Alexander J Solivais, Hannah Boekweg, Lloyd M Smith, William S Noble, Michael R Shortreed, Samuel H Payne, Uri Keich
{"title":"Improved Detection of Differentially Abundant Proteins through FDR-Control of Peptide-Identity-Propagation.","authors":"Alexander J Solivais, Hannah Boekweg, Lloyd M Smith, William S Noble, Michael R Shortreed, Samuel H Payne, Uri Keich","doi":"10.1021/acs.jproteome.5c00065","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00065","url":null,"abstract":"<p><p>The goal of proteomics is to identify and quantify peptides and proteins within a biological sample. Almost all algorithms for the identification of peptides in LC-MS/MS data employ two steps: peptide/spectrum matching and peptide-identity-propagation (PIP), also known as match-between-runs. PIP can routinely account for up to 40% of all results, with that proportion rising as high as 75% in single-cell proteomics. Unlike peptide identities derived through peptide/spectrum matches, for which error estimation has been strictly enforced for decades, peptide identities derived through PIP have not historically been subject to statistical evaluation. As an indispensable component of label-free quantification, PIP needs a statistically rigorous method for estimating its false-discovery rate (FDR). We present a method for FDR control of PIP, called PIP-ECHO, and devise a rigorous protocol for evaluating FDR control of any PIP method. Using three different benchmark data sets, we evaluate PIP-ECHO alongside the PIP procedures implemented by FlashLFQ, IonQuant, and MaxQuant. These analyses show that only PIP-ECHO can accurately control the FDR of PIP at 1% across all data sets. When analyzing a spike-in data set, PIP-ECHO increases both the accuracy and sensitivity of differential expression analysis, yielding substantially more differentially abundant proteins than either MaxQuant or IonQuant.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anton Kalyuzhnyy, Patrick A Eyers, Claire E Eyers, Eric W Deutsch, Andrew R Jones
{"title":"Applying a Conservation-Based Approach for Predicting Novel Phosphorylation Sites in Eukaryotes and Evaluating Their Functional Relevance.","authors":"Anton Kalyuzhnyy, Patrick A Eyers, Claire E Eyers, Eric W Deutsch, Andrew R Jones","doi":"10.1021/acs.jproteome.5c00278","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00278","url":null,"abstract":"<p><p>Protein phosphorylation, a key post-translational modification, is central to cellular signaling and disease pathogenesis. The development of high-throughput proteomics pipelines has led to the discovery of large numbers of phosphorylated protein motifs and sites (phosphosites) across many eukaryotic species. However, the majority of phosphosites are reported from human samples, with most species having a few experimentally confirmed or computationally predicted phosphosites. Furthermore, only a small fraction of the characterized human phosphoproteome has an annotated functional role. A common way of predicting functional phosphosites is through conservation-based sequence analysis, but large-scale evolutionary studies are scarce. In this study, we explore the conservation of 20,751 confident human phosphosites across 100 eukaryotic species and investigate the evolution of associated protein domains and kinases. We categorize protein functions based on phosphosite conservation patterns and demonstrate the importance of conservation analysis in identifying organisms suitable as biological models for studying conserved signaling pathways relevant to human biology and disease. Finally, we use human protein sequences as a reference for propagating over 1,000,000 potential phosphosites to other eukaryotes. Our results can improve proteome annotations of several species and help direct research aimed at exploring the evolution and functional relevance of phosphorylation.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlota Arias-Hidalgo, Pablo Juanes-Velasco, Alba Iglesia-Sánchez, Ana Nuño-Soriano, Quentin Lecrevisse, Raquel Herrero, Antonio Ferruelo, Yasmine Douhal, Hongye Wang, Xiaomei Zhang, Pablo Telleria, Dann K J Pieren, Cécile A C M van Els, Miriam López-Parra, Fermín Sánchez-Guijo, Rafael Góngora, Enrique Montalvillo, José Manuel Sánchez-Santos, Javier De Las Rivas, David Bernardo, José A Lorente, Yajie Wang, Xiabo Yu, Ángela-Patricia Hernández, Manuel Fuentes
