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.

     

Analytical Guidelines for co-fractionation Mass Spectrometry Obtained through Global Profiling of Gold Standard Saccharomyces cerevisiae Protein Complexes

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Highlights

• •Guidelines for studying protein complexes via co-fractionation mass spectrometry.
• •A novel procedure for profiling gold standard protein complexes in CF-MS data.
• •Recommendations for efficient CF-MS fractionation collection.
• •Scoring metric recommendations for precise and sensitive CF-MS data analysis.

     

Proteomic Analysis Reveals a Role for RSK in p120-catenin Phosphorylation and Melanoma Cell-Cell Adhesion

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Highlights

• •BioID reveals the proximity partners of RSK family members.
• •All RSK isoforms associate with and phosphorylate p120ctn on Ser320.
• •RSK negatively regulates adherens junctions and reduces cell-cell adhesion.
• •p120ctn phosphorylation plays a role in the reorganization of proximity partners.

     

Quantitative Proteomics Links the LRRC59 Interactome to mRNA Translation on the ER Membrane

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Highlights

• •Identification of subcellular protein interactomes via proximity labeling and quantitative multiplexed proteomics.
• •SEC61β and RPN1 interactomes overlap with translocon-associated protein networks.
• •SEC62 interacts with redox-linked proteins and ER luminal chaperones.
• •LRRC59 directly interacts with mRNA translation factors and SRP machinery on the ER.

     

Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome

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Highlights

• •Detection of low-abundance phosphotyrosine-containing peptides is challenging.
• •Multiplexed TMT allows inclusion of modification(pTyr)-saturated boost channels.
• •Boost channels facilitate selection of pTyr precursor ions for fragmentation.
• •Quantitation depth is increased while maintaining accuracy and precision.

     

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.

     

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.

     

Slight Deuterium Enrichment in Water Acts as an Antioxidant: Is Deuterium a Cell Growth Regulator?

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Highlights

• •Deuterium enrichment to 350 ppm accelerates cell proliferation, which is opposite to that of deuterium depletion to 80 ppm.
• •The cell proliferation increases through decreasing ROS amount in mitochondria.
• •Deuterium enriched water acts as an anti-oxidant.
• •Deuterium may be a cell growth regulator in the interval between 80 and 350 ppm.

     

ProAlanase is an Effective Alternative to Trypsin for Proteomics Applications and Disulfide Bond Mapping

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Highlights

• •ProAlanase is a powerful protease for efficient low pH disulfide bond mapping.
• •High suitability for analysis of histone family members and their PTMs.
• •Accurate phosphorylation profiling in proline-rich proteins.
• •Sequence coverage increase and full de novo sequencing in combination with trypsin.

     

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.

     

Thorough Performance Evaluation of 213 nm Ultraviolet Photodissociation for Top-down Proteomics

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Highlights

• •Analysis of product ions produced by 213 nm UVPD is used to refine database search.
• •A product ion at the N-terminus of Pro, y-2, is observed in 213 nm UVPD spectra.
• •213 nm UVPD provides more complete proteoform characterization than HCD.
• •HCD and 213 nm UVPD are complementary fragmentation methods for proteoforms <30 kDa.

     

Sharing habitat: Effects of migratory barnacle geese density on meadow breeding waders

• 1.Following targeted conservation actions most goose populations have increased. The growing goose populations caused an increase in human-wildlife conflicts and have the potential to affect nature values. As meadow birds, including meadow-breeding waders, were declining throughout Western Europe, the possible negative effect of rising numbers of foraging barnacle geese on their breeding success has been questioned.
• 2.We used GPS-transmitter data to measure the density of foraging barnacle geese during daylight hours. Using dynamic Brownian Bridge Movement Models (dBBMM), we investigated the effect of barnacle goose density on the territory distribution of five wader species, and on nest success of the locally common Northern lapwing. We used model selection methods to identify the importance of barnacle goose density related to other environmental factors.
• 3.Our results showed an insignificant positive association between barnacle goose density and nest territory density of the Northern lapwing and common redshank. Barnacle goose density had no influence on territory selection of godwit, oystercatcher and ringed plover. We did, however, find a negative correlation between barnacle geese density and the nest success of the Northern Lapwing.
• 4.We infer that either barnacle goose foraging leads to improved territory conditions for some wader species, or that both barnacle geese and waders prefer the same type of habitat for foraging and nesting. Higher barnacle goose density was correlated with fewer Northern lapwing nests being successful.
• 5.Synthesis and application: Experimental research is needed to disentangle the causal chain, but based on our observational findings, we suggest to increase water logging that may attract both barnacle geese and wader species. Further investigation on the effects of barnacle geese on wader species is necessary to identify the cause of the negative correlation between barnacle geese density and nest success of lapwings; nest protection experiments could give further insight.

     

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.

     

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.

     

Immune Signature Against Plasmodium falciparum Antigens Predicts Clinical Immunity in Distinct Malaria Endemic Communities

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Highlights

• •A predictive modelling framework has been established to analyze IgG antibody responses against a large panel of P. falciparum-specific antigens to identify a specific antigen signature of NAI.
• •An individual's immune status can be accurately predicted by measuring IgG responses against a small set of 15 defined parasite antigens.
• •Proteins identified in the 15-antigen signature represent potential candidates for next-generation malaria vaccines or biomarkers for monitoring the impact of malaria interventions.
• •The developed predictive framework can be adapted for developing novel surveillance and intervention tools for other infectious diseases.

     

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.

     

Multiomics Reveals Ectopic ATP Synthase Blockade Induces Cancer Cell Death via a lncRNA-mediated Phospho-signaling Network

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Highlights

• •Ectopic ATP synthase as a therapeutic target for gefitinib-resistant NSCLC.
• •Multiomics uncovers the dynamic network in response to ecto-ATP synthase blockade.
• •Ecto-ATP synthase blockade induces cytotoxicity by CK2/phospho-topo IIα/GAS5 axis.
• •A positive feedforward circuit between phospho-topo IIα and lncRNA-GAS5.

     

The DNA Sensor cGAS is Decorated by Acetylation and Phosphorylation Modifications in the Context of Immune Signaling

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Highlights

• •cGAS acetylations and phosphorylations under basal and immune-stimulated states.
• •K384 and K414 acetylations and S305 phosphorylation inhibit cGAS-mediated apoptosis.
• •Acetylation at K198 stimulates cGAS-dependent interferon signaling.
• •K198 acetylation is decreased upon herpesvirus infection.

     

A Cross-linking Mass Spectrometry Approach Defines Protein Interactions in Yeast Mitochondria

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Highlights

• •XL-MS reveals new PPIs in yeast mitochondria under glycerol and glucose condition.
• •Significant but limited results from quantitative XL-MS experiments.
• •Ndi1 participates in a CIII₂CIV₂ respiratory supercomplex.
• •Min8 promotes assembly of Cox12 into an intermediate complex IV.