Journal articles: 'MALDI mass spectrometry data'

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Ul’shina, D. V., D. A. Kovalev, I. V. Kuznetsova, O. V. Bobrysheva, T. L. Krasovskaya, and A. N. Kulichenko. "Software Solutions for Indication and Identification of Pathogenic Microoranisms Using Time-of-Flight Mass Spectrometry." Problems of Particularly Dangerous Infections, no. 3 (October 23, 2021): 40–50. http://dx.doi.org/10.21055/0370-1069-2021-3-40-50.

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The effectiveness of differentiation of bacterial pathogens using MALDI-TOF mass spectrometry depends on the quality of sample preparation, compliance with mass spectrometric analysis parameters and statistical approaches used, implemented by various modern software tools. The review provides a brief description of the most known software used in the processing and bioinformation analysis of time-of-flight mass spectrometry data. A list of computer platforms, programs and environments, both commercial and publicly available, is presented. The results of indication and identification of pathogens of particularly dangerous and natural-focal infections by MALDI-TOF mass spectrometry using publicly available software – programming language R, Mass-Up, MicrobeMS, licensed – MatLab, ClinProTools, as well as free web applications, including, Speclust, Ribopeaksare provided. The data on usage of such well-known platforms as MALDI BioTyper, SARAMIS Vitek-MS and Andromas (Andromas SAS, France) for inter- and intra-specific differentiation of closely related species are presented. Results of identification and differentiation of microorganisms applying MALDI-TOF mass spectrometry based on detection of specific proteins for cross-comparison – biomarkers – are given. The analysis shows that the programming language R environment is one of the publicly available universal platforms with an optimal combination of algorithms for processing and interpreting of a large array of mass spectrometric data.

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Курченко, Андрей. "MALDI MASS SPECTROMETRY - IN THE ASSESSMENT OF HUMAN MICROBIOTA. CURRENT STATE AND PERSPECTIVES." Immunology and Allergy: Science and Practice, no. 2 (July 29, 2020): 11–18. http://dx.doi.org/10.37321/immunology.2020.02-02.

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Mass spectrometry is a modern physicochemical method of analysis that allows for a qualitative and quantitative analysis of the composition of a substancebased on the preliminary ionization of its constituent atoms or molecules. One of the new methods of ionization, thanks to which the mass spectrometric study of macromolecules has become widespread, is matrix-activated laser desorption / ionization (MALDI), which is a pulsed laser irradiation of the substance under study mixed with a matrix.Тhe article presents modern data on the use of the MALDI mass- spectrometry method for conducting genus and species-specific identification of microorganisms in the practice of diagnostic laboratories. The advantages of MALDI-TOF identification in comparison with other methods of microbiota research are considered.The place of mass spectrometry in the system of laboratory diagnostics of various pathogens is indicated.

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Randolph, Timothy W., Bree L. Mitchell, Dale F. McLerran, Paul D. Lampe, and Ziding Feng. "Quantifying Peptide Signal in MALDI-TOF Mass Spectrometry Data." Molecular & Cellular Proteomics 4, no. 12 (September 29, 2005): 1990–99. http://dx.doi.org/10.1074/mcp.m500130-mcp200.

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Darie-Ion, Laura, Danielle Whitham, Madhuri Jayathirtha, Yashveen Rai, Anca-Narcisa Neagu, Costel C. Darie, and Brînduşa Alina Petre. "Applications of MALDI-MS/MS-Based Proteomics in Biomedical Research." Molecules 27, no. 19 (September 21, 2022): 6196. http://dx.doi.org/10.3390/molecules27196196.

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Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is one of the most widely used techniques in proteomics to achieve structural identification and characterization of proteins and peptides, including their variety of proteoforms due to post-translational modifications (PTMs) or protein–protein interactions (PPIs). MALDI-MS and MALDI tandem mass spectrometry (MS/MS) have been developed as analytical techniques to study small and large molecules, offering picomole to femtomole sensitivity and enabling the direct analysis of biological samples, such as biofluids, solid tissues, tissue/cell homogenates, and cell culture lysates, with a minimized procedure of sample preparation. In the last decades, structural identification of peptides and proteins achieved by MALDI-MS/MS helped researchers and clinicians to decipher molecular function, biological process, cellular component, and related pathways of the gene products as well as their involvement in pathogenesis of diseases. In this review, we highlight the applications of MALDI ionization source and tandem approaches for MS for analyzing biomedical relevant peptides and proteins. Furthermore, one of the most relevant applications of MALDI-MS/MS is to provide “molecular pictures”, which offer in situ information about molecular weight proteins without labeling of potential targets. Histology-directed MALDI-mass spectrometry imaging (MSI) uses MALDI-ToF/ToF or other MALDI tandem mass spectrometers for accurate sequence analysis of peptide biomarkers and biological active compounds directly in tissues, to assure complementary and essential spatial data compared with those obtained by LC-ESI-MS/MS technique.

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Iles, Ray K., Jason K. Iles, Raminta Zmuidinaite, and Michael Roberts. "A How to Guide: Clinical Population Test Development and Authorization of MALDI-ToF Mass Spectrometry-Based Screening Tests for Viral Infections." Viruses 14, no. 9 (September 3, 2022): 1958. http://dx.doi.org/10.3390/v14091958.

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Applying MALDI-ToF mass spectrometry as a clinical diagnostic test for viruses is different from that of bacteria, fungi and other micro-organisms. This is because the systems biology of viral infections, the size and chemical nature of specific viral proteins and the mass spectrometry biophysics of how they are quantitated are fundamentally different. The analytical challenges to overcome when developing a clinical MALDI-ToF mass spectrometry tests for a virus, particularly human pathogenic enveloped viruses, are sample enrichment, virus envelope disruption, optimal matrix formulation, optimal MALDI ToF MS performance and optimal spectral data processing/bioinformatics. Primarily, the instrument operating settings have to be optimized to match the nature of the viral specific proteins, which are not compatible with setting established when testing for bacterial and many other micro-organisms. The capacity to be a viral infection clinical diagnostic instrument often stretches current mass spectrometers to their operational design limits. Finally, all the associated procedures, from sample collection to data analytics, for the technique have to meet the legal and operational requirement for often high-throughput clinical testing. Given the newness of the technology, clinical MALDI ToF mass spectrometry does not fit in with standard criteria applied by regulatory authorities whereby numeric outputs are compared directly to similar technology tests that have already been authorized for use. Thus, CLIA laboratory developed test (LDT) criteria have to be applied. This article details our experience of developing a SAR-CoV-2 MALDI-ToF MS test suitable for asymptomatic carrier infection population screening.

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Trede, Dennis, Jan Hendrik Kobarg, Janina Oetjen, Herbert Thiele, Peter Maass, and Theodore Alexandrov. "On the Importance of Mathematical Methods for Analysis of MALDI-Imaging Mass Spectrometry Data." Journal of Integrative Bioinformatics 9, no. 1 (March 1, 2012): 1–11. http://dx.doi.org/10.1515/jib-2012-189.

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Summary In the last decade, matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS), also called as MALDI-imaging, has proven its potential in proteomics and was successfully applied to various types of biomedical problems, in particular to histopathological label-free analysis of tissue sections. In histopathology, MALDI-imaging is used as a general analytic tool revealing the functional proteomic structure of tissue sections, and as a discovery tool for detecting new biomarkers discriminating a region annotated by an experienced histologist, in particular, for cancer studies.A typical MALDI-imaging data set contains 108 to 109 intensity values occupying more than 1 GB. Analysis and interpretation of such huge amount of data is a mathematically, statistically and computationally challenging problem. In this paper we overview some computational methods for analysis of MALDI-imaging data sets. We discuss the importance of data preprocessing, which typically includes normalization, baseline removal and peak picking, and hightlight the importance of image denoising when visualizing IMS data.

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Creaser, Colin S., James C. Reynolds, Andrew J. Hoteling, William F. Nichols, and Kevin G. Owens. "Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionisation Ion Trap Mass Spectrometry of Synthetic Polymers: A Comparison with Vacuum Matrix-Assisted Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry." European Journal of Mass Spectrometry 9, no. 1 (February 2003): 33–44. http://dx.doi.org/10.1255/ejms.528.