{"title":"Humoral Response Profile in SARS-CoV-2 Infection: Differences across Virus Strains and Influenza.","authors":"Carlota Arias-Hidalgo, Pablo Juanes-Velasco, Alba Iglesia-Sánchez, Ana Nuño-Soriano, Quentin Lecrevisse, Raquel Herrero, Antonio Ferruelo, Yasmine Douhal, Hongye Wang, Xiaomei Zhang, Pablo Telleria, Dann K J Pieren, Cécile A C M van Els, Miriam López-Parra, Fermín Sánchez-Guijo, Rafael Góngora, Enrique Montalvillo, José Manuel Sánchez-Santos, Javier De Las Rivas, David Bernardo, José A Lorente, Yajie Wang, Xiabo Yu, Ángela-Patricia Hernández, Manuel Fuentes","doi":"10.1021/acs.jproteome.4c00935","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00935","url":null,"abstract":"<p><p>The clinical manifestation of COVID-19 after SARS-CoV-2 infection varies greatly, with many patients requiring intensive care due to complications like acute respiratory distress syndrome, reduced respiratory system compliance, and altered iron metabolism, which can be mistaken for worsening Influenza A infection. This highlights the need to study the humoral immune response to better understand the pathophysiology of viral respiratory infections and improve treatments and diagnostics. This study analyzed autoantibody and acute-phase reactant profiles in patients infected with SARS-CoV-2 and Influenza A using customized protein microarrays for sensitive and reproducible results. The findings revealed a significant increase in autoantibodies in SARS-CoV-2 patients, including those targeting calcitonin-related polypeptides, hepatocyte growth factor, or interleukin 8, compared to Influenza A patients, who showed elevated levels of selectin E and surfactant protein D. Additionally, most acute-phase reactants were higher in SARS-CoV-2 patients. The serological profile showed that the wild-type SARS-CoV-2 strain induced both IgM and IgG responses to all viral proteins, while other strains triggered an IgG response only at a later stage. Multiomics factor analysis identified key factors driving variation in COVID-19's heterogeneous disease presentation. These insights offer valuable information for developing vaccines and therapeutic strategies against SARS-CoV-2.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iqbal Mahmud, Wai-Kin Chan, Karen Yannell, Cate Simmermaker, Genevieve C Van de Bittner, Linfeng Wu, Daniel Chan, Sheher Banu Mohsin, Yiwei Liu, John Sausen, John N Weinstein, Philip L Lorenzi
{"title":"Single-Sample, Multiomic Mass Spectrometry for Investigating Drug Effects and Mechanisms.","authors":"Iqbal Mahmud, Wai-Kin Chan, Karen Yannell, Cate Simmermaker, Genevieve C Van de Bittner, Linfeng Wu, Daniel Chan, Sheher Banu Mohsin, Yiwei Liu, John Sausen, John N Weinstein, Philip L Lorenzi","doi":"10.1021/acs.jproteome.5c00203","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00203","url":null,"abstract":"<p><p>Poor therapeutic indexes are a principal cause of drug attrition during development. To develop multiomic methods for elucidating potentially targetable mechanisms of drug toxicity, we performed profiling of the response to subtoxic and toxic doses of l-Asparaginase (ASNase) in immune-compromised mice. ASNase is an enzyme-drug approved for the treatment of pediatric acute lymphoblastic leukemia (ALL) but too toxic for use in adults, making it an ideal test case. We collected 20-μL whole blood samples longitudinally, processed them to plasma, and extracted three molecule types (metabolites, lipids, and proteins) from each sample. We then analyzed the extracts using multiple reaction monitoring (MRM) of 500+ water-soluble metabolites, 750+ lipids, and 375 peptides on a triple quadrupole LC-MS/MS platform. Metabolites, lipids, and peptides that were modulated in a dose-dependent manner appeared to converge on antioxidation, inflammation, autophagy, and cell death pathways, prompting the hypothesis that inhibiting one or more of those pathways might decrease ASNase toxicity while preserving anticancer activity. The present studies were not designed to address therapeutic index directly, because efficacy was not studied. We provide here a streamlined, three-in-one LC-MS/MS workflow for targeted metabolomics, lipidomics, and proteomics and, as a proof of principle, demonstrate its ability to generate new hypotheses about mechanisms of ASNase toxicity.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tarsh Shah, Jackson A Fitzpatrick, Benjamin C Orsburn
