Molecular & Cellular Proteomics最新文献

{"title":"Multitiered Proteome Analysis Displays the Hyperpermeability of the Rheumatoid Synovial Compartment for Plasma Proteins.","authors":"Eva Maria Stork, Sofia Kalaidopoulou Nteak, Danique M H van Rijswijck, J Mirjam A Damen, Hans Ulrich Scherer, Rene E M Toes, Albert Bondt, Tom W J Huizinga, Albert J R Heck","doi":"10.1016/j.mcpro.2024.100900","DOIUrl":"10.1016/j.mcpro.2024.100900","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and cartilage/bone destruction. RA affects the synovial joints, the synovial lining, and the permeability of the synovium. As the latter is of central relevance for the distribution of systemically delivered therapeutics into synovial fluid (SF), we here assessed the protein composition of paired plasma and SF of patients diagnosed with RA at three distinct levels of depth using mass spectrometric approaches: the \"total\" proteome, the \"total\" immunoglobulin G1 (IgG1) antibody repertoire, and the RA-specific anticitrullinated protein IgG1 autoantibody repertoire. The SF proteome was found to be dominated in numbers and concentration by plasma proteins, although we additionally detected several cartilage- and neutrophil-derived proteins of lower abundance. Strikingly, the plasma proteins were not only qualitatively reflected in SF but also quantitatively, independent of their size and/or other biochemical features. Also, the synovial \"total\" IgG1 and autoreactive anticitrullinated protein antibody IgG1 repertoire highly resembled the IgG1 repertoires detected in plasma within the same patient. Our comprehensive multilayer data thus reveals that the proteome, including the dominant, most abundant (auto)antibody clones, present in SF of RA patients is a direct reflection of the proteome present in blood, spiked by the local (immune) processes within the RA joint. We thus conclude that proteins directly pass from blood into SF of these joints without substantial bias. These findings thereby not only exemplify the use of in-depth multilayer proteome analyses to revisit basic concepts underlying RA pathology and to monitor the local (immune) processes destructive to cartilage but also provide evidence indicating that (protein-based) therapeutics may equally enter SF of swollen joints and that pharmacokinetic analyses of such therapeutics in blood are directly relevant to the synovial compartment.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100900"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922072","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":"Early Life Exposure to Deltamethrin Impairs Synaptic Function by Altering the Brain-Derived Extracellular Vesicle Proteome.","authors":"Leandra Koff, Jessica Di Re, Subhash Chand, Yosef Avchalumov, Nghi M Nguyen, Timothy J Baumgartner, Aditya K Singh, Nana A Goode, Mate Marosi, Lance M Hallberg, Bill T Ameredes, Thomas A Green, Sowmya V Yelamanchili, Gurudutt Pendyala, Fernanda Laezza","doi":"10.1016/j.mcpro.2024.100902","DOIUrl":"10.1016/j.mcpro.2024.100902","url":null,"abstract":"<p><p>Pyrethroid pesticides have been associated with neurodevelopmental disorders including attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). While behavioral effects of pyrethroid exposure have been previously reported, the underlying mechanisms remain unclear. Here, we hypothesized that exposure to deltamethrin (DM), a widely used pyrethroid pesticide known for its neurotoxicity during early developmental stages, induces brain dysfunction through alterations in brain-derived extracellular vesicle (BDEV) signaling. Using a well-established rodent model of early life DM exposure within the recommended no observable effect level, we isolated BDEVs from postnatal 30-day-old vehicle-exposed (control) and DM-exposed mice using a differential sucrose density gradient. Following ZetaView nanoparticle tracking and electron microscopy characterization, quantitative mass spectrometry-based proteomics revealed 89 differentially expressed proteins (DEPs) in BDEVs from DM exposed animals compared to control BDEVs. Bioinformatic analysis identified convergence of DEPs on pathways associated with mitochondrial function and synaptic plasticity. PKH67-green conjugated BDEVs derived from either control or DM-exposed mice were bilaterally injected intracerebroventricularly into naive adult mice, and the brain distribution of labeled BDEVs was verified prior to extracellular field recording experiments. Strikingly, long-term potentiation (LTP) at CA3-CA1 hippocampal synapses, a functional correlate of learning and memory, was intact in control BDEVs but absent in naive mice receiving BDEVs from DM exposed mice. Notably, exogenously delivering LRRTM1, one of the DEPs found in DM BDEVs, disrupts synaptic transmission in CA1 neurons consistent with impaired LTP. Thus, differentially regulated signaling in BDEVs represents a novel mechanism of DM neurotoxicity.