Journal of the American Society for Mass Spectrometry最新文献

{"title":"Covalent Labeling Automated Data Analysis Platform for High Throughput in R (coADAPTr): A Proteome-Wide Data Analysis Platform for Covalent Labeling Experiments.","authors":"Raquel L Shortt, Lindsay K Pino, Emily E Chea, Carolina Rojas Ramirez, Daniel A Polasky, Alexey I Nesvizhskii, Lisa M Jones","doi":"10.1021/jasms.4c00196","DOIUrl":"https://doi.org/10.1021/jasms.4c00196","url":null,"abstract":"<p><p>Covalent labeling methods coupled to mass spectrometry have emerged in recent years for studying the higher order structure of proteins. Quantifying the extent of modification of proteins in multiple states (i.e., ligand free vs ligand-bound) can provide information on protein interaction sites and regions of conformational change. Though there are several software platforms that are used to quantify the extent of modification, the process can still be time-consuming, particularly for proteome-wide studies. Here, we present an open-source software for quantitation called Covalent labeling Automated Data Analysis Platform for high Throughput in R (coADAPTr). coADAPTr tackles the need for more efficient data analysis in covalent labeling mass spectrometry for techniques such as hydroxyl radical protein footprinting (HRPF). Traditional methods like Excel's Power Pivot (PP) are cumbersome and time-intensive, posing challenges for large-scale analyses. coADAPTr simplifies analysis by mimicking the functions used in the previous quantitation platform using PowerPivot in Microsoft Excel but with fewer steps, offering proteome-wide insights with enhanced graphical interpretations. Several features have been added to improve the fidelity and throughput compared to those of PowerPivot. These include filters to remove any duplicate data and the use of the arithmetic mean rather than the geometric mean for quantitation of the extent of modification. Validation studies confirm coADAPTr's accuracy and efficiency while processing data up to 200 times faster than conventional methods. Its open-source design and user-friendly interface make it accessible for researchers exploring intricate biological phenomena via HRPF and other covalent labeling MS methods. coADAPTr marks a significant leap in structural proteomics, providing a versatile and efficient platform for data interpretation. Its potential to transform the field lies in its seamless handling of proteome-wide data analyses, empowering researchers with a robust tool for deciphering complex structural biology data.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363933","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 Novel Accurate Peak Extraction Algorithm of Mass Spectrometry Based on Iterative Adaptive Curve Fitting.","authors":"Fulong Deng, Xingliang He, Hanlu Yue, Hongen Sun, Bin Wu, Zhongjun Zhao, Yixiang Duan","doi":"10.1021/jasms.4c00244","DOIUrl":"https://doi.org/10.1021/jasms.4c00244","url":null,"abstract":"<p><p>In the analysis of mass spectrometry, the peak identification from the overlapped region is necessary yet difficult. Although various methods have been developed to identify these peaks, especially the continuous wavelet transformation, their applications are still limited and it is hard to deal with the complex overlapped peaks. In this study, a novel peak extraction algorithm of mass spectrometry based on iterative adaptive curve fitting is proposed to address these challenges. It fully utilizes the global optimization characteristics of adaptive curve fitting. Initial peak parameters are obtained using a window searching method, and the residuals between the adaptive fitting peak and the original data indicate the fit's effectiveness and provide information about the peaks in overlap. Using this information, we performed iterative adaptive fitting, continuously updating the overlapped peaks until the residuals met the completion criteria. All of the peaks within the overlapped region can be successfully extracted by the final fitting. The proposed method is evaluated by the simulated data, the real signal from a public data set, and the spectra of two different mass spectrometry instruments. The results demonstrate that this method can more effectively extract peaks with severe overlap and multiple overlapped peaks, resist noise interference, and offer the potential to process peaks with a high dynamic range. More importantly, the proposed method accurately identifies overlapped peaks in the actual spectra from various mass spectrometry instruments, which helps the qualitative and quantitative analyses to a great extent.