Molecular & Cellular Proteomics最新文献

{"title":"Proteome-Scale Tissue Mapping Using Mass Spectrometry Based on Label-Free and Multiplexed Workflows.","authors":"Yumi Kwon, Jongmin Woo, Fengchao Yu, Sarah M Williams, Lye Meng Markillie, Ronald J Moore, Ernesto S Nakayasu, Jing Chen, Martha Campbell-Thompson, Clayton E Mathews, Alexey I Nesvizhskii, Wei-Jun Qian, Ying Zhu","doi":"10.1016/j.mcpro.2024.100841","DOIUrl":"10.1016/j.mcpro.2024.100841","url":null,"abstract":"<p><p>Multiplexed bimolecular profiling of tissue microenvironment, or spatial omics, can provide deep insight into cellular compositions and interactions in healthy and diseased tissues. Proteome-scale tissue mapping, which aims to unbiasedly visualize all the proteins in a whole tissue section or region of interest, has attracted significant interest because it holds great potential to directly reveal diagnostic biomarkers and therapeutic targets. While many approaches are available, however, proteome mapping still exhibits significant technical challenges in both protein coverage and analytical throughput. Since many of these existing challenges are associated with mass spectrometry-based protein identification and quantification, we performed a detailed benchmarking study of three protein quantification methods for spatial proteome mapping, including label-free, TMT-MS2, and TMT-MS3. Our study indicates label-free method provided the deepest coverages of ∼3500 proteins at a spatial resolution of 50 μm and the highest quantification dynamic range, while TMT-MS2 method holds great benefit in mapping throughput at >125 pixels per day. The evaluation also indicates both label-free and TMT-MS2 provides robust protein quantifications in identifying differentially abundant proteins and spatially covariable clusters. In the study of pancreatic islet microenvironment, we demonstrated deep proteome mapping not only enables the identification of protein markers specific to different cell types, but more importantly, it also reveals unknown or hidden protein patterns by spatial coexpression analysis.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100841"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NovoBoard: A Comprehensive Framework for Evaluating the False Discovery Rate and Accuracy of De Novo Peptide Sequencing.","authors":"Ngoc Hieu Tran, Rui Qiao, Zeping Mao, Shengying Pan, Qing Zhang, Wenting Li, Lei Xin, Ming Li, Baozhen Shan","doi":"10.1016/j.mcpro.2024.100849","DOIUrl":"10.1016/j.mcpro.2024.100849","url":null,"abstract":"<p><p>De novo peptide sequencing is one of the most fundamental research areas in mass spectrometry-based proteomics. Many methods have often been evaluated using a couple of simple metrics that do not fully reflect their overall performance. Moreover, there has not been an established method to estimate the false discovery rate (FDR) of de novo peptide-spectrum matches. Here we propose NovoBoard, a comprehensive framework to evaluate the performance of de novo peptide-sequencing methods. The framework consists of diverse benchmark datasets (including tryptic, nontryptic, immunopeptidomics, and different species) and a standard set of accuracy metrics to evaluate the fragment ions, amino acids, and peptides of the de novo results. More importantly, a new approach is designed to evaluate de novo peptide-sequencing methods on target-decoy spectra and to estimate and validate their FDRs. Our FDR estimation provides valuable information to assess the reliability of new peptides identified by de novo sequencing tools, especially when no ground-truth information is available to evaluate their accuracy. The FDR estimation can also be used to evaluate the capability of de novo peptide sequencing tools to distinguish between de novo peptide-spectrum matches and random matches. Our results thoroughly reveal the strengths and weaknesses of different de novo peptide-sequencing methods and how their performances depend on specific applications and the types of data.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100849"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Proteome Profiling of Inherited Retinal Degeneration Across Three Different Mouse Models Suggests Common Drug Targets in Retinitis Pigmentosa.","authors":"Ahmed B Montaser, Fangyuan Gao, Danielle Peters, Katri Vainionpää, Ning Zhibin, Dorota Skowronska-Krawczyk, Daniel Figeys, Krzysztof Palczewski, Henri Leinonen","doi":"10.1016/j.mcpro.2024.100855","DOIUrl":"10.1016/j.mcpro.2024.100855","url":null,"abstract":"<p><p>Inherited retinal degenerations (IRDs) are a leading cause of blindness among the population of young people in the developed world. Approximately half of IRDs initially manifest as gradual loss of night vision and visual fields, characteristic of retinitis pigmentosa (RP). Due to challenges in genetic testing, and the large heterogeneity of mutations underlying RP, targeted gene therapies are an impractical largescale solution in the foreseeable future. For this reason, identifying key pathophysiological pathways in IRDs that could be targets for