Proteomic analysis articles within Nature Communications

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  • Article
    | Open Access

    The dia-PASEF technology uses ion mobility separation to reduce signal interferences and increase sensitivity of mass spectrometry-based proteomics. The authors present algorithms and a software solution, which boost proteomic depth in dia-PASEF experiments by up to 83% compared to previous work, and are specifically beneficial for fast proteomic experiments and those with low sample amounts.

    • Vadim Demichev
    • , Lukasz Szyrwiel
    •  & Markus Ralser

  • Article
    | Open Access

    Dataset integration is common practice to overcome limitations in statistically underpowered omics datasets. Here the authors present “HarmonizR”, a tool for missing data tolerant experimental variance reduction in large, integrated but independently generated datasets without data imputation, adjustable for individual dataset modalities, correction algorithm, and user preferences.

    • Hannah Voß
    • , Simon Schlumbohm
    •  & Christoph Krisp

  • Article
    | Open Access

    The neurotransmitter dopamine is an important regulator of brain function. Here the authors describe “dopamine hub synapses”, where dopamine transmission may act in synergy with other neurotransmitters.

    • Vincent Paget-Blanc
    • , Marlene E. Pfeffer
    •  & Etienne Herzog

  • Article
    | Open Access

    Current isolation-based approaches for cell type-specific proteomics pose several challenges. Here, the authors present an approach for in vivo cell type-specific protein labeling to characterize proteomic differences between neurons and astrocytes in their native state in adult mouse brain.

    • Sruti Rayaprolu
    • , Sara Bitarafan
    •  & Srikant Rangaraju

  • Article
    | Open Access

    Available methods to identify species from fragmented archaeological bone and remains suffer a trade-off between cost and resolution. Here, the authors present a workflow that uses automated sample preparation, 10 to 20 times faster data acquisition, and computerized data interpretation to make the technology applicable to large-scale studies.

    • Patrick Leopold Rüther
    • , Immanuel Mirnes Husic
    •  & Jesper Velgaard Olsen

  • Article
    | Open Access

    Proteomics can define features of proteome foldedness by assessing the reactivity of surface exposed amino acids. Here, the authors show that such exposure patterns yield insight to structural changes in chaperones as they bind to unfolded proteins in urea-denatured mammalian cell lysate.

    • Dezerae Cox
    • , Ching-Seng Ang
    •  & Danny M. Hatters

  • Article
    | Open Access

    Normal and abnormal pregnancy is challenging to study and involves complex interactions between maternal and fetal cells. Here the authors present an implantation-on-a-chip device capable of modeling trophoblast invasion, a process critical to the establishment of pregnancy.

    • Ju Young Park
    • , Sneha Mani
    •  & Dan Dongeun Huh

  • Article
    | Open Access

    PROTACs and molecular glues target E3 ubiquitin ligases to substrate proteins. Here, the authors develop a proximity biotinylation-based method to identify drug-induced E3 ligase-substrate interactions, enabling the assessment of the target spectrum of PROTACs and molecular glues in cells.

    • Satoshi Yamanaka
    • , Yuto Horiuchi
    •  & Tatsuya Sawasaki

  • Article
    | Open Access

    Protein turnover underpins biology but is challenging to measure in vivo across the entire proteome. Here, the authors provide a comprehensive resource of protein turnover in mouse tissues and develop a visualization platform to analyze these data.

    • Zach Rolfs
    • , Brian L. Frey
    •  & Nathan V. Welham

  • Article
    | Open Access

    RNA-protein interactions play critical roles in post-transcriptional gene regulation. Here the authors demonstrate pRBS-ID, an updated MS/MS-based method that combines the benefits of photoactivatable ribonucleosides and the chemical cleavage of RNA.

    • Jong Woo Bae
    • , Sangtae Kim
    •  & Jong-Seo Kim

  • Article
    | Open Access

    ADP-ribosylation is regulated by HPF1 and ARH3, but the cellular target spectrum of these enzymes is not fully understood. Here, the authors use quantitative proteomics to define the HPF1- and ARH3-dependent ADP-ribosylome, providing evidence that mono-ADP-ribosylation of serine predominates in cells.

    • Ivo A. Hendriks
    • , Sara C. Buch-Larsen
    •  & Michael L. Nielsen

  • Article
    | Open Access

    Peptide mass fingerprinting is a traditional approach for protein identification by mass spectrometry. Here, the authors provide evidence that peptide mass fingerprinting is also feasible using FraC nanopores, demonstrating protein identification based on nanopore measurements of digested peptides.

    • Florian Leonardus Rudolfus Lucas
    • , Roderick Corstiaan Abraham Versloot
    •  & Giovanni Maglia

  • Article
    | Open Access

    “Protein relocalisation plays a major role in the innate immune response but remains incompletely characterised. Here, the authors combine temporal proteomics with LOPIT, a spatial proteomic workflow, in a fully Bayesian framework to elucidate spatiotemporal proteomic changes during the LPS-induced immune response in THP-1 cells.