{"title":"Backyard Proteomics: A Case Study with the Black Widow Spider.","authors":"Tarsh Shah, Jackson A Fitzpatrick, Benjamin C Orsburn","doi":"10.1021/acs.jproteome.5c00342","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00342","url":null,"abstract":"<p><p>Nearly all methods of mass-spectrometry-based proteomics rely on knowing the proteome of the species. In less studied organisms without annotated genomes, it can seem impossible to perform proteomic analysis. In this study, we sought to answer the question: does enough information exist to do proteomics on any organism we want? As a case study, we started with material available due to an infestation of a home with black widow spiders. Thanks to the recent publication of an annotated genome for one species of black widow spider, we were able to identify 5502 protein groups and assign putative annotations using ortholog mapping. We also demonstrate that had we not had this resource, over 2000 proteins could be identified using other available spider genome annotations, despite their unrelatedness. Moreover, regardless of the spider proteome used, proteins annotated as toxins were almost exclusively observed in the main body of the mature female black widow spider. Overall, these results provide a draft proteome map for the black widow spider and valuable data for validating machine learning models while also suggesting that the door to insightful quantitative proteomics may already be open for millions of less studied organisms. All raw and processed proteomic data are available through the ProteomeXchange repository as accession PXD051601.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inês M S Guerra, Helena B Ferreira, Luísa Diogo, Sónia Moreira, Stefano Bonciarelli, Laura Goracci, Tânia Melo, Pedro Domingues, M Rosário Domingues, Ana S P Moreira
{"title":"Lipidomic Profiling of Red Blood Cells in the Mitochondrial Fatty Acid β-oxidation Disorder MCADD Reveals Phospholipid and Sphingolipid Dysregulation.","authors":"Inês M S Guerra, Helena B Ferreira, Luísa Diogo, Sónia Moreira, Stefano Bonciarelli, Laura Goracci, Tânia Melo, Pedro Domingues, M Rosário Domingues, Ana S P Moreira","doi":"10.1021/acs.jproteome.5c00308","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00308","url":null,"abstract":"<p><p>Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is characterized by the accumulation of medium-chain acylcarnitines. Despite the therapeutic approach, changes in lipid homeostasis have been reported in MCADD plasma samples. Compared to plasma lipidomics, red blood cell (RBC) profiling provides a more stable biomarker that is less influenced by dietary changes and reflects long-term metabolic alterations. In this study, we assessed the plasticity of the lipidomic profile of RBC from children with MCADD and controls using C18 liquid chromatography-mass spectrometry. The results revealed significant alterations in 240 lipid species in MCADD, highlighting an upregulation of sphingolipids (sphingomyelins and ceramides) and lysophospholipid species (lysophosphatidylcholines and lysophosphatidylethanolamines) alongside a downregulation of polyunsaturated and ether-linked phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs). Also, altered PC/PE and (PC + SM)/(PE + PS) ratios could be associated with alterations in RBC membranes properties, e.g., fluidity and asymmetry. The observed changes in the lipidome suggest compromised antioxidant defenses, enhanced oxidative stress, and an inflammatory state, with potential systemic implications in MCADD lipid metabolism and long-term complications in older age. This study underscores the utility of RBC lipidomics as a robust tool for understanding the pathophysiology of MCADD. It may prove to be a useful tool for monitoring disease progression in the near future.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tian Xu Qin, Wai Hoe Ng, Siew Kit Ng, Ying Ying Zhu, Min Fey Chek, Kai Dun Tang