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100902"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922070","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":"Chemical Glycoproteomic Profiling in Rice Seedlings Reveals N-glycosylation in the ERAD-L Machinery.","authors":"Cong Lei, Xilong Li, Wenjia Li, Zihan Chen, Simiao Liu, Bo Cheng, Yili Hu, Qitao Song, Yahong Qiu, Yilan Zhou, Xiangbing Meng, Hong Yu, Wen Zhou, Xing Chen, Jiayang Li","doi":"10.1016/j.mcpro.2024.100883","DOIUrl":"10.1016/j.mcpro.2024.100883","url":null,"abstract":"<p><p>As a ubiquitous and essential posttranslational modification occurring in both plants and animals, protein N-linked glycosylation regulates various important biological processes. Unlike the well-studied animal N-glycoproteomes, the landscape of rice N-glycoproteome remains largely unexplored. Here, by developing a chemical glycoproteomic strategy based on metabolic glycan labeling, we report a comprehensive profiling of the N-glycoproteome in rice seedlings. The rice seedlings are incubated with N-azidoacetylgalactosamine-a monosaccharide analog containing a bioorthogonal functional group-to metabolically label N-glycans, followed by conjugation with an affinity probe via click chemistry for the enrichment of the N-glycoproteins. Subsequent mass spectrometry analyses identify a total of 403 N-glycosylation sites and 673 N-glycosylated proteins, which are involved in various important biological processes. In particular, the core components of the endoplasmic reticulum-associated protein degradation machinery are N-glycosylated, and the N-glycosylation is important for the endoplasmic reticulum-associated protein degradation-L function. This work not only provides an invaluable resource for studying rice N-glycosylation but also demonstrates the applicability of metabolic glycan labeling in glycoproteomic profiling for crop species.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100883"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693221","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":"Improving the Depth and Reliability of Glycopeptide Identification Using Protein Prospector.","authors":"Robert J Chalkley, Peter R Baker","doi":"10.1016/j.mcpro.2025.100903","DOIUrl":"10.1016/j.mcpro.2025.100903","url":null,"abstract":"<p><p>Glycosylation is the most common and diverse modification of proteins. It can affect protein function and stability and is associated with many diseases. While proteomic methods to study most post-translational modifications are now quite mature, glycopeptide analysis is still a challenge, particularly from the aspect of data analysis. Several software packages have been developed in the last few years that aim to support omic-level N-linked glycopeptide analysis. This study presents developments of Protein Prospector for the analysis of N-glycopeptide data. Results are compared to other software, showing that Protein Prospector reports many more glycoforms of glycopeptides than competing software. The advantages and disadvantages of considering glycan adducts are also evaluated, showing how considering them can correct previously wrong assignments.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100903"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951613","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":"Electrophoresis-Correlative Ion Mobility Deepens Single-Cell Proteomics in Capillary Electrophoresis Mass Spectrometry.","authors":"Bowen Shen, Fei Zhou, Peter Nemes","doi":"10.1016/j.mcpro.2024.100892","DOIUrl":"10.1016/j.mcpro.2024.100892","url":null,"abstract":"<p><p>Detection of trace-sensitive signals is a current challenge in single-cell mass spectrometry (MS) proteomics. Separation prior to detection improves the fidelity and depth of proteome identification and quantification. We recently recognized capillary electrophoresis (CE) electrospray ionization (ESI) for ordering peptides into mass-to-charge (m/z)-dependent series, introducing electrophoresis-correlative (Eco) data-independent acquisition. Here, we demonstrate that these correlations based on electrophoretic mobility (μ_ef) in the liquid phase are transferred into the gas phase, essentially temporally sorting the peptide ions into charge-dependent ion mobility (IM, 1/K₀) trends (ρ > 0.97). Rather than sampling the entire IM region broadly, we pursued these predictable correlations to schedule narrower frames. Compared to classical data-dependent (dda) PASEF, Eco-framing significantly enhanced the resolution of IM MS (IMS) on a trapped IM mass spectrometer (timsTOF PRO). This approach returned ∼50% more proteins from HeLa proteome digests approximating to one-to-two cells, identifying ∼962 proteins from ∼200 pg in <20 min of effective electrophoresis, without match-between-runs. As a proof of principle, we deployed Eco-IMS to detect 1157 proteins by analyzing <4% of the total proteome content in single, yolk-laden embryonic stem cells (∼80-μm) that were isolated from the animal cap of the South African clawed frog (Xenopus laevis). Quantitative profiling of nine different blastomeres revealed detectable differences among these cells, which are normally fated to form the ectoderm but retain pluripotentiality. Eco-framing in the IM dimension effectively deepens the proteome sensitivity in IMS using ddaPASEF, facilitating the proteome-driven classification of differentiating cells, as demonstrated in the chordate frog embryo in this report.