Journal of the American Society for Mass Spectrometry最新文献

{"title":"Multispectrum ModiFinder Site Localization Performance.","authors":"Mohammad Reza Zare Shahneh, James Pyke, Emma E Rennie, Mingxun Wang","doi":"10.1021/jasms.4c00464","DOIUrl":"https://doi.org/10.1021/jasms.4c00464","url":null,"abstract":"<p><p>Tandem mass spectrometry (MS/MS) is a powerful technique for structural identification of small molecules, yet a significant portion of MS/MS spectra from untargeted experiments remain unidentifiable through spectrum library matching. ModiFinder, a computational tool, tackles this issue by predicting the site of chemical modifications on known analogs of the unidentified compounds using MS/MS data. However, ModiFinder's performance is limited by insufficient peak data and fragmentation annotation ambiguities. In this study, we investigate how incorporating MS/MS spectra from multiple collision energies and mass spectrometry adducts can enhance ModiFinder's localization accuracy. Using a data set from Agilent Technologies comprising 2150 data-rich compounds (five times larger than previously available data sets), we evaluated the impact of complementary spectral information. Our results show that combining spectra from different adducts and collision energies expands ModiFinder's localization abilities to more compounds and improves the overall performance.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass Spectrometry Imaging of Lipid and Metabolite Distributions in Cysts of <i>Besnoitia besnoiti</i>-Infected Bovine Skin.","authors":"Katja R Wiedemann, Stefanie Gerbig, Parviz Ghezellou, Alejandra Pilgram, Carlos Hermosilla, Anja Taubert, Liliana M R Silva, Bernhard Spengler","doi":"10.1021/jasms.4c00466","DOIUrl":"https://doi.org/10.1021/jasms.4c00466","url":null,"abstract":"<p><p>Bovine besnoitiosis is a disease caused by the obligate intracellular parasite <i>Besnoitia besnoiti</i>. During its chronic stage, the parasite forms large, thick-walled cysts of up to 600 μm in diameter in the skin and other tissues. To assess an overview of parasite-induced metabolic changes during chronic infection, <i>B. besnoiti</i>-infected skin samples were analyzed by high-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI). Overall, infection-driven, significant changes of 467 lipids and metabolites were found in comparison to noninfected control samples. Most of them belong to the group of phosphatidic acids (PAs), phosphatidylserines (PSs), phosphatidylcholines (PCs)/phosphatidylethanolamines (PEs), triacylglycerides (TGs), phosphatidylinositols (PIs) and phosphatidylglycerols (PGs). When these quantitative data were combined with analyses on the lateral distribution of respective infection markers, MS images of significantly changed ion signals with specific lateral distributions were generated, matching with typical biological structures as observed in Hematoxylin and eosin (H&E)-stained tissue sections. Ultrahigh-resolution MALDI MSI with a pixel size of 2 μm and 3-dimensional reconstruction gave further insights into cyst construction.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinguishing the Metabolic Effect of Fetal and Adult Fibrinogen on Human Fibroblast Cell Culture by IR-MALDESI Mass Spectrometry Imaging.","authors":"Alena N Joignant, Anastasia Sheridan, Ashley C Brown, David C Muddiman","doi":"10.1021/jasms.5c00027","DOIUrl":"https://doi.org/10.1021/jasms.5c00027","url":null,"abstract":"<p><p>Mass spectrometry imaging (MSI) of cells can elucidate metabolic changes with cellular and molecular specificity. Fibroblasts are mesenchymal cells that are important in tissue homeostasis and wound healing. During early wound healing, fibroblasts adhere to fibrinogen and migrate into fibrin clots, which are important interactions to stabilize early blood clots and promote subsequent tissue remodeling. It is understood that fibrinogen exists in distinct forms, fetal and adult, which have differing glycosylation and morphological effects on fibroblasts. Despite their importance to wound healing and the extracellular environment, fibroblasts are not commonly studied by MSI. While many MSI studies are conducted at the single-cell or subcellular level, there is still utility in accessing a broad view of the metabolic changes in a cell culture above single-cell spatial resolution. This enables imaging a wider area and larger number of cells directly from cell culture. In this work, dermal fibroblasts were imaged directly from cell culture chamber slides by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI). This method enabled treating the chambers with adult or fetal fibrinogen prior to cell culture and reduced sample preparation prior to MSI. Many metabolic effects of serum and fibrinogen type were elucidated, with changes in many membrane lipids such as cholesterol and ceramides potentially contributing to the observed morphological effects of fibrinogen types on fibroblasts.