mutation-agnostic and disease-modifying therapies (DMTs) is warranted. In this study, we investigated the retinal proteome of three distinct IRD mouse models, in comparison to sex- and age-matched wild-type mice. Specifically, we used the Pde6β^Rd10 (rd10) and Rho^P23H/WT (P23H) mouse models of autosomal recessive and autosomal dominant RP, respectively, as well as the Rpe65^-/- mouse model of Leber's congenital amaurosis type 2 (LCA2). The mice were housed at two distinct institutions and analyzed using LC-MS in three separate facilities/instruments following data-dependent and data-independent acquisition modes. This cross-institutional and multi-methodological approach signifies the reliability and reproducibility of the results. The large-scale profiling of the retinal proteome, coupled with in vivo electroretinography recordings, provided us with a reliable basis for comparing the disease phenotypes and severity. Despite evident inflammation, cellular stress, and downscaled phototransduction observed consistently across all three models, the underlying pathologies of RP and LCA2 displayed many differences, sharing only four general KEGG pathways. The opposite is true for the two RP models in which we identify remarkable convergence in proteomic phenotype even though the mechanism of primary rod death in rd10 and P23H mice is different. Our data highlights the cAMP and cGMP second-messenger signaling pathways as potential targets for therapeutic intervention. The proteomic data is curated and made publicly available, facilitating the discovery of universal therapeutic targets for RP.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100855"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LC-SRM Combined With Machine Learning Enables Fast Identification and Quantification of Bacterial Pathogens in Urinary Tract Infections.","authors":"Clarisse Gotti, Florence Roux-Dalvai, Ève Bérubé, Antoine Lacombe-Rastoll, Mickaël Leclercq, Cristina C Jacob, Maurice Boissinot, Claudia Martins, Neloni R Wijeratne, Michel G Bergeron, Arnaud Droit","doi":"10.1016/j.mcpro.2024.100832","DOIUrl":"10.1016/j.mcpro.2024.100832","url":null,"abstract":"<p><p>Urinary tract infections (UTIs) are a worldwide health problem. Fast and accurate detection of bacterial infection is essential to provide appropriate antibiotherapy to patients and to avoid the emergence of drug-resistant pathogens. While the gold standard requires 24 h to 48 h of bacteria culture prior to MALDI-TOF species identification, we propose a culture-free workflow, enabling bacterial identification and quantification in less than 4 h using 1 ml of urine. After rapid and automatable sample preparation, a signature of 82 bacterial peptides, defined by machine learning, was monitored in LC-MS, to distinguish the 15 species causing 84% of the UTIs. The combination of the sensitivity of the SRM mode on a triple quadrupole TSQ Altis instrument and the robustness of capillary flow enabled us to analyze up to 75 samples per day, with 99.2% accuracy on bacterial inoculations of healthy urines. We have also shown our method can be used to quantify the spread of the infection, from 8 × 10⁴ to 3 × 10⁷ CFU/ml. Finally, the workflow was validated on 45 inoculated urines and on 84 UTI-positive urine from patients, with respectively 93.3% and 87.1% of agreement with the culture-MALDI procedure at a level above 1 × 10⁵ CFU/ml corresponding to an infection requiring antibiotherapy.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100832"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Omics Reveals the Metabolic Patterns During Oocyte Growth.","authors":"Xiang Zhang, Juan Ge, Yue Wang, Minjian Chen, Xuejiang Guo, Shuai Zhu, Hui Wang, Qiang Wang","doi":"10.1016/j.mcpro.2024.100862","DOIUrl":"10.1016/j.mcpro.2024.100862","url":null,"abstract":"<p><p>Well-controlled metabolism is associated with high-quality oocytes and optimal development of a healthy embryo. However, the metabolic framework that controls mammalian oocyte growth remains unknown. In the present study, we comprehensively depict the temporal metabolic dynamics of mouse oocytes during in vivo growth through the integrated analysis of metabolomics and proteomics. Many novel metabolic features are discovered during this process. Of note, glycolysis is enhanced, and oxidative phosphorylation capacity is reduced in the growing oocytes, presenting a Warburg-like metabolic program. For nucleotide biosynthesis, the salvage pathway is markedly activated during oocyte growth, whereas the de novo pathway is evidently suppressed. Fatty acid synthesis and channeling into phosphoinositides are specifically elevated in oocytes accompanying primordial follicle activation; nevertheless, fatty acid oxidation is reduced in these oocytes simultaneously. Our data establish the metabolic landscape during in vivo oocyte growth and serve as a broad resource for probing mammalian oocyte metabolism.