Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping

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Highlights

• •Discovery of peptide biomarker candidates of respiratory tract pathogens S. pneumoniae, H. influenzae, M. catarrhalis and S. aureus as target pathogens.
• •Peptide biomarker candidates were experimentally verified in clinical samples.
• •Targeted MS using promising peptide biomarker candidates shown as proof-of-concept.

     

Developments and Applications of Functional Protein Microarrays

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Highlights

• •Summarize the development of functional protein microarray.
• •Application of functional proteome microarray in basic research.
• •Application of functional proteome microarray in translational research.
• •Fabrication of functional membrane protein array using virion display method.

     

Profiling the Surfaceome Identifies Therapeutic Targets for Cells with Hyperactive mTORC1 Signaling

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Highlights

• •Quantitative proteomes of the cellular surface changes induced by mTORC1 signaling.
• •Hit validation in human cancer cell lines and biopsies.
• •Functional studies showing new drug targets to which cancer cells with hyperactive mTORC1 may be addicted.
• •A new paradigm for drug development, namely targeting cell surface proteins regulated by mTORC1.

     

Novel Proteome Extraction Method Illustrates a Conserved Immunological Signature of MSI-H Colorectal Tumors

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Highlights

• •TOP: robust, bio-friendly FFPE proteome extraction method with less fixation bias.
• •Proteome of MSI-H colorectal cancer identifies immunobiology key elements.
• •MSI-H tumor displays an “INFg-STAT1 centric signature”.
• •Long-term IFNg induction In-vitro mimicks MSI-H signature.

     

Serum Protein Profiling Reveals a Landscape of Inflammation and Immune Signaling in Early-stage COVID-19 Infection

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Highlights

• •In-depth profiling of the serum proteome in early-stage COVID-19 patients.
• •A landscape of inflammation and immune signaling related to the SARS-CoV-2 infection.
• •CCL2 and CXCL10 medicated cytokine signaling pathways may correlate with neutrophil and lymphocyte respectively.

     

Immediate Adaptation Analysis Implicates BCL6 as an EGFR-TKI Combination Therapy Target in NSCLC

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Highlights

• •EGFR-TKI molecular response profiling covering 10138 proteins and 13486 mRNAs.
• •EGFR-TKI combination therapy screen using a library of 528 compounds.
• •Several new candidate EGFR-TKI escape mechanisms and combination therapy targets.
• •Combined targeting of the oncogene BCL6 and EGFR results in synergy in NSCLC cells.

     

Molecular Basis of the Mechanisms Controlling MASTL

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Highlights

• •NCMR is crucial for substrate recognition and activity regulation.
• •MASTL conserves a cryptic C-Lobe in the non-conserved middle region.
• •MASTL₄₅₀ containing the cryptic C-lobe is observed in cancer cell lines.
• •Key phosphorylation sites for MASTL provide an activation model.

     

Molecular Dynamics Simulation-assisted Ionic Liquid Screening for Deep Coverage Proteome Analysis

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Highlights

• •Mechanistic insights into ionic liquids and proteins at molecular level.
• •Extractants prescreen for proteome analysis with MD simulation system.
• •A loss-less sample preparation method developed for in-depth proteome profiling.
• •Over 3,300 proteins were confidently identified from 1,000 HeLa cells in a 1 h run.
• •Label-free quantitative proteome analysis of human liver cancer tissues.

     

Guidance Document: Validation of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry Immunopeptidomics Assay for the Identification of HLA Class I Ligands Suitable for Pharmaceutical Therapies

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Highlights

• •Validation of an omic method for antigen identification using LC-MS/MS.
• •Validation of accuracy, precision, specificity, limit of detection and robustness.
• •Validation according to the current FDA and EMA guidelines.

     

Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse

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Highlights

• •Sufficient tumor tissues are often unavailable large HLA peptidome discovery.
• •Using patient derived xenograft (PDX) tumors can overcome this limitation.
• •The large PDX HLA peptidomes expand significantly those of the original biopsies.
• •The HLA peptidomes of the PDX tumors included many tumor antigens.