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100892"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824204","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":"Site-Specific Competitive Kinase Inhibitor Target Profiling Using Phosphonate Affinity Tags.","authors":"Wouter van Bergen, Anneroos E Nederstigt, Albert J R Heck, Marc P Baggelaar","doi":"10.1016/j.mcpro.2025.100906","DOIUrl":"10.1016/j.mcpro.2025.100906","url":null,"abstract":"<p><p>Protein kinases are prime targets for drug development due to their involvement in various cancers. However, selective inhibition of kinases, while avoiding off-target effects remains a significant challenge for the development of protein kinase inhibitors. Activity-based protein profiling (ABPP), in combination with pan-kinase activity-based probes (ABPs) and mass spectrometry-based proteomics, enables the identification of kinase drug targets. Here, we extend existing ABPP strategies for kinase profiling with a site-specific analysis, allowing for protein kinase inhibitor target engagement profiling with amino acid specificity. The site-specific approach involves highly efficient enrichment of ABP-labeled peptides, resulting in a less complex peptide matrix, straightforward data analysis, and the screening of over ∼100 kinase active sites in a single LC-MS analysis. The complementary use of both trypsin and pepsin in parallel to generate the ABP-labeled peptides considerably expanded the coverage of kinases and pinpoint the exact binding sites. Using the site-specific strategy to examine the on- and off-targets of the Ephrin receptor (Eph) B4 inhibitor NVP-BHG712 showed binding to EphA2 with an IC₅₀ of 17 nM and EphB4 with an IC₅₀ of 20 nM. Next to the known targets, EphA2 and EphB4, NVP-BHG712 bound to the discoidin domain-containing receptor 1 with an IC₅₀ of 2.1 nM, suggesting that a discoidin domain-containing receptor 1-targeting regio-isomer of NVP-BHG712 was used. The promiscuity of XO44 toward ATP-binding pockets on nonkinase proteins facilitated the screening of additional off-target sites, revealing inosine-5'-monophosphate dehydrogenase 2 as a putative off-target. Expanding the search to other amino acids revealed that XO44, in addition to 745 lysines, also covalently linked 715 tyrosines, which significantly expands the competitive ABPP search space and highlights the added value of the site-specific method. Therefore, the presented approach, which can be fully automated with liquid handling platforms, provides a straightforward, valuable new approach for competitive site-specific kinase inhibitor target profiling.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100906"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008370","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":"Sensitive and Accurate Proteome Profiling of Embryogenesis Using Real-Time Search and TMTproC Quantification.","authors":"Alex N T Johnson, Jingjing Huang, Argit Marishta, Edward R Cruz, Andrea Mariossi, William D Barshop, Jesse D Canterbury, Rafael Melani, David Bergen, Vlad Zabrouskov, Michael S Levine, Eric Wieschaus, Graeme C McAlister, Martin Wühr","doi":"10.1016/j.mcpro.2024.100899","DOIUrl":"10.1016/j.mcpro.2024.100899","url":null,"abstract":"<p><p>Multiplexed proteomics has become a powerful tool for investigating biological systems. Using balancer-peptide conjugates (e.g., TMTproC complementary ions) in the MS2 spectra for quantification circumvents the ratio distortion problem inherent in multiplexed proteomics. However, TMTproC quantification scans require long Orbitrap transients and extended ion injection times to achieve sufficient ion statistics and spectral resolution. Real-time search (RTS) algorithms have demonstrated increased speed and sensitivity by selectively informing precursor peak quantification. Here, we combine complementary ion quantification with RTS (TMTproC-RTS) to enhance sensitivity while maintaining accuracy and precision in quantitative proteomics at the MS2 level. We demonstrate the utility of this method by quantifying protein dynamics during the embryonic development of Drosophila melanogaster (fly), Ciona robusta (sea squirt), and Xenopus laevis (frog). We quantify 7.8k, 8.6k, and 12.7k proteins in each organism, which is an improvement of 12%, 13%, and 14%, respectively, compared with naive TMTproC analysis. For all three organisms, the newly acquired data outperform previously published datasets and provide a diverse, deep, and accurate database of protein dynamics during embryogenesis, which will advance the study of evolutionary comparison in early embryogenesis.