The Experts below are selected from a list of 5520 Experts worldwide ranked by ideXlab platform
Graham R Cooks - One of the best experts on this subject based on the ideXlab platform.
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Inter-platform assessment of performance of high-throughput Desorption Electrospray Ionization mass spectrometry
'Elsevier BV', 2021Co-Authors: Nicolás M. Morato, Graham R CooksAbstract:High throughput analysis is increasingly relevant in both industry and academia, with applications reaching from enzymology and drug discovery to organic reaction optimization and diagnostics. Currently, chromatography-free mass spectrometry (MS) techniques have acquired an important role in this field due to their inherent speed, versatility, and chemical specificity. Desorption Electrospray Ionization (DESI) MS is one of these approaches, which allows for direct analysis of complex samples in the ambient environment, with throughputs better than 1 sample per second and no need for sample treatment. Here we assess the evolution of the high throughput DESI-MS analytical performance from the early DESI source developed by Prosolia Inc. to the recently commercialized version of Waters Corporation. The evaluation was carried out through both quantitative and qualitative analysis of biologically relevant compounds including metabolites, peptides, lipids and pharmaceuticals. Our results indicate that both platforms are successful at the direct analysis of these species even from complex matrices such as bioassay buffers. However, the newest iteration of the DESI stage, when combined with a quadrupole time-of-flight (Q-ToF) instrument, provides higher sensitivity (1-3 orders of magnitude lower limits of detection) and reproducibility (ca. 10% average reduction in coefficients of variation for quantitation using an internal standard). The cases explored in this study also showcase the broad applicability of high throughput DESI-MS for bioanalysis and quality control
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high throughput label free enzymatic assays using Desorption Electrospray Ionization mass spectrometry
Angewandte Chemie, 2020Co-Authors: Nicolás M. Morato, Dylan T Holden, Graham R CooksAbstract:High-throughput (HT) enzymatic assays, which typically rely on labeled compounds and plate readers, are important for drug discovery. Mass spectrometry (MS) provides an alternative method of performing HT label-free assays. Here we demonstrate the use of a HT platform based on Desorption Electrospray Ionization (DESI) MS for the label-free study of enzymatic reactions directly from the bioassay matrix with an effective analysis time of 0.3 s per sample. This system allows for thorough analysis of the enzymatic process through monitoring of its substrate and product after an external calibration. We show the platform capabilities by an in-depth study of the acetylcholinesterase assay, including kinetic parameter determination, rapid inhibitor screening, and further characterization of positive hits (that is, IC50 and Ki ), as well as inhibition-reactivation assays. We anticipate that the expansion of this platform has high potential impact in label-free enzymology as well as in drug discovery.
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high throughput reaction screening using Desorption Electrospray Ionization mass spectrometry
Chemical Science, 2018Co-Authors: Michael Wleklinski, C R Ferreira, Bradley P Loren, Zinia Jaman, Larisa Avramova, Tiago J P Sobreira, David H Thompson, Graham R CooksAbstract:We report the high throughput analysis of reaction mixture arrays using methods and data handling routines that were originally developed for biological tissue imaging. Desorption Electrospray Ionization (DESI) mass spectrometry (MS) is applied in a continuous on-line process at rates that approach 104 reactions per h at area densities of up to 1 spot per mm2 (6144 spots per standard microtiter plate) with the sprayer moving at ca. 104 microns per s. Data are analyzed automatically by MS using in-house software to create ion images of selected reagents and products as intensity plots in standard array format. Amine alkylation reactions were used to optimize the system performance on PTFE membrane substrates using methanol as the DESI spray/analysis solvent. Reaction times can be <100 μs when reaction acceleration occurs in microdroplets, enabling the rapid screening of processes like N-alkylation and Suzuki coupling reactions as reported herein. Products and by-products were confirmed by on-line MS/MS upon rescanning of the array.