    • Claire M. Mulvey
    • , Lisa M. Breckels
    •  & Kathryn S. Lilley

  • Article
    | Open Access

    Proximity biotinylation is a powerful tool to profile interactomes, but it requires genetic engineering of the target protein. Here, the authors develop a proximity biotinylation enzyme that can be directed to the target using antibodies, enabling interactome profiling of endogenous proteins or PTMs.

    • Irene Santos-Barriopedro
    • , Guido van Mierlo
    •  & Michiel Vermeulen

  • Article
    | Open Access

    Mapping neuronal proteomes with genetic, subcellular, and temporal specificity is a challenging task. This study uncovers proteome dynamics in two classes of striatal spiny projection neurons in the mouse brain using a genetically targeted APEX2-based proximity labeling approach.

    • V. Dumrongprechachan
    • , R. B. Salisbury
    •  & Y. Kozorovitskiy

  • Article
    | Open Access

    Applying complexome profiling, Evers et al. unravel the composition of mitochondrial oxidative phosphorylation complexes in P. falciparum asexual and sexual blood stages. Abundance of these complexes differs between both stages, supporting the hypothesis that a mitochondrial metabolic switch is central to gametocyte development and functioning.

    • Felix Evers
    • , Alfredo Cabrera-Orefice
    •  & Taco W. A. Kooij

  • Article
    | Open Access

    The proximity extension assay (PEA) is a popular tool to measure plasma protein levels. Here, the authors extend the proteome coverage of PEA by combining it with next-generation sequencing, enabling the analysis of nearly 1500 proteins from minute amounts of plasma.

    • Wen Zhong
    • , Fredrik Edfors
    •  & Mathias Uhlén

  • Article
    | Open Access

    The network of proteins secreted for interorgan communication is poorly understood. Here, the authors develop a method, based on protein labeling, to study cell-specific secretomes and interorgan protein trafficking, and demonstrate their approach in Drosophila and mouse models.

    • Ilia A. Droujinine
    • , Amanda S. Meyer
    •  & Norbert Perrimon

  • Article
    | Open Access

    Skeletal muscle conveys the beneficial effects of physical exercise but due to its heterogeneity, studying the effects of exercise on muscle fibres is challenging. Here, the authors carry out proteomic analysis of myofibres from freeze-dried muscle biopsies, show fibre-type specific changes in response to exercise, and show that the oxidative and glycolytic muscle fibers adapt differentially to exercise training.

    • A. S. Deshmukh
    • , D. E. Steenberg
    •  & J. F. P. Wojtaszewski

  • Article
    | Open Access

    Protein ubiquitylation is often studied by proteomics but how data independent acquisition (DIA) may advance these studies remains to be explored. Here, the authors show that DIA improves ubiquitylation site identification and quantification, enabling them to characterize the circadian ubiquitinome in human cells.

    • Fynn M. Hansen
    • , Maria C. Tanzer
    •  & Matthias Mann

  • Article
    | Open Access

    Large population testing is a key step to controlling the COVID-19 pandemic. Here, the authors develop a targeted mass spectrometry system for peptide-based SARS-CoV-2 detection, allowing analysis of over 500 swab samples per day and enabling virus detection even after prolonged sample storage at room temperature.

    • Karina Helena Morais Cardozo
    • , Adriana Lebkuchen
    •  & Valdemir Melechco Carvalho

  • Article
    | Open Access

    How COVID-19 pathology differs from other drivers of pneumonia is unclear. Here the authors analyze urine from patients with COVID-19 and identify an immunosuppressive protein expression pattern that is distinct from the pattern in healthy individuals or patients with non-COVID-19 pneumonia.

    • Wenmin Tian
    • , Nan Zhang
    •  & Catherine C. L. Wong

  • 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

    To investigate the molecular foundation of sporadic Alzheimer’s disease (AD), Beckmann et al. constructed multiscale causal networks on a large human AD multi-omics dataset, detecting AD-associated networks and their top predicted regulator, VGF, with extensive validation in the 5xFAD mouse model.

    • Noam D. Beckmann
    • , Wei-Jye Lin
    •  & Eric E. Schadt

  • Article
    | Open Access

    The heterogeneity of IDH1/2 wild-type glioblastoma limits its prognosis and therapy. Here, the authors show a binary stratification, based on quantitative proteomic analysis of samples from patients with glioblastoma, with different prognosis and therapeutic vulnerabilities.

    • Sejin Oh
    • , Jeonghun Yeom
    •  & Hyun Seok Kim

  • Article
    | Open Access

    The blood circulation time is important to the biomedical application of nanomaterials. Here, the authors explore the effect of protein corona formation on the blood residency of nanomaterials and show circulation times are governed by the dynamic remodelling of protein opsonins in vivo.

