Journal of the American Society for Mass Spectrometry最新文献

{"title":"The Identity Algorithm: How the Most Popular Electron Ionization Mass Spectral Library Search Engine Actually Works.","authors":"Andrey Samokhin","doi":"10.1021/jasms.4c00350","DOIUrl":"10.1021/jasms.4c00350","url":null,"abstract":"<p><p>The Identity algorithm implemented in the MS Search (NIST) software is widely used for library searches of gas chromatography/mass spectrometry data against electron ionization mass spectral databases. It has been available to researchers since 1993, with the release of MS Search 1.5a. Despite its extensive use, the operational details of the algorithm have remained ambiguous. Attempts to replicate the algorithm have been unsuccessful because, as found in this research, the description in the manual is neither fully complete nor accurate. The main novelty of this work is the development of a unique approach for deconstructing the Identity algorithm. It is purely based on analyzing library search results obtained from several groups of synthetic mass spectra, each tailored to isolate and examine specific components of the algorithm. This approach facilitated a comprehensive understanding of the Identity algorithm and led to the development of a custom implementation that fully replicates the results obtained from the original MS Search software. The custom implementation of the Identity algorithm is now available in the mssearchr R package, enhancing accessibility for researchers.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"3178-3183"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646490","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":"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":" ","pages":"3002-3009"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","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":"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":"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":" ","pages":"2824-2835"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623168/pdf/","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":"OA","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":"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":" ","pages":"2869-2876"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622236/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fellgett Revisited: On the Nature of Noise in Two-Dimensional Mass Spectrometry.","authors":"Callan Littlejohn, Meng Li, Pui Yiu Lam, Mark P Barrow, Peter B O'Connor","doi":"10.1021/jasms.4c00294","DOIUrl":"10.1021/jasms.4c00294","url":null,"abstract":"<p><p>Two-dimensional mass spectrometry (2DMS) is a truly data-independent acquisition technique used in the analysis of complex mixtures; however, the nature of the noise within these spectra is not well understood. In this work, 2DMS is tested for conformity with the Fellgett principle: (signal/noise) ∝ √ (no. of data points). Since 2DMS functions through the modulation of ions through a fragmentation region across many scans, the individual scans are considered data points in this experiment. Random noise was shown to be prevalent as the main source of noise in this experiment with minor systematic noise. This means that the minimum size for a 2DMS spectrum that displays a target fragment ion can be determined using a fast-2D equation detailed herein. The effects of existing denoising algorithms were also found to change the relationship between the signal-to-noise ratio and the scan numbers to be of a quasi-linear nature rather than the square root trend observed before denoising.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"2984-2992"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492611","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}

{"title":"Actinide Elemental Ratios of Spent Nuclear Fuel Samples by Resonance Ionization Mass Spectrometry.","authors":"Manuel Raiwa, Michael R Savina, Autumn G Roberts, Danielle Z Shulaker, Brett H Isselhardt","doi":"10.1021/jasms.4c00371","DOIUrl":"10.1021/jasms.4c00371","url":null,"abstract":"<p><p>While resonance ionization mass spectrometry (RIMS) has demonstrated utility in measuring isotopic compositions of elements in complex matrices without the need for chemical separation to remove isobaric interferences, it has had limited application in measuring elemental compositions. The ability to determine elemental compositions via an in situ method like RIMS would be an exceptional asset in spent nuclear fuel analysis, where they are important in assessing reactor histories and whose chemical separation presents a radiological hazard. However, quantitative elemental analysis by RIMS requires special considerations because each element is ionized by its own set of lasers tuned to element specific resonant ionization wavelengths. We present the first comprehensive study of measuring elemental ratios by RIMS in spent nuclear fuel. All actinides produced by neutron capture are enhanced significantly radially from the center to the edge of a fuel pellet. This edge effect is not readily accessible by conventional bulk measurements.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"3233-3241"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611796","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}