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improved spatial resolution in the imaging of biological tissue using Desorption Electrospray Ionization
Analytical and Bioanalytical Chemistry, 2012Co-Authors: Dahlia I Campbell, C R Ferreira, Livia S Eberlin, Graham R CooksAbstract:Desorption Electrospray Ionization imaging allows biomarker discovery and disease diagnosis through chemical characterization of biological samples in their native environment. Optimization of experimental parameters including emitter capillary size, solvent composition, solvent flow rate, mass spectrometry scan-rate and step-size is shown here to improve the resolution available in the study of biological tissue from 180 μm to about 35 μm using an unmodified commercial mass spectrometer. Mouse brain tissue was used to optimize and measure resolution based on known morphological features and their known relationships to major phospholipid components. Features of approximately 35 μm were resolved and correlations drawn between features in grey matter (principally PS (18:0/22:6), m/z 834) and in white matter (principally ST (24:1), m/z 888). The improved spatial resolution allowed characterization of the temporal changes in lipid profiles occurring within mouse ovaries during the ovulatory cycle. An increase in the production of phosphatidylinositol (PI 38:4) m/z 885 and associated fatty acids such as arachidonic acid (FA 20:4) m/z 303 and adrenic acid (FA 22:4) m/z 331was seen with the postovulatory formation of the corpus luteum.
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Desorption Electrospray Ionization mass spectrometry for lipid characterization and biological tissue imaging
Biochimica et Biophysica Acta, 2011Co-Authors: Livia S Eberlin, Allison L. Dill, C R Ferreira, Graham R CooksAbstract:Desorption Electrospray Ionization mass spectrometry (DESI-MS) imaging of biological samples allows untargeted analysis and structural characterization of lipids ionized from the near-surface region of a sample under ambient conditions. DESI is a powerful and sensitive MS Ionization method for 2D and 3D imaging of lipids from direct and unmodified complex biological samples. This review describes the strengths and limitations of DESI-MS for lipid characterization and imaging together with the technical workflow and a survey of applications. Included are discussions of lipid mapping and biomarker discovery as well as a perspective on the future of DESI imaging.
David C Muddiman - One of the best experts on this subject based on the ideXlab platform.
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infrared matrix assisted laser Desorption Electrospray Ionization ir maldesi mass spectrometry imaging analysis of endogenous metabolites in cherry tomatoes
Analyst, 2020Co-Authors: Caleb M Bagley, Crystal L Pace, Mans Ekelof, David C MuddimanAbstract:We report the spatially resolved metabolic profiling of cherry tomatoes using infrared matrix-assisted laser Desorption Electrospray Ionization (IR-MALDESI), a mass spectrometry imaging (MSI) technique that operates at ambient conditions and requires no sample derivatization. Tomatoes were flash frozen, cryosectioned and imaged with adequate spatial resolution to distinguish between the major tissue structures of a tomato including the skin, mesocarp, endocarp, locular tissue, septum, placenta, seed and seed coating. Metabolites were imaged from 100-1200 m/z, enabling significant coverage of a diverse array of metabolites including amino acids and lipids along with the major secondary metabolite classes: terpenes, phenolics, glycosides, and alkaloids. During the metabolic profiling, we found endogenous carotenoid hydrocarbons, namely lycopene or its structural isomer β-carotene, ionized as radical cations. To our knowledge, this is the first demonstration of ionizing hydrocarbons in the MSI field.
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detection of attomole amounts of analyte by Desorption Electrospray Ionization mass spectrometry desi ms determined using fluorescence spectroscopy
Journal of the American Society for Mass Spectrometry, 2007Co-Authors: Michael S Bereman, David C MuddimanAbstract:We report the use of fluorescence spectroscopy to investigate the amount of material removed from a PTFE surface and detected during Desorption Electrospray Ionization (DESI) mass spectrometry measurements. The fluorescence intensity before and after DESI analysis of rhodamine 6G is used to determine the amount of material removed from the surface per mass spectrum. Calculations indicate low attomole amounts are removed per linear ion trap mass spectrum.
