Journal of the American Society for Mass Spectrometry最新文献

{"title":"To Impute or Not To Impute in Untargeted Metabolomics─That is the Compositional Question","authors":"Dennis D. Krutkin,&nbsp;Sydney Thomas,&nbsp;Simone Zuffa,&nbsp;Prajit Rajkumar,&nbsp;Rob Knight,&nbsp;Pieter C. Dorrestein and Scott T. Kelley*,&nbsp;","doi":"10.1021/jasms.4c0043410.1021/jasms.4c00434","DOIUrl":"https://doi.org/10.1021/jasms.4c00434https://doi.org/10.1021/jasms.4c00434","url":null,"abstract":"<p >Untargeted metabolomics often produce large datasets with missing values. These missing values are derived from biological or technical factors and can undermine statistical analyses and lead to biased biological interpretations. Imputation methods, such as <i>k</i>-Nearest Neighbors (kNN) and Random Forest (RF) regression, are commonly used, but their effects vary depending on the type of missing data, e.g., Missing Completely At Random (MCAR) and Missing Not At Random (MNAR). Here, we determined the impacts of degree and type of missing data on the accuracy of kNN and RF imputation using two datasets: a targeted metabolomic dataset with spiked-in standards and an untargeted metabolomic dataset. We also assessed the effect of compositional data approaches (CoDA), such as the centered log-ratio (CLR) transform, on data interpretation since these methods are increasingly being used in metabolomics. Overall, we found that kNN and RF performed more accurately when the proportion of missing data across samples for a metabolic feature was low. However, these imputations could not handle MNAR data and generated wildly inflated or imputed values where none should exist. Furthermore, we show that the proportion of missing values had a strong impact on the accuracy of imputation, which affected the interpretation of the results. Our results suggest imputation should be used with extreme caution even with modest levels of missing data and especially when the type of missingness is unknown.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 4","pages":"742–759 742–759"},"PeriodicalIF":3.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jasms.4c00434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745924","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":"Faces of Mass Spectrometry/Amanda Patrick","authors":"Anne Brenner,&nbsp; and ,&nbsp;J. D. Brookbank,&nbsp;","doi":"10.1021/jasms.5c0004210.1021/jasms.5c00042","DOIUrl":"https://doi.org/10.1021/jasms.5c00042https://doi.org/10.1021/jasms.5c00042","url":null,"abstract":"","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 4","pages":"628–631 628–631"},"PeriodicalIF":3.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745925","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":"Navigating the Postdoc Experience","authors":"Chae Kyung Jeon*,&nbsp;Daniel D. Vallejo and Michael T. Marty,&nbsp;","doi":"10.1021/jasms.4c0044810.1021/jasms.4c00448","DOIUrl":"https://doi.org/10.1021/jasms.4c00448https://doi.org/10.1021/jasms.4c00448","url":null,"abstract":"<p >There are many reasons to consider postdoctoral research after completing a Ph.D. For those interested in academic careers at all levels, a postdoctoral research associate (PDRA) position is often required or at least preferred. Even for those interested in industry, government, or alternative careers, postdoctoral research provides opportunities to expand your knowledge and skill sets beyond your Ph.D. training. It can be a wonderful time to focus on research with minimal distractions and interruptions. However, there has been little discussion about the challenges of the postdoc transition. The postdoc experience can vary widely, but common challenges include transitioning into a new environment, learning new skills, serving in multiple roles as a mentor and mentee, different and sometimes unclear positions in the institution, and competition for limited opportunities. In this Commentary, we draw on our personal experiences and interviews with postdocs of various backgrounds and intersectionalities (gender, race, first-gen, neurodiversity, etc.) to discuss how to successfully navigate various aspects of the postdoc experience. Our perspective comes primarily within mass spectrometry (MS) research, but the interviews include several experiences outside of the MS field to develop discussions applicable to a broad range of PDRA experiences.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"622–626 622–626"},"PeriodicalIF":3.