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338949","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":"Assessment of the Migration of Polar Compounds from Petroleum-Contaminated Soil Using a Column Leaching Experiment.","authors":"Jianwen Wang, Yufu Han, Zibin Zhao, Chao Ma, Guanghui Yu, Yulin Qi","doi":"10.1021/jasms.4c00305","DOIUrl":"https://doi.org/10.1021/jasms.4c00305","url":null,"abstract":"<p><p>When petroleum leaks into soil, the polar compounds exhibit strong biological toxicity, causing serious damage to soil animals, plants, and microorganisms and potentially threatening human health. However, the systematic comprehension of the migration of polar compounds in petroleum-contaminated soil remains limited. Herein, we employed elemental analysis, stable carbon isotope analysis, and high-resolution mass spectrometry techniques to study the migration of polar compounds in petroleum-contaminated soil using a column leaching experiment. The results indicate that petroleum migration ability in soil is limited, and the compounds are primarily concentrated in the soil above 40 cm. The C/N, C/H, and δ¹³C ratios of organic matter in soils are highly affected by petroleum contamination. Meanwhile, the different compound classes show varying migration abilities, with N₁ and N₁O₁ compounds exhibiting stronger adsorption capacity on soil, while oxygen-containing compounds are more likely to migrate with water to deeper soil. Additionally, molecular polarity, unsaturation degree, and size are key factors affecting the migration of polar compounds in petroleum within the soil. This simulation experiment offers valuable insights into comprehending migration of polar compounds in petroleum-contaminated soil and their potential impacts for soil ecological environment.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338952","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":"Annotation of Metabolites in Stable Isotope Tracing Untargeted Metabolomics via Khipu-web.","authors":"Joshua M Mitchell, Yuanye Chi, Shujian Zheng, Maheshwor Thapa, Eric Wang, Shuzhao Li","doi":"10.1021/jasms.4c00175","DOIUrl":"https://doi.org/10.1021/jasms.4c00175","url":null,"abstract":"<p><p>Stable isotope tracing is a crucial technique for understanding the metabolic wiring of biological systems, determining metabolic flux through pathways of interest, and detecting novel metabolites and pathways. Despite the potential insights provided by this technique, its application remains limited to a small number of targeted molecules and pathways. Because previous software tools usually require chemical formulas to find relevant features, and the data are highly complex, especially in untargeted metabolomics and when the downstream reactions and metabolites are poorly characterized. We report here Khipu version 2 and its new user-friendly web application. New functions are added to enhance analyzing stable isotope tracing data including metrics that evaluate peak enrichment in labeled samples, scoring methods to facilitate robust detection of intensity patterns and integrated natural abundance correction. We demonstrate that this approach can be applied to untargeted metabolomics to systematically extract isotope-labeled compounds and annotate the unidentified metabolites.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338951","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":"Microbial Metabolomics' Latest SICRIT: Soft Ionization by Chemical Reaction In-Transfer Mass Spectrometry.","authors":"Allyson McAtamney, Allison Ferranti, Denise A Ludvik, Fitnat H Yildiz, Mark J Mandel, Taylor Hayward, Laura M Sanchez","doi":"10.1021/jasms.4c00309","DOIUrl":"10.1021/jasms.4c00309","url":null,"abstract":"<p><p>Microbial metabolomics studies are a common approach for identifying microbial strains that have a capacity to produce new chemistries both <i>in vitro</i> and <i>in situ</i>. A limitation to applying microbial metabolomics to the discovery of new chemical entities is the rediscovery of known compounds, or \"known unknowns.