Uncovering Thousands of New Peptides with Sequence-Mask-Search Hybrid De Novo Peptide Sequencing Framework

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Highlights

• •Deep learning-based hybrid de novo sequencing with database search strategy.
• •Accurate identifications via ability to revise confidence scores and amino acids.
• •Discovery of >10,000 potential new HLA antigens and human phosphopeptides.
• •A dataset of >26 million annotated HCD spectra from Q Exactive instruments.

     

Estimating the Contribution of Proteasomal Spliced Peptides to the HLA-I Ligandome*

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Highlights

• •Reported proteasomal spliced HLA peptides do not fit the consensus binding motifs.
• •Their MS/MS spectrum matches suggest that many of them are ambiguous.
• •Our workflow is based on de novo sequencing, alignment, and multiple search tools.
• •The upper bound proportion of cis-spliced peptides is 2–6% and likely much smaller.

     

A New Tool to Reveal Bacterial Signaling Mechanisms in Antibiotic Treatment and Resistance

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Highlights

• •Quantitative (phospho)proteome analysis of antibiotic treatment in E. coli.
• •Largest bacterial phosphorylation catalogue.
• •Specific phosphorylation motifs changes during resistance development.
• •Phosphorylation mediated signaling could be a potential target for drug design.

     

Salmonella Effectors SseK1 and SseK3 Target Death Domain Proteins in the TNF and TRAIL Signaling Pathways*

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Highlights

• •MS-based method to detect native arginine-GlcNAcylation during Salmonella infection.
• •Demonstration that SseK1 targets TRADD, whereas SseK3 targets the death receptors, TNFR1 and TRAILR.
• •Evidence that effector overexpression results in misleading identification of host targets.
• •Crystal structure of SseK3.

     

Integrated Succinylome and Metabolome Profiling Reveals Crucial Role of S-Ribosylhomocysteine Lyase in Quorum Sensing and Metabolism of Aeromonas hydrophila,

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Highlights

• •A global lysine succinylome was investigated in A. hydrophila.
• •The lysine succinylation modifications play crucial role on various metabolic pathways.
• •Reversible succinylation on Lys23 and Lys30 regulates the activity of S-ribosylhomocysteine lyase LuxS.
• •Lysine succinylation modifications of LuxS affect quorum sensing and metabolism.

     

Integration of Two In-depth Quantitative Proteomics Approaches Determines the Kallikrein-related Peptidase 7 (KLK7) Degradome in Ovarian Cancer Cell Secretome

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Highlights

• •Kallikrein-related peptidase 7 is over expressed in ovarian cancer.
• •Quantitative PROTOMAP and TAILS approaches identified putative substrates of KLK7.
• •Pro-MMP10 is activated by KLK7.
• •KLK7 cleaves thrombospondin 1 and IGFBP6 in vitro.

     

Metabolic,Anti-apoptotic and Immune Evasion Strategies of Primary Human Myeloma Cells Indicate Adaptations to Hypoxia*

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Highlights

• •In-depth proteome profiling of primary human myeloma cells
• •Characteristics of myeloma cells are related to hypoxic bone marrow conditions
• •Myeloma cells show specific immune evasion strategies
• •Metabolic adaptations involve tumor and stroma cells

     

Integrated Analysis of Transcriptomic,miRNA and Proteomic Changes of a Novel Hybrid Yellow Catfish Uncovers Key Roles for miRNAs in Heterosis

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Highlights

• •mRNA-seq, miRNA-seq, proteomes of P. fulvidraco, P. vachelli, hybrid Huangyou-1.
• •Predicted miRNA-mRNA-protein pairs were found and validated by qRT-PCR and PRM.
• •Immune, metabolism, digestion, absorption, proliferation, development generate heterosis.
• •High parental gene/protein with low parental miRNAs inherit from the mother or father.

     

Metabolic Cross-talk Between Human Bronchial Epithelial Cells and Internalized Staphylococcus aureus as a Driver for Infection*

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Highlights

• •Interplay of epithelial cells and internalized S. aureus was dissected over 96 h.
• •Surviving host cells contain nonreplicating bacteria that persists in the cytoplasm.
• •Competition over resources triggers temporal metabolic changes.
• •Metabolic adaptation of host and bacteria determines the outcome of infection.

