Molecular & Cellular Proteomics最新文献

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Data-Driven Extraction of Human Kinase-Substrate Relationships From Omics Datasets. 从组学数据集中提取人类激酶-底物关系的数据驱动。
IF 5.5 2区 生物学
Molecular & Cellular Proteomics Pub Date : 2025-08-01 Epub Date: 2025-05-15 DOI: 10.1016/j.mcpro.2025.100994
Benjamin Dominik Maier, Borgthor Petursson, Alessandro Lussana, Evangelia Petsalaki
{"title":"Data-Driven Extraction of Human Kinase-Substrate Relationships From Omics Datasets.","authors":"Benjamin Dominik Maier, Borgthor Petursson, Alessandro Lussana, Evangelia Petsalaki","doi":"10.1016/j.mcpro.2025.100994","DOIUrl":"10.1016/j.mcpro.2025.100994","url":null,"abstract":"<p><p>Phosphorylation forms an important part of the signaling system that cells use for decision making and regulation of processes such as cell division and differentiation. In human, >90% of identified phosphosites do not have annotations regarding the relevant upstream kinase. At the same time around 30% of kinases (as annotated in UniProt) have no known target. This knowledge gap stresses the need to make large-scale, data-driven computational predictions. In this study, we have created a machine learning-based model to derive a probabilistic kinase-substrate network from omics datasets. Our methodology displays improved performance compared to other state-of-the-art kinase-substrate prediction methods and provides predictions for more kinases. Importantly, it better captures new experimentally identified kinase-substrate relationships. It can therefore allow the improved prioritization of kinase-substrate pairs for illuminating the dark human cell signaling space. Our model is integrated into a web server, SELPHI<sub>2.0</sub>, to allow unbiased analysis of phosphoproteomics data, facilitating the design of downstream experiments to uncover mechanisms of signal transduction across conditions and cellular contexts.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100994"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093630","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}
引用次数: 0
A Roadmap for Improving Reliability and Data Sharing in Crosslinking Mass Spectrometry. 提高交联质谱可靠性和数据共享的路线图。
IF 5.5 2区 生物学
Molecular & Cellular Proteomics Pub Date : 2025-08-01 Epub Date: 2025-06-26 DOI: 10.1016/j.mcpro.2025.101024
Juri Rappsilber, James Bruce, Colin Combe, Stephen D Fried, Andrea Graziadei, Albert J R Heck, Claudio Iacobucci, Alexander Leitner, Karl Mechtler, Petr Novak, Francis O'Reilly, David C Schriemer, Andrea Sinz, Florian Stengel, Konstantinos Thalassinos
{"title":"A Roadmap for Improving Reliability and Data Sharing in Crosslinking Mass Spectrometry.","authors":"Juri Rappsilber, James Bruce, Colin Combe, Stephen D Fried, Andrea Graziadei, Albert J R Heck, Claudio Iacobucci, Alexander Leitner, Karl Mechtler, Petr Novak, Francis O'Reilly, David C Schriemer, Andrea Sinz, Florian Stengel, Konstantinos Thalassinos","doi":"10.1016/j.mcpro.2025.101024","DOIUrl":"10.1016/j.mcpro.2025.101024","url":null,"abstract":"<p><p>Crosslinking mass spectrometry (MS) can uncover protein-protein interactions and provide structural information on proteins in their native cellular environments. Despite its promise, the field remains hampered by inconsistent data formats, variable approaches to error control, and insufficient interoperability with global data repositories. Recent advances, especially in false discovery rate models and pipeline benchmarking, show that crosslinking MS data can reach a reliability that matches the demand of integrative structural biology. To drive meaningful progress, however, the community must agree on error estimation, open data formats, and streamlined repository submissions. This perspective highlights these challenges, clarifies remaining barriers, and frames practical next steps. Successful field harmonization will enhance the acceptance of crosslinking MS in the broader biological community and is critical for the dependability of the data, no matter where it is produced.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101024"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528913","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}
引用次数: 0
Extracellular vesicles bearing vimentin drive epithelial-mesenchymal transition. 携带波形蛋白的细胞外囊泡驱动上皮-间质转化。