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100862"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Plastidial Protein Acetyltransferase GNAT1 Forms a Complex With GNAT2, yet Their Interaction Is Dispensable for State Transitions.","authors":"Annika Brünje, Magdalena Füßl, Jürgen Eirich, Jean-Baptiste Boyer, Paulina Heinkow, Ulla Neumann, Minna Konert, Aiste Ivanauskaite, Julian Seidel, Shin-Ichiro Ozawa, Wataru Sakamoto, Thierry Meinnel, Dirk Schwarzer, Paula Mulo, Carmela Giglione, Iris Finkemeier","doi":"10.1016/j.mcpro.2024.100850","DOIUrl":"10.1016/j.mcpro.2024.100850","url":null,"abstract":"<p><p>Protein N-acetylation is one of the most abundant co- and post-translational modifications in eukaryotes, extending its occurrence to chloroplasts within vascular plants. Recently, a novel plastidial enzyme family comprising eight acetyltransferases that exhibit dual lysine and N-terminus acetylation activities was unveiled in Arabidopsis. Among these, GNAT1, GNAT2, and GNAT3 reveal notable phylogenetic proximity, forming a subgroup termed NAA90. Our study focused on characterizing GNAT1, closely related to the state transition acetyltransferase GNAT2. In contrast to GNAT2, GNAT1 did not prove essential for state transitions and displayed no discernible phenotypic difference compared to the wild type under high light conditions, while gnat2 mutants were severely affected. However, gnat1 mutants exhibited a tighter packing of the thylakoid membranes akin to gnat2 mutants. In vitro studies with recombinant GNAT1 demonstrated robust N-terminus acetylation activity on synthetic substrate peptides. This activity was confirmed in vivo through N-terminal acetylome profiling in two independent gnat1 knockout lines. This attributed several acetylation sites on plastidial proteins to GNAT1, reflecting a subset of GNAT2's substrate spectrum. Moreover, co-immunoprecipitation coupled with mass spectrometry revealed a robust interaction between GNAT1 and GNAT2, as well as a significant association of GNAT2 with GNAT3 - the third acetyltransferase within the NAA90 subfamily. This study unveils the existence of at least two acetyltransferase complexes within chloroplasts, whereby complex formation might have a critical effect on the fine-tuning of the overall acetyltransferase activities. These findings introduce a novel layer of regulation in acetylation-dependent adjustments in plastidial metabolism.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100850"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen/Deuterium Exchange Mass Spectrometry: Fundamentals, Limitations, and Opportunities.","authors":"Lars Konermann, Pablo M Scrosati","doi":"10.1016/j.mcpro.2024.100853","DOIUrl":"10.1016/j.mcpro.2024.100853","url":null,"abstract":"<p><p>Hydrogen/deuterium exchange mass spectrometry (HDX-MS) probes dynamic motions of proteins by monitoring the kinetics of backbone amide deuteration. Dynamic regions exhibit rapid HDX, while rigid segments are more protected. Current data readouts focus on qualitative comparative observations (such as \"residues X to Y become more protected after protein exposure to ligand Z\"). At present, it is not possible to decode HDX protection patterns in an atomistic fashion. In other words, the exact range of protein motions under a given set of conditions cannot be uncovered, leaving space for speculative interpretations. Amide back exchange is an under-appreciated problem, as the widely used (m-m₀)/(m₁₀₀-m₀) correction method can distort HDX kinetic profiles. Future data analysis strategies require a better fundamental understanding of HDX events, going beyond the classical Linderstrøm-Lang model. Combined with experiments that offer enhanced spatial resolution and suppressed back exchange, it should become possible to uncover the exact range of motions exhibited by a protein under a given set of conditions. Such advances would provide a greatly improved understanding of protein behavior in health and disease.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100853"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights Into Glycobiology and the Protein-Glycan Interactome Using Glycan Microarray Technologies.","authors":"Jamie Heimburg-Molinaro, Akul Y Mehta, Catherine A Tilton, Richard D Cummings","doi":"10.1016/j.mcpro.2024.100844","DOIUrl":"10.1016/j.mcpro.2024.100844","url":null,"abstract":"<p><p>Glycans linked to proteins and lipids and also occurring in free forms have many functions, and these are partly elicited through specific interactions with glycan-binding proteins (GBPs). These include lectins, adhesins, toxins, hemagglutinins, growth factors, and enzymes, but antibodies can also bind glycans. While humans and other animals generate a vast repertoire of GBPs and different glycans in their glycomes, other organisms, including phage, microbes, protozoans, fungi, and plants also express glycans and GBPs, and these can also interact with their host glycans. This can be termed the protein-glycan interactome, and in nature is likely to be vast, but is so far very poorly described. Understanding the breadth of the protein-glycan interactome is also a key to unlocking our understanding of infectious diseases involving glycans, and