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547242","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":"HRMS-Viewer: Software for High Resolution Mass Spectrometry Formula Assignment and Data Visualization","authors":"Junyang Chen,&nbsp;Chen He,&nbsp;Jianxun Wu,&nbsp;Yahe Zhang and Quan Shi*,&nbsp;","doi":"10.1021/jasms.4c0044210.1021/jasms.4c00442","DOIUrl":"https://doi.org/10.1021/jasms.4c00442https://doi.org/10.1021/jasms.4c00442","url":null,"abstract":"<p >Accurately assigning formulas to thousands of peaks generated by ultrahigh resolution mass spectrometry in a single analysis poses a significant challenge, especially when dealing with diverse molecular compositions across complex mixtures. This difficulty is further compounded by the lack of an established universal mass calibration and formula assignment method. We have developed HRMS-Viewer, a Python-based software tool designed for processing ultrahigh resolution mass spectrometry data specific to petroleum and natural organic matter (NOM). The software employs an efficient, experience-driven approach for small molecule formula assignment, offering a streamlined yet intuitive workflow. Key features include advanced noise reduction, automatic or manual recalibration, real-time visualization of formula assignment results, and options for manual correction. During the workflow, HRMS-Viewer enables the visualization and manual control of critical steps including noise reduction, recalibration, peak identification, and data review.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"565–572 565–572"},"PeriodicalIF":3.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547494","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":"Unveiling Readily Ionized and Robust Anionic Species: A Gateway to Enhanced Ionization Efficiency in ESI-MS Analysis","authors":"Benjamin B. Warnes,&nbsp;Jasmine Chihabi and Jeffrey M. Manthorpe*,&nbsp;","doi":"10.1021/jasms.4c0040010.1021/jasms.4c00400","DOIUrl":"https://doi.org/10.1021/jasms.4c00400https://doi.org/10.1021/jasms.4c00400","url":null,"abstract":"<p >Electrospray ionization mass spectrometry has long been a prevalent ionization method in the analysis of low volatility molecules with biological, environmental, and industrial relevance. To address analytical challenges associated with molecules suffering from low ionization efficiencies (IEs), chemical derivatization (CD) strategies have been developed and are frequently adopted into workflows. However, only a minute number of CD techniques have been developed for negative polarity. To address this disparity, we evaluated 27 anions based on three criteria: (1) IE relative to a sodium dodecyl sulfate (<b>11</b> + Na⁺) internal standard; (2) stability to collision induced dissociation; (3) diagnostic tandem mass spectrometry behavior. Highly fluorous ions exhibiting weakly coordinating and hydrophobic properties displayed enhanced IE. Trifluoromethanesulfonyl-containing ions proved to be unexpectedly labile, while tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (<b>23</b>) and bis(nonafluoro-1-butane)sulfonimidate (<b>25</b>) were determined to be of optimal IE of 332% ± 25% and 939% ± 92%, respectively, and in tandem MS exhibited survival yields of 100% ± 0% and 72.6% ± 0.8% at −50 eV. <b>23</b> and <b>25</b> were also comparable in IE across several solvents, and combinations thereof, that are ubiquitous in liquid chromatography. Various salts of <b>25</b> were evaluated for cation effects, where the IE of <b>25</b> ranged from 939% ± 92% to 3195% ± 145% across K⁺, NH₄⁺, Na⁺, and H⁺. Compared to tetra-<i>n</i>-butylammonium, tetra-<i>n</i>-butylphosphonium, and (4-methylphenyl)diphenylsulfonium cations, <b>25</b> displayed signal enhancements ranging from 136% ± 6% to 181% ± 14%, thereby making it an optimal candidate for CD development.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"524–533 524–533"},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547398","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":"Detection and Structural Elucidation of Copper Binding Tri- and Tetrapyrrole Ligands Produced by the Marine Diatom Phaeodactylum Tricornutum","authors":"Lydia Babcock-Adams,&nbsp;Jingxuan Li,&nbsp;Amy M. McKenna,&nbsp;Christopher L. Hendrickson and Daniel J. Repeta*,&nbsp;","doi":"10.1021/jasms.4c0038010.1021/jasms.4c00380","DOIUrl":"https://doi.org/10.1021/jasms.4c00380https://doi.org/10.1021/jasms.4c00380","url":null,"abstract":"<p >In seawater, most dissolved copper (Cu) is complexed by organic ligands, many of which are thought to be produced by phytoplankton. Although very little is known about the composition and structure of these ligands, they play an important role in determining the reactivity and bioavailability of Cu. In this study, <i>Phaeodactylum tricornutum</i>, a marine diatom known to produce Cu ligands (CuLs), was grown in laboratory pure