\" One factor contributing to this rediscovery is that the majority of laboratories use one ionization source─electrospray ionization (ESI)─to conduct metabolomics studies. Although ESI is an efficient, widely adopted ionization method, its widespread use may contribute to the reidentification of known metabolites. Here, we present the use of a dielectric barrier discharge ionization (DBDI) for microbial metabolomics applications through the use of soft ionization chemical reaction in-transfer (SICRIT). Additionally, we compared SICRIT to ESI using two different <i>Vibrio</i> species: <i>Vibrio fischeri</i>, a symbiotic marine bacterium, and <i>Vibrio cholerae</i>, a pathogenic bacterium. Overall, we found that the SICRIT source ionizes a different set of metabolites than ESI, and it has the ability to ionize lipids more efficiently than ESI in the positive mode. This work highlights the value of using more than one ionization source for the detection of metabolites.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338955","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 Spectral Feature Analysis of Ubiquitylated Peptides Provides Insights into Probing the Dark Ubiquitylome.","authors":"Regina M Edgington, Damien B Wilburn","doi":"10.1021/jasms.4c00213","DOIUrl":"10.1021/jasms.4c00213","url":null,"abstract":"<p><p>Ubiquitylation is a structurally and functionally diverse post-translational modification that involves the covalent attachment of the small protein ubiquitin to other protein substrates. Trypsin-based proteomics is the most common approach for globally identifying ubiquitylation sites. However, we estimate that such methods are unable to detect ∼40% of ubiquitylation sites in the human proteome, <i>i.e.</i>, \"the dark ubiquitylome\", including many important for human health and disease. In this meta-analysis of three large ubiquitylomic data sets, we performed a series of bioinformatic analyses to assess experimental features that could aid in uniquely identifying site-specific ubiquitylation events. Spectral predictions from Prosit were compared to experimental spectra of tryptic ubiquitylated peptides, revealing previously uncharacterized fragmentation of the diGly scar. Analysis of the LysC-derived ubiquitylated peptides reveals systematic, multidimensional peptide fragmentation, including diagnostic b-ions from fragmentation of the LysC ubiquitin scar. Comprehensively, these findings provide diagnostic spectral signatures of modification events that could be applied to new analysis methods for nontryptic ubiquitylomics.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338954","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":"Development of an Ultrasonic Nebulization System for an Inverse Low Temperature Plasma Ionization Source.","authors":"Alexandra Pape, Juan F Ayala-Cabrera, Florian Stappert, Florian Uteschil, Cedric Thom, Shinji Yoshioka, Yasushi Terui, Oliver J Schmitz","doi":"10.1021/jasms.4c00259","DOIUrl":"https://doi.org/10.1021/jasms.4c00259","url":null,"abstract":"<p><p>An effective nebulization and evaporation of a liquid sample, like in liquid chromatography, mass spectrometry (LC-MS) couplings, is an essential requirement for the ionization of analyte molecules in the gas phase by, for example, atmospheric pressure chemical ionization (APCI) or the novel low temperature plasma (LTP)-based ion source. These LTP-based ion sources have recently gained interest in the field of atmospheric pressure ion sources, as they can cover a wide range of polarity and molecular mass. They can be used in combination with separation techniques like liquid chromatography or used as an ambient ion source. However, commercial nebulizer systems are of course not constructed to fit to home-built LTP-based ion sources, and this was one incentive to develop a new nebulization system. Instead of an atmospheric pressure chemical ionization (APCI) nebulizer, two commercial nebulizers were disassembled and remodeled to be used as nebulizing systems in an LC-MS setup using an LTP-based ion source. Based on these results, a novel nebulizer system was subsequently developed. To further improve the degree of ionization, cones to focus the LC eluent spray on the plasma region, heating applications, and auxiliary nitrogen gas for dispersion of the solvent droplets were implemented. The LOD that could be calculated via the rule of three resulted in an average of 2.0 μg/L for the APCI-nebulizer and 41 μg/L for the USN. Both could be reduced to 1.4 and 18 μg/L, respectively, by using a TPI-configuration instead of an iLTP. The linearity was equally good for both types of nebulization devices. The final nebulizer could also be operated with a high water content and flow rates higher than those of the two previous ones, indicating an important improvement step.