IF 6.1 2区 生物学
Molecular & Cellular Proteomics Pub Date : 2025-07-04 DOI: 10.1016/j.mcpro.2025.101028
Sepideh Parvanian, Leila S Coelho-Rato, Michael Santos Silva, Giulia Sultana, Arun P Venu, Pallavi Vilas Devre, Mayank Kumar Modi, John E Eriksson
{"title":"Extracellular vesicles bearing vimentin drive epithelial-mesenchymal transition.","authors":"Sepideh Parvanian, Leila S Coelho-Rato, Michael Santos Silva, Giulia Sultana, Arun P Venu, Pallavi Vilas Devre, Mayank Kumar Modi, John E Eriksson","doi":"10.1016/j.mcpro.2025.101028","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101028","url":null,"abstract":"<p><p>Epithelial-mesenchymal transition (EMT) is a key biological process in physiological and pathological conditions, spanning development, wound healing, and cancer. Vimentin, a key cytoskeletal intermediate filament (IF) protein, is an established intracellular determinant of EMT. Recently, extracellular vimentin has also emerged with important functions, and we demonstrated that vimentin from fibroblast-derived extracellular vesicles (EVs) promotes wound healing. Building on these findings, we explored whether extracellular vimentin regulates EMT. We employed fibroblast-derived EVs to assess their EMT-driving capacity. Using co-culture models and EV treatments from wild-type and vimentin-knockout fibroblasts, we observed that fibroblasts induce an EMT phenotype in epithelial cells, marked by elevated mesenchymal markers and reduced epithelial markers. EVs from vimentin-deficient fibroblasts showed a decreased EMT-inducing capacity and failed to stimulate cell cover closure, underscoring vimentin's critical role in orchestrating these processes. Co-culturing epithelial cells with wild-type fibroblasts mirrored these outcomes, while vimentin-deficient fibroblasts produced similarly poor EMT induction. Proteomic profiling revealed that wild-type EVs contained an enriched set of EMT-associated proteins, including those involved in cytoskeletal organization, cell adhesion, and EMT-regulating signaling pathways. Notably, these proteins, such as fibronectin and N-cadherin, were significantly diminished in vimentin-deficient EVs. Moreover, we identified over 600 additional proteins uniquely present in WT-derived EVs, with enrichment in key biological processes like wound healing and cell migration. These findings demonstrate that vimentin-positive EVs drive EMT by transmitting a specific protein cargo that supports EMT-related cellular changes. The vimentin-positive EV proteome will help understand EMT mechanisms and develop targeted therapies for pathological conditions related to abnormal EMT.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101028"},"PeriodicalIF":6.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575912","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}
引用次数: 0
UniScore, a Unified and Universal Measure for Peptide Identification by Multiple Search Engines. UniScore是一种统一的、通用的多肽识别方法,可通过多个搜索引擎进行识别。
IF 5.5 2区 生物学
Molecular & Cellular Proteomics Pub Date : 2025-07-01 Epub Date: 2025-06-02 DOI: 10.1016/j.mcpro.2025.101010
Tsuyoshi Tabata, Akiyasu C Yoshizawa, Kosuke Ogata, Chih-Hsiang Chang, Norie Araki, Naoyuki Sugiyama, Yasushi Ishihama
{"title":"UniScore, a Unified and Universal Measure for Peptide Identification by Multiple Search Engines.","authors":"Tsuyoshi Tabata, Akiyasu C Yoshizawa, Kosuke Ogata, Chih-Hsiang Chang, Norie Araki, Naoyuki Sugiyama, Yasushi Ishihama","doi":"10.1016/j.mcpro.2025.101010","DOIUrl":"10.1016/j.mcpro.2025.101010","url":null,"abstract":"<p><p>We propose UniScore as a metric for integrating and standardizing the outputs of multiple search engines in the analysis of data-dependent acquisition (DDA) data from LC/MS/MS-based bottom-up proteomics. UniScore is calculated from the annotation information attached to the product ions alone by matching the amino acid sequences of candidate peptides suggested by the search engine with the product ion spectrum. The acceptance criteria are controlled independently of the score values by using the false discovery rate based on the target-decoy approach. Compared to other rescoring methods that use deep learning-based spectral prediction, larger amounts of data can be processed using minimal computing resources. When applied to large-scale global proteome data and phosphoproteome data, the UniScore approach outperformed each of the conventional single search engines examined (Comet, X! Tandem, Mascot, and MaxQuant). Furthermore, UniScore could also be directly applied to peptide matching in chimeric spectra without any additional filters.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101010"},"PeriodicalIF":5.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225898","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}