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Atmospheric pressure matrix-assisted laser desorption/ionisation quadrupole ion trap (AP-MALDI/QIT) mass spectrometry has been investigated for the analysis of polyethylene glycol (PEG 1500) and a hyperbranched polymer (polyglycidol) in the presence of alkali–metal salts. Mass spectra of PEG 1500 obtained at atmospheric pressure showed dimetallated matrix/analyte adducts, in addition to the expected alkali–metal/PEG ions, for all matrix/alkali–metal salt combinations. The relative intensities of the desorbed ions were dependent on the matrix, the alkali–metal salt added to aid cationisation and the ion trap interface conditions [capillary temperature, in-source collisionally-induced dissociation (CID)]. These data indicate that the adducts are rapidly stabilised by collisional cooling enabling them to be transferred into the ion trap. Experiments using identical sample preparation conditions were carried out on a vacuum MALDI time-of-flight (ToF) mass spectrometer. In all cases, vacuum MALDI-ToF spectra showed only alkali–metal/PEG ions and no matrix/analyte adducts. The tandem mass spectrometry (MS/MS) capability of the ion trap has been demonstrated for a lithiated polyglycol yielding a rich fragment-ion spectrum. Analysis of the hyperbranched polymer polyglycidol by AP-MALDI/QIT reveals the characteristic ion series for these polymers as also observed under vacuum MALDI-ToF conditions.

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Kepper, Pamela, Richard Reinhardt, Andreas Dahl, Hans Lehrach, and Sascha Sauer. "Matrix-Assisted Laser Desorption/Ionization Mass Spectrometric Analysis of DNA on Microarrays." Clinical Chemistry 52, no. 7 (July 1, 2006): 1303–10. http://dx.doi.org/10.1373/clinchem.2006.067264.

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Abstract Background: Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is a powerful tool in biomolecule analysis with a wide range of application possibilities, including genotyping of single-base variations (also known as single-nucleotide polymorphisms, or SNPs) for candidate gene studies and diagnostic typing of DNA markers. We tested a method that does not require stringent purification of the nucleic acids and/or the use of modification chemistry before mass spectrometry analysis. Methods: We used an alternative direct analysis approach that allows MALDI analysis of crude DNA samples printed on microscope slides densely coated with primary amino groups that efficiently bind negatively charged DNA. After simple washing of the slides, we applied MALDI matrix and used a conventional MALDI mass spectrometer to detect DNA products. Results: We analyzed crude oligonucleotide samples and performed automated genotyping of single-base variations in 72 DNA samples. Conclusion: This procedure offers an operational short-cut compared with standard MALDI procedures for preparation of oligonucleotides, including purification, and thus is an efficient tool for genotyping applications, particularly those requiring accurate, flexible, and rapid data generation and medium throughput.

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Dannhorn, Andreas, Emine Kazanc, Gregory Hamm, John G. Swales, Nicole Strittmatter, Gareth Maglennon, Richard J. A. Goodwin, and Zoltan Takats. "Correlating Mass Spectrometry Imaging and Liquid Chromatography-Tandem Mass Spectrometry for Tissue-Based Pharmacokinetic Studies." Metabolites 12, no. 3 (March 18, 2022): 261. http://dx.doi.org/10.3390/metabo12030261.

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Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a standard tool used for absolute quantification of drugs in pharmacokinetic (PK) studies. However, all spatial information is lost during the extraction and elucidation of a drugs biodistribution within the tissue is impossible. In the study presented here we used a sample embedding protocol optimized for mass spectrometry imaging (MSI) to prepare up to 15 rat intestine specimens at once. Desorption electrospray ionization (DESI) and matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) were employed to determine the distributions and relative abundances of four benchmarking compounds in the intestinal segments. High resolution MALDI-MSI experiments performed at 10 µm spatial resolution allowed to determine the drug distribution in the different intestinal histological compartments to determine the absorbed and tissue bound fractions of the drugs. The low tissue bound drug fractions, which were determined to account for 56–66% of the total drug, highlight the importance to understand the spatial distribution of drugs within the histological compartments of a given tissue to rationalize concentration differences found in PK studies. The mean drug abundances of four benchmark compounds determined by MSI were correlated with the absolute drug concentrations. Linear regression resulted in coefficients of determination (R2) ranging from 0.532 to 0.926 for MALDI-MSI and R2 values ranging from 0.585 to 0.945 for DESI-MSI, validating a quantitative relation of the imaging data. The good correlation of the absolute tissue concentrations of the benchmark compounds and the MSI data provides a bases for relative quantification of compounds within and between tissues, without normalization to an isotopically labelled standard, provided that the compared tissues have inherently similar ion suppression effects.

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Ulshina, D. V., D. A. Kovalev, A. M. Zhirov, N. V. Zharinova, A. A. Khudoleev, O. I. Kogotkova, V. I. Efremenko, N. I. Evchenko, and A. N. Kulichenko. "FEATURES OF MASS-SPECTROMETRIC PROTEIN PROFILES OF STRAINS OF BRUCELLOSIS CAUSATIVE AGENT DURING PREPARATION OF CULTURE ON VARIOUS NUTRIENT MEDIA." Journal of microbiology epidemiology immunobiology, no. 1 (February 28, 2016): 29–34. http://dx.doi.org/10.36233/0372-9311-2016-1-29-34.

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Aim. Carry out comparative analysis using time-of-flight mass-spectrometry with matrix laser desorption/ionization (MALDI-TOF MS) of protein profiles of brucellosis causative agents (Brucella melitensis Rev-1 and Brucella abortus 19BA), cultivated in various nutrient media: Albimi agar, brucellagar and erythrit-agar. Materials and methods. Vaccine strains: Brucella melitensis Rev-1 and Brucella abortus 19BA. Protein profiling in linear mode on Microflex «Bruker Daltonics» MALDI-TOF mass-spectrometer. Results. A number of characteristic features of brucella mass-spectra was detected: in particular, preservation of the total qualitative composition of protein profiles of cultures and significant differences in the intensity of separate peaks depending on the nutrient medium used. Conclusion. Based on the analysis of the data obtained, use of Albimi agar as the nutrient medium for preparation of brucella culture samples for mass-spectrometric analysis was shown to be optimal.

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Samoilova, A. A., I. V. Likhachev, E. V. Zueva, E. V. Rogacheva, L. A. Kraeva, and N. V. Mikhailov. "Determination of sensitivity of microorganisms of the Klebsiella genus to antimicrobial drugs by the MALDI-TOF MS method." Bacteriology 5, no. 3 (2020): 8–13. http://dx.doi.org/10.20953/2500-1027-2020-3-8-13.

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Actual microbiological diagnostics of infections caused by Klebsiella spp. should include isolation of the strain, its identification and fastest possible determination of the pathogen susceptibility to antimicrobial agents. We evaluated the prospects of using MALDI-TOF mass spectrometry to determine the susceptibility of Klebsiella spp. strains to antimicrobial agents. According to the results of mass spectrometry Klebsiella spp. strains analysis, we carried out cluster analysis by the UPGMA method based on mass spectra and data on the susceptibility of the studied strains to antimicrobial agents, and then studied the obtained dendrograms. We identified the areas with the highest probability of the location of antibiotic resistance markers by comparing the mass spectra of susceptible and resistant microorganisms at different concentrations of antimicrobial agents. Thus, using MALDI-TOF mass spectrometry, a new direction in assessing the susceptibility of Klebsiella spp. to antimicrobial agents can be formed. Key words: antibiotic resistance, Klebsiella spp., MALDI-TOF mass spectrometry

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Kett, Warren C., and Deirdre R. Coombe. "A structural analysis of heparin‒like glycosaminoglycans using MALDI‒TOF mass spectrometry." Spectroscopy 18, no. 2 (2004): 185–201. http://dx.doi.org/10.1155/2004/392536.

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Mass spectrometry (MS) techniques have spear‒headed the field of proteomics. Recently, MS has been used to structurally analyse carbohydrates. The heparin/heparan sulfate‒like glycosaminoglycans (HLGAGs) present a special set of difficulties for structural analysis because they are highly sulfated and heterogeneous. We have used a matrix‒assisted laser desorption/ionization time of flight mass spectrometry (MALDI‒MS) technique in which heparin fragments are non‒covalently bound to basic peptides of a known mass, so as to limit in‒source desulfation and hence afford an accurate mass. We examined a range of different sized fragments with varying degrees of sulfation. The potential of combining the MALDI‒MS technique with enzymatic digestion to obtain saccharide sequence information on heparin fragments was explored. A disaccharide analysis greatly assists in determining a sequence from MALDI‒MS data. Enzymatic digestion followed by MALDI‒MS allows structural data on heparin fragments too large for direct MALDI‒MS to be obtained. We demonstrate that synthetic sulfated oligosaccharides can also be analysed by MALDI‒MS. There are advantages and limitations with this methodology, but until superior MS techniques become readily accessible to biomedical scientists the MALDI‒MS method provides a means to structurally analyse HLGAG fragments that have therapeutic potential because of their ability to bind to and functionally regulate a host of clinically important proteins.