culture, and the CuLs were recovered from the growth media. Using liquid chromatography coupled to ultrahigh resolution tandem mass spectrometry, 11 Cu ligand complexes were identified and assigned molecular formulas. Molecular formulas were confirmed by comparing the expected and observed relative abundances of ¹⁵N, ¹³C, ⁶⁵Cu, and ¹⁸O isotopologues. The CuLs had molecular weights from 520 to 719 Da and molecular formulas of C_26–35H_23–36O_5–9N_3–4Cu with an average assignment error of 56 ppb. High-resolution tandem mass spectrometry of the Cu-bound and metal-free ligands revealed these to be a suite of tri- and tetrapyrroles stabilized through complexation of Cu by N. The ligands share similar parent structures but differ in the number, type, and arrangement of functional groups that decorate the pyrroles. The similarity of CuL structures with known catabolites of chlorophyll suggests these ligands may be widely produced by marine photoautotrophs.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 4","pages":"713–720 713–720"},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745872","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":"PNGaseF-Generated N-Glycans Adduct onto Peptides in the Gas Phase","authors":"Valentina Rangel-Angarita,&nbsp;Joann Chongsaritsinsuk,&nbsp;Keira E. Mahoney,&nbsp;Lea M. Kim,&nbsp;Ryan J. Chen,&nbsp;Akua A. Appah-Sampong,&nbsp;Isabella P. Tran,&nbsp;Alexandra D. Steigmeyer,&nbsp;Marie A. Hollenhorst and Stacy A. Malaker*,&nbsp;","doi":"10.1021/jasms.4c0043110.1021/jasms.4c00431","DOIUrl":"https://doi.org/10.1021/jasms.4c00431https://doi.org/10.1021/jasms.4c00431","url":null,"abstract":"<p >Glycoproteomics has recently increased in popularity due to instrumental and methodological advances. That said, O-glycoproteomic analysis is still challenging for various reasons, including signal suppression, search algorithm limitations, and co-occupancy of N- and O-glycopeptides. To decrease sample complexity and simplify analysis, most O-glycoproteomic workflows include PNGaseF digestion, which is an endoglycosidase that removes most N-glycan structures. Here, we report that N-glycans released from PNGaseF digestion were identified during data acquisition and hampered detection of O-glycopeptides. Importantly, we noted instances where free glycans adducted to unmodified peptides in the gas phase and were misidentified by search algorithms as O-glycopeptides. We confirmed the presence of free glycans in other experiments performed in our laboratory, as well as from data generated by other groups. To overcome this limitation, we demonstrated that released N-glycans can be removed using a molecular weight cut off filter prior to (glyco)protease digestion, which improves O-glycoproteomic coverage.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"542–552 542–552"},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547391","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 Electrostatic-to-Covalent Gas Phase Cross-linkers for Protein Structure Measurements by Mass Spectrometry","authors":"Kacy L. Black,&nbsp; and ,&nbsp;Ian K. Webb*,&nbsp;","doi":"10.1021/jasms.4c0036310.1021/jasms.4c00363","DOIUrl":"https://doi.org/10.1021/jasms.4c00363https://doi.org/10.1021/jasms.4c00363","url":null,"abstract":"<p >The benefits of native mass spectrometry have led to the extensive study of proteins inside mass spectrometers in the gas phase. The expansion of native mass spectrometry requires novel tools for gaining greater insights into protein structures. Herein, we introduce a new approach utilizing gas phase ion/ion reactions, where cross-linking reagents link unprotonated lysine residues, arginine residues, and N-termini with their protonated forms. We used three lengths of linkers, determining that different length cross-linkers resulted in different residues being cross-linked, as we have previously observed for electrostatic-to-electrostatic cross-linkers. However, this new method allows for the probing of both protonated and neutral lysine and arginine residues. Native mass spectrometry often produces fewer charges than protonatable sites, allowing access to a greater number of sites on proteins using an electrostatic-to-covalent cross-linking approach. In this report, we describe the reaction phenomenology and trends at reaction sites. We envision electrostatic-to-covalent cross-linking as a useful structural tool to provide complementary information to other native MS-based measurements such as collision cross section.