     

Kinome Profiling of Primary Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 as Candidate Therapeutic Target

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Highlights

• •SRPK1 is overexpressed in endometrial cancer and associated with poor survival.
• •SRPK1 promotes endometrial cancer cell growth under nutrient-deprived conditions.
• •Activation of EGFR-IGF1R-AKT signaling promotes resistance to SRPK1 inhibitors.
• •Co-targeting SRPK1 and EGFR-IGF1R synergize blocking endometrial cancer cell growth.

     

Improving Identification of In-organello Protein-Protein Interactions Using an Affinity-enrichable,Isotopically Coded,and Mass Spectrometry-cleavable Chemical Crosslinker

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Highlights

• •Used affinity-enrichable, isotopically coded, and MS-cleavable crosslinker.
• •Targeted acquisition strategy based on isotopic-coding described and evaluated.
• •Novel data analysis pipeline developed provides improved crosslink identification.
• •Large dataset reveals hundreds of mitochondrial protein-protein interactions.

     

Genetic Profile and Functional Proteomics of Anal Squamous Cell Carcinoma: Proposal for a Molecular Classification

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Highlights

• •Two molecular groups in anal squamous carcinoma according proteomic profile.
• •Differences in possible targeted processes such as metabolism or immune response.
• •Different percentage of tumor lymphocyte infiltration.
• •Difference in the frequency of ATM variants, related to PPAR inhibitors.

     

Upregulation of CD73 Confers Acquired Radioresistance and is Required for Maintaining Irradiation-selected Pancreatic Cancer Cells in a Mesenchymal State

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Highlights

• •CD73 is one of the most upregulated proteins in the radioresistant cells.
• •CD73 upregulation confers radioresistance and irradiation-induced apoptosis.
• •CD73 confers radioresistance potentially through inactivating protein BAD.
• •Elevated CD73 is required for maintaining the resistant cells in a mesenchymal state.

     

The Human Immunopeptidome Project: A Roadmap to Predict and Treat Immune Diseases

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Highlights

• •Immunopeptidomics bears the potential to link diseases to antigen representation.
• •We suggest to achieve this by analyzing the immunopeptidomes of cohorts of patients.
• •Current mass spectrometry-based techniques to analyze immunopeptidomes are described.
• •We term the proposed approach “Immunopeptidome-wide association studies” (IWAS).

     

Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines

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Highlights

• •pY phosphoproteomes and dedicated ranking analyses for 16 AML cell lines.
• •RTK drivers, 6 mutant cell lines confirmed, identification for 4 more cell lines.
• •MAPK1/3 phosphorylation for cell lines without TK driver, indicating RAS mutation.
• •Drug target space phosphorylation correlates with drug IC50s in specific cell lines.

     

Radiosensitization by Kinase Inhibition Revealed by Phosphoproteomic Analysis of Pancreatic Cancer Cells

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Highlights

• •Proteomes and phosphoproteomes of radiosensitive and radioresistant PDAC cell lines.
• •Common activation of DDR is proven by ATM activity on known and novel substrates.
• •Resistant cells bear raised NQO1 expression, actin dynamics including FAK activity.
• •Inhibitors of CHEK Rabusertib and FAK Defactinib radiosensitize PDAC cells.

     

Combined EGFR and ROCK Inhibition in Triple-negative Breast Cancer Leads to Cell Death Via Impaired Autophagic Flux

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Highlights

• •We used phosphoproteomics to reveal the underlying mechanisms of drug synergy on EGFR and ROCK co-inhibition in TNBC cells.
• •EGFR inhibition alone induces autophagy activation in TNBC cells as a cytoprotective mechanism.
• •Combinatorial treatment leads to impaired autophagic flux resulting in a strong accumulation of autophagic vacuoles.
• •We hypothesize that ROCKi-induced cytoskeletal changes impair autophagosome clearance ultimately leading to cell death.

     

Characterization of Prenylated C-terminal Peptides Using a Thiopropyl-based Capture Technique and LC-MS/MS

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Highlights

• •Brain membrane protein extraction.
• •Protein prenylation.
• •Prenyl peptide capture and characterization by LC-MS/MS.
• •HCD and EThcD peptide fragmentation.