     

DECA,A Comprehensive,Automatic Post-processing Program for HDX-MS Data*

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Highlights

• •Open source software for comprehensive HDX-MS data analysis.
• •Automatic back-exchange correction options.
• •Rigorous statistical analysis of the significance of uptake differences.
• •High quality visualization tools.

     

NOTCH Activation Promotes Valve Formation by Regulating the Endocardial Secretome

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Highlights

• •MEEC are a reliable endocardial in vitro model.
• •Quantitative proteomics to characterize the NOTCH-driven endocardial secretome.
• •NOTCH pathway status underlies different paracrine biological functions.
• •New insights into secreted factors involved in cardiac valve development.

     

Conodipine-P1-3, the First Phospholipases A2 Characterized from Injected Cone Snail Venom*

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Highlights

• •Three novel Conodipines P1-3 in the injected venom of Conus purpurascens.
• •Conodipines P1-3 have consensus catalytic characteristics of sPLA₂.
• •We determined multiple modification sites in Conodipines P1-3.
• •Evaluated the activity of Conohyal-P1 by a MS-based method.

     

Mapping Spatiotemporal Microproteomics Landscape in Experimental Model of Traumatic Brain Injury Unveils a link to Parkinson's Disease,

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Highlights

• •Spatiotemporal microproteomics analysis of TBI.
• •Injury site microproteomics reveal distinct phases in 10-day frame post TBI.
• •Uninjured proteomic profile is restored in TBI at 10 days post injury.
• •Substantia nigra protein post 3 days suggest link to Parkinson's disease.

     

Multi-isotype Glycoproteomic Characterization of Serum Antibody Heavy Chains Reveals Isotype- and Subclass-Specific N-Glycosylation Profiles

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Highlights

• •nLC-MS/MS method to analyze immunoglobulin (Ig) N-glycopeptides from human serum.
• •Multi-isotype, site-specific characterization of immunoglobulin N-glycosylation.
• •IgA2 sequence and glycosylation-site variant analyses.
• •Platform to define disease-specific N-glycan signatures for different Ig isotypes.

     

Comparative Secretome Analyses of Human and Zoonotic Staphylococcus aureus Isolates CC8, CC22, and CC398

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Highlights

• •Proteogenomics and secretome comparison of human and zoonotic Staphylococcus aureus lineages.
• •869 secreted proteins identified in eight S. aureus isolates of CC8, CC22 and CC398.
• •CC398 lower secretion of surface proteins and higher secretion of hemolysins and exoenzymes.
• •Regulatory differences in the secretomes could be linked to lower SigB activity in CC398.

     

Proteomics of Asrij Perturbation in Drosophila Lymph Glands for Identification of New Regulators of Hematopoiesis

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Highlights

• •First report on the quantitative proteomic profiling of Drosophila lymph glands.
• •Comparative proteomic analysis under conditions of perturbed blood cell homeostasis.
• •Resource for identifying new regulators of insect and vertebrate hematopoiesis.

     

Virulence Factors Produced by Staphylococcus aureus Biofilms Have a Moonlighting Function Contributing to Biofilm Integrity

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Highlights

• •Establishment of a flow system allowing multi-omics analysis of S. aureus biofilms.
• •Biofilm proteome profiling (intracellular and ECM) plus metabolic footprint analysis.
• •Virulence factors and ribosomal proteins stabilize the ECM as moonlighting proteins.
• •They act as electrostatic bridges between anionic cell surfaces, eDNA and metabolites.

     

Quantitative Mass Spectrometry to Interrogate Proteomic Heterogeneity in Metastatic Lung Adenocarcinoma and Validate a Novel Somatic Mutation CDK12-G879V

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Highlights

• •Serial biopsies and autopsy from a metastatic lung cancer patient over 7 years.
• •Tumor heterogeneity characterized by quantifying the proteome and phosphoproteome.
• •Patient-specific database built using whole genome sequencing data from tumors.
• •MRM assay and functional validation of a novel lung-specific CDK12-G879V mutant.

     

Multidimensional Proteomics Identifies Declines in Protein Homeostasis and Mitochondria as Early Signals for Normal Aging and Age-associated Disease in Drosophila,

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Highlights

• •Proteomic landscapes of Drosophila somatic and reproductive tissues during aging.
• •Pulsed metabolic labeling determines a decline in protein synthesis with age.
• •Drosophila model of human Parkinson's disease signifies an early-onset decline in protein synthesis.
• •Collapse of proteostasis and mitochondria are early signals for normal aging.