Proteomic Analysis Reveals that Topoisomerase 2A is Associated with Defective Sperm Head Morphology

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Highlights

• •Human spermatozoa possess cells of poor morphology that lack nuclear integrity.
• •These cells can be isolated by density separation.
• •Mass spectrometry reveals their nuclei contain excess protein.
• •TOP2A is a promising marker of this poor nuclear development.

     

Reproducibility,Specificity and Accuracy of Relative Quantification Using Spectral Library-based Data-independent Acquisition

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Highlights

• •Provision of data generated on the basis of a gold standard spike-in sample set.
• •Choice of spectral library has great impact on identification and quantification.
• •DIA is superior to DDA in quantification reproducibility, specificity and accuracy.
• •DIA outperforms DDA in the quantification of low protein amounts.
• •Quantification on peptide level is generally preferable.

     

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.

     

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.

     

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).

     

An Interaction Network of RNA-Binding Proteins Involved in Drosophila Oogenesis

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Highlights

• •Label-free and dimethyl labeling MS analysis of 6 RBPs from Drosophila ovaries.
• •Functionally related RBPs show overlapping proteomes.
• •Selective co-purification of splicing factors and translational regulators.
• •Validation of 26 novel interactions by co-immunoprecipitation.

     

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.

     

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.

     

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.

     

Identification of a Multiplex Biomarker Panel for Hypertrophic Cardiomyopathy Using Quantitative Proteomics and Machine Learning

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Highlights

• •Quantitative proteomics and machine learning to study plasma biomarkers in HCM.
• •Six peptides are increased in plasma of LVH+ HCM compared to controls.
• •Peptide biomarkers correlate with imaging markers of phenotype severity.
• •Peptide biomarkers correlate with the estimated sudden cardiac death risk.

     

Temporal Quantitative Proteomics of mGluR-induced Protein Translation and Phosphorylation in Neurons

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Highlights

• •Integrated phosphoproteomics and analyses of newly synthesized proteins in neurons.
• •Resource of temporal mGluR-induced signaling pathways upon DHPG stimulation.
• •Validation of PKC, MAPK1, CAMKIIa, and CDK2 in mGluR-activation and signaling.
• •Validation of Intersectin-1 in DHPG-induced AMPAR internalization.

     

The Challenge of Classifying Metastatic Cell Properties by Molecular Profiling Exemplified with Cutaneous Melanoma Cells and Their Cerebral Metastasis from Patient Derived Mouse Xenografts

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Highlights

• •Comprehensive molecular profiling of cutaneous and cerebellar metastasis variants.
• •Identification of differentially regulated metastasis-associated molecules.
• •Evidence for individually distinct patterns of metastasis-associated molecules.
• •Highlighting the evident need for establishing meta-analyses strategies.

     

MaxQuant Software for Ion Mobility Enhanced Shotgun Proteomics

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Highlights

• •Highly parallelizable 4D feature detection in ion mobility enhanced shotgun proteomics.
• •Multidimensional non-linear mass, retention time and ion mobility recalibration.
• •Collision cross section aware matching between runs.
• •Label-free quantification of ion mobility MS data.

     

Global Proteome and Phosphoproteome Characterization of Sepsis-induced Kidney Injury

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Highlights

• •Cecal Ligation Puncture (CLP) mouse model to study sepsis-induced kidney disease.
• •Quantitative global proteome and phosphoproteome profiling of mouse kidneys.
• •Highly significant candidate markers for onset and progression of AKI to CKD.
• •Mechanistic insights into sepsis-associated kidney injuries.

     

The Mouse Heart Mitochondria N Terminome Provides Insights into ClpXP-Mediated Proteolysis

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Highlights

• •Mitochondrial heart N terminome shows aminopeptidase processing after MTS cleavage.
• •CLPP-deficiency alters protein processing patterns in mouse heart mitochondria.
• •Candidate substrates identified by N termini accumulation and interaction with inactive ClpXP.
• •UQCRC1, HSPA9 and OAT validated biochemically as high confidence ClpXP substrates.

     

Profiling Cell Signaling Networks at Single-cell Resolution

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Highlights

• •Signaling networks can be highly heterogeneous across cells in a tissue.
• •Various technologies allow analyzing signaling networks at single-cell resolution.
• •The advantages and limitations of each single-cell approach are summarized.
• •Confounding factors in single-cell signaling network analysis are discussed.

     

Glutathionylation Decreases Methyltransferase Activity of PRMT5 and Inhibits Cell Proliferation

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Highlights

• •PRMT5 glutathionylation is increased in aged mice or under oxidative stress.
• •Deglutathionylation of PRMT5 is catalyzed by glutaredoxin-1.
• •PRMT5 glutathionylation decreases its methyltransferase activity.
• •PRMT5 glutathionylation results in G2/M arrest and inhibits cell proliferation.

     

PolySTest: Robust Statistical Testing of Proteomics Data with Missing Values Improves Detection of Biologically Relevant Features

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Highlights

• •Novel statistical test combining missingness and quantitative profiles.
• •Unification of different statistical tests into a PolySTest FDR provides higher robustness and confidence.
• •PolySTest provides higher coverage of relevant biological pathways.
• •User-friendly interactive web service for statistical analysis and visualization.

     

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.

     

An in-depth Comparison of the Pediatric and Adult Urinary N-glycomes

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Highlights

• •N-glycan patterns are distinct in pediatric and adult urine.
• •Sex differences of N-glycans are much larger in adults.
• •Pediatric urine has almost no sex differences in N-glycan levels.
• •In adults, the majority of N-glycans were more abundant in males.