{"title":"Mediator Complex Subunit 27-Enriched Small Extracellular Vesicles Mediate the Crosstalk between Periodontal Bacteria and HPV-Driven Head and Neck Cancer.","authors":"Tian Xu Qin, Wai Hoe Ng, Siew Kit Ng, Ying Ying Zhu, Min Fey Chek, Kai Dun Tang","doi":"10.1021/acs.jproteome.5c00373","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00373","url":null,"abstract":"<p><p>It is well-documented in the literature that two well-known periodontal bacteria, <i>Fusobacterium nucleatum</i> and <i>Porphyromonas gingivalis</i>, play a pivotal role in regulating the cancer stemness properties of head and neck cancer (HNC); however, their role in human papillomavirus-driven HNC (HPV-driven HNC) remains unexplored. Here, we report for the first time that periodontal bacteria actively interplay with HPV-driven head and neck cancer stem cells (CSCs) via the activation of signaling pathways mediated by small extracellular vesicles (sEVs), leading to the rapid enrichment of CSCs during HPV-driven HNC progression and development. We observed an upregulation of Mediator Complex Subunit 27 (MED27) in sEVs derived from periodontal bacteria-infected HPV-driven HNC, as evidenced by 4D-microDIA quantitative proteomics analysis. Meanwhile, the silencing of MED27 resulted in the suppression of migratory, invasive, and sphere-forming abilities of HPV-driven HNC cells. Subsequent clinical data analysis revealed that the elevated level of MED27 was significantly correlated with aggressive clinicopathologic features and shorter survival in HNC patients. Most importantly, MED27 was expressed at a higher mRNA level in HPV-driven HNC patients when compared to controls and non-HPV-driven HNC patients, suggesting its potential as a diagnostic biomarker for HPV-driven HNC. This novel mechanistic insight could advance HPV-driven HNC diagnostic and therapeutic strategies.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samantha Lodge, Reika Masuda, Philipp Nitschke, John P Beilby, Jennie Hui, Michael Hunter, Edward Litton, Edward Raby, Andrew Currie, Bu B Yeap, Oscar Millet, Claire Cannet, Hartmut Schaefer, Manfred Spraul, Elaine Holmes, Julien Wist, Jeremy K Nicholson
{"title":"NMR Spectroscopy-Based Lipoprotein and Glycoprotein Biomarkers Differentiate Acute and Chronic Inflammation in Diverse Healthy and Disease Population Cohorts.","authors":"Samantha Lodge, Reika Masuda, Philipp Nitschke, John P Beilby, Jennie Hui, Michael Hunter, Edward Litton, Edward Raby, Andrew Currie, Bu B Yeap, Oscar Millet, Claire Cannet, Hartmut Schaefer, Manfred Spraul, Elaine Holmes, Julien Wist, Jeremy K Nicholson","doi":"10.1021/acs.jproteome.5c00300","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00300","url":null,"abstract":"<p><p>Understanding the distribution and variation in NMR-based inflammatory markers is crucial to the evaluation of their clinical utility in disease prognosis and diagnosis. We applied high-resolution <sup>1</sup>H NMR spectroscopy of blood plasma and serum to measure the acute phase reactive glycoprotein signals (GlycA and GlycB) and the subregions of the lipoprotein-based Supramolecular Phospholipid Composite signals (SPC<sub>1</sub>, SPC<sub>2</sub>, and SPC<sub>3</sub>) in a large multicohort population study. A total of 5702 samples were studied to determine the signal variations in a range of chronic and acute inflammatory conditions. We found that while GlycA and GlycB were increased in inflammation, the SPC regions behaved independently of Glyc signals, with SPC<sub>2</sub> and SPC<sub>3</sub> being reduced in chronic inflammation in comparison to healthy controls (<i>p</i>-value SPC<sub>2</sub> = 2.9 × 10<sup>-10</sup>, <i>p</i>-value SPC<sub>3</sub> = 2.2 × 10<sup>-3</sup>) and SPC<sub>1</sub> (<i>p</i>-value = 0.29) being unchanged. SPC<sub>1</sub> was decreased in acute inflammation, indicating a link to the immune response (<i>p</i>-value = 2.5 × 10<sup>-11</sup>). These findings confirm the independent biological relevance of all three SPC subregions and contraindicate the use of aggregate SPC values as general inflammatory markers.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qinghua Xing, Xinyi Tao, Shanshan Zhang, Noha M Mesbah, Xinwei Mao, Xiaomeng Guo, Qingping Hu, Haisheng Wang, Baisuo Zhao
