Journal of the American Society for Mass Spectrometry最新文献

{"title":"Investigation and Development of the BODIPY-Embedded Isotopic Signature for Chemoproteomics Labeling and Targeted Profiling","authors":"Rachel Joshi,&nbsp; and ,&nbsp;Adam M. Hawkridge*,&nbsp;","doi":"10.1021/jasms.4c0024610.1021/jasms.4c00246","DOIUrl":"https://doi.org/10.1021/jasms.4c00246https://doi.org/10.1021/jasms.4c00246","url":null,"abstract":"<p >A common goal in mass spectrometry-based chemoproteomics is to directly measure the site of conjugation between the target protein and the small molecule ligand. However, these experiments are inherently challenging due to the low abundance of labeled proteins and the difficulty in identifying modification sites using standard proteomics software. Reporter tags that either generate signature fragment ions or isotopically encode target peptides can be used for the preemptive discovery of labeled peptides even in the absence of identification. We investigated the potential of BODIPY FL azide as a click chemistry enabled chemoproteomics reagent due to the presence of boron and the unique 1:4 natural abundance ratio of ¹⁰B:¹¹B. The isotopes of boron encode BODIPY-labeled peptides with a predictable pattern between the monoisotopic (M) and M+1 peaks. BODIPY-labeled peptides were identified in MS1 spectra using an R script that filters for the signature ¹⁰B:¹¹B intensity ratio and mass defect. Application of the boron detection script resulted in three times the labeled peptide coverage achieved for a BODIPY-conjugated BSA sample compared with untargeted data-dependent acquisition sequencing. Furthermore, we used the inherent HF neutral loss signature from BODIPY to assist with BODIPY-modified peptide identification. Finally, we demonstrate the application of this approach using the BODIPY-conjugated BSA sample spiked into a complex <i>E. coli</i>. digest. In summary, our results show that the commercially available BODIPY FL azide clicked to alkyne-labeled peptides provides a unique isotopic signature for pinpointing the site(s) of modification with the added potential for on- or off-line UV or fluorescence detection.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jasms.4c00246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407914","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":"Polystyrene Chain Geometry Probed by Ion Mobility Mass Spectrometry and Molecular Dynamics Simulations","authors":"Sarajit Naskar, Andrea Minoia, Quentin Duez, Aidan Izuagbe, Julien De Winter, Stephen J. Blanksby, Christopher Barner-Kowollik, Jérôme Cornil, Pascal Gerbaux","doi":"10.1021/jasms.4c00231","DOIUrl":"https://doi.org/10.1021/jasms.4c00231","url":null,"abstract":"Polystyrene (PS) is a thermoplastic polymer commonly used in various applications due to its bulk properties. Designing functional polystyrenes with well-defined structures for targeted applications is of significant interest due to the rigid and apolar nature of the polymer chain. Progress is hindered to date by the limitations of current analytical methods in defining the atomistic-level folding of the polymer chain. The integration of ion mobility spectrometry and molecular dynamics simulations is beneficial in addressing these challenges. However, data on gas-phase polystyrene ions are rarely reported in the literature. We herein investigate the gas phase structure of polystyrene ions with different end groups to establish how the nature and the rigidity of the monomer unit affect the charge stabilization. We find that, in contrast to polar polymers in which the charges are located deep in the ionic globules, the charges in the PS ions are rather located at the periphery of the polymer backbone, leading to singly and doubly charged PS ions adopting dense elliptic-shaped structures. Molecular dynamics (MD) simulations indicate that the folding of the PS rigid chain is controlled by phenyl ring interactions with the charge ultimately remaining excluded from the core of the globular ions, whereas the folding of polyether ions is initiated by the folding of the flexible polyether chain around the sodium ion that remains deeply enclosed in the core of the ions.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257801","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":"Polystyrene Chain Geometry Probed by Ion Mobility Mass Spectrometry and Molecular Dynamics Simulations","authors":"Sarajit Naskar,&nbsp;Andrea Minoia,&nbsp;Quentin Duez,&nbsp;Aidan Izuagbe,&nbsp;Julien De Winter,&nbsp;Stephen J. Blanksby,&nbsp;Christopher Barner-Kowollik,&nbsp;Jérôme Cornil and Pascal Gerbaux*,&nbsp;","doi":"10.1021/jasms.4c0023110.1021/jasms.4c00231","DOIUrl":"https://doi.org/10.1021/jasms.4c00231https://doi.org/10.1021/jasms.4c00231","url":null,"abstract":"<p >Polystyrene (PS) is a thermoplastic polymer commonly used in various applications due to its bulk properties. Designing functional polystyrenes with well-defined structures for targeted applications is of significant interest due to the rigid and apolar nature of the polymer chain. Progress is hindered to date by the limitations of current analytical methods in defining the atomistic-level folding of the polymer chain. The integration of ion mobility spectrometry and molecular dynamics simulations is beneficial in addressing these challenges. However, data