Proteomics articles within Nature Communications

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  • Article
    | Open Access

    The human proteome represents a crucial link between complex disease and genetic/environmental factors. Here, the authors investigate 257 cardiometabolic-relevant protein biomarkers in whole genome sequencing data from 1328 individuals, revealing the genetic architecture underlying biomarker variation.

    • Arthur Gilly
    • , Young-Chan Park
    •  & Eleftheria Zeggini

  • Article
    | Open Access

    Thermostability of the peptide-MHC interaction is important for immunogenicity. Here the authors present a mass spectrometry method to measure thermostability among thousands of peptide-MHC complexes in parallel and a trained artificial neural network to predict immunogenenicity of cancer antigens.

    • Emma C. Jappe
    • , Christian Garde
    •  & Anthony W. Purcell

  • Article
    | Open Access

    N-phosphorylation plays a critical role in central metabolism and signaling processes, however, enrichment methods for N-phosphopeptides are limited by the P-N bond lability. Here, the authors report the synthesis and use of silica microspheres functionalized with bis(zinc(II)-dipicolylamine) in N-phosphopeptides effective enrichment.

    • Yechen Hu
    • , Bo Jiang
    •  & Yukui Zhang

  • Article
    | Open Access

    Single-cell immunoblotting previously separated proteins on a polyacrylamide slab in the xy direction and was limited by throughput and sample consumption. Here the authors adapt the system to separate proteins in the z direction, allowing for closer spacing of sample wells and improved sample consumption.

    • Samantha M. Grist
    • , Andoni P. Mourdoukoutas
    •  & Amy E. Herr

  • Perspective
    | Open Access

    The IMEx consortium provides one of the largest resources of curated, experimentally verified molecular interaction data. Here, the authors review how IMEx evolved into a fundamental resource for life scientists and describe how IMEx data can support biomedical research.

    • Pablo Porras
    • , Elisabet Barrera
    •  & Sandra Orchard

  • Article
    | Open Access

    Protein O-GlcNAcylation is involved in regulating gene expression and maintaining cellular homeostasis. Here, the authors develop a chemical reporter-based strategy for the proteomic profiling and genome-wide mapping of genotoxic stress-induced O-GlcNAcylated chromatin-associated proteins.

    • Yubo Liu
    • , Qiushi Chen
    •  & Jianing Zhang

  • Article
    | Open Access

    Multi-Omic approaches are a powerful way for obtaining in-depth understanding of a cell’s state. Here the authors present DISCO, combining digital microfluidics, laser cell lysis, and artificial intelligence-driven image processing to analyze single-cell genomes, transcriptomes and proteomes in a mixed population.

    • Julian Lamanna
    • , Erica Y. Scott
    •  & Aaron R. Wheeler

  • Article
    | Open Access

    The human skin is a highly complex organ comprising multiple tissue layers and diverse cell types. Here, the authors present a spatially-resolved quantitative proteomic atlas of the healthy human skin, characterizing the protein profiles of four skin layers and nine cell types.

    • Beatrice Dyring-Andersen
    • , Marianne Bengtson Løvendorf
    •  & Matthias Mann

  • Article
    | Open Access

    Comprehensive quantitative profiling of intact glycopeptides remains technically challenging. To address this, the authors here develop an integrated quantitative glycoproteomic workflow, including optimized sample preparation, multiplexed quantification and a dedicated data processing tool.

    • Pan Fang
    • , Yanlong Ji
    •  & Henning Urlaub

  • Perspective
    | Open Access

    The Human Proteome Project (HPP) was launched in 2010 to enhance accurate annotation of the genome-encoded proteome. Ten years later, the HPP releases its first blueprint of the human proteome, annotating 90% of all known proteins at high-stringency and discussing the implications of proteomics for precision medicine.

    • Subash Adhikari
    • , Edouard C. Nice
    •  & Mark S. Baker

  • Article
    | Open Access

    Distributed multi-omic digitization of clinical specimen across multiple sites is a prerequisite for turning molecular precision medicine into reality. Here, the authors show that coordinated proteotype data acquisition is feasible using standardized MS data acquisition and analysis strategies.

    • Yue Xuan
    • , Nicholas W. Bateman
    •  & Thomas P. Conrads

  • Article
    | Open Access

    ADP-ribose binding macro domains facilitate the enrichment and detection of cellular ADP-ribosylation. Here, the authors generate an engineered macro domain with increased ADP-ribose affinity, improving the identification of ADP-ribosylated proteins by proteomics, western blot and immunofluorescence.

    • Kathrin Nowak
    • , Florian Rosenthal
    •  & Michael O. Hottiger

  • Article
    | Open Access

    Cell surface proteins contribute to neuronal development and activity-dependent synaptic plasticity. Here, the authors perform a time-resolved surfaceome analysis of developing primary neurons and in response to homeostatic synaptic scaling and chemical long-term potentiation (cLTP), revealing surface proteome remodeling largely independent of global proteostasis.