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"483–494 483–494"},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547474","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":"What Drives the Vehicle Mechanism? Protonation Isomer Interconversion of Arylamine Derivatives Probed with Solvent-Mediated Kinetics","authors":"Boris Ucur,&nbsp;Oisin J. Shiels,&nbsp;Alan T. Maccarone,&nbsp;Stephen J. Blanksby and Adam J. Trevitt*,&nbsp;","doi":"10.1021/jasms.4c0047010.1021/jasms.4c00470","DOIUrl":"https://doi.org/10.1021/jasms.4c00470https://doi.org/10.1021/jasms.4c00470","url":null,"abstract":"<p >Reactions with mobile protons occur under electrospray ionization (ESI) in many applications of mass spectrometry. Understanding how protonation isomers (protomers) form and how molecular structure influences protomer interconversion provides fundamental insight into ESI mechanisms, which can then be exploited to rationalize ion mobility and ion activation processes for robust analyte detection. Using ten arylamine protomer systems, this paper establishes the key substrate properties that influence protomer isomerism. Protomers from ten arylamines are separated by differential ion mobility spectrometry (DMS) mass spectrometry and identified by characteristic collision-induced dissociation mass spectra. These assignments are further rationalized using quantum chemical calculations (M06-2X/6-31G(2df,p)). Based on these assignments, mobility-selected protomers are then allowed to react with methanol vapor under atmospheric and reduced pressure conditions (2.5 mTorr, 300 K). The latter enabled measurements of the second-order rate coefficients for methanol-catalyzed protomer isomerization, which span 3.9 × 10^–11–2 × 10^–13 cm³ molecule^–1 s^–1. Double-hybrid quantum chemical calculations (DSD-PBEP86-D3(BJ)/aug-cc-pVDZ) show that the direction of proton transfer is controlled by protomer relative stability, whereas reaction rates are controlled by a key transition state that separates the protonation sites. Computational exploration of a larger substituted-arylamine test-set shows that the protomer proton affinity generally correlates with energy of the key transition state. Applying the Bell–Evans–Polanyi principle to this reaction set highlights that outliers in the predictive model correspond to transition states with significant displacements along the reaction coordinate. This archetype system of derivatized arylamines provides a foundation to understand how substrate functionalization influences protomer isomerism for ions during ESI and predicts protonation isomer distributions.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"601–612 601–612"},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547397","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 a Bunching Ionizer for TOF Mass Spectrometers with Reduced Resources","authors":"Oya Kawashima*,&nbsp;Satoshi Kasahara,&nbsp;Yoshifumi Saito,&nbsp;Masafumi Hirahara,&nbsp;Kazushi Asamura and Shoichiro Yokota,&nbsp;","doi":"10.1021/jasms.4c0043610.1021/jasms.4c00436","DOIUrl":"https://doi.org/10.1021/jasms.4c00436https://doi.org/10.1021/jasms.4c00436","url":null,"abstract":"<p >In some types of mass spectrometers, such as time-of-flight mass spectrometers (TOF-MSs), it is necessary to control pulsed beams of ions. This can be easily accomplished by applying a pulsed voltage to the pusher electrode while the ionizer is continuously flowing ions. This method is preferred for its simplicity, although the ion utilization efficiency is not optimized. Here we employed another pulse-control method with a higher ion utilization rate, which is to bunch ions and kick them out instead of letting them stream. The benefit of this method is that higher sensitivity can be achieved; since the start of new ions cannot be allowed during TOF separation, it is highly advantageous to bunch ions that would otherwise be unusable. In this study, we used analytical and numerical methods to design a new bunching ionizer with reduced resources, adopting the principle of the electrostatic ion beam trap. The test model experimentally demonstrated the bunching performance with respect to the sample gas density and ion bunching time using gas samples and electron impact ionization. We also conducted an experiment connecting the newly developed bunching ionizer with a miniature TOF-MS. As a result, the sensitivity was improved by an order of magnitude compared to the case using a nonbunching ionizer. Since the device is capable of bunching ions with low voltage and power consumption, it will be possible to find applications in portable mass spectrometers with reduced resources.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"553–564 553–564"},"PeriodicalIF":3.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547461","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}