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Jagadeesan, Kishore Kumar, and Simon Ekström. "MALDIViz: A Comprehensive Informatics Tool for MALDI-MS Data Visualization and Analysis." SLAS DISCOVERY: Advancing the Science of Drug Discovery 22, no. 10 (August 21, 2017): 1246–52. http://dx.doi.org/10.1177/2472555217727517.

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Recently, mass spectrometry (MS) has emerged as an important tool for high-throughput screening (HTS) providing a direct and label-free detection method, complementing traditional fluorescent and colorimetric methodologies. Among the various MS techniques used for HTS, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) provides many of the characteristics required for high-throughput analyses, such as low cost, speed, and automation. However, visualization and analysis of the large datasets generated by HTS MALDI-MS can pose significant challenges, especially for multiparametric experiments. The datasets can be generated fast, and the complexity of the experimental data (e.g., screening many different sorbent phases, the sorbent mass, and the load, wash, and elution conditions) makes manual data analysis difficult. To address these challenges, a comprehensive informatics tool called MALDIViz was developed. This tool is an R-Shiny-based web application, accessible independently of the operating system and without the need to install any program locally. It has been designed to facilitate easy analysis and visualization of MALDI-MS datasets, comparison of multiplex experiments, and export of the analysis results to high-quality images.

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Spitsyn, A. N., D. V. Utkin, V. E. Kuklev, S. A. Portenko, V. G. Germanchuk, and N. A. Osina. "Application of MALDI Mass-Spectrometry for Diagnostics of Particularly Dangerous Infectious Diseases: Current State of Affairs and Prospects." Problems of Particularly Dangerous Infections, no. 3 (September 20, 2014): 77–82. http://dx.doi.org/10.21055/0370-1069-2014-3-77-82.

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Mass spectrometry is a modern physical-chemical analytical method that provides for qualitative and quantitative assessment of the substance composition. It is based on pre-ionization of the atoms and molecules included into it. One of the advanced methods of ionization, due to which mass-spectrometry investigation of macromolecules has become a frequent practice, is matrix-assisted laser desorption/ionization (MALDI). The essence of it is the pulsed laser irradiation of the matter under study, mixed with the matrix. The review discusses current data on MALDI mass-spectrometry application for the performance of species-specific and genus-specific identification of microorganisms at the premises of diagnostic laboratories. Considered are the basic advantages of MALDI-TOF identification as compared to bacteriologic, immunologic, and molecular-genetic methods of assessment. Allocated is the mass-spectrometry position in the system of laboratory diagnostics of infectious diseases, including particularly dangerous ones, in the territory of the Russian Federation.

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Gonçalves, R. F., C. R. Ferreira, C. M. B. Orlandi, V. C. Sartori, H. N. Ferreira, F. C. Gozzo, S. A. Saraiva, E. J. Pilau, and M. N. Eberlin. "111 SINGLE EQUINE EMBRYO LIPID FINGERPRINTING BY MASS SPECTROMETRY." Reproduction, Fertility and Development 23, no. 1 (2011): 160. http://dx.doi.org/10.1071/rdv23n1ab111.

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Matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS) allows the lipid profile study of individual mammal embryos. The data collection is rapid, highly sensitive, can tolerate some level of impurities, and is easy to interpret. The aim of this study was to report the lipid profile obtained from a single equine embryo by MALDI-MS. Follicles ≥30 mm in diameter were monitored daily until ovulation (Day 0). The insemination was performed close to ovulation with fresh diluted semen, and the embryo recovery was performed on Day 9 (D9) post ovulation. The equine embryo was placed in 50/50 (v/v) methanol/phosphate buffer solution and transported at 4°C to the laboratory. MALDI-MS spectra were acquired in the positive ion mode using MALDI Synapt HDMS mass spectrometer (Waters, Manchester, UK) m/z 700–950 range. The sample was coated with a 1.2 μL matrix of 2,5-dihydroxybenzoic acid (DHB) 1.0 mL L–1 in methanol. Due to the equine embryo volume, it was possible to divide it and get two mass spectra, which were identical. Spectra processing was performed using the MassLynx 4.0 software (Waters, Manchester, UK). It was observed the presence protonated and sodiated species of sphingomyelins (SM), phosphatidylcholines (PC), and triacylglycerols (TAG). The most intense ions assigned by comparison with data obtained from bovine embryos were m/z 723.5 [PC (34:1) and loss of N(CH3)3]+, 725.5. [SM (16:0) + Na]+, 754.6 [PC (32:1) + Na]+, 778.6 [PC (36:1) + Na]+, 780.6 [PC (34:2) + Na]+ or [PC (36:5) + H]+, 782.6 [PC (36:4) + H]+ or [PC (34:1) + Na]+, 788.6 [PC (36:1) + H]+, 806.6 [PC (38:6) + H]+ or [PC (36:3) + Na]+, 808.6 [PC (38:5) + H]+ or [PC (36:2) + Na]+, 810.6 [PC (38:4) + H]+ or [PC (36:1) + Na]+, 907.7 [TAG (54:3) + Na]+ and 909.7 [TAG (54:2) + Na] +. Regarding the lipid profile by MALDI-TOF previously reported for oocytes and embryos of several species (Ferreira et al. 2010, J. Lipid Res., 51, 1218–1227), it detected similar lipid species, but with different relative intensities. Because of the single equine embryo volume and MALDI-MS technique sensitivity, we intend to observe if there will be differences between the lipid profile of the inner cell mass and trophoblast in the future. The analysis of a greater number of embryos as well as different development periods and MS/MS experiments will contribute to building a database of lipid profiles that allows a better understanding of the lipid profile physiology in equine embryos and the meaning of differences among other mammalian embryos. FAPESP (São Paulo Research Foundation).

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Heap, Rachel E., Anthony G. Hope, Lesley-Anne Pearson, Kathleen M. S. E. Reyskens, Stuart P. McElroy, C. James Hastie, David W. Porter, J. Simon C. Arthur, David W. Gray, and Matthias Trost. "Identifying Inhibitors of Inflammation: A Novel High-Throughput MALDI-TOF Screening Assay for Salt-Inducible Kinases (SIKs)." SLAS DISCOVERY: Advancing the Science of Drug Discovery 22, no. 10 (July 10, 2017): 1193–202. http://dx.doi.org/10.1177/2472555217717473.

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Matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometry has become a promising alternative for high-throughput drug discovery as new instruments offer high speed, flexibility and sensitivity, and the ability to measure physiological substrates label free. Here we developed and applied high-throughput MALDI TOF mass spectrometry to identify inhibitors of the salt-inducible kinase (SIK) family, which are interesting drug targets in the field of inflammatory disease as they control production of the anti-inflammatory cytokine interleukin-10 (IL-10) in macrophages. Using peptide substrates in in vitro kinase assays, we can show that hit identification of the MALDI TOF kinase assay correlates with indirect ADP-Hunter kinase assays. Moreover, we can show that both techniques generate comparable IC50 data for a number of hit compounds and known inhibitors of SIK kinases. We further take these inhibitors to a fluorescence-based cellular assay using the SIK activity-dependent translocation of CRTC3 into the nucleus, thereby providing a complete assay pipeline for the identification of SIK kinase inhibitors in vitro and in cells. Our data demonstrate that MALDI TOF mass spectrometry is fully applicable to high-throughput kinase screening, providing label-free data comparable to that of current high-throughput fluorescence assays.

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Montaudo, Giorgio, Filippo Samperi, Maurizio S. Montaudo, Sabrina Carroccio, and Concetto Puglisi. "Current Trends in Matrix-Assisted Laser Desorption/Ionization of Polymeric Materials." European Journal of Mass Spectrometry 11, no. 1 (February 2005): 1–14. http://dx.doi.org/10.1255/ejms.718.