{"title":"Multiomics Reveals the Mechanism of <i>Natranaerobius thermophilus</i> Adaptation to Combined Hypersaline, Alkaline, and Elevated Temperature Environments.","authors":"Qinghua Xing, Xinyi Tao, Shanshan Zhang, Noha M Mesbah, Xinwei Mao, Xiaomeng Guo, Qingping Hu, Haisheng Wang, Baisuo Zhao","doi":"10.1021/acs.jproteome.5c00395","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00395","url":null,"abstract":"<p><p>The halophilic alkalithermophile <i>N. thermophilus</i> grows optimally at the combined extremes of 3.3-3.9 M Na<sup>+</sup>, pH 9.5, and 53 °C. This study aims to uncover its unique adaptations to the combined extremes of high salt, alkaline pH, and high temperature. Due to the difficulties of genetic manipulation, we used a multiomics approach to reveal the comprehensive transcriptomic, proteomic, and metabolomic landscapes of <i>N. thermophilus</i> under the triple extremes. Specifically, two distinct conditions were evaluated: high salt-alkaline-thermal (HSAT, 4 M Na<sup>+</sup>/ pH 9.8/52 °C) stress and low salt-alkaline-thermal (LSAT, 3 M Na<sup>+</sup>/ pH 8.8/42 °C) stress. Under HSAT stress, <i>N. thermophilus</i> increased the level of saturated fatty acids and uncharged polar lipids to remodel its cell membrane, enhanced Na<sup>+</sup>-driven flagellar motility, accumulated various compatible solutes, redirected amino acid metabolism for energy, and adjusted the activity of ion transporters and chaperones. These findings exemplify the \"No Free Lunch\" principle in polyextremophiles. By examining changes in gene, protein, and metabolic regulation levels in <i>N. thermophilus</i> under the simultaneous influence of three extremes, this study provides a comprehensive analysis of the survival mechanisms of polyextremophiles in hypersaline, alkaline, and high-temperature environments. Our findings offer valuable insights into the origins of life on Earth and the potential for extraterrestrial life.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proteomic Comparison between Hyphae and Spores Reveals Pathogenicity of <i>Mucor Irregularis</i>.","authors":"Meijie Zhang, Xiaowei Zhou, Yuhan Zhang, Ge Song, Xiaofang Li, Weida Liu, Guanzhao Liang","doi":"10.1021/acs.jproteome.5c00214","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00214","url":null,"abstract":"<p><p><i>Mucor irregularis</i>, an emerging causative agent of disfiguring mucormycosis, demonstrates distinct clinical manifestations between hyphae and spore forms, though the pathogenic determinants between these two forms remain elusive. Utilizing TMT (tandem mass tag)-based quantitative proteomics (ProteomeXchange: PXD055430), we conducted a comparative analysis of these morphotypes, followed by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein-protein interaction network construction. Critically, we identified the following: (i) tRNA sulfur modification (NCS6) in spore dormancy maintenance; (ii) adenylate kinase (adenylate kinase 1)-mediated energy metabolism during germination; and (iii) COQ3-dependent mitochondrial function in spore germination. This first proteomic profiling of <i>M. irregularis</i> morphotypes delineates distinct phase-specific adaptations. Notably, the ribosomal and dormancy-associated machinery as NCS6 in spores contrasts sharply with the metabolic activation and upregulated virulence determinants as PAC1 in hyphae. Findings highlight NAT10 critical for spore readiness and RhoGEF GTPases central to hyphal invasion as particularly promising candidate therapeutic targets. Building upon this foundation, future investigations must now delineate the immunomodulatory roles of these effector proteins during host invasion to advance mucormycosis management strategies.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}