    • Marc van Oostrum
    • , Benjamin Campbell
    •  & Bernd Wollscheid

  • Article
    | Open Access

    Herpesviruses code for conserved protein kinases (CHPKs) that exert several regulatory functions by interacting with cellular factors. Here, the authors use affinity purification mass spectrometry (AP–MS) to identify differential interaction partners of CHPKs from seven different human herpesviruses, finding Cyclin A and associated factors as a specific signature of β-herpesvirus kinases.

    • Boris Bogdanow
    • , Max Schmidt
    •  & Lüder Wiebusch

  • Article
    | Open Access

    Yeast exhibit oscillations that share features with circadian rhythms. The authors show that bioenergetic constraints promote oscillatory behaviour: resources are stored until supplies can support translational bursting, this is licensed by ion transport and release from membrane-less compartments.

    • John S. O’Neill
    • , Nathaniel P. Hoyle
    •  & Helen C. Causton

  • Article
    | Open Access

    Here, Giansanti et al. perform a system-wide and time-resolved characterization of the changes in the host cell proteome and phosphoproteome of cells infected with the enterovirus coxsackievirus B3 during a full round of replication and identify mTORC1 signalling as a major regulation network during virus infection.

    • Piero Giansanti
    • , Jeroen R. P. M. Strating
    •  & Frank J. M. van Kuppeveld

  • Article
    | Open Access

    O-glycosylation is an abundant post-translational modification but its relevance for bioactive peptides is unclear. Here, the authors detect O-glycans on almost one third of the classified peptide hormones and show that O-glycosylation can modulate peptide half-lives and receptor activation properties.

    • Thomas D. Madsen
    • , Lasse H. Hansen
    •  & Katrine T. Schjoldager

  • Article
    | Open Access

    Epigenetic information is transmitted from mother to daughter cells through mitosis. Here, the authors isolate native chromosomes from metaphase-arrested cells and perform LC-MS/MS to identify chromosome-bound proteins in pluripotent stem cells during mitosis and reveal that PRC2, DNA methylation and Mecp2 are required to maintain chromosome compaction.

    • Dounia Djeghloul
    • , Bhavik Patel
    •  & Amanda G. Fisher

  • Article
    | Open Access

    Mass spectrometry-based proteomics is the method of choice for the global mapping of post-translational modifications, but matching and scoring peaks with unknown masses remains challenging. Here, the authors present a refined open search strategy to score all peaks with higher sensitivity and accuracy.

    • Fengchao Yu
    • , Guo Ci Teo
    •  & Alexey I. Nesvizhskii

  • Article
    | Open Access

    Top-down proteomics can provide unique insights into the biological variations of protein biomarkers but detecting low-abundance proteins in body fluids remains challenging. Here, the authors develop a nanoparticle-based top-down proteomics approach enabling enrichment and detailed analysis of cardiac troponin I in human serum.

    • Timothy N. Tiambeng
    • , David S. Roberts
    •  & Ying Ge

  • Article
    | Open Access

    The mechanism underlying the cellular entry of Zika virus is not fully understood. Here, the authors use a chemically modified virus and time-resolved proteomics to capture interacting host proteins during virus entry and identify NCAM1 as a ZIKV receptor.

    • Mayank Srivastava
    • , Ying Zhang
    •  & W. Andy Tao

  • Article
    | Open Access

    Clinical proteomics critically depends on the ability to acquire highly reproducible data over an extended period of time. Here, the authors assess reproducibility over four months across different mass spectrometers and develop a computational approach to mitigate variation among instruments over time.

    • Rebecca C. Poulos
    • , Peter G. Hains
    •  & Qing Zhong

  • Article
    | Open Access

    Large-scale, unbiased proteomics studies of biological samples like plasma are constrained by the complexity of the proteome. Herein, the authors develop a highly parallel protein quantitation platform leveraging multi nanoparticle protein coronas for deep proteome sampling and biomarker discovery.

    • John E. Blume
    • , William C. Manning
    •  & Omid C. Farokhzad

  • Article
    | Open Access

    Proteome activity has a major role in cancer progression and response to drugs. Here, the authors use comprehensive proteomic and phosphoproteomic data, in conjunction with drug-sensitivity screens, to generate a community resource consisting of landscapes of pathway and kinase activity across different cell lines

    • Martin Frejno
    • , Chen Meng
    •  & Bernhard Kuster

  • Article
    | Open Access

    Diseases can be associated with various mutations of the same gene, but the molecular consequences of specific mutations remain incompletely understood. Here, the authors present an integrated proteomic workflow to determine the molecular response of cells to different cancer-associated mutations of the kinase Dyrk2.

    • Martin Mehnert
    • , Rodolfo Ciuffa
    •  & Ruedi Aebersold

  • Article
    | Open Access

    Here the authors describe PhosID, an enrichment strategy using phosphonate-handles, that combines click chemistry and IMAC-based phospho-enrichment for quantitative proteomics analysis of newly synthesized proteins.

