Proteomics最新文献

{"title":"Metaproteomics and Meta-Omics to Decrypt Microbiome Functionality.","authors":"Lucia Grenga, Magnus Øverlie Arntzen, Jean Armengaud","doi":"10.1002/pmic.70029","DOIUrl":"https://doi.org/10.1002/pmic.70029","url":null,"abstract":"","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":"e70029"},"PeriodicalIF":3.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Lipidomics With High-Resolution Ion Mobility-Mass Spectrometry.","authors":"Gaoyuan Lu, Shuling Xu, Penghsuan Huang, Lingjun Li","doi":"10.1002/pmic.70026","DOIUrl":"10.1002/pmic.70026","url":null,"abstract":"<p><p>Lipids, indispensable yet structurally intricate biomolecules, serve as critical regulators of cellular function and disease progression. Conventional lipidomics, constrained by limited resolution for isomeric and low-abundance species, has been transformed by ion mobility-mass spectrometry (IM-MS). This technology augments analytical power through enhanced orthogonal separation, collision cross-section (CCS)-based identification, and improved sensitivity. This review examines the transformative advances in IM-MS-driven lipidomics, focusing on three major pillars: (1) a critical evaluation of leading ion mobility spectrometry (IMS) platforms, emphasizing innovative instrument geometries and breakthroughs in resolving lipid isomers; (2) an exploration of lipid CCS databases and predictive frameworks, spotlighting computational modeling and machine learning strategies that synergize experimental data with molecular representations for high-confidence lipid annotation; (3) emerging multi-dimensional lipidomics workflows integrating CCS with liquid chromatography-MS/MS to boost identification and depth, alongside mass spectrometry imaging for spatially resolved lipidomics. By unifying cutting-edge instrumentation, computational advances, and biological insights, this review outlines a roadmap for leveraging IM-MS to unravel lipidome complexity, catalyzing biomarker discovery and precision medicine innovation.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":"e70026"},"PeriodicalIF":3.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIMPLEX Enriches Hydrophobic and Lipidated Proteins in Membrane Proteomics Experiments","authors":"Tingting Li,&nbsp;Alexander Wenger,&nbsp;Cristina Coman,&nbsp;Corinna Borutzki,&nbsp;Michael R. Kreutz,&nbsp;Robert Ahrends","doi":"10.1002/pmic.70016","DOIUrl":"10.1002/pmic.70016","url":null,"abstract":"<p>Synaptosomes (Syn) and synaptic junctions (SJ) are key neuronal compartments that have been widely characterized in omics studies to understand neurotransmitter- and signal transduction-related events. While synapses are lipid-rich, multiomics approaches integrating lipids and proteins remain largely underexplored. Liquid–liquid extraction (LLE), commonly used in lipidomics, offers significant potential for multiomics analyses by enabling the extraction of diverse molecular classes from a single sample. However, its impact on protein and phosphoprotein analysis in membrane-enriched samples has not been thoroughly investigated or compared to one-phase extraction methods. In this study, we assessed SIMPLEX (Simultaneous Metabolite, Protein, Lipid Extraction), an LLE-based method, against conventional acetone protein precipitation for mass spectrometry-based protein identification. SIMPLEX proved superior for proteomics and phosphoproteomics of SJ, achieving a 42% enrichment in membrane proteins compared to acetone precipitation. It enriched not only transmembrane proteins but also S-palmitoylated proteins. Enriched phosphoproteins included those with beta-transducin repeats (WD40), Armadillo repeats (ARM), and various transmembrane domains, highlighting the SIMPLEX potential and enhanced performance for multiomics analyses.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 16","pages":"28-39"},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Analysis of Bone Marrow CD138+ Cells to Identify Proteins Associated With the Response of Multiple Myeloma Patients to Commonly Used Therapeutic Regimens","authors":"Foteini Paradeisi,&nbsp;Aggeliki Tserga,&nbsp;Vasiliki Lygirou,&nbsp;Manousos Makridakis,&nbsp;Rafael Stroggilos,&nbsp;Grigoris Georgiou,&nbsp;George M. Spyrou,&nbsp;Ioannis V. Kostopoulos,&nbsp;Christine-Ivy Liacos,&nbsp;Aikaterini Termentzi,&nbsp;Meletios A. Dimopoulos,&nbsp;Ourania Tsitsilonis,&nbsp;Antonia Vlahou,&nbsp;Efstathios Kastritis,&nbsp;Jerome Zoidakis","doi":"10.1002/pmic.70025","DOIUrl":"10.1002/pmic.70025","url":null,"abstract":"<p>Multiple myeloma (MM) remains incurable; gaps in our understanding of MM molecular pathogenesis and drugs’ resistance mechanisms are involved in the failure of therapies. This study aims to identify proteins significantly impacting MM patients’ response to commonly used therapeutic regimens. Bone marrow CD138+ selected plasma cells were isolated from patients who had achieved