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direct characterization of intact polypeptides by matrix assisted laser Desorption Electrospray Ionization quadrupole fourier transform ion cyclotron resonance mass spectrometry
Rapid Communications in Mass Spectrometry, 2007Co-Authors: Jason S Sampson, Adam M Hawkridge, David C MuddimanAbstract:We report the characterization of a recently introduced hybrid Ionization source, matrix-assisted laser Desorption Electrospray Ionization (MALDESI), coupled to a quadrupole Fourier transform ion cyclotron resonance mass spectrometry (QFT-ICR-MS) system. We first demonstrate the ability of MALDESI-QFT-ICR MS to directly analyze and provide high mass measurement accuracy (approximately 1 part-per-million) of a polypeptide using internal calibration. Second, we show the potential of MALDESI-QFT-ICR MS for the top-down characterization of multiply charged polypeptide cations. Finally, we demonstrate sub-femtomole detection limits in MALDESI-QFT-ICR MS using a combination of naturally occurring peptides and their respective stable isotope labeled forms. The results presented herein demonstrate the feasibility of several potential applications for MALDESI-QFT-ICR MS for the direct analysis of intact biological molecules.
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direct high resolution peptide and protein analysis by Desorption Electrospray Ionization fourier transform ion cyclotron resonance mass spectrometry
Rapid Communications in Mass Spectrometry, 2006Co-Authors: Michael S Bereman, Leonard Nyadong, Facundo M Fernandez, David C MuddimanAbstract:We report the first coupling of a Desorption Electrospray Ionization (DESI) ion source to Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR-MS) for high-resolution protein analysis. The DESI FT-ICR-MS source design is described in detail along with preliminary data obtained on peptides and proteins ranging from 1 to 5.7 kDa.
Facundo M Fernandez - One of the best experts on this subject based on the ideXlab platform.
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omnispect an open matlab based tool for visualization and analysis of matrix assisted laser Desorption Ionization and Desorption Electrospray Ionization mass spectrometry images
Journal of the American Society for Mass Spectrometry, 2013Co-Authors: Mitchell R Parry, Asiri S Galhena, May D Wang, Chaminda M Gamage, Rachel V Bennett, Facundo M FernandezAbstract:We present omniSpect, an open source web- and MATLAB-based software tool for both Desorption Electrospray Ionization (DESI) and matrix-assisted laser Desorption Ionization (MALDI) mass spectrometry imaging (MSI) that performs computationally intensive functions on a remote server. These functions include converting data from a variety of file formats into a common format easily manipulated in MATLAB, transforming time-series mass spectra into mass spectrometry images based on a probe spatial raster path, and multivariate analysis. OmniSpect provides an extensible suite of tools to meet the computational requirements needed for visualizing open and proprietary format MSI data.
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enhanced direct ambient analysis by differential mobility filtered Desorption Electrospray Ionization mass spectrometry
Analytical Chemistry, 2010Co-Authors: Asiri S Galhena, Glenn A Harris, Mark Kwasnik, Facundo M FernandezAbstract:Desorption Electrospray Ionization (DESI) is rapidly becoming established as one of the most powerful Ionization techniques allowing direct surface analysis by mass spectrometry (MS) in the ambient environment. DESI provides a significant number of unique analytical capabilities for a broad range of applications, both quantitative and qualitative in nature including biological tissue imaging, pharmaceutical quality control, in vivo analysis, proteomics, metabolomics, forensics, and explosives detection. Despite its growing adoption as a powerful high throughput analysis tool, DESI-MS analysis at trace levels often suffers from background chemical interferences generated during the Electrospray Ionization processes. In order to improve sensitivity and selectivity, a differential mobility (DM) ion separation cell was successfully interfaced to a custom-built DESI ion source. This new hybrid platform can be operated in two modes: the “DM-off” mode for standard DESI analysis and “DM-on mode” where DESI-genera...
