Digging More Missing Proteins Using an Enrichment Approach with ProteoMiner

Li, Siqi; He, Yuexin; Lin, Zhilong; Xu, Shaohang; Zhou, Ruo; Liang, Feng; Wang, Jian; Yang, Huanming; Liu, Siqi; Ren, Yan

doi:10.1021/acs.jproteome.7b00353

Cited by 28 publications

(47 citation statements)

References 58 publications

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“…At first, it might seem that the number of total quantified proteins using our approach was not high, but this result is typical of non-depleted serum samples. Depletion of abundant proteins using commercially available antibody-coated LC columns or cartridges 29 as well as other approaches, such as those based on the use of combinatorial hexapeptide ligand libraries 30 , enables a higher coverage of the serum and plasma proteome in mass spectrometry-based studies but at the cost of losing information from highly abundant proteins and protein complexes. In a previous multilaboratory experiment (Proteored Multicenter Experiment 6), several groups were able to identify more than one hundred different proteins in the "bound" fraction of a immune-depleted serum sample with a commercial column supposed to bind only the 20 most abundant serum proteins 31 .…”

Section: Discussionmentioning

confidence: 99%

Serum proteomics of active tuberculosis patients and contacts reveals unique processes activated during Mycobacterium tuberculosis infection

Mateos

Estévez

González-Fernández

et al. 2020

Sci Rep

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Tuberculosis (TB) is the most lethal infection among infectious diseases. The specific aim of this study was to establish panels of serum protein biomarkers representative of active tB patients and their household contacts who were either infected (LtBi) or uninfected (eMi-tB Discovery cohort, Pontevedra Region, Spain). A TMT (Tamdem mass tags) 10plex-based quantitative proteomics study was performed in quintuplicate containing a total of 15 individual serum samples per group. Peptides were analyzed in an Lc-orbitrap elite platform, and raw data were processed using proteome Discoverer 2.1. A total of 418 proteins were quantified. The specific protein signature of active tB patients was characterized by an accumulation of proteins related to complement activation, inflammation and modulation of immune response and also by a decrease of a small subset of proteins, including apolipoprotein A and serotransferrin, indicating the importance of lipid transport and iron assimilation in the progression of the disease. This signature was verified by the targeted measurement of selected candidates in a second cohort (EMI-TB Verification Cohort, Maputo Region, Mozambique) by ELISA and nephelometry techniques. These findings will aid our understanding of the complex metabolic processes associated with tB progression from LtBi to active disease. Tuberculosis (TB) is currently a global pandemic that kills approximately 1.3 million people worldwide each year 1. Although the incidence of TB is decreasing each year, the rate of that decline is not high enough to accomplish the TB Global Strategy for the 2015-2035 period 2,3. Mycobacterium tuberculosis (MTB) is the causal agent of the pulmonary TB 4 , which is air-transmitted by nasal/oral inhalation of aerosol droplets carrying the pathogen from an active TB patient to a healthy individual usually through coughing or sneezing 5. Small droplets that are able to reach the lower lung induce formation of a granuloma 6 , which is a host-defensive structure providing, a fibrotic physical barrier between the infected and the healthy neighboring tissues 7. Latently infected individuals (LTBI) represent roughly a quarter of the global population 8. Tuberculin Skin Test (TST) and Interferon-Gamma Release Assay (IGRA) are commonly used for diagnosis 9,10 of LTBI individuals. Although they cannot infect a healthy person, MTB activation occurs in roughly 10% of cases due to recurrent infections or a compromised immune system in the host 11 .

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Section: Discussionmentioning

confidence: 99%

Serum proteomics of active tuberculosis patients and contacts reveals unique processes activated during Mycobacterium tuberculosis infection

Mateos

Estévez

González-Fernández

et al. 2020

Sci Rep

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“…The editorial for the JPR 2017 special issue 12 highlighted six papers that used a variety of promising methods to find Missing Proteins, with a total of 32 identified for validation as PE1: 15 from Li et al 13 using Triton X-100 solubilization plus ProteoMiner hexapeptide-covered beads as an enrichment/equalization strategy for low-abundance proteins with kidney, bladder, liver, and colorectal specimens, and confirmation with PRM; 12 from Carapito et al 14 on the sperm proteome with PRM confirmation; 3 from Wang et al 15 using a multi-protease strategy on testis; 1 from Peng 16 from the kidney phosphoproteome; 1 from Meyfour et al 17 based on biological studies of a Y chromosome protein in cardiac development; plus 41 cautiously forwarded from Elguoshy et al 18 using the stranded peptides approach described below. Twenty MP reported by Li et al 8 , including 5 without PRM validation that had not been counted in the editorial, are now classified as canonical in PeptideAtlas and validated as PE1 in neXtProt.…”