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In the last few years, mass spectrometry has rapidly become indispensable in polymer analysis and complements, in many ways, the structural data provided by nuclear magnetic resonance. Mass spectrometry of polymers is emerging as a revolutionary technique, capable of challenging the techniques and protocols established for years for the characterization of synthetic polymers. Matrix-assisted laser desorption/ionization (MALDI) has become a widely applied method for the structural characterization of synthetic polymers. The primary aim of this review is to illustrate some recent advances in the study of macromolecular systems by MALDI. MALDI allows the identification of repeat units and end groups, the structural analysis of linear and cyclic oligomers and the estimate of composition and sequence for co-polymers. MALDI is also quite useful for the measurement of molar mass and bivariate distributions in polymers and for the detection of self-association in macromolecules, performed by coupling MALDI with size exclusion chromatography (SEC). Recently MALDI has been applied, with remarkable success, to the study of thermal and oxidative processes in polymers and to the characterization of co-polymers obtained by reactive polymer blending. Selected applications of MALDI to polymers are illustrated herewith.

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Kanter, Frederic, Jan Lellmann, Herbert Thiele, Steve Kalloger, David F. Schaeffer, Axel Wellmann, and Oliver Klein. "Classification of Pancreatic Ductal Adenocarcinoma Using MALDI Mass Spectrometry Imaging Combined with Neural Networks." Cancers 15, no. 3 (January 22, 2023): 686. http://dx.doi.org/10.3390/cancers15030686.

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Despite numerous diagnostic and therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate, and is the fourth leading cause of cancer death in developing countries. Besides its increasing prevalence, pancreatic malignancies are characterized by poor prognosis. Omics technologies have potential relevance for PDAC assessment but are time-intensive and relatively cost-intensive and limited by tissue heterogeneity. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can obtain spatially distinct peptide-signatures and enables tumor classification within a feasible time with relatively low cost. While MALDI-MSI data sets are inherently large, machine learning methods have the potential to greatly decrease processing time. We present a pilot study investigating the potential of MALDI-MSI in combination with neural networks, for classification of pancreatic ductal adenocarcinoma. Neural-network models were trained to distinguish between pancreatic ductal adenocarcinoma and other pancreatic cancer types. The proposed methods are able to correctly classify the PDAC types with an accuracy of up to 86% and a sensitivity of 82%. This study demonstrates that machine learning tools are able to identify different pancreatic carcinoma from complex MALDI data, enabling fast prediction of large data sets. Our results encourage a more frequent use of MALDI-MSI and machine learning in histopathological studies in the future.

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Wu, Baolin, Tom Abbott, David Fishman, Walter Mcmurray, Gil Mor, Kathryn Stone, David Ward, Kenneth Williams, and Hongyu Zhao. "Ovarian Cancer Classification Based on Mass Spectrometry Analysis of Sera." Cancer Informatics 2 (January 2006): 117693510600200. http://dx.doi.org/10.1177/117693510600200031.

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In our previous study [ 1 ], we have compared the performance of a number of widely used discrimination methods for classifying ovarian cancer using Matrix Assisted Laser Desorption Ionization (MALDI) mass spectrometry data on serum samples obtained from Reflectron mode. Our results demonstrate good performance with a random forest classifier. In this follow-up study, to improve the molecular classification power of the MALDI platform for ovarian cancer disease, we expanded the mass range of the MS data by adding data acquired in Linear mode and evaluated the resultant decrease in classification error. A general statistical framework is proposed to obtain unbiased classification error estimates and to analyze the effects of sample size and number of selected m/z features on classification errors. We also emphasize the importance of combining biological knowledge and statistical analysis to obtain both biologically and statistically sound results. Our study shows improvement in classification accuracy upon expanding the mass range of the analysis. In order to obtain the best classification accuracies possible, we found that a relatively large training sample size is needed to obviate the sample variations. For the ovarian MS dataset that is the focus of the current study, our results show that approximately 20–40 m/z features are needed to achieve the best classification accuracy from MALDI-MS analysis of sera. Supplementary information can be found at http://bioinformatics.med.yale.edu/proteomics/BioSupp2.html .

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Coombes, Kevin R., John M. Koomen, Keith A. Baggerly, Jeffrey S. Morris, and Ryuji Kobayashi. "Understanding the Characteristics of Mass Spectrometry Data through the use of Simulation." Cancer Informatics 1 (January 2005): 117693510500100. http://dx.doi.org/10.1177/117693510500100103.

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Background Mass spectrometry is actively being used to discover disease-related proteomic patterns in complex mixtures of proteins derived from tissue samples or from easily obtained biological fluids. The potential importance of these clinical applications has made the development of better methods for processing and analyzing the data an active area of research. It is, however, difficult to determine which methods are better without knowing the true biochemical composition of the samples used in the experiments. Methods We developed a mathematical model based on the physics of a simple MALDI-TOF mass spectrometer with time-lag focusing. Using this model, we implemented a statistical simulation of mass spectra. We used the simulation to explore some of the basic operating characteristics of MALDI or SELDI instruments. Results The simulation reproduced several characteristics of actual instruments. We found that the relative mass error is affected by the time discretization of the detector (about 0.01%) and the spread of initial velocities (about 0.1%). The accuracy of calibration based on external standards decays rapidly outside the range spanned by the calibrants. Natural isotope distributions play a major role in broadening peaks associated with individual proteins. The area of a peak is a more accurate measure of its size than the height. Conclusions The model described here is capable of simulating realistic mass spectra. The simulation should become a useful tool for generating spectra where the true inputs are known, allowing researchers to evaluate the performance of new methods for processing and analyzing mass spectra. Availability http://bioinformatics.mdanderson.org/cromwell.html

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Lieb, Florian, Tobias Boskamp, and Hans-Georg Stark. "Peak detection for MALDI mass spectrometry imaging data using sparse frame multipliers." Journal of Proteomics 225 (August 2020): 103852. http://dx.doi.org/10.1016/j.jprot.2020.103852.

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Barkauskas, Donald A., Scott R. Kronewitter, Carlito B. Lebrilla, and David M. Rocke. "Analysis of MALDI FT-ICR mass spectrometry data: A time series approach." Analytica Chimica Acta 648, no. 2 (August 2009): 207–14. http://dx.doi.org/10.1016/j.aca.2009.06.064.

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Yu, Weichuan, Baolin Wu, Ning Lin, Kathy Stone, Kenneth Williams, and Hongyu Zhao. "Detecting and aligning peaks in mass spectrometry data with applications to MALDI." Computational Biology and Chemistry 30, no. 1 (February 2006): 27–38. http://dx.doi.org/10.1016/j.compbiolchem.2005.10.006.

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Braga, Patrícia A. C., Juliano L. Gonçalves, Juliana R. Barreiro, Christina R. Ferreira, Tiago Tomazi, Marcos N. Eberlin, and Marcos V. Santos. "Rapid identification of bovine mastitis pathogens by MALDI-TOF Mass Spectrometry." Pesquisa Veterinária Brasileira 38, no. 4 (April 2018): 586–94. http://dx.doi.org/10.1590/1678-5150-pvb-4821.

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ABSTRACT: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been shown to be an alternative method for identification of bacteria via their protein profile spectra, being able to identify bacteria at the genus, species and even at subspecies level. With the aim of large-scale identification of pathogens causing mastitis by this platform, a total of 305 isolates of bacteria identified from cows with subclinical mastitis were analyzed by conventional microbiological culture (MC) as well as by MALDI-TOF MS coupled with Biotyper data processing. Approximately 89% of the identifications performed by MALDI-TOF MS were consistent with results obtained by MC. From the remaining isolates (11%), 6.3% of isolates were classified as misidentified (discordance for both genus and species level), and 4.7% showed identification agreement at the genus level but not at the species level, being classified as unidentified at species level. The disagreement results were mostly associated with identification of Streptococcus and Enterococcus species probably due to the narrow phenotypic similarity between these two genera. These disagreement results suggest that biochemical assays might be prone to identification errors and, MALDI-TOF MS therefore may be an alternative to overcome incorrect species-specific identification. Standard microbiological methods for bovine mastitis diagnosis are time consuming, laborious and prone to errors for some bacteria genera. In our study, we showed that MALDI-TOF MS coupled with Biotyper may be an alternative method for large-scale identification of bacteria isolated from milk samples compared to classical microbiological routine protocols.

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Zambonin, Carlo. "MALDI-TOF Mass Spectrometry Applications for Food Fraud Detection." Applied Sciences 11, no. 8 (April 9, 2021): 3374. http://dx.doi.org/10.3390/app11083374.