引用次数: 0
Global Analysis of Protein and Small-Molecule Substrates of Ubiquitin-Like Proteins. 泛素样蛋白(UBLs)的蛋白质和小分子底物的全局分析。
IF 5.5 2区 生物学
Molecular & Cellular Proteomics Pub Date : 2025-07-01 Epub Date: 2025-04-18 DOI: 10.1016/j.mcpro.2025.100975
Guang-Can Shao, Zhen-Lin Chen, Shan Lu, Qing-Cui Wu, Yao Sheng, Jing Wang, Yan Ma, Jian-Hua Sui, Hao Chi, Xiang-Bing Qi, Si-Min He, Li-Lin Du, Meng-Qiu Dong
{"title":"Global Analysis of Protein and Small-Molecule Substrates of Ubiquitin-Like Proteins.","authors":"Guang-Can Shao, Zhen-Lin Chen, Shan Lu, Qing-Cui Wu, Yao Sheng, Jing Wang, Yan Ma, Jian-Hua Sui, Hao Chi, Xiang-Bing Qi, Si-Min He, Li-Lin Du, Meng-Qiu Dong","doi":"10.1016/j.mcpro.2025.100975","DOIUrl":"10.1016/j.mcpro.2025.100975","url":null,"abstract":"<p><p>Ubiquitin-like proteins (UBLs) constitute a family of evolutionarily conserved proteins that share similarities with ubiquitin in 3D structures and modification mechanisms. For most UBLs including small-ubiquitin-like modifiers (SUMO), their modification sites on substrate proteins cannot be identified using the mass spectrometry-based method that has been successful for identifying ubiquitination sites, unless a UBL protein is mutated accordingly. To identify UBL modification sites without having to mutate UBL, we have developed a dedicated search engine pLink-UBL on the basis of pLink, a software tool for the identification of cross-linked peptide pairs. pLink-UBL exhibited superior precision, sensitivity, and speed than \"make-do\" search engines such as MaxQuant, pFind, and pLink. For example, compared to MaxQuant, pLink-UBL increased the number of identified SUMOylation sites by 50 ∼ 300% from the same datasets. Additionally, we present a method for identifying small-molecule modifications of UBLs. This method involves antibody enrichment of a UBL C-terminal peptide following enrichment of a UBL protein, followed by LC-MS/MS analysis and a pFind 3 blind search to identify unexpected modifications. Using this method, we have discovered nonprotein substrates of SUMO, of which spermidine is the major one for fission yeast SUMO Pmt3. Spermidine can be conjugated to the C-terminal carboxylate group of Pmt3 through its N<sup>1</sup> or also likely, N<sup>8</sup> amino group in the presence of SUMO E1, E2, and ATP. Pmt3-spermidine conjugation does not require E3 and can be reversed by SUMO isopeptidase Ulp1. SUMO-spermidine conjugation is present in mice and humans. Also, spermidine can be conjugated to ubiquitin in vitro by E1 and E2 in the presence of ATP. The above observations suggest that spermidine may be a common small molecule substrate of SUMO and possibly ubiquitin across eukaryotic species.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100975"},"PeriodicalIF":5.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035372","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}
引用次数: 0
Proteome-Wide Investigation of Proline Hydroxylation in Pancreatic Ductal Adenocarcinoma Using DiLeu Isobaric Labeling Strategy. 应用DiLeu等压标记策略研究胰导管腺癌中脯氨酸羟基化的蛋白质组研究。
IF 5.5 2区 生物学
Molecular & Cellular Proteomics Pub Date : 2025-07-01 Epub Date: 2025-04-09 DOI: 10.1016/j.mcpro.2025.100969
Feixuan Wu, Dylan Nicholas Tabang, Danqing Wang, Jon S Odorico, Lingjun Li