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338953","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":"Characterization of Anticancer Drug Protomers Using Electrospray Ionization and Ion Mobility Spectrometry-Mass Spectrometry.","authors":"Pallab Basuri, Marc Safferthal, Borislav Kovacevic, Pascal Schorr, Jerome Riedel, Kevin Pagel, Dietrich A Volmer","doi":"10.1021/jasms.4c00233","DOIUrl":"https://doi.org/10.1021/jasms.4c00233","url":null,"abstract":"<p><p>We used electrospray ionization and ion mobility spectrometry-mass spectrometry to detect and characterize the three anticancer drugs palbociclib, copanlisib, and olaparib. Ion mobility-mass spectrometry and density functional theory revealed that these compounds generate isomers during ionization (protomers) due to the presence of multiple protonation sites within their chemical structures. Our work has implications for understanding the solution- and gas-phase chemistry of these molecules during spray-based ionization processes.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360906","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":"An Integrated Strategy to Identify Tyrosine Sulfation from the Therapeutic Proteins.","authors":"Eunju Jang, Fengfei Ma, Daniela Tomazela, Laurence Fayadat-Dilman, Mohammad Ahmed Al-Sayah","doi":"10.1021/jasms.4c00303","DOIUrl":"https://doi.org/10.1021/jasms.4c00303","url":null,"abstract":"<p><p>Posttranslational modifications (PTMs) are potential critical quality attributes in biotherapeutic development, as they can affect drug efficacy and safety. Tyrosine sulfation plays a critical role in protein-protein interactions and has been found on many surface receptors as well as antibody complementarity-determining regions (CDR). However, the presence and function of tyrosine sulfation in therapeutic proteins have not been broadly investigated due to difficulties in detecting the modification. Here, we establish an integrated strategy to identify tyrosine sulfation in biotherapeutic proteins. In silico prediction was used to estimate possible modification sites, followed by the elucidation with intact LCMS and native SCX-MS. The combination of these three steps takes less than 1 h, which provides quick and confident preliminary detection of potential CQAs. Taking NB1 as an example, three +80 Da mass shifts were observed from intact mass analysis and three acidic peaks were monitored by SCX, allowing confirmation of modification as either phosphorylation or sulfation. Peptide mapping, Fe³⁺-IMAC enrichment, and dephosphorylation were further conducted to provide improved signal intensity and differentiation of modification such as sulfation or phosphorylation. With this integrated strategy, we were able to identify for the first time both tyrosine sulfation and serine phosphorylation in one therapeutic protein.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338950","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":"Text Mining and Computational Chemistry Reveal Trends in Applications of Laser Desorption/Ionization Techniques to Small Molecules","authors":"Nina P. Bergman,&nbsp;Jonas Bergquist,&nbsp;Mikael Hedeland and Magnus Palmblad*,&nbsp;","doi":"10.1021/jasms.4c0029310.1021/jasms.4c00293","DOIUrl":"https://doi.org/10.1021/jasms.4c00293https://doi.org/10.1021/jasms.4c00293","url":null,"abstract":"<p >Continued development of laser desorption/ionization (LDI) since its inception in the 1960s has produced an explosion of soft ionization techniques, where ionization is assisted by the physical or chemical properties of a structure or matrix. While many of these techniques have primarily been used to ionize large biomolecules, including proteins, some have recently seen increasing applications to small molecules such as pharmaceuticals. Small molecules pose particular challenges for LDI techniques, including interference from the matrix or support in the low mass range. To investigate trends in the application of soft LDI techniques to small molecules, we combined text mining and computational chemistry, looking specifically at matrix substances, analyte properties, and the research domain. In addition to making visible the history of LDI techniques, the results may inform the choice of method and suggest new avenues of method development. All software and collected data are freely available on GitHub (https://github.com/ReinV/SCOPE), VOSviewer (https://www.vosviewer.com), and OSF (https://osf.io/zkmua/).</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jasms.4c00293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142403912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}