The ProteomeXchange consortium in 2020: enabling ‘big data’ approaches in proteomics

Deutsch, Eric W.; Bandeira, Nuno; Sharma, Vagisha; Pérez-Riverol, Yasset; Carver, Jeremy; Kundu, Deepti Jaiswal; García-Seisdedos, David; Jarnuczak, Andrew F.; Hewapathirana, Suresh; Pullman, Benjamin; Wertz, Julie; Sun, Zhi; Kawano, Shin; Okuda, Shujiro; Watanabe, Yu; Hermjakob, Henning; MacLean, Brendan; MacCoss, Michael J.; Zhu, Yunping; Ishihama, Yasushi; Vizcaíno, Juan Antonio

doi:10.1093/nar/gkz984

Cited by 613 publications

(606 citation statements)

References 42 publications

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“…The adaptive Benjamini-Hochberg procedure was applied to adjust the p-values and FDR values under 1per cent were achieved. Complete dataset has been deposited to the ProteomeXchange Consortium via the PRIDE partner repos-itory5 with the dataset identifier PXD020180 (Deutsch et al, 2020).…”

Section: R a F Tmentioning

confidence: 99%

Ral GTPases promote metastasis by controlling biogenesis and organ colonization of exosomes

Ghoroghi

Mary

Larnicol

et al. 2020

Preprint

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Cancer extracellular vesicles (EVs) mainly exert pro-tumoral functions by changing the phenotypes of stromal cells to the benefit of tumor growth and metastasis. In particular, they shuttle to distant organs and seed pre-metastatic niches facilitating subsequent colonization by circulating tumor cells. The levels of tumor secreted EVs have been correlated with tumor aggressiveness, however, the link between EV secretion mechanisms and their capacity to form pre-metastatic niches remains obscure. Here, we show that GTPases of the Ral family control, through the phospholipase D1 (PLD1), multi-vesicular bodies homeostasis and thereby tune the biogenesis and secretion of pro-metastatic EVs. Mice experiments revealed that RalA and RalB promote lung metastasis of mammary carcinoma cells without affecting their invasive behaviors. Importantly, we demonstrate that EVs from RalA or RalB depleted cells have limited organotropic capacities in vivo and, as a consequence, are less efficient in seeding lung metastasis. Furthermore, we show that such EVs lack the adhesion molecule MCAM/CD146, which is responsible for EVs organotropism. Finally, we observe that RalA and RalB have increased expression in human breast cancer patients with lung metastasis. Altogether, our study identifies Ral GTPases as central molecules linking the mechanisms of EVs secretion, cargo loading to their capacity to disseminate and induce pre-metastatic niches.

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Section: R a F Tmentioning

confidence: 99%

Ral GTPases promote metastasis by controlling biogenesis and organ colonization of exosomes

Ghoroghi

Mary

Larnicol

et al. 2020

Preprint

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“…The RAW files were processed via MaxQuant [ 98 ] using a FASTA file containing protein sequences of S. lycopersicum (via Uniprot [ 99 ]), ToMoV DNA A (NC_001939.1), and DNA B (NC_001938.1). The raw data have been submitted to the ProteomeXchange ( , identifier PXD019197) [ 100 ]. With few exceptions, the default MaxQuant spectral search parameters were left, and they included the variable oxidation of methionine and N-termini as well as a fixed carbamidomethylation with a maximum number of 5 modifications per peptide.…”

Section: Methodsmentioning

confidence: 99%

Characterization of Local and Systemic Impact of Whitefly (Bemisia tabaci) Feeding and Whitefly-Transmitted Tomato Mottle Virus Infection on Tomato Leaves by Comprehensive Proteomics