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100899"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896139","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":"High-Throughput Determination of Exchange Rates of Unmodified and PTM-Containing Peptides Using HX-MS.","authors":"Jamie A Moroco, Alvaro Sebastian Vaca Jacome, Pierre Michel Jean Beltran, Andrew Reiter, Charlie Mundorff, Miklos Guttman, Jeff Morrow, Stephen Coales, Leland Mayne, Yoshitomo Hamuro, Steven A Carr, Malvina Papanastasiou","doi":"10.1016/j.mcpro.2025.100904","DOIUrl":"10.1016/j.mcpro.2025.100904","url":null,"abstract":"<p><p>Despite the widespread use of MS for hydrogen/deuterium exchange measurements, no systematic, large-scale study has been conducted to compare the observed exchange rates in protein-derived, unstructured peptides measured by MS to the predicted exchange rates calculated from NMR-derived values and how neighboring residues and post-translational modifications influence those exchange rates. In this study, we sought to test the accuracy of predicted values by performing hydrogen exchange measurements on whole cell digests to generate an unbiased dataset of 563 unique peptides derived from naturally occurring protein sequences. A remarkable 97% of observed exchange rates of peptides are within two-fold of predicted values. Using fully deuterated controls, we found that for approximately 50% of the peptides, the amino acid sequence and, consequently, the intrinsic exchange rate, are the primary contributors to back exchange. A meta-analysis of the remaining physicochemical properties of peptides revealed multiple features that contribute either positively or negatively to back exchange discrepancies. Employing our workflow for comparable measurements on synthetic peptide mixtures containing post-translational modifications, and their unmodified counterparts, we show that lysine acetylation has a strong effect on the observed exchange rate, whereas serine/threonine phosphorylation does not. Our automated workflow enables high-throughput determination of exchange rates in complex biological peptide mixtures with diverse properties.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100904"},"PeriodicalIF":6.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951556","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":"Single Cell Proteomics Reveals Specific Cellular Subtypes in Cardiomyocytes Derived from Human iPSCs and Adult Hearts.","authors":"Lizhuo Ai, Aleksandra Binek, Vladimir Zhemkov, Jae Hyung Cho, Ali Haghani, Simion Kreimer, Edo Israely, Madelyn Arzt, Blandine Chazarin, Niveda Sundararaman, Arun Sharma, Eduardo Marbán, Clive N Svendsen, Jennifer E Van Eyk","doi":"10.1016/j.mcpro.2025.100910","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.100910","url":null,"abstract":"<p><p>Single cell proteomics was performed on human induced pluripotent stem cells (iPSCs), iPSC-derived cardiomyocytes, and adult cardiomyocytes. Over 700 proteins could be simultaneously measured in each cell revealing unique subpopulations. A sub-set of iPSCs expressed higher levels of Lin28a and Tra-1-60 towards the outer edge of cell colonies. In the cardiomyocytes, two distinct populations were found that exhibited complementary metabolic profiles. Cardiomyocytes from iPSCs showed a glycolysis profile while adult cardiomyocytes were enriched in proteins involved with fatty acid metabolism. Interestingly, rare single cells also co-expressed markers of both cardiac and neuronal lineages, suggesting there maybe a novel hybrid cell type in the human heart.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100910"},"PeriodicalIF":6.1,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040243","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":"Recent Advances in Mass Spectrometry-Based Protein Interactome Studies.","authors":"Shaowen Wu, Sheng Zhang, Chun-Ming Liu, Alisdair R Fernie, Shijuan Yan","doi":"10.1016/j.mcpro.2024.100887","DOIUrl":"10.1016/j.mcpro.2024.100887","url":null,"abstract":"<p><p>The foundation of all biological processes is the network of diverse and dynamic protein interactions with other molecules in cells known as the interactome. Understanding the interactome is crucial for elucidating molecular mechanisms but has been a longstanding challenge. Recent developments in mass spectrometry (MS)-based techniques, including affinity purification, proximity labeling, cross-linking, and co-fractionation mass spectrometry (MS), have significantly enhanced our abilities to study the interactome. They do so by identifying and quantifying protein interactions yielding profound insights into protein organizations and functions. This review summarizes recent advances in MS-based interactomics, focusing on the development of techniques that capture protein-protein, protein-metabolite, and protein-nucleic acid interactions. Additionally, we discuss how integrated MS-based approaches have been applied to diverse biological samples, focusing on significant discoveries that have leveraged our understanding of cellular functions. Finally, we highlight state-of-the-art bioinformatic approaches for predictions of interactome and complex modeling, as well as strategies for combining experimental interactome data with computation methods, thereby enhancing the ability of MS-based techniques to identify protein interactomes. Indeed, advances in MS technologies and their integrations with computational biology provide new directions and avenues for interactome research, leveraging new insights into mechanisms that govern the molecular architecture of living cells and, thereby, our comprehension of biological processes.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100887"},"PeriodicalIF":6.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751252","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}