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and Energetic Effects of the 2-Amino and 2'- and 3'-Hydroxy Substituents of Protonated Guanosine Nucleosides: IRMPD, ER-CID, and Theoretical Studies of Protonated Guanosine and Inosine Nucleosides.","authors":"Liam P Quick, N M R Frieler, Zachary J Devereaux, Erik O Soley, E Israel, Giel Berden, Jonathan Martens, M T Rodgers","doi":"10.1021/jasms.5c00028","DOIUrl":"https://doi.org/10.1021/jasms.5c00028","url":null,"abstract":"<p><p>Inosine is a naturally occurring modified RNA nucleoside. Guanosine differs from inosine only by the 2-amino substituent of its nucleobase. The effects of the 2-amino and 2'- and 3'-hydroxy substituents on structure and glycosidic bond stability are examined via comparative studies of protonated guanosine vs inosine nucleoside analogues. Infrared multiple photon dissociation (IRMPD) action spectroscopy experiments are performed to probe structural effects, whereas energy-resolved collision-induced dissociation (ER-CID) experiments combined with survival yield analyses are performed to probe their effects on glycosidic bond stability. Density functional theory (DFT) calculations are performed to determine the stable low-energy conformations available to these systems, their relative stabilities, and infrared (IR) spectra. The structures experimentally populated are determined via comparisons of the measured IRMPD and predicted IR spectra. DFT calculations are also employed to map detailed mechanistic pathways for N-glycosidic bond cleavage of the protonated guanosine and inosine nucleosides. The influences of the 2-amino and 2'- and 3'-hydroxy substituents on glycosidic bond stability are determined from the trends in the energy-dependence of their ER-CID behavior and the activation energies predicted for glycosidic bond cleavage. The 2-amino substituent of the guanosine nucleosides has little effect on structure and is found to strengthen the glycosidic bond. The 2'- and 3'-hydroxy substituents exert a greater influence on structure via stabilizing hydrogen-bonding interactions enabled by their presence. The influences of the 2'- and 3'-hydroxy substituents on glycosidic bond stability differ. The 2'-hydroxy substituent significantly enhances glycosidic bond stability, whereas the 3'-hydroxy substituent slightly weakens glycosidic bond stability.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Fragmentation Pathways of New-Generation Synthetic Cannabinoids (INACA, IATA, FUPPYCA, and OXIZID Type Compounds) Based on Electrospray Ionization High-Resolution Mass Spectrometry.","authors":"Karolina Sekuła, Roman Stanaszek, Zuzanna Wysokińska, Dariusz Zuba","doi":"10.1021/jasms.5c00002","DOIUrl":"https://doi.org/10.1021/jasms.5c00002","url":null,"abstract":"<p><p>A rapid introduction of new psychoactive substances onto the illicit drug market and the dynamic changes in their structures cause the identification of novel compounds to be difficult and time-consuming. This is related to the possible lack of mass spectra of new substances in spectral libraries or the unavailability of certified reference materials. Therefore, this study analyzed the fragmentation patterns of 24 synthetic cannabinoids recently reported to the European Early Warning System. The tested compounds were divided into subgroups based on similarity of core structure and linker moiety, i.e., the synthetic cannabinoids with the acronym INACA (containing an indazole core and a carboxamide linker), the IATA compounds with an indole core and an acetamide linker, the FUPPYCA synthetic cannabinoids (containing a 4-fluorophenyl-pyrazole core and a carboxamide linker), and the OXIZID compounds which are characterized by a 2-oxindole core and a hydrazide linker. The analysis was carried out by quadrupole time-of-flight mass spectrometry with electrospray ionization (ESI-QTOFMS). High mass accuracy of the applied technique allowed us to determine the preferred fragmentation routes of novel synthetic cannabinoids. The main cleavage for the compounds with the acronyms INACA, IATA, and FUPPYCA occurred on the bond adjacent to the carbonyl group constituting part of the molecule linker. Instead, for the OXIZID type group, neither ions originating from the core of the molecule nor ions from the linker and tail were observed. Knowledge of the characteristic ions of compounds from a certain chemical group can be helpful in the elucidation of the structure of new substances that may appear in products seized on the drug market.