ACS Publications最新文献_第4页

Unlocking the Potential of Single-Cell Omics

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-04-04 DOI: 10.1021/acs.jproteome.5c0019710.1021/acs.jproteome.5c00197

Nikolai Slavov*,

引用次数: 0

Comprehensive Protein Inference Analysis with PyProteinInference Elucidates Biological Understanding of Tandem Mass Spectrometry Data.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-04-04 Epub Date: 2025-02-28 DOI: 10.1021/acs.jproteome.4c00734

Trent B Hinkle, Corey E Bakalarski

{"title":"Comprehensive Protein Inference Analysis with PyProteinInference Elucidates Biological Understanding of Tandem Mass Spectrometry Data.","authors":"Trent B Hinkle, Corey E Bakalarski","doi":"10.1021/acs.jproteome.4c00734","DOIUrl":"10.1021/acs.jproteome.4c00734","url":null,"abstract":"Selection and application of protein inference algorithms can have a significant impact on the data output from tandem mass spectrometry (MS/MS) experiments. However, this critical step is often taken for granted, with many studies simply utilizing the inference method embedded within the end-to-end software pipeline employed for analysis without consideration of the particular algorithm's suitability for the experiment at hand or its effects on the resulting data. Although many individual inference algorithms have been demonstrated, few unified tools are available that allow the researcher to quickly apply a variety of different inference algorithms to meet the needs of their analysis, are agnostic of other tools in the analysis pipeline, and are easy to use for the bench biologist. PyProteinInference provides a comprehensive suite of tools that enable researchers to apply different inference algorithms and compute protein-level set-based false discovery rates (FDR) from MS/MS data through a unified interface. Here, we describe the software and its application to a traditional protein inference benchmarking data set and to a K562 whole-cell lysate to demonstrate its utility in facilitating conclusions about underlying biological mechanisms in proteomic data.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"2135-2140"},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522096","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

Discovery of Key Candidate Protein Biomarkers in Early-Stage Nonsmall Cell Lung Carcinoma through Quantitative Proteomics.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-04-04 Epub Date: 2025-02-27 DOI: 10.1021/acs.jproteome.4c00764

Baby Rorielyn T Dimayacyac-Esleta, Ferdinand D Mira, Lorenzo M Zarate, Ben Joshua O Porras, Dave Laurence A Juntilla, Lara Beatrice L Suñga, Venus B Pondevida, Sullian S Naval, Treah May S Sayo, Herdee Gloriane C Luna, Eloise I Prieto

{"title":"Discovery of Key Candidate Protein Biomarkers in Early-Stage Nonsmall Cell Lung Carcinoma through Quantitative Proteomics.","authors":"Baby Rorielyn T Dimayacyac-Esleta, Ferdinand D Mira, Lorenzo M Zarate, Ben Joshua O Porras, Dave Laurence A Juntilla, Lara Beatrice L Suñga, Venus B Pondevida, Sullian S Naval, Treah May S Sayo, Herdee Gloriane C Luna, Eloise I Prieto","doi":"10.1021/acs.jproteome.4c00764","DOIUrl":"10.1021/acs.jproteome.4c00764","url":null,"abstract":"Difficulties in early-stage diagnosis are among the factors contributing to the high mortality of nonsmall cell lung carcinoma (NSCLC) patients. Unfortunately, diagnostic biomarkers are currently lacking, limiting options in the clinic. To discover proteins that have potential for biomarker applications, we performed an in-depth quantitative proteomic analysis on a cohort of Filipino early-stage NSCLC lung adenocarcinoma (LUAD) patients. Differentially expressed proteins (DEPs) were obtained by using tandem mass tag (TMT) labeling and mass spectrometry (MS)-based quantitative proteomics. A total of 6240 quantified proteins were identified with 3155 significantly upregulated and 1248 significantly downregulated. Integration of the proteomic result with curated transcriptome data allowed the identification of 33 proteins with biomarker potential. This study also provided insights into relevant pathways in NSCLC LUAD, such as protein translation and metabolic pathways. Interestingly, all of the enzymes in the hexosamine biosynthetic pathway (HBP) are found to be upregulated, suggesting its important role in NSCLC LUAD. It is worthwhile to look at the potential of targeting the metabolic vulnerability of NSCLC LUAD as a new strategy in drug development. All MS data were deposited into ProteomeXchange with the identifier PXD050598.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"1701-1714"},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522108","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