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Desorption Electrospray Ionization mass spectrometry reveals surface mediated antifungal chemical defense of a tropical seaweed
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Amy L Lane, Leonard Nyadong, Asiri S Galhena, Mark Kwasnik, Tonya L Shearer, Paige E Stout, Mitchell R Parry, May D Wang, Mark E Hay, Facundo M FernandezAbstract:Organism surfaces represent signaling sites for attraction of allies and defense against enemies. However, our understanding of these signals has been impeded by methodological limitations that have precluded direct fine-scale evaluation of compounds on native surfaces. Here, we asked whether natural products from the red macroalga Callophycus serratus act in surface-mediated defense against pathogenic microbes. Bromophycolides and callophycoic acids from algal extracts inhibited growth of Lindra thalassiae, a marine fungal pathogen, and represent the largest group of algal antifungal chemical defenses reported to date. Desorption Electrospray Ionization mass spectrometry (DESI-MS) imaging revealed that surface-associated bromophycolides were found exclusively in association with distinct surface patches at concentrations sufficient for fungal inhibition; DESI-MS also indicated the presence of bromophycolides within internal algal tissue. This is among the first examples of natural product imaging on biological surfaces, suggesting the importance of secondary metabolites in localized ecological interactions, and illustrating the potential of DESI-MS in understanding chemically-mediated biological processes.
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reactive Desorption Electrospray Ionization linear ion trap mass spectrometry of latest generation counterfeit antimalarials via noncovalent complex formation
Analytical Chemistry, 2007Co-Authors: Leonard Nyadong, Paul N. Newton, Michael D Green, Victor R De Jesus, Facundo M FernandezAbstract:Desorption Electrospray Ionization mass spectrometry (DESI MS) is rapidly becoming accepted as a powerful surface characterization tool for a wide variety of samples in the open air. Besides its well-established high-throughput capabilities, a unique feature of DESI is that chemical reactions between the charged spray microdroplets and surface molecules can be exploited to enhance Ionization. Here, we present a rapid screening assay for artesunate antimalarials based on reactive DESI. Artesunate is a vital therapy for Plasmodium falciparum malaria, but artesunate tablets have been counterfeited on a very large scale in SE Asia, and more recently in Africa. For this reason, faster and more sensitive screening tests are urgently needed. The proposed DESI assay is based on the formation of stable noncovalent complexes between linear alkylamines dissolved in the DESI spray solution and artesunate molecules exposed on the tablet surface. We found that, depending on amine type and concentration, a sensitivity g...
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Combined Fourier-transform infrared imaging and Desorption Electrospray-Ionization linear ion-trap mass spectrometry for analysis of counterfeit antimalarial tablets
Analytical and Bioanalytical Chemistry, 2007Co-Authors: Camilla Ricci, Leonard Nyadong, Facundo M Fernandez, Paul N. Newton, Sergei G KazarianAbstract:This paper reports use of a combination of Fourier-transform infrared (FTIR) spectroscopic imaging and Desorption Electrospray Ionization linear ion-trap mass spectrometry (DESI MS) for characterization of counterfeit pharmaceutical tablets. The counterfeit artesunate antimalarial tablets were analyzed by both techniques. The results obtained revealed the ability of FTIR imaging in non-destructive micro-attenuated total reflection (ATR) mode to detect the distribution of all components in the tablet, the identities of which were confirmed by DESI MS. Chemical images of the tablets were obtained with high spatial resolution. The FTIR spectroscopic imaging method affords inherent chemical specificity with rapid acquisition of data. DESI MS enables high-sensitivity detection of trace organic compounds. Combination of these two orthogonal surface-characterization methods has great potential for detection and analysis of counterfeit tablets in the open air and without sample preparation.
Richard N Zare - One of the best experts on this subject based on the ideXlab platform.
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hydrogen deuterium exchange Desorption Electrospray Ionization mass spectrometry visualizes an acidic tumor microenvironment
Analytical Chemistry, 2021Co-Authors: Qingce Zang, Xiaowei Song, Richard N ZareAbstract:We report that microdroplet hydrogen-deuterium exchange (HDX) detected by Desorption Electrospray Ionization mass spectrometry imaging (DESI-MSI) allows the measurement of the acidity of a tissue sample. The integration of HDX and DESI-MSI has been applied to visualize the acidic tumor microenvironment (TME). HDX-DESI-MSI enables the simultaneous collection of regional pH variation and its corresponding in-depth metabolomic changes. This technique is a cost-effective tool for providing insight into the pH-dependent tumor metabolism heterogeneity.