on gas-phase polystyrene ions are rarely reported in the literature. We herein investigate the gas phase structure of polystyrene ions with different end groups to establish how the nature and the rigidity of the monomer unit affect the charge stabilization. We find that, in contrast to polar polymers in which the charges are located deep in the ionic globules, the charges in the PS ions are rather located at the periphery of the polymer backbone, leading to singly and doubly charged PS ions adopting dense elliptic-shaped structures. Molecular dynamics (MD) simulations indicate that the folding of the PS rigid chain is controlled by phenyl ring interactions with the charge ultimately remaining excluded from the core of the globular ions, whereas the folding of polyether ions is initiated by the folding of the flexible polyether chain around the sodium ion that remains deeply enclosed in the core of the ions.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142403017","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 Untargeted Lipidomics Workflow Incorporating High-Resolution Demultiplexing (HRdm) Drift Tube Ion Mobility-Mass Spectrometry","authors":"David C. Koomen,&nbsp;Jody C. May,&nbsp;Alexander J. Mansueto,&nbsp;Todd R. Graham and John A. McLean*,&nbsp;","doi":"10.1021/jasms.4c0025110.1021/jasms.4c00251","DOIUrl":"https://doi.org/10.1021/jasms.4c00251https://doi.org/10.1021/jasms.4c00251","url":null,"abstract":"<p >Global discovery lipidomics can provide comprehensive chemical information toward understanding the intricacies of metabolic lipid disorders such as dyslipidemia; however, the isomeric complexity of lipid species remains an analytical challenge. Orthogonal separation strategies, such as ion mobility (IM), can be inserted into liquid chromatography-mass spectrometry (LC-MS) untargeted lipidomic workflows for additional isomer separation and high-confidence annotation, and the emergence of high-resolution ion mobility (HRIM) strategies provides marked improvements to the resolving power (<i>R</i>_p &gt; 200) that can differentiate small structural differences characteristic of isomers. One such HRIM strategy, high-resolution demultiplexing (HRdm), utilizes multiplexed drift tube ion mobility spectrometry (DTIMS) with post-acquisition algorithmic deconvolution to access high IM resolutions while retaining the measurement precision inherent to the drift tube technique; however, HRdm has yet to be utilized in untargeted studies. In this manuscript, a proof-of-concept study using ATP10D dysfunctional murine models was investigated to demonstrate the utility of HRdm-incorporated untargeted lipidomic analysis pipelines. Total lipid features were found to increase by 2.5-fold with HRdm compared to demultiplexed DTIMS as a consequence of more isomeric lipids being resolved. An example lipid, PC 36:5, was found to be significantly higher in dysfunctional ATP10D mice with two resolved peaks observed by HRdm that were absent in both the functional ATP10D mice and the standard demultiplexed DTIMS acquisition mode. The benefits of utilizing HRdm for discerning isomeric lipids in untargeted workflows have the potential to enhance our analytical understanding of lipids related to disease complexity and biologically relevant studies.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jasms.4c00251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142403015","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":"An Untargeted Lipidomics Workflow Incorporating High-Resolution Demultiplexing (HRdm) Drift Tube Ion Mobility-Mass Spectrometry","authors":"David C. Koomen, Jody C. May, Alexander J. Mansueto, Todd R. Graham, John A. McLean","doi":"10.1021/jasms.4c00251","DOIUrl":"https://doi.org/10.1021/jasms.4c00251","url":null,"abstract":"Global discovery lipidomics can provide comprehensive chemical information toward understanding the intricacies of metabolic lipid disorders such as dyslipidemia; however, the isomeric complexity of lipid species remains an analytical challenge. Orthogonal separation strategies, such as ion mobility (IM), can be inserted into liquid chromatography-mass spectrometry (LC-MS) untargeted lipidomic workflows for additional isomer separation and high-confidence annotation, and the emergence of high-resolution ion mobility (HRIM) strategies provides marked improvements to the resolving power (<i>R</i>_p &gt; 200) that can differentiate small structural differences characteristic of isomers. One such HRIM strategy, high-resolution demultiplexing (HRdm), utilizes multiplexed drift tube ion mobility spectrometry (DTIMS) with post-acquisition algorithmic deconvolution to access high IM resolutions while retaining the measurement precision inherent to the drift tube technique; however, HRdm has yet to be utilized in untargeted studies. In this manuscript, a proof-of-concept study using ATP10D dysfunctional murine models was investigated to demonstrate the utility of HRdm-incorporated untargeted lipidomic analysis pipelines. Total lipid features were found to increase by 2.5-fold with HRdm compared to demultiplexed DTIMS as a consequence of more isomeric lipids being resolved. An example lipid, PC 36:5, was found to be significantly higher in dysfunctional ATP10D mice with two resolved peaks observed by HRdm that were absent in both the functional ATP10D mice and the standard demultiplexed DTIMS acquisition mode. The benefits of utilizing HRdm for discerning isomeric lipids in untargeted workflows have the potential to enhance our analytical understanding of lipids related to disease complexity and biologically relevant studies.