Large-Scale Quantitative Cross-Linking and Mass Spectrometry Provide New Insight into Protein Conformational Plasticity within Organelles, Cells, and Tissues.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-04-04 Epub Date: 2025-03-24 DOI: 10.1021/acs.jproteome.4c01030

Andrew Keller, Anna Bakhtina, James E Bruce

{"title":"Large-Scale Quantitative Cross-Linking and Mass Spectrometry Provide New Insight into Protein Conformational Plasticity within Organelles, Cells, and Tissues.","authors":"Andrew Keller, Anna Bakhtina, James E Bruce","doi":"10.1021/acs.jproteome.4c01030","DOIUrl":"10.1021/acs.jproteome.4c01030","url":null,"abstract":"Many proteins can exist in multiple conformational states in vivo to achieve distinct functional roles. These states include alternative conformations, variable post-translational modifications (PTMs), and associations with interacting protein, nucleotide, and ligand partners. Quantitative chemical cross-linking of live cells, organelles, or tissues together with mass spectrometry provides the relative abundance of cross-link levels formed in two or more compared samples, which depends both on the relative levels of existent protein conformational states in the compared samples and on the relative likelihood of the cross-link originating from each. Because cross-link conformational state preferences can vary widely, one expects intraprotein cross-link levels from proteins with high conformational plasticity to display divergent quantitation among samples with differing conformational ensembles. Here we use the large volume of quantitative cross-linking data available on the public XLinkDB database to cluster intraprotein cross-links according to their quantitation in many diverse compared samples to provide the first widescale glimpse of cross-links grouped according to the protein conformational state(s) from which they predominantly originate. We further demonstrate how cluster cross-links can be aligned with any protein structure to assess the likelihood that they were derived from it.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"2017-2025"},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690444","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

Targeted Lipidomics and Transcriptomics Unveil Aberrant Lipid Metabolic Remodeling in Visceral and Subcutaneous Adipose Tissue under ER Stress.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-04-04 Epub Date: 2025-03-11 DOI: 10.1021/acs.jproteome.4c00952

Ping He, Li Zhang, Peng Ma, Tianshu Xu, Zijing Wang, Li Li, Guanhua Du, Guifen Qiang, Cuiqing Liu

{"title":"Targeted Lipidomics and Transcriptomics Unveil Aberrant Lipid Metabolic Remodeling in Visceral and Subcutaneous Adipose Tissue under ER Stress.","authors":"Ping He, Li Zhang, Peng Ma, Tianshu Xu, Zijing Wang, Li Li, Guanhua Du, Guifen Qiang, Cuiqing Liu","doi":"10.1021/acs.jproteome.4c00952","DOIUrl":"10.1021/acs.jproteome.4c00952","url":null,"abstract":"Endoplasmic reticulum (ER) stress is known to impair the function of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), disrupting lipid metabolism. Despite the crucial role lipid plays in regulating adipose tissue function, the specific lipidomic alterations in VAT and SAT under ER stress remain unclear. In this study, ER stress was induced in VAT and SAT, and targeted lipidomic and transcriptomic approaches were used to analyze lipid metabolism and gene expression profiles. The results revealed that VAT exhibited a stronger ER stress response, characterized by a significant increase in binding immunoglobulin protein (BiP) expression and notable lipidomic disruptions, especially in glycerides and sterols. These disruptions were marked by a decrease in protective polyunsaturated fatty acyl species and the accumulation of lipotoxic molecules. In contrast, SAT displayed less severe lipidomic alterations. Transcriptomic analysis indicated that VAT was more susceptible to immune activation, inflammation, and metabolic dysfunction, while SAT primarily showed alterations in protein folding processes. These findings underscore the tissue-specific mechanisms of ER stress adaptation in VAT and SAT. In conclusion, VAT appears to be a critical target for addressing metabolic dysfunction in obesity and related disorders, with potential therapeutic implications for managing ER stress-induced metabolic diseases.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"1971-1982"},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603063","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

Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-04-04 Epub Date: 2025-03-12 DOI: 10.1021/acs.jproteome.4c01129

Stanley I Goldstein, Alice C Fan, Zihao Wang, Sai K Naineni, Regina Cencic, Steve B Garcia-Gutierrez, Kesha Patel, Sidong Huang, Lauren E Brown, Andrew Emili, John A Porco

{"title":"Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays.","authors":"Stanley I Goldstein, Alice C Fan, Zihao Wang, Sai K Naineni, Regina Cencic, Steve B Garcia-Gutierrez, Kesha Patel, Sidong Huang, Lauren E Brown, Andrew Emili, John A Porco","doi":"10.1021/acs.jproteome.4c01129","DOIUrl":"10.1021/acs.jproteome.4c01129","url":null,"abstract":"Uncompetitive inhibition is an effective strategy for suppressing dysregulated enzymes and their substrates, but discovery of suitable ligands depends on often-unavailable structural knowledge and serendipity. Hence, despite surging interest in mass spectrometry-based target identification, proteomic studies of substrate-dependent target engagement remain sparse. Herein, we describe a strategy for the discovery of substrate-dependent ligand binding. Using proteome integral solubility alteration (PISA) assays, we show that simple biochemical additives can enable detection of RNA-protein-small molecule complexes in native cell lysates. We apply our approach to rocaglates, molecules that specifically clamp RNA to eukaryotic translation initiation factor 4A (eIF4A), DEAD-box helicase 3X (DDX3X), and potentially other members of the DEAD-box (DDX) helicase family. To identify unexpected interactions, we used a target class-specific thermal window and compared ATP analog and RNA base dependencies for key rocaglate-DDX interactions. We report novel DDX targets of high-profile rocaglates-including the clinical candidate Zotatifin-and validate our findings using limited proteolysis-mass spectrometry and fluorescence polarization (FP) experiments. We also provide structural insight into divergent DDX3X affinities between synthetic rocaglates. Taken together, our study provides a model for screening uncompetitive inhibitors using a chemical proteomics approach and uncovers actionable DDX clamping targets, clearing a path toward characterization of novel molecular clamps and associated RNA helicases.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"2026-2039"},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612826","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

Classification of Collagens via Peptide Ambiguation, in a Paleoproteomic LC-MS/MS-Based Taxonomic Pipeline.

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2025-04-04 Epub Date: 2025-03-13 DOI: 10.1021/acs.jproteome.4c00962

Ian Engels, Alexandra Burnett, Prudence Robert, Camille Pironneau, Grégory Abrams, Robbin Bouwmeester, Peter Van der Plaetsen, Kévin Di Modica, Marcel Otte, Lawrence Guy Straus, Valentin Fischer, Fabrice Bray, Bart Mesuere, Isabelle De Groote, Dieter Deforce, Simon Daled, Maarten Dhaenens

{"title":"Classification of Collagens via Peptide Ambiguation, in a Paleoproteomic LC-MS/MS-Based Taxonomic Pipeline.","authors":"Ian Engels, Alexandra Burnett, Prudence Robert, Camille Pironneau, Grégory Abrams, Robbin Bouwmeester, Peter Van der Plaetsen, Kévin Di Modica, Marcel Otte, Lawrence Guy Straus, Valentin Fischer, Fabrice Bray, Bart Mesuere, Isabelle De Groote, Dieter Deforce, Simon Daled, Maarten Dhaenens","doi":"10.1021/acs.jproteome.4c00962","DOIUrl":"10.1021/acs.jproteome.4c00962","url":null,"abstract":"Liquid chromatography-mass spectrometry (LC-MS/MS) extends the matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) Zooarcheology by Mass Spectrometry (ZooMS) \"mass fingerprinting\" approach to species identification by providing fragmentation spectra for each peptide. However, ancient bone samples generate sparse data containing only a few collagen proteins, rendering target-decoy strategies unusable and increasing uncertainty in peptide annotation. To ameliorate this issue, we present a ZooMS/MS data pipeline that builds on a manually curated Collagen database and comprises two novel algorithms: isoBLAST and ClassiCOL. isoBLAST first extends peptide ambiguity by generating all \"potential peptide candidates\" isobaric to the annotated precursor. The exhaustive set of candidates created is then used to retain or reject different potential paths at each taxonomic branching point from superkingdom to species, until the greatest possible specificity is reached. Uniquely, ClassiCOL allows for the identification of taxonomic mixtures, including contaminated samples, as well as suggesting taxonomies not represented in sequence databases, including extinct taxa. All considered ambiguity is then graphically represented with clear prioritization of the potential taxa in the sample. Using public as well as in-house data acquired on different instruments, we demonstrate the performance of this universal postprocessing and explore the identification of both genetic and sample mixtures. Diet reconstruction from 40,000-year-old cave hyena coprolites illustrates the exciting potential of this approach.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"1907-1925"},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622881","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