Ogden

Boukari

Nava

et al. 2020

IJMS

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Tomato mottle virus (ToMoV) is a single-stranded DNA (ssDNA) begomovirus transmitted to solanaceous crops by the whitefly species complex (Bemisia tabaci), causing stunted growth, leaf mottling, and reduced yield. Using a genetic repertoire of seven genes, ToMoV pathogenesis includes the manipulation of multiple plant biological processes to circumvent antiviral defenses. To further understand the effects of whitefly feeding and whitefly-transmitted ToMoV infection on tomato plants (Solanum lycopersicum ‘Florida Lanai’), we generated comprehensive protein profiles of leaves subjected to feeding by either viruliferous whiteflies harboring ToMoV, or non-viruliferous whiteflies, or a no-feeding control. The effects of whitefly feeding and ToMoV infection were measured both locally and systemically by sampling either a mature leaf directly from the site of clip-cage confined whitefly feeding, or from a newly formed leaf 10 days post feeding (dpf). At 3 dpf, tomato’s response to ToMoV included proteins associated with translation initiation and elongation as well as plasmodesmata dynamics. In contrast, systemic impacts of ToMoV on younger leaves 10 dpf were more pronounced and included a virus-specific change in plant proteins associated with mRNA maturation and export, RNA-dependent DNA methylation, and other antiviral plant processes. Our analysis supports previous findings and provides novel insight into tomato’s local and systemic response to whitefly feeding and ToMoV infection.

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“…The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (55,56) Data were exported to Microsoft Excel and unannotated effector proteins manually annotated. Data were imported into the R framework (https://www.r-project.org) integrated with R studio (https://rstudio.com/products/rstudio/) for generation for comparison with C. burnetii protein enrichment alongside purified mitochondria and generation of graphics.…”

Section: Data Availabilitymentioning

confidence: 99%

Proteomic identification ofCoxiella burnetiieffector proteins targeted to the host cell mitochondria during infection

Fielden

Scott

Palmer

et al. 2020

Preprint

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Modulation of the host cell is integral to the survival and replication of microbial pathogens. Several intracellular bacterial pathogens deliver a cohort of bacterial proteins, termed ‘effector proteins’ into the host cell during infection by sophisticated protein translocation systems which manipulate cellular processes and functions. Despite the importance of these proteins during infection the functional contribution of individual effectors is poorly characterised, particularly in intracellular bacterial pathogens with large effector protein repertoires. Technical caveats have limited the capacity to study these proteins during a native infection, with many effector proteins having only been demonstrated to be translocated during over-expression of tagged versions. Here we present development of a novel strategy to examine effector proteins in the context of infection. We coupled a broad, unbiased proteomics-based screen with organelle purification to study the host-pathogen interactions occurring between the host cell mitochondrion and the Gram-negative, Q fever pathogen Coxiella burnetii. We identify 4 novel mitochondrially-targeted C. burnetii effector proteins, renamed Mitochondrial Coxiella effector protein (Mce) B to E. Examination of the subcellular localisation of ectopically expressed proteins in epithelial cells confirmed the mitochondrial localisation, demonstrating the robustness of our approach. Subsequent biochemical analysis and affinity enrichment proteomics of one of these effector proteins, MceC, revealed the protein is imported into mitochondria and can interact with components of the mitochondrial quality control machinery. Our study adapts high-sensitivity proteomics to the study of intracellular host-pathogen interactions occurring during infection, providing a robust strategy to examine the sub-cellular localisation of effector proteins during native infection. This approach could be applied to a range of pathogens and host cell compartments to provide a rich map of effector dynamics throughout infection.

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The ProteomeXchange consortium in 2020: enabling ‘big data’ approaches in proteomics

Cited by 613 publications

References 42 publications

Ral GTPases promote metastasis by controlling biogenesis and organ colonization of exosomes

Ral GTPases promote metastasis by controlling biogenesis and organ colonization of exosomes

Characterization of Local and Systemic Impact of Whitefly (Bemisia tabaci) Feeding and Whitefly-Transmitted Tomato Mottle Virus Infection on Tomato Leaves by Comprehensive Proteomics

Proteomic identification ofCoxiella burnetiieffector proteins targeted to the host cell mitochondria during infection

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