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Chemical analysis of food products relating to the detection of the most common frauds is a complex task due to the complexity of the matrices and the unknown nature of most processes. Moreover, frauds are becoming more and more sophisticated, making the development of reliable, rapid, cost-effective new analytical methods for food control even more pressing. Over the years, MALDI-TOF MS has demonstrated the potential to meet this need, also due to a series of undeniable intrinsic advantages including ease of use, fast data collection, and capability to obtain valuable information even from complex samples subjected to simple pre-treatment procedures. These features have been conveniently exploited in the field of food frauds in several matrices, including milk and dairy products, oils, fish and seafood, meat, fruit, vegetables, and a few other categories. The present review provides a comprehensive overview of the existing MALDI-based applications for food quality assessment and detection of adulterations.

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Rathore, Rakesh, Jay Corr, George Scott, Pauline Vollmerhaus, and Kenneth D. Greis. "Development of an Inhibitor Screening Platform via Mass Spectrometry." Journal of Biomolecular Screening 13, no. 10 (November 21, 2008): 1007–13. http://dx.doi.org/10.1177/1087057108326143.

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Commonly used methods for isolated enzyme inhibitor screening typically rely on fluorescent or chemiluminescent detection techniques that are often indirect and/or coupled assays. Mass spectrometry (MS) has been widely reported for measuring the conversion of substrates to products for enzyme assays and has more recently been demonstrated as an alternative readout system for inhibitor screening. In this report, a high-throughput mass spectrometry (HTMS) readout platform, based on the direct measurement of substrate conversion to product, is presented. The rapid ionization and desorption features of a new generation matrix-assisted laser desorption ionization-triple quadrupole (MALDI-QqQ) mass spectrometer are shown to improve the speed of analysis to greater than 1 sample per second while maintaining excellent Z′ values. Furthermore, the readout was validated by demonstrating the ability to measure IC50 values for several known kinase inhibitors against cyclic AMP—dependent protein kinase (PKA). Finally, when the assay performance was compared with a common ADPaccumulation readout system, this HTMS approach produced better signal-to-background ratios, higher Z′ values, and a reagent cost of about $0.03 per well compared with about $0.60 per well for the fluorescence assay. Collectively, these data demonstrate that a MALDI-QqQ-MS—based readout platform offers significant advantages over the commonly used assays in terms of speed, sensitivity, reproducibility, and reagent cost. ( Journal of Biomolecular Screening 2008:1007-1013)

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Hsieh, Frank, Hasmik Keshishian, and Craig Muir. "Automated High Throughput Multiple Target Screening of Molecular Libraries by Microfluidic MALDI-TOF MS." Journal of Biomolecular Screening 3, no. 3 (April 1998): 189–98. http://dx.doi.org/10.1177/108705719800300305.

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Novel analytical techniques are demanded in parallel in the automated combinatorial library syntheses for accelerating the process of drug discovery. In this study, the integration of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and robotics for simultaneously identifying lead compounds with activity against multiple enzyme targets has been shown. MALDI-TOF MS monitors the interactions between multienzyme targets and a library of compounds and then identifies individual compounds from molecular libraries that affect the enzymatic activities of multiplexed target molecules to catalyze the conversion of substrates to products. The novel mass spectrometry screening in high-density format (~4,000 samples in a single 4.5 × 4.5 cm MALDI plate) provides much higher throughput over traditional screening approaches in terms of multiplex targets, attomole-level sensitivity, very low volume of samples required (10−9−10−12 1), and data acquisition for each sample within ten sec. The microfluidic multiple target screening approach mass spectrometry was shown for discovery of enzyme inhibitors as potential lead compounds.

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Povey, Jane F., Emily Saintas, Adewale V. Aderemi, Florian Rothweiler, Richard Zehner, Wilhelm G. Dirks, Jindrich Cinatl, et al. "Intact-Cell MALDI-ToF Mass Spectrometry for the Authentication of Drug-Adapted Cancer Cell Lines." Cells 8, no. 10 (October 2, 2019): 1194. http://dx.doi.org/10.3390/cells8101194.

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The use of cell lines in research can be affected by cell line misidentification. Short tandem repeat (STR) analysis is an effective method, and the gold standard, for the identification of the genetic origin of a cell line, but methods that allow the discrimination between cell lines of the same genetic origin are lacking. Here, we use intact cell MALDI-ToF mass spectrometry analysis, routinely used for the identification of bacteria in clinical diagnostic procedures, for the authentication of a set of cell lines consisting of three parental neuroblastoma cell lines (IMR-5, IMR-32 and UKF-NB-3) and eleven drug-adapted sublines. Principal component analysis (PCA) of intact-cell MALDI-ToF mass spectrometry data revealed clear differences between most, but not all, of the investigated cell lines. Mass spectrometry whole-cell fingerprints enabled the separation of IMR-32 and its clonal subline IMR-5. Sublines that had been adapted to closely related drugs, for example, the cisplatin- and oxaliplatin-resistant UKF-NB-3 sublines and the vincristine- and vinblastine-adapted IMR-5 sublines, also displayed clearly distinctive patterns. In conclusion, intact whole-cell MALDI-ToF mass spectrometry has the potential to be further developed into an authentication method for mammalian cells of a common genetic origin.

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Westblade, Lars F., Omai B. Garner, Karen MacDonald, Constance Bradford, David H. Pincus, A. Brian Mochon, Rebecca Jennemann, et al. "Assessment of Reproducibility of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Bacterial and Yeast Identification." Journal of Clinical Microbiology 53, no. 7 (April 29, 2015): 2349–52. http://dx.doi.org/10.1128/jcm.00187-15.

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Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) has revolutionized the identification of clinical bacterial and yeast isolates. However, data describing the reproducibility of MALDI-TOF MS for microbial identification are scarce. In this study, we show that MALDI-TOF MS-based microbial identification is highly reproducible and can tolerate numerous variables, including differences in testing environments, instruments, operators, reagent lots, and sample positioning patterns. Finally, we reveal that samples of bacterial and yeast isolates prepared for MALDI-TOF MS identification can be repeatedly analyzed without compromising organism identification.

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Surkova, R., R. Sharov, N. Polovets, A. Lipnitsky, and A. Murugova. "The use of MALDI-TOF massspectrometry for the identification of fungal pathogens." Immunopathology, Allergology, Infectology 2021, no. 3 (July 1, 2021): 73–78. http://dx.doi.org/10.14427/jipai.2021.3.73.

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Here we review modern data on the advantages and disadvantages of identifying mycoses pathogens using the MALDI-TOF mass spectrometry method. The advantages of this method are the high accuracy of the results obtained, the simplicity of the analysis, and the ability to determine the indicators of sensitivity to antifungal drugs. Limitations in using the method are associated with the lack of reference mass spectra of many micromycetes in the databases and standardized protocols for preparing micromycete cultures for MALDI-TOF mass spectrometry. Additional difficulties arise in the identification of pathogens of especially dangerous mycoses due to the limited representation of reference mass spectra in databases. When developing unified protocols for sample preparation, it is also necessary to take into account the growth phase of dimorphic micromycetes.

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Mittal, Paul, Mark R. Condina, Manuela Klingler-Hoffmann, Gurjeet Kaur, Martin K. Oehler, Oliver M. Sieber, Michelle Palmieri, et al. "Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging." Cancers 13, no. 21 (October 27, 2021): 5388. http://dx.doi.org/10.3390/cancers13215388.

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Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) can determine the spatial distribution of analytes such as protein distributions in a tissue section according to their mass-to-charge ratio. Here, we explored the clinical potential of machine learning (ML) applied to MALDI MSI data for cancer diagnostic classification using tissue microarrays (TMAs) on 302 colorectal (CRC) and 257 endometrial cancer (EC)) patients. ML based on deep neural networks discriminated colorectal tumour from normal tissue with an overall accuracy of 98% in balanced cross-validation (98.2% sensitivity and 98.6% specificity). Moreover, our machine learning approach predicted the presence of lymph node metastasis (LNM) for primary tumours of EC with an accuracy of 80% (90% sensitivity and 69% specificity). Our results demonstrate the capability of MALDI MSI for complementing classic histopathological examination for cancer diagnostic applications.

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Lapolla, Annunziata, Laura Molin, and Pietro Traldi. "Protein Glycation in Diabetes as Determined by Mass Spectrometry." International Journal of Endocrinology 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/412103.