Dual-Mode RPA/CRISPR-Cas12a Biosensor Based on Silica and Magnetic Hybrid Nanobeads for Rapid Detection of Campylobacter jejuni.

IF 4.6

ACS Applied Bio Materials Pub Date : 2025-04-04 DOI: 10.1021/acsabm.4c01810

Fareeha Arshad, Anis Nadiah Abdillah, Pooja Shivanand, Minhaz Uddin Ahmed

{"title":"Dual-Mode RPA/CRISPR-Cas12a Biosensor Based on Silica and Magnetic Hybrid Nanobeads for Rapid Detection of Campylobacter jejuni.","authors":"Fareeha Arshad, Anis Nadiah Abdillah, Pooja Shivanand, Minhaz Uddin Ahmed","doi":"10.1021/acsabm.4c01810","DOIUrl":"https://doi.org/10.1021/acsabm.4c01810","url":null,"abstract":"In this study, we developed a biosensor that makes use of recombinase polymerase amplification (RPA) along with a CRISPR/Cas12a system integrated with silica nanobeads and a magnetic nanoparticle nanohybrid complex that displayed peroxidase-mimicking properties. This nanohybrid nanozyme (NZ) integration with the CRISPR/Cas system allowed dual-mode fluorometric and colorimetric responses . The nanohybrid NZ was a conjugated ssDNA quencher probe sequence with inherent fluorometric properties. In the presence of target RPA amplicons, the CRISPR/Cas12a system gets activated, cleaving the probe sequence attached to the NZ complex and leading to fluorescence signal generation. Post-CRISPR/Cas12a assay, the presence of the NZ in the reaction mixture, after being cleaved away from the probe sequence, gave a colourimetric response directly proportional to the target DNA concentration, as the ssDNA probe sequence no longer hindered its catalytic activity. Therefore, the dual-mode detection using the CRISPR/Cas12a-based fluorometric response and NZ-based colorimetric detection conferred high sensitivity and selectivity toward Campylobacter detection. The developed sensor could detect the pathogenic DNA at concentrations as low as 0.98 pg/μL and 0.96 pg/μL via fluorescence and absorbance spectroscopy, respectively. In addition, our method was also tested in raw food analysis and showed good recovery.","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigation of Structural, Optical, Electrical, and Biological Properties of a Porous Platinum Electrode for Neurostimulation Devices.

IF 4.6

ACS Applied Bio Materials Pub Date : 2025-04-04 DOI: 10.1021/acsabm.4c01974

Lee-Woon Jang, Jeong-Hun Kim, Wonseok Lee, Jung-Hyun Lee, Gwang-Geun Oh, Hachul Jung, Seong-Woo Kim, Dae-Woo Jeon, Tae-Young Ha, Keun-A Chang, Jungsuk Kim

引用次数: 0

Minimal Structural Variation of GPR84 Full Agonist Causes Functional Switch to Inverse Agonism.

IF 6.8 1区医学

Journal of Medicinal Chemistry Pub Date : 2025-04-04 DOI: 10.1021/acs.jmedchem.4c02335

Loukas Ieremias, Asmita Manandhar, Katrine Schultz-Knudsen, Mads Holmgaard Kaspersen, Christina Ioanna Vrettou, Elisabeth Rexen Ulven, Trond Ulven

引用次数: 0