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massexplorer a computational tool for analyzing Desorption Electrospray Ionization mass spectrometry data
Bioinformatics, 2021Co-Authors: Vishnu Shankar, Robert Tibshirani, Richard N ZareAbstract:Summary In the last few years, Desorption Electrospray Ionization mass spectrometry imaging (DESI-MSI) has been increasingly used for simultaneous detection of thousands of metabolites and lipids from human tissues and biofluids. To successfully find the most significant differences between two sets of DESI-MSI data (e.g., healthy vs disease) requires the application of accurate computational and statistical methods that can pre-process the data under various normalization settings and help identify these changes among thousands of detected metabolites. Here, we report MassExplorer, a novel computational tool, to help pre-process DESI-MSI data, visualize raw data, build predictive models using the statistical lasso approach to select for a sparse set of significant molecular changes, and interpret selected metabolites. This tool, which is available for both online and offline use, is flexible for both chemists and biologists and statisticians as it helps in visualizing structure of DESI-MSI data and in analyzing the statistically significant metabolites that are differentially expressed across both sample types. Based on the modules in MassExplorer, we expect it to be immediately useful for various biological and chemical applications in mass spectrometry. Availability and implementation MassExplorer is available as an online R-Shiny application or Mac OS X compatible standalone application. The application, sample performance, source code and corresponding guide can be found at: https://zarelab.com/research/massexplorer-a-tool-to-help-guide-analysis-of-mass-spectrometry-samples/. Supplementary informationMATION Supplementary data are available at Bioinformatics online.
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Diagnosis of prostate cancer by Desorption Electrospray Ionization mass spectrometric imaging of small metabolites and lipids
2020Co-Authors: Shibdas Banerjee, Richard N Zare, Robert Tibshirani, Christian A Kunder, Rosalie Nolley, James D Brooks, Richard Fan, Geoffrey A SonnAbstract:Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon's ability to best determine resection margins during prostatectomy. We performed Desorption Electrospray Ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z <200), which we found to be highly informative in distinguishing cancer from benign tissue. Malignant prostate cells showed marked metabolic derangements compared with their benign counterparts. Using the "Least absolute shrinkage and selection operator" (Lasso), we analyzed all metabolites from the DESI-MS data and identified parsimonious sets of metabolic profiles for distinguishing between cancer and normal tissue. In an independent set of samples, we could use these models to classify prostate cancer from benign specimens with nearly 90% accuracy per patient. Based on previous work in prostate cancer showing that glucose levels are high while citrate is low, we found that measurement of the glucose/citrate ion signal ratio accurately predicted cancer when this ratio exceeds 1.0 and normal prostate when the ratio is less than 0.5. After brief tissue preparation, the glucose/citrate ratio can be recorded on a tissue sample in 1 min or less, which is in sharp contrast to the 20 min or more required by histopathological examination of frozen tissue specimens. prostate cancer | Krebs cycle | metabolism | Desorption Electrospray Ionization | mass spectrometry P rostate cancer (PCa) is the most commonly diagnosed solidorgan cancer and the second leading cause of cancer death in men in the United States (1). Because of prostate-specific antigen (PSA) screening in the United States, most PCas are discovered when they are confined to the prostate (2). Many of these localized PCas are treated by surgical removal of the entire prostate (radical prostatectomy). The presence of cancer cells at the edge of the surgical resection, or positive surgical margins, is associated with higher rates of recurrence and death from PCa (3, 4). Therefore, an important clinical challenge in PCa management is to devise a rapid and highly accurate method to detect cancerous cells in real time to allow resection of additional periprostatic tissues and reduce cancer recurrence after surgery. Over the last decade, several innovative analytical techniques (5-12) have been developed to distinguish cancer from benign tissue in various organs. However, none has achieved wide clinical adoption for various reasons including inconvenience, narrow information content, unavailability, poor sensitivity, slowness of adoption, and operating room workflow incompatibility. In PCa, intraoperative frozen sections have been used to attempt to identify PCa at the margin based on analysis of histology. However, frozen sections