Response (Responders, R) and those who were Non-Responders (NR) to their primary MM therapy. We used LC-MS/MS to investigate the proteomic profile of MM samples, followed by bioinformatics analysis. We identified 1190 proteins, of which 230 showed a statistically significant difference between R and NR, with 27 proteins being upregulated and 203 downregulated in R compared to NR. Pathway enrichment analysis identified pathways related to the immune response and protein synthesis regulation, closely associated with MM progression and response to therapy. The results were validated through individual RNA dataset analysis, corroborating the differential expression of several proteins, including proteins associated with MM (e.g., MIF, ILF3) as well as novel findings (e.g., DCPS and SET). Collectively, proteomics data obtained from R and NR to MM therapy displayed significant changes in the immune system and protein synthesis regulation, supporting their potential role in progression and therapeutic response of MM.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 16","pages":"48-60"},"PeriodicalIF":3.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information: Proteomics 15'25","authors":"","doi":"10.1002/pmic.70027","DOIUrl":"10.1002/pmic.70027","url":null,"abstract":"","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 15","pages":"1-5"},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/pmic.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145128855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Metabolism in Heterozygous Mice With a Mutation in the Motor Domain of Cytoplasmic Dynein, DYNC1H1 (AAA4; c9052C>T(P3018S))","authors":"Simone Sidoli,&nbsp;Mikhail Kislin,&nbsp;Ankita Poojari,&nbsp;Bridget Shafit-Zagardo","doi":"10.1002/pmic.70014","DOIUrl":"10.1002/pmic.70014","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;DYNC1H1 encodes the cytoplasmic dynein heavy chain, a key motor protein involved in intracellular transport and neural development. While mutations in DYNC1H1 are known to cause a range of neurodevelopmental and motor disorders, the molecular mechanisms linking genotype to phenotype remain poorly defined. Here, we investigated how a patient-derived missense mutation in the motor domain of DYNC1H1 (c.9052C&gt;T; P3018S) affects brain metabolism and behavior using a heterozygous knock-in mouse model. Behavioral phenotyping revealed increased locomotor activity without significant changes in sociability or novelty-seeking behavior. To uncover potential molecular correlates of this hyperactive phenotype, we performed label-free quantitative proteomics on cerebrum and cerebellum tissue from male and female mice. Over 80 mitochondrial proteins exhibited differential abundance in HET mice relative to WT controls, particularly in pathways related to oxidative phosphorylation and carbohydrate metabolism. These proteomic signatures were more pronounced in the cerebrum and showed sex-specific patterns. Our findings support the hypothesis that dysregulated mitochondrial metabolism contributes to the behavioral phenotype observed in DYNC1H1 HET mice, and they provide a molecular framework for understanding how cytoplasmic dynein mutations may lead to neurodevelopmental disorders.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Summary&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;Cytoplasmic dynein is a multi-subunit motor protein complex essential for intracellular cargo transport and proper neural function.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;Mutations in DYNC1H1 are increasingly recognized as a cause of pediatric motor and cognitive disorders, yet the molecular underpinnings of these phenotypes are not fully understood.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;The P3018S mutation in DYNC1H1 disrupts the motor domain and has been associated with abnormal neuronal migration, cortical malformations, and developmental delay.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;In this study, we used a knock-in mouse model carrying the P3018S mutation to explore how dynein dysfunction affects brain metabolism and behavior.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;Our proteomic analysis of cerebrum and cerebellum samples revealed widespread differential abundance of mitochondrial proteins, particularly those involved in oxidative phosphorylation and carbohydrate metabolism.