{"title":"Proteome-Wide Investigation of Proline Hydroxylation in Pancreatic Ductal Adenocarcinoma Using DiLeu Isobaric Labeling Strategy.","authors":"Feixuan Wu, Dylan Nicholas Tabang, Danqing Wang, Jon S Odorico, Lingjun Li","doi":"10.1016/j.mcpro.2025.100969","DOIUrl":"10.1016/j.mcpro.2025.100969","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a dense fibrotic stroma intertwined with a collagen-rich extracellular matrix (ECM), which significantly contributes to tumor progression. In this study, we developed a high-throughput quantitative method that integrates enhanced hydrophilic interaction liquid chromatography (HILIC) with modified elution conditions and 12-plex N,N-dimethyl leucine (DiLeu) isobaric tags, facilitating efficient multiplexed quantitative analysis of hydroxyproline. This approach was applied to human pancreatic samples and resulted in the identification of 194 hydroxyproline peptides from 157 hydroxyproline sites and 59 proline-hydroxylated proteins, representing the first and the largest hydroxyproline proteomics dataset reported for the pancreas to date. This dataset lays a molecular foundation for understanding the structure-function relationships of hydroxyproline-containing proteins and their roles in pancreatic physiology and pathology. We then apply this strategy to investigating proline hydroxylation alterations in benign pancreatic tumors, PDAC, and their normal adjacent tissues (NAT). Our findings suggest significant biological functions related to proline hydroxylation, including altered patterns of key proteins such as collagen alpha-1(I) chain and collagen alpha-1(XII) chain. These proteins emerge as potential targets for further studies on proline hydroxylation in PDAC, potentially elucidating its role in modifying protein structures and influencing cancer progression.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100969"},"PeriodicalIF":5.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005674","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}
引用次数: 0
LncRNA MALAT1 Facilitates HIV-1 Replication by Upregulation of CHCHD2 and Downregulation of IFN-I Expression. LncRNA MALAT1通过上调CHCHD2和下调IFN-I表达促进HIV-1复制。
IF 5.5 2区 生物学
Molecular & Cellular Proteomics Pub Date : 2025-07-01 Epub Date: 2025-05-23 DOI: 10.1016/j.mcpro.2025.100997
Mei-Rong Wang, Cheng-Si Bai, Jian-Wei Dai, Lan Yang, Fang-Yi Quan, Jian-Chun Ma, Xing-Yuan Chen, Shao-Wei Zhu, Ying-Qi Xu, Zhou-Fu Xiang, Ya-le Jiang, Qi Cheng, Wei-Hao Zhang, Ke-Han Chen, Jian-Hua Wang, Yong Feng, Xiao-Ping Chen, Yong Xiong, Shu-Liang Chen, Wei Hou, Hai-Rong Xiong
{"title":"LncRNA MALAT1 Facilitates HIV-1 Replication by Upregulation of CHCHD2 and Downregulation of IFN-I Expression.","authors":"Mei-Rong Wang, Cheng-Si Bai, Jian-Wei Dai, Lan Yang, Fang-Yi Quan, Jian-Chun Ma, Xing-Yuan Chen, Shao-Wei Zhu, Ying-Qi Xu, Zhou-Fu Xiang, Ya-le Jiang, Qi Cheng, Wei-Hao Zhang, Ke-Han Chen, Jian-Hua Wang, Yong Feng, Xiao-Ping Chen, Yong Xiong, Shu-Liang Chen, Wei Hou, Hai-Rong Xiong","doi":"10.1016/j.mcpro.2025.100997","DOIUrl":"10.1016/j.mcpro.2025.100997","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) are effective regulators of both RNA and protein functions throughout cell biology, including viral replication. Emerging studies have shown that lncRNAs activate or inhibit the replication and latency of HIV-1 by regulating different cellular mechanisms. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an oncogenic lncRNA required for paraspeckle integrity and has been proven to be linked to viral infection. However, the mechanisms by which it influences HIV-1 infection in macrophages remain unclear. In this study, we performed RNA-deep sequencing to compare the profiles of lncRNAs in macrophages with or without HIV-1 and found that MALAT1 was dramatically upregulated in HIV-1-infected macrophages. MALAT1 knockdown inhibited HIV-1 infection, whereas MALAT1 overexpression enhanced viral replication, indicating that MALAT1 promotes HIV-1 replication. We further performed proteomics analysis and found that coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) was the most downregulated protein affected by RNAi-mediated knockdown of MALAT1. We next demonstrated that MALAT1 favored HIV-1 replication in a CHCHD2-dependent manner and functioned as a competing endogenous RNA to regulate CHCHD2 expression by sponging miR-145-5p, which could mutually bind the MALAT1 and 3'UTR of chchd2 mRNA. Furthermore, knockdown of endogenous MALAT1 or CHCHD2 with specific small interfering RNAs (siRNAs) promoted the expression of IRF7, and enhanced the promoter activities of interferons-α and -β, increasing their production as well as that of a critical interferon-stimulated gene (ISG), myxovirus resistance protein B (MxB). Moreover, MALAT1 or CHCHD2 knockdown promoted the expression of STAT2 to enhance the production of downstream MxB, which expanded the role of CHCHD2 as a negative regulator of the innate immune response. These findings improve our understanding of MALAT1/miR-145-5p/CHCHD2 pathway regulation of HIV-1 replication in macrophages, providing new insights into potential targeted therapeutic interventions.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100997"},"PeriodicalIF":5.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143009","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}
