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A metaproteomic approach to study human-microbial ecosystems at the mucosal luminal interface

Li, X and LeBlanc, J and Truong, A and Vuthoori, R and Chen, SS and Lustgarten, JL and Roth, B and Allard, J and Ippoliti, A and Presley, LL and Borneman, J and Bigbee, WL and Gopalakrishnan, V and Graeber, TG and Elashoff, D and Braun, J and Goodglick, L (2011) A metaproteomic approach to study human-microbial ecosystems at the mucosal luminal interface. PLoS ONE, 6 (11).

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Aberrant interactions between the host and the intestinal bacteria are thought to contribute to the pathogenesis of many digestive diseases. However, studying the complex ecosystem at the human mucosal-luminal interface (MLI) is challenging and requires an integrative systems biology approach. Therefore, we developed a novel method integrating lavage sampling of the human mucosal surface, high-throughput proteomics, and a unique suite of bioinformatic and statistical analyses. Shotgun proteomic analysis of secreted proteins recovered from the MLI confirmed the presence of both human and bacterial components. To profile the MLI metaproteome, we collected 205 mucosal lavage samples from 38 healthy subjects, and subjected them to high-throughput proteomics. The spectral data were subjected to a rigorous data processing pipeline to optimize suitability for quantitation and analysis, and then were evaluated using a set of biostatistical tools. Compared to the mucosal transcriptome, the MLI metaproteome was enriched for extracellular proteins involved in response to stimulus and immune system processes. Analysis of the metaproteome revealed significant individual-related as well as anatomic region-related (biogeographic) features. Quantitative shotgun proteomics established the identity and confirmed the biogeographic association of 49 proteins (including 3 functional protein networks) demarcating the proximal and distal colon. This robust and integrated proteomic approach is thus effective for identifying functional features of the human mucosal ecosystem, and a fresh understanding of the basic biology and disease processes at the MLI. © 2011 Li et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Li, X
LeBlanc, J
Truong, A
Vuthoori, R
Chen, SS
Lustgarten, JL
Roth, B
Allard, J
Ippoliti, A
Presley, LL
Borneman, J
Bigbee, WL
Gopalakrishnan, Vvanathi@pitt.eduVANATHI
Graeber, TG
Elashoff, D
Braun, J
Goodglick, L
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 21 November 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 11
DOI or Unique Handle: 10.1371/journal.pone.0026542
Schools and Programs: School of Medicine > Computational and Systems Biology
School of Medicine > Pathology
Refereed: Yes
MeSH Headings: Biopsy; Ecosystem; Female; Health; Humans; Intestinal Mucosa--microbiology; Intestinal Mucosa--pathology; Male; Middle Aged; Molecular Sequence Annotation; Phylogeny; Proteome--genetics; Proteome--metabolism; Proteomics--methods; Reproducibility of Results; Specimen Handling; Transcriptome--genetics
Other ID: NLM PMC3221670
PubMed Central ID: PMC3221670
PubMed ID: 22132074
Date Deposited: 07 Sep 2012 19:46
Last Modified: 13 Oct 2017 23:00


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