    • Fleur Kleinpenning
    • , Barbara Steigenberger
    •  & Albert J. R. Heck

  • Article
    | Open Access

    Matching mass spectra to peptide sequences is the usual first step in proteomics data analysis, often followed by peptide quantification. Here, the authors show that clustering and quantifying mass spectral features prior to peptide identification can increase the sensitivity of label-free quantitative proteomics.

    • Matthew The
    •  & Lukas Käll

  • Article
    | Open Access

    Formaldehyde (FA) is a popular cross-linking reagent, but applying it for cross-linking mass spectrometry (XLMS) has been largely unsuccessful. Here, the authors show that cross-links in structured proteins are the product of two FA molecules and identify hundreds of FA cross-links by XLMS in vitro and in situ.

    • Tamar Tayri-Wilk
    • , Moriya Slavin
    •  & Nir Kalisman

  • Article
    | Open Access

    Cross-linking mass spectrometry (MS) is an important tool in structural biology, but its application to protein-DNA complexes has been hampered by low cross-linking efficiency. Here, the authors develop a femtosecond UV-laser induced cross-linking MS workflow to map protein-DNA interactions in vitro and in cells.

    • Alexander Reim
    • , Roland Ackermann
    •  & Michael Wierer

  • Article
    | Open Access

    Some human amyloid proteins have been shown to interact with viral proteins, suggesting that they may have potential as therapeutic agents. Here the authors design synthetic amyloids specific for influenza A and Zika virus proteins, respectively, and show that they can inhibit viral replication.

    • Emiel Michiels
    • , Kenny Roose
    •  & Joost Schymkowitz

  • Article
    | Open Access

    Previous study identified in vivo structured mRNA regions in Saccharomyces cerevisiae by dimethyl sulfate-sequencing. Here the authors use quantitative proteomics to identify protein interactors of 186 RNA folds in S. cerevisiae, providing functional links between RNA binding proteins and distinct mRNA fold.

    • Nuria Casas-Vila
    • , Sergi Sayols
    •  & Falk Butter

  • Article
    | Open Access

    Immunopeptidomics allows identifying the cellular repertoire of MHC-bound peptides, but quantifying them remains challenging. Here, the authors present a method to efficiently generate internal peptide MHC standards and calibration curves, facilitating relative and absolute quantitative immunopeptidomics.

    • Lauren E. Stopfer
    • , Joshua M. Mesfin
    •  & Forest M. White

  • Article
    | Open Access

    Study of human heart failure is limited by access to human tissue. Here, the authors apply multi-omic screening in human ischaemic and dilated myocardial tissue and matched controls to determine molecular changes common and unique to each aetiology and to reveal differences between male and female hearts.

    • Mengbo Li
    • , Benjamin L. Parker
    •  & John F. O’Sullivan

  • Article
    | Open Access

    Androgen receptor (AR) signalling regulates cellular metabolism in prostate cancer. Here, the authors perform a proteomics and metabolomics characterisation of prostate cancer cells adapted to long-term resistance to AR inhibition and show rewiring of glucose and lipid metabolism, and further identify a signature associated with resistance to AR inhibition.

    • Arnaud Blomme
    • , Catriona A. Ford
    •  & Hing Y. Leung

  • Article
    | Open Access

    Enteric pathogens such as Salmonella depend on propanediol-utilising microcompartments (Pdu MCP), which self-assemble from cytosolic proteins. Using mass spectrometry-based absolute quantification, the authors here define the protein stoichiometry and propose an organizational model of a Salmonella Pdu MCP.

    • Mengru Yang
    • , Deborah M. Simpson
    •  & Lu-Ning Liu

  • Article
    | Open Access

    The mechanisms of action of proteasome inhibitors (PI) in multiple myeloma (MM) treatment are not fully elucidated. Here, the authors use unbiased phosphoproteomics in PI-treated MM and show increased phosphorylation of splicing-associated proteins, ultimately revealing splicing interference as a mode of PI action as well as demonstrating the spliceosome as a specific therapeutic vulnerability in this disease.

    • Hector H. Huang
    • , Ian D. Ferguson
    •  & Arun P. Wiita

  • Article
    | Open Access

    Identifying mutation-derived neoantigens by proteogenomics requires robust strategies for quality control. Here, the authors propose peptide retention time as an evaluation metric for proteogenomics quality control methods, and develop a deep learning algorithm for accurate retention time prediction.

    • Bo Wen
    • , Kai Li
    •  & Bing Zhang

  • Article
    | Open Access

    Metaplastic breast carcinoma (MBC) is among the most aggressive subtypes of triple-negative breast cancer (TNBC) but the underlying proteome profiles are unknown. Here, the authors characterize the protein signatures of human MBC tissue samples and their relationship to TNBC and normal breast tissue.

    • Sabra I. Djomehri
    • , Maria E. Gonzalez
    •  & Celina G. Kleer

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