Section: The Fate Of Missing Proteins Nominated For Nextprot Review Imentioning

confidence: 99%

Progress on Identifying and Characterizing the Human Proteome: 2018 Metrics from the HUPO Human Proteome Project

et al. 2018

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The Human Proteome Project (HPP) annually reports on progress throughout the field in credibly identifying and characterizing the human protein parts list and making proteomics an integral part of multiomics studies in medicine and the life sciences. NeXtProt release 2018-01-17, the baseline for this sixth annual HPP special issue of the Journal of Proteome Research, contains 17 470 PE1 proteins, 89% of all neXtProt predicted PE1-4 proteins, up from 17 008 in release 2017-01-23 and 13 975 in release 2012-02-24. Conversely, the number of neXtProt PE2,3,4 missing proteins has been reduced from 2949 to 2579 to 2186 over the past two years. Of the PE1 proteins, 16 092 are based on mass spectrometry results, and 1378 on other kinds of protein studies, notably protein-protein interaction findings. PeptideAtlas has 15 798 canonical proteins, up 625 over the past year, including 269 from SUMOylation studies. The largest reason for missing proteins is low abundance. Meanwhile, the Human Protein Atlas has released its Cell Atlas, Pathology Atlas, and updated Tissue Atlas, and is applying recommendations from the International Working Group on Antibody Validation. Finally, there is progress using the quantitative multiplex organ-specific popular proteins targeted proteomics approach in various disease categories.

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“…MPs, as carried out by Carapito and collaborators on ejaculated spermatozoa 17 . Equalization of Page 29 of 42 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 30 protein abundance using the Proteominer approach may also be relevant for the identification of low expressed MPs 34 , particularly for the identification of membrane or nuclear MPs. The use of RNA-Seq information on MP gene expression will be an important asset to design proteotypic peptides for selected protein candidates prior to targeted-MS analyses.…”

Section: Resultsmentioning

confidence: 99%

Deciphering the Dark Proteome: Use of the Testis and Characterization of Two Dark Proteins

Melaine

Com

Bellaud³

et al. 2018

J. Proteome Res.

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For the C-HPP consortium, dark proteins include not only uPE1, but also missing proteins (MPs, PE2-4), smORFs, proteins from lncRNAs, and products from uncharacterized transcripts. Here, we investigated the expression of dark proteins in the human testis by combining public mRNA and protein expression data for several tissues and performing LC-MS/MS analysis of testis protein extracts. Most uncharacterized proteins are highly expressed in the testis. Thirty could be identified in our data set, of which two were selected for further analyses: (1) A0AOU1RQG5, a putative cancer/testis antigen specifically expressed in the testis, where it accumulates in the cytoplasm of elongated spermatids; and (2) PNMA6E, which is enriched in the testis, where it is found in the germ cell nuclei during most stages of spermatogenesis. Both proteins are coded on Chromosome X. Finally, we studied the expression of other dark proteins, uPE1 and MPs, in a series of human tissues. Most were highly expressed in the testis at both the mRNA and protein levels. The testis appears to be a relevant organ to study the dark proteome, which may have a function related to spermatogenesis and germ cell differentiation. The mass spectrometry proteomics data have been deposited with the ProteomeXchange Consortium under the data set identifier PXD009598.

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Digging More Missing Proteins Using an Enrichment Approach with ProteoMiner

Cited by 28 publications

References 58 publications

Serum proteomics of active tuberculosis patients and contacts reveals unique processes activated during Mycobacterium tuberculosis infection

Serum proteomics of active tuberculosis patients and contacts reveals unique processes activated during Mycobacterium tuberculosis infection

Progress on Identifying and Characterizing the Human Proteome: 2018 Metrics from the HUPO Human Proteome Project

Deciphering the Dark Proteome: Use of the Testis and Characterization of Two Dark Proteins

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