immunology associated with antibodies binding to glycans. A key technological advance in this area has been the development of glycan microarrays. This is a display technology in which minute quantities of glycans are attached to the surfaces of slides or beads. This allows the arrayed glycans to be interrogated by GBPs and antibodies in a relatively high throughput approach, in which a protein may bind to one or more distinct glycans. Such binding can lead to novel insights and hypotheses regarding both the function of the GBP, the specificity of an antibody and the function of the glycan within the context of the protein-glycan interactome. This article focuses on the types of glycan microarray technologies currently available to study animal glycobiology and examples of breakthroughs aided by these technologies.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100844"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Start Codons of Small Open Reading Frames by N-Terminomics Approach.","authors":"Mingbo Peng, Tianjing Wang, Yujie Li, Zheng Zhang, Cuihong Wan","doi":"10.1016/j.mcpro.2024.100860","DOIUrl":"10.1016/j.mcpro.2024.100860","url":null,"abstract":"<p><p>sORF-encoded peptides (SEPs) refer to proteins encoded by small open reading frames (sORFs) with a length of less than 100 amino acids, which play an important role in various life activities. Analysis of known SEPs showed that using non-canonical initiation codons of SEPs was more common. However, the current analysis of SEP sequences mainly relies on bioinformatics prediction, and most of them use AUG as the start site, which may not be completely correct for SEPs. Chemical labeling was used to systematically analyze the N-terminal sequences of SEPs to accurately define the start sites of SEPs. By comparison, we found that dimethylation and guanidinylation are more efficient than acetylation. The ACN precipitation and heating precipitation performed better in SEP enrichment. As an N-terminal peptide enrichment material, Hexadhexaldehyde was superior to CNBr-activated agarose and NHS-activated agarose. Combining these methods, we identified 128 SEPs with 131 N-terminal sequences. Among them, two-thirds are novel N-terminal sequences, and most of them start from the 11-31st amino acids of the original sequence. Partial novel N-termini were produced by proteolysis or signal peptide removal. Some SEPs' transcription start sites were corrected to be non-AUG start codons. One novel start codon was validated using GFP-tag vectors. These results demonstrated that the chemical labeling approaches would be beneficial for identifying the start codons of sORFs and the real N-terminal of their encoded peptides, which helps better understand the characterization of SEPs.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100860"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Proteomic Analysis Reveals Distinct Features and a Diagnostic Biomarker Panel for Early Pregnancy Loss in Histological Subtypes.","authors":"Yating Zhao, Yingjiqiong Liang, Luya Cai, Limeng Cai, Bo Huang, Peilin Han, Xiaofei Zhang, Huifang Zhang, Zhen Chen, Xiangang Yin, Ping Duan, Huafeng Shou, Xiaoxu Zhu, Zhe Wang, Qihong Wan, Jinyan Huang, Jianhua Qian","doi":"10.1016/j.mcpro.2024.100848","DOIUrl":"10.1016/j.mcpro.2024.100848","url":null,"abstract":"<p><p>Early pregnancy loss (EPL) is a common event in human reproduction and is classified into histological subtypes such as hydropic abortion (HA) and hydatidiform moles, including complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs). However, accurate diagnosis and improved patient management remain challenging due to high rates of misdiagnosis and diverse prognostic risks. Therefore, diagnostic biomarkers for EPL are urgently needed. Our study aimed to identify biomarkers for EPL through comprehensive proteomic analysis. Ten CHMs, six PHMs, ten HAs, and 10 normal control products of conception were used to obtain a proteomic portrait. Parallel reaction monitoring-targeted proteomic and regression analyses were used to verify and select the diagnostic signatures. Finally, 14 proteins were selected and a panel of diagnostic classifiers (DLK1, SPTB/COL21A1, and SAR1A) was built to represent the CHM, PHM, and normal control groups (area under the receiver operating characteristic curve = 0.900, 0.804/0.885, and 0.991, respectively). This high diagnostic power was further validated in another independent cohort (n = 148) by immunohistochemistry (n = 120) and Western blot analyses (n = 28). The protein SPTB was selected for further biological behavior experiments in vitro. Our data suggest that SPTB maintains trophoblast cell proliferation, angiogenesis, cell motility, and the cytoskeleton network. This study provides a comprehensive proteomic portrait and identifies potential diagnostic biomarkers. These findings enhance our understanding of EPL pathogenesis and offer novel targets for diagnosis and therapeutic interventions.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100848"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}