have been shown to have poor sensitivity and specificity for the detection of PCa and currently are not recommended Recently, a label-free molecular imaging method called Desorption Electrospray Ionization mass spectrometric imaging (DESI-MSI) has been developed (15-17). DESI-MSI can rapidly evaluate the tissue metabolome in situ by simultaneously characterizing hundreds of lipids and metabolites. In the last 5 y, reports from our group Given the known alterations in metabolic pathways in PCa, we tested whether DESI-MSI of metabolites and lipids could have utility in discriminating cancer from normal tissue obtained from radical prostatectomy. Using tandem and high-resolution mass spectrometry we have characterized the distinct metabolite and lipid profiles of normal and malignant prostate. Although many earlier DESI-MSI studies considered only lipid profiles in identification of cancer, here we report imaging small metabolite Significance Desorption Electrospray Ionization mass spectrometry imaging (DESI-MSI) is a label-free molecular imaging technique that provides a window into the biochemical processes present in benign and malignant prostate tissue. This is important both in improving the understanding of tissue biology and in achieving rapid cancer diagnosis. We applied DESI-MSI to record lipid, carbohydrate, and most importantly, small metabolite images from 54 normal and malignant prostate tissue specimens. Several Krebs cycle intermediates were present at different concentrations in prostate cancer compared with normal tissue. Statistical calculations identified panels of metabolites that could readily distinguish prostate cancer from normal tissue with nearly 90% accuracy in a validation set. The results also indicated that the ratio of glucose to citrate ion signals could be used to accurately identify prostate cancer
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early detection of unilateral ureteral obstruction by Desorption Electrospray Ionization mass spectrometry
Scientific Reports, 2019Co-Authors: Richard N Zare, Shibdas Banerjee, Robert Tibshirani, Xin Yan, Anny Chuuyun Wong, Hongjuan Zhao, James D BrooksAbstract:Desorption Electrospray Ionization mass spectrometry (DESI-MS) is an emerging analytical tool for rapid in situ assessment of metabolomic profiles on tissue sections without tissue pretreatment or labeling. We applied DESI-MS to identify candidate metabolic biomarkers associated with kidney injury at the early stage. DESI-MS was performed on sections of kidneys from 80 mice over a time course following unilateral ureteral obstruction (UUO) and compared to sham controls. A predictive model of renal damage was constructed using the LASSO (least absolute shrinkage and selection operator) method. Levels of lipid and small metabolites were significantly altered and glycerophospholipids comprised a significant fraction of altered species. These changes correlate with altered expression of lipid metabolic genes, with most genes showing decreased expression. However, rapid upregulation of PG(22:6/22:6) level appeared to be a hitherto unknown feature of the metabolic shift observed in UUO. Using LASSO and SAM (significance analysis of microarrays), we identified a set of well-measured metabolites that accurately predicted UUO-induced renal damage that was detectable by 12 h after UUO, prior to apparent histological changes. Thus, DESI-MS could serve as a useful adjunct to histology in identifying renal damage and demonstrates early and broad changes in membrane associated lipids.
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combining Desorption Electrospray Ionization mass spectrometry imaging and machine learning for molecular recognition of myocardial infarction
Analytical Chemistry, 2018Co-Authors: Katherine Margulis, Zhenpeng Zhou, Qizhi Fang, Richard E Sievers, Randall J Lee, Richard N ZareAbstract:Lipid profile changes in heart muscle have been previously linked to cardiac ischemia and myocardial infarction, but the spatial distribution of lipids and metabolites in ischemic heart remains to be fully investigated. We performed Desorption Electrospray Ionization mass spectrometry imaging of hearts from in vivo myocardial infarction mouse models. In these mice, myocardial ischemia was induced by blood supply restriction via a permanent ligation of left anterior descending coronary artery. We showed that applying the machine learning algorithm of gradient boosting tree ensemble to the ambient mass spectrometry imaging data allows us to distinguish segments of infarcted myocardium from normally perfused hearts on a pixel by pixel basis. The machine learning algorithm selected 62 molecular ion peaks important for classification of each 200 μm-diameter pixel of the cardiac tissue map as normally perfused or ischemic. This approach achieved very high average accuracy (97.4%), recall (95.8%), and precision ...
Leonard Nyadong - One of the best experts on this subject based on the ideXlab platform.