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Internal Standard Utilization Strategies for Quantitative Paper Spray Mass Spectrometry.","authors":"Lucas R Abruzzi, John-Clare Laxton, Taelor M Zarkovic, Chris G Gill","doi":"10.1021/jasms.5c00036","DOIUrl":"https://doi.org/10.1021/jasms.5c00036","url":null,"abstract":"<p><p>Premixing internal standards (ISTD) with liquid samples prior to paper spray mass spectrometry (PS-MS) analysis consumes unnecessary amounts of ISTD and is not feasible for all sample types and applications. Depositing ISTD directly on the paper independently from sample has been successfully employed in the literature but can negatively affect quantitative performance. We evaluated different ISTD utilization strategies using drugs of misuse as test analytes to investigate the sources of irreproducibility and bias. Performance was assessed using both pre- and postdeposited ISTD (relative to sample loading) at different volumes with a constant final mass loading of 1 ng of each ISTD compound. Precision and accuracy were lower when using independently deposited ISTD compared to premixed ISTD (average CV = 18% vs 1% and average |bias| = 61% vs 5% for independently deposited ISTD and premixed ISTD, respectively). The use of a robotic liquid sample handling system to deposit ISTD was compared with results obtained via manually pipetting. Predeposited ISTD performed best at lower deposition volumes when a robotic liquid handler was used (average CV = 8% and 11% for 2 and 10 μL, respectively), but manual pipetting of low volume ISTD depositions performed poorly. Postdeposited ISTD was inferior to predeposited ISTD strategies, favoring larger deposition volumes regardless of deposition method (average CV = 22% and 16% for 2 and 10 μL, respectively). Systematic biases associated with each ISTD utilization strategy were effectively corrected for using strategy-matched calibrations, and AAFS (American Academy of Forensic Sciences) accuracy and precision requirements were achieved in almost all cases.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Ion Mobility Data Acquisition, Calibration, and Processing for Small Molecules: A Cross-Platform Assessment of Drift Tube and Traveling Wave Methodologies.","authors":"James N Dodds, Lucie C Ford, Jack P Ryan, Amie M Solosky, Ivan Rusyn, Erin S Baker","doi":"10.1021/jasms.5c00056","DOIUrl":"10.1021/jasms.5c00056","url":null,"abstract":"<p><p>As ion mobility spectrometry (IMS) separations continue to be added to analytical workflows due to their power in environmental and biological sample analyses, harmonization and capability understanding between existing and newly released instruments are desperately needed. Developments in IMS platforms often exhibit focus on increasing resolving power (R_p) to better separate molecules of similar structure. While the additional separation capacity is advantageous, ensuring these developments coincide with appropriate data extraction and analysis methods is imperative to ensure routine adoption. Herein, we assess the performance of the MOBILion MOBIE in relation to a commercially available drift tube IMS-MS, the Agilent 6560, and evaluate feature extraction and analysis pipelines. Both instruments were operated using matched conditions when possible, and performance metrics of scan speed, R_p, limits of detection (LOD), and propensity for isomer separation via LC-IMS-MS were evaluated. Similar scan speeds pertaining to IMS-MS frame generation were noted for both platforms, and collision cross section (CCS) values for the MOBIE were generally within ≤ 1% difference from previously reported drift tube values. Both platforms were also able to generate quantitative data (comparable limits of detection) in experiments with perfluoroalkyl substances (PFAS) mixtures in a cell-based model (both medium and cell lysates), as demonstrated in Skyline with adjusted mobility filtering parameters. Higher R_p was, however, noted on the MOBIE in comparison to the 6560 (200-300 vs 45-60 CCS/ΔCCS without data processing), allowing the detection of more PFAS isomers and indicating promise toward future applications in chemical exposomics studies and biomarker discovery when molecules exhibit similar structures.