引用次数: 0
msqrob2TMT: Robust Linear Mixed Models for Inferring Differential Abundant Proteins in Labeled Experiments With Arbitrarily Complex Design. msqrob2TMT:在任意复杂设计的标记实验中推断差异丰富蛋白的鲁棒线性混合模型。
IF 5.5 2区 生物学
Molecular & Cellular Proteomics Pub Date : 2025-07-01 Epub Date: 2025-05-30 DOI: 10.1016/j.mcpro.2025.101002
Stijn Vandenbulcke, Christophe Vanderaa, Oliver Crook, Lennart Martens, Lieven Clement
{"title":"msqrob2TMT: Robust Linear Mixed Models for Inferring Differential Abundant Proteins in Labeled Experiments With Arbitrarily Complex Design.","authors":"Stijn Vandenbulcke, Christophe Vanderaa, Oliver Crook, Lennart Martens, Lieven Clement","doi":"10.1016/j.mcpro.2025.101002","DOIUrl":"10.1016/j.mcpro.2025.101002","url":null,"abstract":"<p><p>Labeling strategies in mass spectrometry-based proteomics enhance sample throughput by enabling the acquisition of multiplexed samples within a single run. However, contemporary experiments often involve increasingly complex designs, where the number of samples exceeds the capacity of a single run, resulting in a complex correlation structure that must be addressed for accurate statistical inference and reliable biomarker discovery. To this end, we introduce msqrob2TMT, a suite of mixed model-based workflows specifically designed for differential abundance analysis in labeled mass spectrometry-based proteomics data. msqrob2TMT accommodates both sample-specific and feature-specific (e.g., peptide or protein) covariates, facilitating inference in experiments with arbitrarily complex designs and allowing for explicit correction of feature-specific covariates. We benchmark our innovative workflows against state-of-the-art tools, including DEqMS, MSstatsTMT, and msTrawler, using two spike-in studies. Our findings demonstrate that msqrob2TMT offers greater flexibility, improved modularity, and enhanced performance, particularly through the application of robust ridge regression. Finally, we demonstrate the practical relevance of msqrob2TMT in a real mouse study, highlighting its capacity to effectively account for the complex correlation structure in the data.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101002"},"PeriodicalIF":5.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199619","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}
引用次数: 0
Closer Peptide Repertoire Similarity of HLA-B∗14:03 and HLA-B∗27:05 Sheds Light on Ankylosing Spondylitis Susceptibility. HLA-B*14:03和HLA-B*27:05肽库相似性揭示强直性脊柱炎易感性
IF 5.5 2区 生物学
Molecular & Cellular Proteomics Pub Date : 2025-07-01 Epub Date: 2025-06-02 DOI: 10.1016/j.mcpro.2025.101008
Laura Cobos-Figueroa, Javier Robles-Parrado, Elisenda Alari-Pahissa, Begoña Galocha, Carmen Mir, Ana Pintor-Poveda, Eilon Barnea, Arie Admon, Pilar Lauzurica, Elena Lorente
{"title":"Closer Peptide Repertoire Similarity of HLA-B∗14:03 and HLA-B∗27:05 Sheds Light on Ankylosing Spondylitis Susceptibility.","authors":"Laura Cobos-Figueroa, Javier Robles-Parrado, Elisenda Alari-Pahissa, Begoña Galocha, Carmen Mir, Ana Pintor-Poveda, Eilon Barnea, Arie Admon, Pilar Lauzurica, Elena Lorente","doi":"10.1016/j.mcpro.2025.101008","DOIUrl":"10.1016/j.mcpro.2025.101008","url":null,"abstract":"<p><p>The human major histocompatibility complex class I gene HLA-B∗27 is the main risk factor for ankylosing spondylitis (AS) through a mechanism that remains unknown. In African populations, where B∗27 is rare, the B∗14:03 allotype is strongly associated with AS, whereas B∗14:02, which differs at only one residue (L156R), is not associated. Using large-scale mass spectrometry-based peptide sequencing, we analyzed the peptidomes of HLA-B∗14:03, HLA-B∗14:02, and HLA-B∗27:05, obtaining more than 2000 ligands for each. Remarkably, we identified 1011 peptides shared by the AS-associated HLA-B∗27:05 and B∗14:03 alleles but not by the non-AS-associated B∗14:02 allele. Surprisingly, although B∗14:03 and B∗27:05 differ by 15 amino