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Diabetes is a common endocrine disorder characterized by hyperglycemia leading to nonenzymatic glycation of proteins, responsible for chronic complications. The development of mass spectrometric techniques able to give highly specific and reliable results in proteome field is of wide interest for physicians, giving them new tools to monitor the disease progression and the possible complications related to diabetes, as well as the effectiveness of therapeutic treatments. This paper reports and discusses some of the data pertaining protein glycation in diabetic subjects obtained by matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS). The preliminary studies carried out byin vitroprotein glycation experiments show clear differences in molecular weight of glycated and unglycated proteins. Then, the attention was focused on plasma proteins human serum albumin (HSA) and immunoglobulin G (IgG). Enzymatic degradation products ofin vitroglycated HSA were studied in order to simulate thein vivoenzymatic digestion of glycated species by the immunological system leading to the highly reactive advanced glycation end-products (AGEs) peptides. Further studies led to the evaluation of glycated Apo A-I and glycated haemoglobin levels. A different MALDI approach was employed for the identification of markers of disease in urine samples of healthy, diabetic, nephropathic, and diabetic-nephropathic subjects.

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Lapolla, Annunziata, and Pietro Traldi. "Proteomic Approaches in the Study of Placenta of Pregnancy Complicated by Gestational Diabetes Mellitus." Biomedicines 10, no. 9 (September 14, 2022): 2272. http://dx.doi.org/10.3390/biomedicines10092272.

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Gestational diabetes mellitus (GDM), a glucose intolerance developing or first recognized during pregnancy, leads to a series of short- and long-term maternal and fetal complications, somehow related to placenta structural and functional changes. The focus and the objective of the present review are to discuss the results which can be obtained by different mass spectrometric approaches in the study of placenta protein profile. Thus, matrix-assisted laser desorption/ionization mass spectrometry (MALDI) has been applied on placenta omogenates before and after one-dimensional electrophoretic separation, followed by tryptic digestion. MALDI imaging was used for direct investigation on the placenta tissue (both maternal and fetal sides). The results showed that some differences among the absolute abundances of some proteins are present for placenta samples from GDM patients. The majority of investigations were carried out by two-dimensional electrophoresis (2DE) followed by LC-MS/MS or, directly by the label-free LC-MSE approach. It should be emphasized that all these techniques were showed differences in the protein expression between the placenta samples from healthy or GDM subjects. 2DE was also employed to separate and compare placental protein levels from GDM and the control groups: differentially expressed proteins between the two groups were identified by MALDI-TOF/TOF mass spectrometry and were further confirmed by Western blotting. The physiopathological significance of the obtained results are reported and discussed in this narrative review. The experimental data obtained until now show that the newest, mass spectrometric approaches can be considered a valid tool to investigate the possible changes of placenta in the presence of GDM.

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Spinali, Sébastien, Alex van Belkum, Richard V. Goering, Victoria Girard, Martin Welker, Marc Van Nuenen, David H. Pincus, Maud Arsac, and Géraldine Durand. "Microbial Typing by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry: Do We Need Guidance for Data Interpretation?" Journal of Clinical Microbiology 53, no. 3 (July 23, 2014): 760–65. http://dx.doi.org/10.1128/jcm.01635-14.

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The integration of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) in clinical microbiology has revolutionized species identification of bacteria, yeasts, and molds. However, beyond straightforward identification, the method has also been suggested to have the potential for subspecies-level or even type-level epidemiological analyses. This minireview explores MALDI-TOF MS-based typing, which has already been performed on many clinically relevant species. We discuss the limits of the method's resolution and we suggest interpretative criteria allowing valid comparison of strain-specific data. We conclude that guidelines for MALDI-TOF MS-based typing can be developed along the same lines as those used for the interpretation of data from pulsed-field gel electrophoresis (PFGE).

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Luu, Gordon T., Alanna R. Condren, Lisa Juliane Kahl, Lars E. P. Dietrich, and Laura M. Sanchez. "Evaluation of Data Analysis Platforms and Compatibility with MALDI-TOF Imaging Mass Spectrometry Data Sets." Journal of the American Society for Mass Spectrometry 31, no. 6 (April 24, 2020): 1313–20. http://dx.doi.org/10.1021/jasms.0c00039.

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Haslam, Carl, John Hellicar, Adrian Dunn, Arne Fuetterer, Neil Hardy, Peter Marshall, Rainer Paape, Michelle Pemberton, Anja Resemannand, and Melanie Leveridge. "The Evolution of MALDI-TOF Mass Spectrometry toward Ultra-High-Throughput Screening: 1536-Well Format and Beyond." Journal of Biomolecular Screening 21, no. 2 (October 1, 2015): 176–86. http://dx.doi.org/10.1177/1087057115608605.

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Mass spectrometry (MS) offers a label-free, direct-detection method, in contrast to fluorescent or colorimetric methodologies. Over recent years, solid-phase extraction–based techniques, such as the Agilent RapidFire system, have emerged that are capable of analyzing samples in <10 s. While dramatically faster than liquid chromatography–coupled MS, an analysis time of 8–10 s is still considered relatively slow for full-diversity high-throughput screening (HTS). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) offers an alternative for high-throughput MS detection. However, sample preparation and deposition onto the MALDI target, as well as interference from matrix ions, have been considered limitations for the use of MALDI for screening assays. Here we describe the development and validation of assays for both small-molecule and peptide analytes using MALDI-TOF coupled with nanoliter liquid handling. Using the JMJD2c histone demethylase and acetylcholinesterase as model systems, we have generated robust data in a 1536 format and also increased sample deposition to 6144 samples per target. Using these methods, we demonstrate that this technology can deliver fast sample analysis time with low sample volume, and data comparable to that of current RapidFire assays.

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Boskamp, Tobias, Rita Casadonte, Lena Hauberg-Lotte, Sören Deininger, Jörg Kriegsmann, and Peter Maass. "Cross-Normalization of MALDI Mass Spectrometry Imaging Data Improves Site-to-Site Reproducibility." Analytical Chemistry 93, no. 30 (July 23, 2021): 10584–92. http://dx.doi.org/10.1021/acs.analchem.1c01792.

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Nicola, Anthony J., Arkady I. Gusev, and David M. Hercules. "Direct Quantitative Analysis from Thin-Layer Chromatography Plates Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry." Applied Spectroscopy 50, no. 12 (December 1996): 1479–82. http://dx.doi.org/10.1366/0003702963904458.

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Direct quantitative analysis using thin-layer chromatography (TLC) coupled with matrix-assisted laser desorption/ionization mass spectrometry (MALDI) has been demonstrated. An internal standard and a data collection protocol were used for analysis directly from TLC plates to compensate for shot-to-shot signal degradation, as well as deviations of analyte and internal standard spatial distributions within the TLC spot. Cocaine hydrochloride was used as a model compound for this study, and cocaine- d3 was used as the internal standard. Quantitative analysis by TLC/MALDI yielded comparable results to those obtained with stainless steel substrates (the standard MALDI method) for point-to-point repeatability, % RSD of the standard curve, and measurement precision. For silica gel and reverse-phase TLC plates, the relative standard deviation of the standard curve slope was better than 3%, the relative standard deviations of the analyte/internal standard intensity ratios ranged from 3.8% to 9.5%, the precision was estimated to be better than 12%, and the detection limits were estimated to be 60 pg for both TLC plate types. Quantitative analysis using stainless steel substrates yielded a lower detection limit than that obtained by TLC/MALDI by a factor of six. Perspectives for improving the detection limits of direct TLC/MALDI quantitative analysis are discussed. Index Headings: MALDI; TLC; Quantification.

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Huber, Charlotte A., Sarah J. Reed, and David L. Paterson. "Bacterial Sub-Species Typing Using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry: What Is Promising?" Current Issues in Molecular Biology 43, no. 2 (July 20, 2021): 749–57. http://dx.doi.org/10.3390/cimb43020054.

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Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is routinely used for bacterial identification. It would be highly beneficial to also be able to use the technology as a fast way to detect clinically relevant clones of bacterial species. However, studies to this aim have often had limited success. The methods used for data acquisition, processing and data interpretation are highly diverse amongst studies on MALDI-TOF MS sub-species typing. In addition to this, feasibility may depend on the bacterial species and strains investigated, making it difficult to determine what methods may or may not work. In our paper, we have reviewed recent research on MALDI-TOF MS typing of bacterial strains. Although we found a lot of variation amongst the methods used, there were approaches shared by multiple research groups. Multiple spectra of the same isolate were often combined before further analysis for strain distinction. Many groups used a protein extraction step to increase resolution in their MALDI-TOF MS results. Peaks at a high mass range were often excluded for data interpretation. Three groups have found ways to determine feasibility of MALDI-TOF MS typing for their set of strains at an early stage of their project.