    • Srinivas Abbina
    • , Lily E. Takeuchi
    •  & Jayachandran N. Kizhakkedathu

  • Article
    | Open Access

    Extracellular vesicles (EVs) in plasma can affect pathogenesis of parasites, but details remain unclear. Here, Toda et al. characterize plasma-derived EVs from Plasmodium vivax patients and show that PvEVs are preferentially taken up by human spleen fibroblasts, facilitating parasite cytoadherence.

    • Haruka Toda
    • , Miriam Diaz-Varela
    •  & Hernando A. del Portillo

  • Article
    | Open Access

    Here, Hashimoto et al. apply mass spectrometry-based thermal proximity coaggregation to characterize the temporal dynamics of virus-host protein-protein interactions during human cytomegalovirus (HCMV) infection, uncovering proviral functions including the internalization of the HCMV receptor integrin beta 1 with CD63.

    • Yutaka Hashimoto
    • , Xinlei Sheng
    •  & Ileana M. Cristea

  • Article
    | Open Access

    Mass spectrometry-based proteomics typically relies on highly sensitive nano-flow liquid chromatography (LC) but this can reduce robustness and reproducibility. Here, the authors show that micro-flow LC enables robust and reproducible high-throughput proteomics experiments at a very moderate loss of sensitivity.

    • Yangyang Bian
    • , Runsheng Zheng
    •  & Bernhard Kuster

  • Article
    | Open Access

    Data-independent acquisition (DIA) is an emerging technology in proteomics but it typically relies on spectral libraries built by data-dependent acquisition (DDA). Here, the authors use deep learning to generate in silico spectral libraries directly from protein sequences that enable more comprehensive DIA experiments than DDA-based libraries.

    • Yi Yang
    • , Xiaohui Liu
    •  & Liang Qiao

  • Article
    | Open Access

    Analysis of the cell surface proteome (surfaceome) is essential for cell classification but is technically challenging. Here the authors miniaturize and automate the Cell Surface Capture method to increase sensitivity, reproducibility and throughput, and use it to create population-specific surfaceome maps of developing mouse B cells.

    • Marc van Oostrum
    • , Maik Müller
    •  & Bernd Wollscheid

  • Comment
    | Open Access

    John Fenn’s electrospray mass spectrometry (ESMS) was awarded the chemistry Nobel Prize in 2002 and is now the basis of the entire field of MS-based proteomics. Technological progress continues unabated, enabling single cell sensitivity and clinical applications.

    • Matthias Mann

  • Article
    | Open Access

    Comprehensive mapping of binary protein-protein interactions requires to combine several complementary assays. Here, the authors show that complete coverage could be reached with a minimal number of assays as long as they explore various experimental conditions.

    • Soon Gang Choi
    • , Julien Olivet
    •  & Yves Jacob

  • Article
    | Open Access

    The use of antibodies to capture and profile exosomes limits the number of target proteins that can be detected. Here the authors develop a proximity-dependent barcoding assay that allows profiling of 38 surface proteins on individual exosomes from heterogeneous samples such as serum and seminal fluid.

    • Di Wu
    • , Junhong Yan
    •  & Masood Kamali-Moghaddam

  • Article
    | Open Access

    Multi-omic profiling is a powerful approach to dissecting molecular mechanisms in disease. Here the authors generate whole proteome, phosphoproteome and transcriptome profiles from two mouse models of high-grade glioma driven by different oncogenes, and validate identified master regulators with a CRISPR screen.

    • Hong Wang
    • , Alexander K. Diaz
    •  & Junmin Peng

  • Article
    | Open Access

    Squamous cell lung cancer has dismal prognosis due to the dearth of effective treatments. Here, the authors perform an integrated proteogenomic analysis of the disease, revealing three proteomics-based subtypes and suggesting potential therapeutic opportunities.

    • Paul A. Stewart
    • , Eric A. Welsh
    •  & Eric B. Haura

  • Article
    | Open Access

    Understanding of the genetic factors and molecular mechanisms underlying neurodevelopmental disorders remains incomplete. In this study, authors show that microdeletions in the gene ANKS1B lead to loss of the neuronal synapse-enriched protein AIDA-1 and to a novel neurodevelopmental syndrome

    • Abigail U. Carbonell
    • , Chang Hoon Cho
    •  & Bryen A. Jordan

  • Article
    | Open Access

    The identification of cross-linked peptides at a proteome scale for interactome analyses represents a complex challenge. Here the authors report an efficient and reliable search engine pLink 2 for proteome-scale cross-linking mass spectrometry analyses, and demonstrate how to systematically evaluate the credibility of search engines.

    • Zhen-Lin Chen
    • , Jia-Ming Meng
    •  & Si-Min He

  • Article
    | Open Access

    Simultaneous quantification of DNA, RNA and protein at the single cell level has not yet been possible. Here the authors introduce a molecular labelling and detection strategy to quantify synthesis of these biomolecules and couple it to transient cell states through parallel quantification of state-dependent biomolecules.

    • Samuel C. Kimmey
    • , Luciene Borges
    •  & Sean C. Bendall

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