{"title":"Infrared Laser Ablation and Capture of Formalin-Fixed Paraffin-Embedded Tissue.","authors":"Blessing C Egbejiogu, Fabrizio Donnarumma, Kermit K Murray","doi":"10.1021/jasms.4c00299","DOIUrl":"10.1021/jasms.4c00299","url":null,"abstract":"<p><p>Formalin-fixed paraffin-embedded (FFPE) tissue is a ubiquitous and invaluable resource for biomedical research and clinical applications. However, FFPE tissue proteomics is challenging due to protein cross-linking and chemical modification. Laser ablation sampling allows precise removal of material from tissue sections with high spatial control and reproducibility for offline proteomics by liquid chromatography coupled with tandem mass spectrometry. In this work, we used a pulsed mid-infrared laser for microsampling of rat liver tissue for subsequent identification and quantification of proteins. It was found that more proteins were identified by FFPE tissue laser ablation sampling compared to fresh frozen (FF) tissue laser ablation sampling and that more proteins were identified by laser ablation than by manual dissection of FFPE tissue. In contrast to previous studies, no loss of hydrophilic proteins due to residual cross-linking was observed. The efficient capture of proteins by laser ablation microsampling is attributed to efficient laser breakup of the tissue which facilitates downstream processing of the proteins.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"2993-3001"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567165","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":"Systematic Optimization of Activity-Based Protein Profiling for Identification of Polysorbate-Degradative Enzymes in Biotherapeutic Drug Substance down to 10 ppb.","authors":"Taku Tsukidate, Anita P Liu, Shannon Rivera, Alyssa Q Stiving, Jonathan Welch, Xuanwen Li","doi":"10.1021/jasms.4c00387","DOIUrl":"10.1021/jasms.4c00387","url":null,"abstract":"<p><p>The identification and control of high-risk host cell proteins (HCPs) in biotherapeutics development are crucial for ensuring product quality and shelf life. Specifically, HCPs with hydrolase activity can cause the degradation of excipient polysorbates (PS), leading to a decrease in the shelf life of the drug product. In this study, we systematically optimized every step of an activity-based protein profiling (ABPP) workflow to identify trace amounts of active polysorbate-degradative enzymes (PSDEs) in biotherapeutic process intermediates. Evaluation of various parameters during sample preparation pinpointed the optimal pH level and fluorophosphonate (FP)-biotin concentration. Moreover, the combined use of a short liquid chromatography gradient and the fast-scanning parallel accumulation-serial fragmentation (PASEF) methodology increased sample throughput without compromising identification coverage. Tuning the trapped ion mobility spectrometry (TIMS) parameters further enhanced sensitivity. In addition, we evaluated various data acquisition modes, including PASEF combined with data-dependent acquisition (DDA PASEF), data-independent acquisition (diaPASEF), or parallel reaction monitoring (prm-PASEF). By employing the newly optimized ABPP workflow, we successfully identified PSDEs at a concentration as low as 10 ppb in a drug substance sample. Finally, the new workflow enabled us to detect a PSDE that could not be detected with the original workflow during a PS degradation root-cause investigation.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"3256-3264"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685730","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":"AI-Guided Design of MALDI Matrices: Exploring the Electron Transfer Chemical Space for Mass Spectrometric Analysis of Low-Molecular-Weight Compounds.","authors":"Carlos A Padilla, Luis M Díaz-Sánchez, Cristian Blanco-Tirado, Aldo F Combariza, Marianny Y Combariza","doi":"10.1021/jasms.4c00186","DOIUrl":"10.1021/jasms.4c00186","url":null,"abstract":"<p><p>The development of matrices for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI MS) has traditionally relied on experimental efforts. Here, we propose a Goal-Directed artificial intelligence generative model, fueled by computational chemistry calculated data, to construct a chemical space optimized for Electron Transfer (ET) processes in MALDI analysis. We utilized a group of 30 reported ET matrices, subjected to structural enumeration and molecular properties prediction using semiempirical and <i>ab initio</i> calculations, to establish a comprehensive database comprising diverse structural and property data. Subsequently, employing a protocol of structural enumeration with 68 canonical SMILES of Bemis-Murcko (BM) fragments, we expanded the structural complexity of the initial library. This process generated 82753 compounds organized into 10 scaffold levels, with a p50 index from the Cyclic System Retrieval (CSR) curve of scaffolds of 50%. From the resulting enumerated library, a diverse subset of structures was selected by using the Jarvis-Patrick clustering method. These structures, along with their associated properties measured from quantum mechanics and experimental data, were used to train a Machine Learning (ML) model to predict ionization energy (<i>E</i>_<i>i</i>) values. Subsequently, a Scoring Neural Network (SNN), coupled with our Goal-Directed generative model using a Recurrent Neural Network (RNN) with Deep Learning (DL) architectures, was trained. The generative model was guided using a prior network within a Reinforcement/Transfer Learning environment. The final AI-generative model learned that structures with high unsaturation, H/C ratios under 1, and molecular weights between 100 and 300 u are favorable for ET MALDI matrices, as well as those with few aromatic rings and zero aliphatic rings. Other molecular features were also favored. The resulting AI-generated library exhibits <i>E</i>_<i>i</i> values over 8.0 eV, akin to those of reported \"good\" ET MALDI matrices, indicating successful design with high synthesis accessibility scores. In conclusion, our generative model provided valuable insights into the molecular features ideal for ET MALDI compounds while generating a wide range of structurally diverse molecules within a similar molecular property space. The next critical step in this process is to synthesize a selection of these generated compounds for the experimental validation and further characterization.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"2836-2848"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455367","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":"Impact of Hydrothermal Fluids on Hydrocarbon Generation and Solid Bitumen Formation in the Kongdian Formation, Huanghua Depression, China.","authors":"Yufu Han, Yuanjia Han, Li Wang, Dietrich A Volmer, Yulin Qi","doi":"10.1021/jasms.4c00403","DOIUrl":"10.1021/jasms.4c00403","url":null,"abstract":"<p><p>Hydrothermal fluid plays a crucial role in the generation and migration of hydrocarbons within sedimentary basins. Herein, we employed bulk analysis and high-resolution mass spectrometry techniques to investigate the transformation dynamics from source rock to hydrocarbons under conditions influenced by magmatic activities in the Kongdian Formation, Huanghua Depression, China. The results revealed that hydrocarbon generation in the Ek₂ shale of the study area was significantly influenced by abnormal heating from hydrothermal fluids. High temperatures associated with these fluids accelerated the conversion of organic matter within source rocks, enhancing hydrocarbon generation rates. Subsequently, the hydrocarbons migrated into fracture networks, where they solidified as low-reflectance solid bitumen, forming trapped fractures of pyrobitumen and authigenic mineral aggregates leached from thermal fluid. High aliphatic fractions were noted in the source rock extracts, while extracts from low-reflectance solid bitumen exhibited higher aromatic fraction. Aliphatic and aromatic compounds in extracts from both the low-reflectance solid bitumen and the source rock exhibited similar maturities and origins. Regarding polar compounds, the compound classes O₁, O₂, N₁O₁, and N₁O₂ showed higher abundances in source rock extracts compared to those in low-reflectance solid bitumen, while the S₁ and N₁ classes showed the opposite trend. Thus, fractionation clearly occurs when hydrocarbons expelled from source rocks by thermal fluids solidify into low-reflectance solid bitumen. This unique study provides valuable insights into understanding the fate of hydrocarbons originating from source rocks heated by thermal fluids, and explores the potential for unconventional oil in regions with intense hydrothermal alteration.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"3274-3285"},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666634","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}