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;These findi","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 16","pages":"9-16"},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Quantitation of Phosphotyrosine-Containing Proteins in T-Cell Receptor Signaling Using a SureQuant-Based Mass Spectrometry Approach","authors":"Firdous A. Bhat,&nbsp;Husheng Ding,&nbsp;Dong-Gi Mun,&nbsp;Jane A. Peterson,&nbsp;Mary Cristine Charlesworth,&nbsp;Richard K. Kandasamy,&nbsp;Akhilesh Pandey","doi":"10.1002/pmic.70023","DOIUrl":"10.1002/pmic.70023","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;T-cell receptor (TCR) signaling plays a crucial role in various biological processes and is usually studied using global mass spectrometry-based phosphoproteomic studies. Despite advancements in targeted mass spectrometry-based assays for protein quantification, their application in studying signaling processes, for example, reproducible measurements of post-translational modifications (PTMs) such as phosphorylation, remains limited. Tyrosine phosphorylation is critical for many signaling pathways but presents challenges due to the low abundance of phosphotyrosine-containing peptides. Conventional untargeted methods often encounter data gaps when analyzing large sample sets, particularly for low-abundance peptides. To address this issue, a targeted proteomics method called “SureQuant” was employed, which relies on triggered data acquisition with heavy isotope-labeled peptides. This method has been shown to provide sensitive and reproducible quantification of low-abundance peptides. Here we describe the development of a SureQuant-based method to quantify phosphotyrosine peptides that are involved in the TCR signaling pathway. To monitor the change in phosphotyrosine signals upon activation, the T-cells were stimulated with anti-CD3/CD28 antibodies. We successfully quantified changes in important phosphotyrosine peptides in primary T-cells upon stimulation with anti-CD3/CD28 antibodies. This study showcases the ability of the SureQuant approach to accurately quantify low-abundance phosphotyrosine peptides, highlighting its broader potential to study a diverse set of PTMs in physiological or clinical settings.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Summary&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;T-cell receptor (TCR) signaling plays a fundamental role in immune responses, regulating T-cell activation, differentiation, and function. While tyrosine phosphorylation is a key regulatory mechanism in this pathway, the low abundance of phosphotyrosine peptides presents a major challenge for their detection and quantification in complex biological samples. By employing the SureQuant targeted mass spectrometry approach, we achieved highly sensitive and reproducible quantification of key phosphotyrosine sites involved in T-cell activation.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;This study provides a systematic view of TCR signaling dynamics, revealing distinct phosphorylation patterns across different activation timepoints. Our findings demonstrate the effectiveness of SureQuant in quantifying low-abundance, post-translationally modified peptides, offering a valuable tool for studying signaling pathways with greater precision.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 ","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 16","pages":"40-47"},"PeriodicalIF":3.9,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144905448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the Heterogeneity of Extracellular Vesicles: From Population to Single Particle Level.","authors":"Aixiang Bu, Guangyao Wu, Lianghai Hu","doi":"10.1002/pmic.70024","DOIUrl":"https://doi.org/10.1002/pmic.70024","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are secreted by cells and enclosed within lipid bilayers. These vesicles contain diverse biomolecular components, including proteins, nucleic acids, lipids, and metabolites. They serve critical roles in intercellular communication and regulate multiple physiological and pathological processes, such as immune modulation, angiogenesis, and tumorigenesis and metastasis. Notably, EVs exhibit marked heterogeneity in both physical characteristics and biomolecular composition. This article will systematically characterize the multidimensional heterogeneity of EVs at the population level through comprehensive analysis of their biogenesis origins, size distribution, surface protein, surface glycan chains, and surface lipid. Conventional population-level analyzes yield averaged molecular profiles that obscure subtype-specific functional correlations, thereby limiting mechanistic insights into EV subpopulation biology. To further understand EV heterogeneity, it is necessary to enhance our understanding about molecular characteristics of EVs from the population to the single particle level. Current single EVs analysis techniques mainly include super-resolution microscopy (SRM), atomic force microscopy (AFM), nanoparticle tracking Analysis (NTA), flow cytometry (FCM), surface enhanced Raman spectroscopy (SERS), mass spectrometry (MS), and proximity barcoding assay (PBA). In this review, we systematically examine population-level EV heterogeneity; evaluate single-particle detection methodologies; and discuss emerging technologies (e.g., click chemistry, Olink proteomics, and molecular imprinting) for resolving single EV heterogeneity.