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257800","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":"GlyCombo Enables Rapid, Complete Glycan Composition Identification across Diverse Glycomic Sample Types","authors":"Maia I. Kelly,&nbsp; and ,&nbsp;Christopher Ashwood*,&nbsp;","doi":"10.1021/jasms.4c0018810.1021/jasms.4c00188","DOIUrl":"https://doi.org/10.1021/jasms.4c00188https://doi.org/10.1021/jasms.4c00188","url":null,"abstract":"<p >Glycans are sugar-based polymers found to modify biomolecules, including lipids and proteins, as well as occur unconjugated as free polysaccharides. Due to their ubiquitous cellular presentation, glycans mediate crucial biological processes and are frequently sought after as biomarkers for a wide range of diseases. Identification of glycans present in samples acquired with mass spectrometry (MS) is a cornerstone of glycomics research; thus, the ability to rapidly identify glycans in each acquisition is integral to glycomics analysis pipelines. Here we introduce GlyCombo (https://github.com/Protea-Glycosciences/GlyCombo), an open-source, freely available software tool designed to rapidly assign monosaccharide combinations to glycan precursor masses including those subjected to MS2 in LC-MS/MS experiments. GlyCombo was evaluated across six diverse data sets, demonstrating MS vendor, derivatization, and glycan-type neutrality. Compositional assignments using GlyCombo are shown to be faster than the current predominant approach, GlycoMod, a closed-source web application. Two unique features of GlyCombo, multiple adduct search and off-by-one error anticipation, reduced unassigned MS2 scans in a benchmark data set by 40%. Finally, the comprehensiveness of glycan feature identification is exhibited in Skyline, a software that requires predefined transitions that are derived from GlyCombo output files.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407481","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":"GlyCombo Enables Rapid, Complete Glycan Composition Identification across Diverse Glycomic Sample Types","authors":"Maia I. Kelly, Christopher Ashwood","doi":"10.1021/jasms.4c00188","DOIUrl":"https://doi.org/10.1021/jasms.4c00188","url":null,"abstract":"Glycans are sugar-based polymers found to modify biomolecules, including lipids and proteins, as well as occur unconjugated as free polysaccharides. Due to their ubiquitous cellular presentation, glycans mediate crucial biological processes and are frequently sought after as biomarkers for a wide range of diseases. Identification of glycans present in samples acquired with mass spectrometry (MS) is a cornerstone of glycomics research; thus, the ability to rapidly identify glycans in each acquisition is integral to glycomics analysis pipelines. Here we introduce GlyCombo (https://github.com/Protea-Glycosciences/GlyCombo), an open-source, freely available software tool designed to rapidly assign monosaccharide combinations to glycan precursor masses including those subjected to MS2 in LC-MS/MS experiments. GlyCombo was evaluated across six diverse data sets, demonstrating MS vendor, derivatization, and glycan-type neutrality. Compositional assignments using GlyCombo are shown to be faster than the current predominant approach, GlycoMod, a closed-source web application. Two unique features of GlyCombo, multiple adduct search and off-by-one error anticipation, reduced unassigned MS2 scans in a benchmark data set by 40%. Finally, the comprehensiveness of glycan feature identification is exhibited in Skyline, a software that requires predefined transitions that are derived from GlyCombo output files.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257804","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":"Revisiting Dissolved Organic Matter Analysis Using High-Resolution Trapped Ion Mobility and FT-ICR Mass Spectrometry","authors":"Pablo R. B. Oliveira, Dennys Leyva, Lilian V. Tose, Chad Weisbrod, Anton N. Kozhinov, Konstantin O. Nagornov, Yury O. Tsybin, Francisco Fernandez-Lima","doi":"10.1021/jasms.4c00232","DOIUrl":"https://doi.org/10.1021/jasms.4c00232","url":null,"abstract":"The molecular level characterization of complex mixtures remains an analytical challenge. We have shown that the integration of complementary, high-resolution, gas-phase separations allows for chemical formula level isomeric content description. In the current work, we revisited the current challenges associated with the analysis of dissolved organic matter using high-resolution trapped ion mobility separation (TIMS) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). In particular, we evaluated the separation capabilities provided by TIMS-MS compared to MS alone, the use of ICR complementary data acquisition (DAQ) systems and transient processing strategies, ICR cell geometries (e.g., Infinity cell vs harmonized cell), and magnetic field strengths (7 T vs 9.4 T vs 21 T) for the case of a Harney River DOM sample. Results showed that the external high-performance DAQ enables direct representation of mass spectra in absorption mode FT (aFT), doubling the MS resolution compared to the default magnitude mode FT (mFT). Changes between half- vs full-apodization result in greater MS signal/noise vs superior MS resolving power (RP); in the case of DOM analysis, a 45% increase in assigned formulas is observed when employing the DAQ half (Kaiser-type)-apodization window and aFT when compared to the default instrument mFT. Results showed the advantages of reprocessing 2D-TIMS-FT-ICR MS data with higher RP and magnetic field chemical formulas generated list acquired (e.g., 21 T led to a 24% increase in isomers reported) or the implementation of alternative strategies.