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Aslanova, Mariya M., Darya V. Rakitina, Tamari R. Maniya, Ivan A. Abramov, and Vladimir P. Sergiev. "MALDI-TOF mass spectrometric analysis for identification of parasitic disease causes: current status and prospects." Hygiene and sanitation 101, no. 5 (May 31, 2022): 583–88. http://dx.doi.org/10.47470/0016-9900-2022-101-5-583-588.

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Introduction. The general issues of methodology, approaches and technologies in laboratory diagnostics of parasitic infections include MALDI-ToF MS-analysis (Matrix-Assisted Lazer Desorption/Ionization Time-of-Flight Mass Spectrometry; matrix-activated laser desorption-ionization time-of-Flight mass spectrometry), as well as a number of specific issues related to the relevance and timely application of this highly specific technologies in identification and typing of pathogens of parasitic diseases. An important and practically unsolved problem in parasitology is high-quality, highly effective, highly sensitive laboratory diagnostics of parasitoses. The object of this study is to analyze and evaluate the current state and perspectives of MALDI-TOF as an instrument of identification of diverse parasites in vples. Materials and methods. Federal statistics data on infectious and parasitic morbidity, own experimental studies, retrospectively analyzed literary data of foreign and Russian authors. Results. A steady decline in the detection of cases of parasitic invasions is associated with the lack of highly effective and sensitive diagnostic methods. Limitations. In the process of studying the effectiveness of the MALDI-TOF MS method in parasitological laboratories (departments), we analyzed our own experimental data (samples with artificial introduction of parasitic pathogens) and analyzed data on the main parasitic nosologies circulating in the territory of the Russian Federation for three years from 2017-2019, which are reflected in the state reports of of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing, which is a fairly reference sample. Conclusions. Studies comparing the results of mass spectrometric typing and traditional diagnostic methods are promising, which are necessary to clarify the capabilities of the method and determine its place in the laboratory diagnosis of infections caused by parasitic pathogens.

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Michálek, Jan, Karel Štěpka, Michal Kozubek, Jarmila Navrátilová, Barbora Pavlatovská, Markéta Machálková, Jan Preisler, and Adam Pruška. "Quantitative Assessment of Anti-Cancer Drug Efficacy From Coregistered Mass Spectrometry and Fluorescence Microscopy Images of Multicellular Tumor Spheroids." Microscopy and Microanalysis 25, no. 6 (October 1, 2019): 1311–22. http://dx.doi.org/10.1017/s1431927619014983.

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AbstractSpheroids—three-dimensional aggregates of cells grown from a cancer cell line—represent a model of living tissue for chemotherapy investigation. Distribution of chemotherapeutics in spheroid sections was determined using the matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). Proliferating or apoptotic cells were immunohistochemically labeled and visualized by laser scanning confocal fluorescence microscopy (LSCM). Drug efficacy was evaluated by comparing coregistered MALDI MSI and LSCM data of drug-treated spheroids with LSCM only data of untreated control spheroids. We developed a fiducial-based workflow for coregistration of low-resolution MALDI MS with high-resolution LSCM images. To allow comparison of drug and cell distribution between the drug-treated and untreated spheroids of different shapes or diameters, we introduced a common diffusion-related coordinate, the distance from the spheroid boundary. In a procedure referred to as “peeling”, we correlated average drug distribution at a certain distance with the average reduction in the affected cells between the untreated and the treated spheroids. This novel approach makes it possible to differentiate between peripheral cells that died due to therapy and the innermost cells which died naturally. Two novel algorithms—for MALDI MS image denoising and for weighting of MALDI MSI and LSCM data by the presence of cell nuclei—are also presented.

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Kamceva, Tina, Maja Nesic, Milovan Stoiljkovic, Iva Popovic, Jadranka Miletic, Boris Rajcic, Marijana Petkovic, and Suzana Velickovic. "Determination of isotopic distribution of lead by a matrix assisted laser desorption/ionization versus a laser desorption/ionization time of flight mass spectrometry." Chemical Industry 71, no. 1 (2017): 19–26. http://dx.doi.org/10.2298/hemind151218013k.

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In this work it has been shown that both the laser desorption/ionization mass spectrometry (LDI MS) and the matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) are the simple and quick methods for determination of relative natural isotopic distribution of lead. The analysis of metal salts with these approaches does not require any time-consuming preparation of samples: a single run can take only a minute, and numerous information can be obtained. Results obtained in this work show that chosen matrix has no negative effect on quantitative determination of lead isotopes and support once more the applicability of MALDI TOF MS for lead isotope distribution determination in the sample, and accuracy of data obtained. Additionally, the generation of PbnOn and PbnOn-1 (n: 2 - 6) clusters have been successfully achieved in the positive mode, using the both LDI and MALDI methods. All stoichiometries were confirmed using isotopic pattern modelling.

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Eiersbrock, Fabian B., Julian M. Orthen, and Jens Soltwisch. "Validation of MALDI-MS imaging data of selected membrane lipids in murine brain with and without laser postionization by quantitative nano-HPLC-MS using laser microdissection." Analytical and Bioanalytical Chemistry 412, no. 25 (July 25, 2020): 6875–86. http://dx.doi.org/10.1007/s00216-020-02818-y.

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Abstract MALDI mass spectrometry imaging (MALDI-MSI) is a widely used technique to map the spatial distribution of molecules in sectioned tissue. The technique is based on the systematic generation and analysis of ions from small sample volumes, each representing a single pixel of the investigated sample surface. Subsequently, mass spectrometric images for any recorded ion species can be generated by displaying the signal intensity at the coordinate of origin for each of these pixels. Although easily equalized, these recorded signal intensities, however, are not necessarily a good measure for the underlying amount of analyte and care has to be taken in the interpretation of MALDI-MSI data. Physical and chemical properties that define the analyte molecules’ adjacencies in the tissue largely influence the local extraction and ionization efficiencies, possibly leading to strong variations in signal intensity response. Here, we inspect the validity of signal intensity distributions recorded from murine cerebellum as a measure for the underlying molar distributions. Based on segmentation derived from MALDI-MSI measurements, laser microdissection (LMD) was used to cut out regions of interest with a homogenous signal intensity. The molar concentration of six exemplary selected membrane lipids from different lipid classes in these tissue regions was determined using quantitative nano-HPLC-ESI-MS. Comparison of molar concentrations and signal intensity revealed strong deviations between underlying concentration and the distribution suggested by MSI data. Determined signal intensity response factors strongly depend on tissue type and lipid species.

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Koteneva, E. A., E. S. Kotenev, A. V. Kalinin, N. S. Tsarеva, L. A. Kot, N. V. Zharinova, A. A. Zaitsev, and G. A. Pechkovsky. "Proteomic profiling of Yersinia pestis strains circulating in the area of natural plague foci of North Caucasus and Transcaucasia." Journal of microbiology epidemiology immunobiology, no. 4 (September 2, 2019): 18–25. http://dx.doi.org/10.36233/0372-9311-2019-4-18-25.

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Aim. To create a database of mass spectra of Yersinia pestis strains, which will differentiate the strains of the main and Caucasian subspecies of the plague agent by MALDI-TOF MS. Materials and methods. MALDITOF mass spectrometry was used to study 50 strains of Y. pestis, isolated on the territory of 7 natural plague foci of the Caucasus and Transcaucasia in the period 1950-2012. The removal of mass spectra of extracts of cells of Y. pestis was performed using the mass spectrometer Microflex LT «Bruker Daltonics». The results were processed and analyzed in FlexAnalysis programs, аnd MALDI Biotyper V. 3.0. Results. Тhis study showed that mass spectra have characteristic features that allow differentiating strains of the main (Y. pestis pestis) and subspecies (Y. pestis caucasica). Peaks characteristic of each subspecies were detected. The presence in Y. pestis caucasica subspecies peaks characteristic of the ancestral form — Y. pseudotuberculosis indicates the ancient origin of this group, which is consistent with the data of molecular genetic and WGS analysis given in other publications. Conclusion. Тhis work shows the possibility of applying the MALDI-TOF method of mass spectrometry for rapid differentiation of strains of the main subspecies Y. pestis pestis from the subspecies Y. pestis caucasica, which have different significance in the development and maintenance of the epizootic process in natural plague foci as well as different virulence for humans. Identification of the strain to the subspecies level requires carrying out culture and biochemical tests, which can take several days. The proposed method makes it possible to differentiate and obtain a result within half an hour after receiving a pure culture.

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Myers, Brittany K., Joanna E. Lapucha, and Scott M. Grayson. "Synthesis and MALDI-ToF characterization of dendronized poly(ethylene glycol)s." Brazilian Journal of Pharmaceutical Sciences 49, spe (2013): 45–55. http://dx.doi.org/10.1590/s1984-82502013000700005.