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Proteome Landscape During Preimplantation Human Embryo Development and Trophectoderm Stem Cell-Differentiation","authors":"Alin Rai,&nbsp;Qi Hui Poh,&nbsp;Hiroaki Okae,&nbsp;Takahiro Arima,&nbsp;Mehdi Totonchi,&nbsp;David W. Greening","doi":"10.1002/pmic.70017","DOIUrl":"10.1002/pmic.70017","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;Embryo development involves fertilization of a mature ovum, which, after sequential cell divisions (2-,4-8-cells and morula), undergoes differentiation into implantation competent blastocyst. The blastocyst comprises of inner cell mass surrounded by an outer layer of cells called the trophoblast (TSblast) that, upon attachment to the endometrium, differentiates into extravillous trophoblasts (EVTs) that facilitates embryo invasion into the endometrium for intrauterine embryo development, and syncytiotrophoblast (ST) that form the placenta. Such cellular differentiation stages are critical for embryogenesis and implantation, although the protein expression landscape remains poorly understood in humans. Using quantitative mass spectrometry analysis, we systematically monitored the protein expression landscape and their dynamic regulation between human ovum (M2), 8-cell embryo, and blastocysts stages, and trophoblast lineage-specific differentiation into EVTs and ST. Proteins temporally regulated from M2-8 cell-blastocyst stage displayed significant enrichment for metabolic protein networks. We specifically identified 156 proteins associated with 8-cell embryos to blastocyst development, 54 displayed similar correlation at the transcriptomic level including mitochondrial, junction/secretory granule-associated proteins that carry glycolytic, antioxidant, and telomerase maintenance functions. We reveal a striking lineage-specific reprogramming of TSblast proteome during fate-specification. These findings extend our knowledge of the sequential order of protein landscape reprogramming and processes during early human embryogenesis and trophoblast function.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Summary&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Although genomic and transcriptomic studies have provided key understanding of the genetic programs underlying preimplantation embryo development, the protein expression landscape remains unexplored. Here, a quantitative proteomic study of human preimplantation embryo stages reveal a dynamic proteome landscape from M2, 8-cell, and blastocyst stage, and during trophoblast stem cell (TS) differentiation.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Identified key factors in early human embryos and lineage-specific trophoblast proteome profiles, further correlated with transcriptomic analyses.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;This direct proteomic analysis provides a quantitative and temporal analysis of the dynamic protein expression in human embryos during preimplantation development and a powerful resource to enable further mechanistic studies on human trophoblast development and function.&lt;/li&gt;\u0000 &lt;/ul&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":224,"journal":{"name":"Proteomics","volume":"25 15","pages":"72-89"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical Proteomics Probes: Classification, Applications, and Future Perspectives in Proteome-Wide Studies.","authors":"Xiaoyue Tan, Dan Wang, Yingrui Yao, Kaixuan Liu, Yuzhou Chen, Songsen Fu, Feng Ni","doi":"10.1002/pmic.70019","DOIUrl":"https://doi.org/10.1002/pmic.70019","url":null,"abstract":"<p><p>Chemical proteomics probes serve as critical tools for investigating small molecule-protein interactions within complex biological systems. Traditionally, they are categorized into covalent probes and photoaffinity probes. They facilitate drug target discovery, targeted ligand screening, dynamic evaluation of enzyme activities in disease contexts, protein modification mapping, and bridging proteomics with other omics platforms. Despite their significant utility, challenges remain in probe design optimization, reduction of non-specific interactions, and expansion of targetable proteomic landscapes. Future research efforts are expected to focus on the development of novel probes, the integration of chemical proteomics with structural biology and artificial intelligence, and the advancement of clinical applications. These innovations will deepen our understanding of protein functions and support the advancement of precision medicine. In this review, we summarize the classification and fundamental principles of chemical proteomics probes and provide an in-depth discussion of their diverse applications.</p>","PeriodicalId":224,"journal":{"name":"Proteomics","volume":" ","pages":"e70019"},"PeriodicalIF":3.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}