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257799","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":"Revisiting Dissolved Organic Matter Analysis Using High-Resolution Trapped Ion Mobility and FT-ICR Mass Spectrometry","authors":"Pablo R. B. Oliveira,&nbsp;Dennys Leyva,&nbsp;Lilian V. Tose,&nbsp;Chad Weisbrod,&nbsp;Anton N. Kozhinov,&nbsp;Konstantin O. Nagornov,&nbsp;Yury O. Tsybin and Francisco Fernandez-Lima*,&nbsp;","doi":"10.1021/jasms.4c0023210.1021/jasms.4c00232","DOIUrl":"https://doi.org/10.1021/jasms.4c00232https://doi.org/10.1021/jasms.4c00232","url":null,"abstract":"<p >The molecular level characterization of complex mixtures remains an analytical challenge. We have shown that the integration of complementary, high-resolution, gas-phase separations allows for chemical formula level isomeric content description. In the current work, we revisited the current challenges associated with the analysis of dissolved organic matter using high-resolution trapped ion mobility separation (TIMS) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). In particular, we evaluated the separation capabilities provided by TIMS-MS compared to MS alone, the use of ICR complementary data acquisition (DAQ) systems and transient processing strategies, ICR cell geometries (e.g., Infinity cell vs harmonized cell), and magnetic field strengths (7 T vs 9.4 T vs 21 T) for the case of a Harney River DOM sample. Results showed that the external high-performance DAQ enables direct representation of mass spectra in absorption mode FT (aFT), doubling the MS resolution compared to the default magnitude mode FT (mFT). Changes between half- vs full-apodization result in greater MS signal/noise vs superior MS resolving power (RP); in the case of DOM analysis, a 45% increase in assigned formulas is observed when employing the DAQ half (Kaiser-type)-apodization window and aFT when compared to the default instrument mFT. Results showed the advantages of reprocessing 2D-TIMS-FT-ICR MS data with higher RP and magnetic field chemical formulas generated list acquired (e.g., 21 T led to a 24% increase in isomers reported) or the implementation of alternative strategies.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407897","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":"Evaluation of Serum Proteome Sample Preparation Methods to Support Clinical Proteomics Applications","authors":"Carly A. I. Twigg, Jesenia M. Perez, Joohyun Ryu, Benjamin K. Hanson, Valerie J. Barrera Estrada, Stefani N. Thomas","doi":"10.1021/jasms.4c00131","DOIUrl":"https://doi.org/10.1021/jasms.4c00131","url":null,"abstract":"Serum contains several proteins that are associated with disease-related processes. Mass spectrometry (MS)-based proteomics approaches greatly facilitate serum protein biomarker development. However, the serum proteome complexity presents a technical challenge for the accurate, sensitive, and reproducible quantification of proteins by MS. Thus, efficient sample preparation methods are of critical importance for serum proteome analyses. In this study, we evaluated the technical performance of two serum proteome sample preparation methods using sera from patients with high-grade serous ovarian cancer and patients with benign nongynecological conditions with a goal of providing insight into their compatibility with clinical proteomics workflows. One method entailed the use of immobilized trypsin (SMART Digest Trypsin) with RapiGest SF, an acid-labile surfactant designed to enhance the in-solution enzymatic digestion of proteins. The other method incorporated a commercially available sample preparation kit, iST-BCT, which contains standardized reagents. Significantly higher protein sequence coverage, albeit with lower digestion efficiency, was obtained with the immobilized trypsin + RapiGest SF workflow, whereas the iST-BCT workflow was quicker and had marginally better reproducibility. Protein relative abundance analysis revealed that the serum proteomes clustered primarily by the sample processing workflow and secondarily by disease state. We conducted a time course study to determine whether differences in the relative abundance of diagnostic high-grade serous ovarian cancer serum protein biomarker candidates were biased according to the duration of enzymatic digestion. Our results highlight the importance of optimizing enzymatic digestion kinetics according to the peptide targets of interest while considering the sensitivity of the downstream analytical method utilized in clinical proteomics workflows designed to measure biomarkers.","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221987","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}