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Desorption Electrospray Ionization mass spectrometry reveals surface mediated antifungal chemical defense of a tropical seaweed
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Amy L Lane, Leonard Nyadong, Asiri S Galhena, Mark Kwasnik, Tonya L Shearer, Paige E Stout, Mitchell R Parry, May D Wang, Mark E Hay, Facundo M FernandezAbstract:Organism surfaces represent signaling sites for attraction of allies and defense against enemies. However, our understanding of these signals has been impeded by methodological limitations that have precluded direct fine-scale evaluation of compounds on native surfaces. Here, we asked whether natural products from the red macroalga Callophycus serratus act in surface-mediated defense against pathogenic microbes. Bromophycolides and callophycoic acids from algal extracts inhibited growth of Lindra thalassiae, a marine fungal pathogen, and represent the largest group of algal antifungal chemical defenses reported to date. Desorption Electrospray Ionization mass spectrometry (DESI-MS) imaging revealed that surface-associated bromophycolides were found exclusively in association with distinct surface patches at concentrations sufficient for fungal inhibition; DESI-MS also indicated the presence of bromophycolides within internal algal tissue. This is among the first examples of natural product imaging on biological surfaces, suggesting the importance of secondary metabolites in localized ecological interactions, and illustrating the potential of DESI-MS in understanding chemically-mediated biological processes.
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reactive Desorption Electrospray Ionization linear ion trap mass spectrometry of latest generation counterfeit antimalarials via noncovalent complex formation
Analytical Chemistry, 2007Co-Authors: Leonard Nyadong, Paul N. Newton, Michael D Green, Victor R De Jesus, Facundo M FernandezAbstract:Desorption Electrospray Ionization mass spectrometry (DESI MS) is rapidly becoming accepted as a powerful surface characterization tool for a wide variety of samples in the open air. Besides its well-established high-throughput capabilities, a unique feature of DESI is that chemical reactions between the charged spray microdroplets and surface molecules can be exploited to enhance Ionization. Here, we present a rapid screening assay for artesunate antimalarials based on reactive DESI. Artesunate is a vital therapy for Plasmodium falciparum malaria, but artesunate tablets have been counterfeited on a very large scale in SE Asia, and more recently in Africa. For this reason, faster and more sensitive screening tests are urgently needed. The proposed DESI assay is based on the formation of stable noncovalent complexes between linear alkylamines dissolved in the DESI spray solution and artesunate molecules exposed on the tablet surface. We found that, depending on amine type and concentration, a sensitivity g...
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Combined Fourier-transform infrared imaging and Desorption Electrospray-Ionization linear ion-trap mass spectrometry for analysis of counterfeit antimalarial tablets
Analytical and Bioanalytical Chemistry, 2007Co-Authors: Camilla Ricci, Leonard Nyadong, Facundo M Fernandez, Paul N. Newton, Sergei G KazarianAbstract:This paper reports use of a combination of Fourier-transform infrared (FTIR) spectroscopic imaging and Desorption Electrospray Ionization linear ion-trap mass spectrometry (DESI MS) for characterization of counterfeit pharmaceutical tablets. The counterfeit artesunate antimalarial tablets were analyzed by both techniques. The results obtained revealed the ability of FTIR imaging in non-destructive micro-attenuated total reflection (ATR) mode to detect the distribution of all components in the tablet, the identities of which were confirmed by DESI MS. Chemical images of the tablets were obtained with high spatial resolution. The FTIR spectroscopic imaging method affords inherent chemical specificity with rapid acquisition of data. DESI MS enables high-sensitivity detection of trace organic compounds. Combination of these two orthogonal surface-characterization methods has great potential for detection and analysis of counterfeit tablets in the open air and without sample preparation.
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direct high resolution peptide and protein analysis by Desorption Electrospray Ionization fourier transform ion cyclotron resonance mass spectrometry
Rapid Communications in Mass Spectrometry, 2006Co-Authors: Michael S Bereman, Leonard Nyadong, Facundo M Fernandez, David C MuddimanAbstract:We report the first coupling of a Desorption Electrospray Ionization (DESI) ion source to Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR-MS) for high-resolution protein analysis. The DESI FT-ICR-MS source design is described in detail along with preliminary data obtained on peptides and proteins ranging from 1 to 5.7 kDa.