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.

     

Why Glycosylation Matters in Building a Better Flu Vaccine

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Highlights

• •Glycosylation is not currently considered in flu vaccine design.
• •Glycosylation influences on immunodominance are not well understood.
• •Identification of site-specific glycosylation using mass spectrometry has matured.
• •New methods are needed to quantify site-specific glycosylation for vaccine design.

     

HLA-DO Modulates the Diversity of the MHC-II Self-peptidome

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Highlights

• •MHC-II-bound peptide repertoires from DO-sufficient and DO-deficient cells.
• •Fewer unique peptides and core epitopes were presented in the absence of DO.
• •Immunopeptidome differences appeared to result from reduced DM editing.
• •DO-dependent self-epitopes elicited CD4 T cell responses in mice.

     

Deep Protein Methylation Profiling by Combined Chemical and Immunoaffinity Approaches Reveals Novel PRMT1 Targets

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Highlights

• •Enrichment of methyl peptides using two orthogonal techniques.
• •Knockdown of PRMT1 leads to substantial changes in protein arginine “methylome”.
• •Discrimination of ADMA and SDMA using characteristic neutral losses.
• •Identification of PRMT1 targets and substrate scavenged by other PRMTs in the absence of PRMT1 activity.

     

Apolipoprotein A1 Forms 5/5 and 5/4 Antiparallel Dimers in Human High-density Lipoprotein

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Highlights

• •Zero-length chemical cross-linking of APOA1 peptides in HDL.
• •Cross-links match antiparallel isomers of APOA dimers in molecular modeling.
• •Identical MS/MS spectra of native and synthetic cross-linked peptides.
• •First biochemical evidence of LL5/5 and LL5/4 isomers in human HDL.

     

Precision De Novo Peptide Sequencing Using Mirror Proteases of Ac-LysargiNase and Trypsin for Large-scale Proteomics

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Highlights

• •The developed Ac-LysargiNase showed higher stability and activity than before.
• •The merged spectra of the mirror peptides achieved nearly complete ion coverage.
• •pNovoM obviously increased the efficiency and accuracy of peptide sequencing.
• •The mirror enzymatic strategy achieved precision de novo sequencing on proteome scales.

     

PACAP and Other Neuropeptide Targets Link Chronic Migraine and Opioid-induced Hyperalgesia in Mouse Models*

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Highlights

• •Characterized the peptides involved in migraine and opioid-induced hyperalgesia (OIH).
• •Identified more than 1500 peptides in seven nervous system regions.
• •Discovered seven peptides significantly changed with migraine and nine with OIH.
• •Validated PACAP involvement in both conditions via pharmacological studies.

     

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

     

Bayesian Confidence Intervals for Multiplexed Proteomics Integrate Ion-statistics with Peptide Quantification Concordance,

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Highlights

• •Bayesian Beta-Binomial model integrates ion statistics with peptide ratio agreement.
• •Model appropriately interprets information from low signal peptides.
• •Confidence can be assigned even without replicates.
• •Model adds sensitivity to detection of small changes.

     

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.

     

FusionPro,a Versatile Proteogenomic Tool for Identification of Novel Fusion Transcripts and Their Potential Translation Products in Cancer Cells,

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Highlights

• •FusionPro, a versatile tool for studying fusion proteoforms, has been developed.
• •Fusion peptides were identified against a customized database built by FusionPro.
• •Types and features of fusion proteoforms were efficiently predicted by FusionPro.

     

DIAlignR Provides Precise Retention Time Alignment Across Distant Runs in DIA and Targeted Proteomics

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Highlights

• •Retention time shift can lead to inversion of elution order of peptides.
• •Global alignment methods are suboptimal for alignment of distant runs.
• •DIAlignR employs hybrid (global + local) RT alignment approach.
• •DIAlignR can align swapped peaks accurately across distant runs.

     

Analysis of Endogenous Peptides Released from Osteoarthritic Cartilage Unravels Novel Pathogenic Markers,

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Highlights

• •Shotgun identification of neopeptides released from osteoarthritic cartilage.
• •Specific endogenous peptides from the cartilage ECM are measured by MRM.
• •Identification of neopeptides differentially generated from diseased tissue.
• •The peptide DSNKIETIPN shows the best metrics as biomarker of OA cartilage.

     

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.

     

An Advanced Strategy for Comprehensive Profiling of ADP-ribosylation Sites Using Mass Spectrometry-based Proteomics*

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Highlights

• •Comparing proteolytic digestions and precursor fragmentation methods for MS of ADPr
• •Identification of 11,265 unique ADPr-modified peptides
• •Mapping of hundreds of peptides co-modified by phosphorylation and ADPr
• •ADPr modification of specific residue types displays spatial preferences

     

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.

     

Common Metabolic Pathways Implicated in Resistance to Chemotherapy Point to a Key Mitochondrial Role in Breast Cancer,

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Highlights

• •OMICS distinguish cancer cells from resistant or cancer stem cells.
• •Bactericidal antibiotics and mitochondria.
• •Linezolid and anticancer therapy.