V vs Ag/Ag+ (10 mM), an irreversible reduction of RhIII/I at −0.73 V vs Ag/Ag+, and two quasi-reversible dpp/dpp− couples with E1/2 = −1.11 and −1.36 V vs Ag/Ag+ at a Pt electrode with a scan rate of 50 mV s−1. In 0.20 M Tris buffer solution (pH 7.4), an irreversible, overlapping RuII/III oxidation at +1.48 V vs Ag/AgCl (3 M KCl), and an irreversible reduction of RhIII/II at −0.78 V vs Ag/AgCl were observed at a glassy carbon electrode with a scan rate of 50 mV/s. Investigations on the electrogenerated chemiluminescence (ECL) of the complex revealed that 2-(dibutylamino) ethanol (DBAE) was superior to tri-n-propylamine (TPrA) as an ECL coreactant within their entire concentration range of 10−100 mM in MeCN, and in aqueous media, as low as 1.0 nM of the complex can be detected using TPrA coreactant ECL. A maximum ECL emission of 640 nm, which is about 55 nm blue shift to its fluorescence, was observed in MeCN with DBAE as a coreactant. Interactions of the complex with calf thymus DNA (ctDNA) were conducted with a flow-cell based quartz-crystal microbalance, and a binding constant of 2.5 × 105 M−1 was calculated on the basis of the Langmuir isotherm equation.

  • 40.
    Wiberg, Karin
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Letcher, Robert
    Sandau, Courtney
    Duffe, Jason
    Norstrom, Ross
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bidleman, Terry
    Enantioselective gas chromatography/mass spectrometry of methylsulfonyl PCBs with application to arctic marine mammals1998In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 70, no 18, p. 3845-3852Article in journal (Refereed)
    Abstract [en]

    Four different commercially available cyclodextrin (CD) capillary gas chromatography (GC) columns were tested for the enantioselective separation of nine environmentally persistent atropisomeric 3- and 4-methylsulfonyl PCBs (MeSO2-CBs). The selected columns contained cyclodextrins with various cavity diameters (β- or γ-CD), which were methylated and/or tert-butyldimethylsilylated (TBDMS) in the 2,3,6-O-positions. The β-CD column with TBDMS substituents in all of the 2,3,6-O-positions was by far the most selective column for the MeSO2-CBs tested. Enantiomers of congeners with 3-MeSO2 substitution were more easily separated than those with 4-MeSO2 substitution. The separation also seemed to be enhanced for congeners with the chlorine atoms on the non-MeSO2-containing ring and clustered on one side of the same ring. The 2,3-di-O-methyl-6-O-TBDMS-β-CD was found to give somewhat better selectivity than the corresponding γ-CD, in comparison between the two columns, which were identical in all other respects. Enantioselective analysis of arctic ringed seal (Phoca hispida) and polar bear (Ursus maritimus) adipose tissue revealed a strong dominance of certain enantiomers. For example, the enantiomer ratio (ER) of 3-MeSO2-CB149 was 0.32 and <0.1 in ringed seal blubber and polar bear fat, respectively. These low ER values are indicative of highly enantioselective formation, enantioselective metabolism, enantioselective transport across cell membranes, or a combination of the three in both species. Comparable results for the enantiomeric analysis of MeSO2-CBs in biotic tissue extracts were obtained using two highly selective mass spectrometric techniques, ion trap mass spectrometry/mass spectrometry and electron capture negative ion low-resolution mass spectrometry.

  • 41.
    Wiklund, Susanne
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Johansson, Erik
    Sjöström, Lina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Mellerowicz, Ewa J
    Edlund, Ulf
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Shockcor, John P
    Gottfries, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Moritz, Thomas
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Visualization of GC/TOF-MS-based metabolomics data for identification of biochemically interesting compounds using OPLS class models2008In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 80, no 1, p. 115-22Article in journal (Refereed)
    Abstract [en]

    Metabolomics studies generate increasingly complex data tables, which are hard to summarize and visualize without appropriate tools. The use of chemometrics tools, e.g., principal component analysis (PCA), partial least-squares to latent structures (PLS), and orthogonal PLS (OPLS), is therefore of great importance as these include efficient, validated, and robust methods for modeling information-rich chemical and biological data. Here the S-plot is proposed as a tool for visualization and interpretation of multivariate classification models, e.g., OPLS discriminate analysis, having two or more classes. The S-plot visualizes both the covariance and correlation between the metabolites and the modeled class designation. Thereby the S-plot helps identifying statistically significant and potentially biochemically significant metabolites, based both on contributions to the model and their reliability. An extension of the S-plot, the SUS-plot (shared and unique structure), is applied to compare the outcome of multiple classification models compared to a common reference, e.g., control. The used example is a gas chromatography coupled mass spectroscopy based metabolomics study in plant biology where two different transgenic poplar lines are compared to wild type. By using OPLS, an improved visualization and discrimination of interesting metabolites could be demonstrated.

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