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Well-defined hybrids of linear poly(ethylene glycol)s (PEGs) and dendritic polyesters were prepared via the dendronization of the alcohol end groups of the mono and difunctional linear PEGs. Though useful for rudimentary product characterization, GPC and NMR could not verify the overall structural purity of these linear-dendritic hybrids. On the other hand, the detailed data provided by MALDI-ToF mass spectrometry enabled confirmation of the high structural purity of the dendronized PEGs at each step of the dendronization procedure. The well-defined number of functionalities on these dendronized PEGs, renders them particularly useful for research in the biomedical sphere where functionality and purity are of the utmost importance. The MALDI-ToF mass spectrometric approach described herein represents a valuable technique for detailed monitoring of these dendronization reactions, as well as a variety of other polymer end group modifications.

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Svetličić, Ema, Lucija Dončević, Luka Ozdanovac, Andrea Janeš, Tomislav Tustonić, Andrija Štajduhar, Antun Lovro Brkić, Marina Čeprnja, and Mario Cindrić. "Direct Identification of Urinary Tract Pathogens by MALDI-TOF/TOF Analysis and De Novo Peptide Sequencing." Molecules 27, no. 17 (August 25, 2022): 5461. http://dx.doi.org/10.3390/molecules27175461.

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For mass spectrometry-based diagnostics of microorganisms, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is currently routinely used to identify urinary tract pathogens. However, it requires a lengthy culture step for accurate pathogen identification, and is limited by a relatively small number of available species in peptide spectral libraries (≤3329). Here, we propose a method for pathogen identification that overcomes the above limitations, and utilizes the MALDI-TOF/TOF MS instrument. Tandem mass spectra of the analyzed peptides were obtained by chemically activated fragmentation, which allowed mass spectrometry analysis in negative and positive ion modes. Peptide sequences were elucidated de novo, and aligned with the non-redundant National Center for Biotechnology Information Reference Sequence Database (NCBInr). For data analysis, we developed a custom program package that predicted peptide sequences from the negative and positive MS/MS spectra. The main advantage of this method over a conventional MALDI-TOF MS peptide analysis is identification in less than 24 h without a cultivation step. Compared to the limited identification with peptide spectra libraries, the NCBI database derived from genome sequencing currently contains 20,917 bacterial species, and is constantly expanding. This paper presents an accurate method that is used to identify pathogens grown on agar plates, and those isolated directly from urine samples, with high accuracy.

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Rosulek, Darebna, Pompach, Slavata, and Novak. "Proteases Immobilization for In Situ Time-Limited Proteolysis on MALDI Chips." Catalysts 9, no. 10 (October 3, 2019): 833. http://dx.doi.org/10.3390/catal9100833.

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A large number of different enzyme immobilization techniques are used in the field of life sciences, clinical diagnostics, or biotechnology. Most of them are based on a chemically mediated formation of covalent bond between an enzyme and support material. The covalent bond formation is usually associated with changes of the enzymes’ three-dimensional structure that can lead to reduction of enzyme activity. The present work demonstrates a potential of an ambient ion-landing technique to effectively immobilize enzymes on conductive supports for direct matrix-assisted laser desorption/ionization (MALDI) mass spectrometry analyses of reaction products. Ambient ion landing is an electrospray-based technique allowing strong and stable noncovalent and nondestructive enzyme deposition onto conductive supports. Three serine proteolytic enzymes including trypsin, α-chymotrypsin, and subtilisin A were immobilized onto conductive indium tin oxide glass slides compatible with MALDI mass spectrometry. The functionalized MALDI chips were used for in situ time-limited proteolysis of proteins and protein–ligand complexes to monitor their structural changes under different conditions. The data from limited proteolysis using MALDI chips fits to known or predicted protein structures. The results show that functionalized MALDI chips are sensitive, robust, and fast and might be automated for general use in the field of structural biology.

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Bothner, Brian, Laurie Carmitchel, Kristin Staniszewski, Martin Sonderegger, and Gary Siuzdak. "Biomolecule structure characterization in the gas phase using mass spectrometry." Spectroscopy 16, no. 2 (2002): 71–79. http://dx.doi.org/10.1155/2002/243284.

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Carbohydrate/cation interactions were examined in the gas phase using mass spectrometry and the results were compared with computer generated models of the complexes. Monosaccharide/alkali cation complexes of five carbohydrates, D-fructose, D-glucose, D-galactose, D-mannose, and a deuterated analog of D-glucose, 6,6-D-glucose-d2, were studied. Among the technuques used in this effort were electrospray ionization (ESI), desorption/ionization on silicon (DIOS), matrix-assisted laser desorption/ionization (MALDI) and fast atom/ion bombardment (FAB) mass spectrometry. A series of ESI, DIOS, MALDI and FAB-MS experiments were used to obtain relative cation binding preferences of each monosaccharide. Heterodimers of 6,6-D-glucose-d2formed with each of the monosaccharides show that Na+binding for D-fructose, D-mannose and D-galactose is similar, while D-glucose was 25% weaker. Modeling studies and energy minimization calculations on the alpha and beta forms of the monosaccharide alkali cation complexes are consistent with the experimental data and indicate that D-fructose, D-galactose, and D-mannose undergo tridentate and tetradentate binding with Na+and Li+while D-glucose would only form a bidentate complex.

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Trauger, Sunia A., William Webb, and Gary Siuzdak. "Peptide and protein analysis with mass spectrometry." Spectroscopy 16, no. 1 (2002): 15–28. http://dx.doi.org/10.1155/2002/320152.

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Mass spectrometry (MS) is rapidly becoming a fundamental tool for biologists and biochemists in their efforts to characterize cellular function. Recent advancements in MS technology and front-end methodologies, along with the completion of the human genome have greatly popularized its use by researchers for protein identification and characterization. This paper is a general overview of how mass spectrometry is being used for the analysis of peptides and proteins, focusing on its application to molecular weight determination. Sample preparatory and cleanup techniques used in our laboratory for protein and peptide analysis are provided, along with a discussion of data interpretation. The utility of mass spectrometry for protein and peptide analyses lies in its ability to provide highly accurate molecular weight information on intact molecules. The ability to generate such accurate information can be extremely useful for protein identification and characterization. For example, a protein can often be unambiguously identified by the accurate mass analysis of its constituent peptides produced by either chemical or enzymatic treatment of the sample. Furthermore, protein identification can also be facilitated by analysis of the protein's proteolytic peptide fragments in the gas phase; fragment ions generated inside the mass spectrometer via collision-induced dissociation (CID) to yield information about the primary structure and modifications. This overview describes how electrospray ionization (ESI) and matrix‒assisted laser desorption/ionization (MALDI) mass spectrometry is being used for peptide and protein characterization focusing on its application to molecular weight determination.

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Simon, Roman P., Martin Winter, Carola Kleiner, Robert Ries, Gisela Schnapp, Annekatrin Heimann, Jun Li, et al. "MALDI-TOF Mass Spectrometry-Based High-Throughput Screening for Inhibitors of the Cytosolic DNA Sensor cGAS." SLAS DISCOVERY: Advancing the Science of Drug Discovery 25, no. 4 (October 4, 2019): 372–83. http://dx.doi.org/10.1177/2472555219880185.

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Comprehensive and unbiased detection methods are a prerequisite for high-throughput screening (HTS) campaigns within drug discovery research. Label-free matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has been introduced as an HTS-compatible readout for biochemical test systems to support the drug discovery process. So far, reported HTS applications were based on surface-modified systems or proof-of-concept studies. We present the utilization of a MALDI-TOF-based screening platform to identify inhibitors of human cyclic GMP-AMP synthase (cGAS), a mediator of innate immune response whose aberration has been causally correlated to a number of inflammatory disorders. In this context, the development and validation of a MALDI-TOF-based activity assay is reported to demonstrate fast, robust, and accurate detection of chemical cGAS inhibition by direct quantification of the physiological reaction product cyclic GMP-ATP (cGAMP). Results from a screen of a diverse library of more than 1 million small molecules in 1536-well format against the catalytic cGAS activity are presented with excellent assay performance and data quality. Identified hits were qualified in dose–response experiments and confirmed by RapidFire-MS measurements. Conclusively, the presented data provide the first proof of applicability of direct automated MALDI-TOF MS as a readout strategy for large-scale drug discovery HTS campaigns.

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Journal articles on the topic 'MALDI mass spectrometry data'

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