acids in their peptide-binding domain, they share a large portion of their ligands (64 and 43%, respectively), while B∗14:03 and B∗14:02, differing by only one residue, show less overlap (33-35%). The B∗14:03 peptide repertoire most closely resembles that of B∗27:05 at the P1, P2, and P5 peptide positions but diverges at the C-terminus, where B∗14:03 is more selective. Structural modeling suggests that the L156R difference between B∗14 alleles may induce long-range effects on peptide binding at P1, P2, and P5 residues, explaining the distinct repertoires. Most of the 1011 shared ligands contained R/K/A/G at P1, R at P2, and L/F at the C-terminus. Of these, ten peptides were previously identified as ligands of the three HLA-B∗27 subtypes most strongly associated with AS and are absent in nonassociated subtypes, while four peptides from the HLA 169 to 181 region-previously implicated in AS pathogenesis-were also identified, suggesting that differential peptide binding may influence disease development. In summary, the AS-associated allotypes B∗14:03 and B∗27:05, but not the non-AS-associated allotype B∗14:02, share similar peptide repertoires and binding characteristics, supporting specific common peptide ligands of HLA-B∗27:05 and B∗14:03 as a mechanism to explain the development of AS.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101008"},"PeriodicalIF":5.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225896","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}
引用次数: 0
Data-Independent Acquisition Proteomics Identifies Plasma Prostaglandin-H2 D-Isomerase as an Early Diagnostic Biomarker for STEMI and NSTEMI. 数据独立获取蛋白质组学鉴定血浆前列腺素- hdd异构酶作为STEMI和NSTEMI的早期诊断生物标志物。
IF 5.5 2区 生物学
Molecular & Cellular Proteomics Pub Date : 2025-07-01 Epub Date: 2025-05-23 DOI: 10.1016/j.mcpro.2025.100996
Hong-Mei Xue, Hai-Tao Hou, Yu Song, Huan-Xin Chen, Yun-Qiang Zhang, Wen-Tao Sun, Jie Zhou, Xiao-Lin Zhou, Na Sun, Qin Yang, Guo-Wei He
{"title":"Data-Independent Acquisition Proteomics Identifies Plasma Prostaglandin-H2 D-Isomerase as an Early Diagnostic Biomarker for STEMI and NSTEMI.","authors":"Hong-Mei Xue, Hai-Tao Hou, Yu Song, Huan-Xin Chen, Yun-Qiang Zhang, Wen-Tao Sun, Jie Zhou, Xiao-Lin Zhou, Na Sun, Qin Yang, Guo-Wei He","doi":"10.1016/j.mcpro.2025.100996","DOIUrl":"10.1016/j.mcpro.2025.100996","url":null,"abstract":"<p><p>Myocardial infarction (MI), including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), remains a leading cause of death worldwide. This study aimed to identify the early diagnostic biomarkers for STEMI and NSTEMI. Plasma samples from 386 patients were classified into four groups: control (CON) (n = 62), unstable angina (UA) (n = 62), STEMI (n = 182), and NSTEMI (n = 80). The protein profiles were analyzed using data-independent acquisition (DIA)-based proteomics to identify differentially abundant proteins (DAPs) followed by bioinformatics analysis and ELISA validation. In STEMI, 93 DAPs were detected. Among the selected DAPs that were further validated in a new cohort of patients, prostaglandin-H2 D-isomerase (PTGDS) was elevated at the earliest onset time of STEMI (T1, 1.45 h (95% CI: 1.16-1.73)) or NSTEMI (T1, 1.48 h (95% CI: 0.97-1.98)) while the current biomarkers (hs-TnI, Myo, CK-MB, and BNP) remained within normal ranges. The analysis of diagnostic indices for plasma PTGDS demonstrated a sensitivity of 63.95% and specificity of 65.38% in STEMI, 70% and 71.15% in NSTEMI. Moreover, AUC was 0.61 (95% CI: 0.53-0.69) in STEMI and 0.78 (95% CI: 0.70-0.86) in NSTEMI. The present study demonstrates that in patients with MI, plasma PTGDS increases at an earlier stage of onset time than the current biomarkers, with similar sensitivity and specificity. Therefore, PTGDS has high potential to be developed as an early diagnostic biomarker. In particular, PTGDS might be of greater clinical significance for patients suspected of NSTEMI, for which the biomarker could be more effective in identifying high-risk patients suffering from MI at an early stage.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100996"},"PeriodicalIF":5.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12226359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143004","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}
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