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Norm ISWSVR Enhanced Data Repeatability and Accuracy in Large-Scale Targeted Quantification Metabolomics.","authors":"Jinpeng Bai, Chenxi Li, Mingmin Qian, Xian Ding, Qian Li, Yanhua Chen, Zhaoying Wang, Zeper Abliz","doi":"10.1021/jasms.4c00467","DOIUrl":"https://doi.org/10.1021/jasms.4c00467","url":null,"abstract":"<p><p>Targeted quantification metabolomics provides dynamic insights across various domains within the life sciences. Nevertheless, maintaining high-quality data obtained through liquid chromatography-mass spectrometry presents ongoing challenges. It is essential to develop normalization methods to correct for unwanted variations in metabolomic profiling such as batch effects and analytical drift. In this study, we assessed the normalization efficacy of Norm ISWSVR in targeted quantification metabolomics by comparing it with IS normalization and SERRF normalization. Consequently, Norm ISWSVR demonstrated exceptional efficacy in mitigating batch effects and reducing the relative standard deviation of quality control samples, in addition to correcting signal drift. Following normalization with Norm ISWSVR, the number of metabolites suitable for quantification increased with high precision. Collectively, Norm ISWSVR proves to be a robust and reliable method for enhancing data quality in targeted metabolomics, establishing itself as a promising approach for metabolomics research.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Practical Approach for Internal Energy Tuning in LDI-MS: Porous Silicon Substrates as a Case Study.","authors":"Clara Whyte Ferreira, Bastien Cabrera-Tejera, Bernard Leyh, Romain Tuyaerts, Gilles Scheen, Yannick Coffinier, Edwin De Pauw, Gauthier Eppe","doi":"10.1021/jasms.4c00462","DOIUrl":"https://doi.org/10.1021/jasms.4c00462","url":null,"abstract":"<p><p>This study presents a methodical procedure for optimizing laser desorption/ionization mass spectrometry (LDI-MS) supports using porous silicon (PSi) substrates. The approach involves the use of substituted benzyl-pyridinium salts (thermometer ions) to obtain one metric that assesses analyte fragmentation (the effective temperature of vibration). Porous silicon substrates were synthesized via electrochemical etching of p-type silicon wafers (10-20 mΩ·cm), with etching parameters adjusted to vary porosity while maintaining a layer thickness between 700 and 1200 nm. The results revealed that PSi substrates with 40-60% porosity achieved the lowest fragmentation levels. This finding was validated through the analysis of N-acetyl glucosamine, a carbohydrate, which confirmed the effective temperature trend. Further analysis involving peptides, specifically P14R and a peptide mix (Peptide Calibration Standard II, Bruker), demonstrated that the optimized PSi substrates enabled the desorption and ionization of peptides with a maximum mass at <i>m</i>/<i>z</i> 2465, corresponding to ACTH clip 1-17. These results highlight the critical role of substrate porosity in minimizing analyte fragmentation and enhancing LDI-MS performance.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Binding Domains of Viral and Allergenic Proteins with Dual-Cleavable Cross-Linking Technology.","authors":"Akash Talukder, Saiful M Chowdhury","doi":"10.1021/jasms.4c00398","DOIUrl":"10.1021/jasms.4c00398","url":null,"abstract":"<p><p>The dual-cleavable nature of the cross-linking technology (DUCCT) enhances the reliable identification of cross-linked peptides via mass spectrometry. The DUCCT approach uses a cross-linking agent that can be selectively cleaved by two different tandem mass spectrometry techniques: collision-induced dissociation (CID) and electron transfer dissociation (ETD). This results in distinct signatures in two independent mass spectra for the same cross-linked precursor, leading to unambiguous identification and the validation of the spectra. In this study, we expanded the application of the DUCCT cross-linker to evaluate the binding domains of a specific cat dander allergen, Fel d 1, which exists as the Fel d 1 A and B protein complex, and a viral spike protein from SARS-CoV-2, which invades host cells. To assess the cross-linked products obtained by DUCCT, we utilized a software tool called Cleave-XL, which effectively identified cross-linked sites using data from CID and ETD. Dual cleavable cross-linking studies identified cross-linked peptides in these complexes, which have been reported in bioinformatics analysis and proposed for immunotherapy using synthetic peptides. A benchmark study was also conducted using a commercial cross-linker disuccinimidyl suberate (DSS). Overall, we expect that DUCCT cross-linking technology will greatly facilitate the rapid screening of binding interfaces, thereby advancing structural biology and cell signaling investigations.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"721-731"},"PeriodicalIF":3.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}