High-level integration of murine intestinal transcriptomics data highlights the importance of the complement system in mucosal homeostasis

Nirupama Benis*, Jerry M. Wells, Mari A. Smits, Soumya Kanti Kar, Bart van der Hee, Vitor A.P. Martins dos Santos, Maria Suarez-Diez, Dirkjan Schokker

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: The mammalian intestine is a complex biological system that exhibits functional plasticity in its response to diverse stimuli to maintain homeostasis. To improve our understanding of this plasticity, we performed a high-level data integration of 14 whole-genome transcriptomics datasets from samples of intestinal mouse mucosa. We used the tool Centrality based Pathway Analysis (CePa), along with information from the Reactome database. Results: The results show an integrated response of the mouse intestinal mucosa to challenges with agents introduced orally that were expected to perturb homeostasis. We observed that a common set of pathways respond to different stimuli, of which the most reactive was the Regulation of Complement Cascade pathway. Altered expression of the Regulation of Complement Cascade pathway was verified in mouse organoids challenged with different stimuli in vitro. Conclusions: Results of the integrated transcriptomics analysis and data driven experiment suggest an important role of epithelial production of complement and host complement defence factors in the maintenance of homeostasis.

Original languageEnglish
Article number1028
JournalBMC Genomics
Volume20
Issue number1
DOIs
Publication statusPublished - 30 Dec 2019

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Homeostasis
Intestinal Mucosa
Organoids
Intestines
Maintenance
Genome
Databases
In Vitro Techniques
Datasets

Keywords

  • Complement pathway
  • Data integration
  • Homeostasis
  • Intestine
  • Pathway analysis
  • Transcriptomics

Cite this

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title = "High-level integration of murine intestinal transcriptomics data highlights the importance of the complement system in mucosal homeostasis",
abstract = "Background: The mammalian intestine is a complex biological system that exhibits functional plasticity in its response to diverse stimuli to maintain homeostasis. To improve our understanding of this plasticity, we performed a high-level data integration of 14 whole-genome transcriptomics datasets from samples of intestinal mouse mucosa. We used the tool Centrality based Pathway Analysis (CePa), along with information from the Reactome database. Results: The results show an integrated response of the mouse intestinal mucosa to challenges with agents introduced orally that were expected to perturb homeostasis. We observed that a common set of pathways respond to different stimuli, of which the most reactive was the Regulation of Complement Cascade pathway. Altered expression of the Regulation of Complement Cascade pathway was verified in mouse organoids challenged with different stimuli in vitro. Conclusions: Results of the integrated transcriptomics analysis and data driven experiment suggest an important role of epithelial production of complement and host complement defence factors in the maintenance of homeostasis.",
keywords = "Complement pathway, Data integration, Homeostasis, Intestine, Pathway analysis, Transcriptomics",
author = "Nirupama Benis and Wells, {Jerry M.} and Smits, {Mari A.} and Kar, {Soumya Kanti} and {van der Hee}, Bart and {Martins dos Santos}, {Vitor A.P.} and Maria Suarez-Diez and Dirkjan Schokker",
year = "2019",
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T1 - High-level integration of murine intestinal transcriptomics data highlights the importance of the complement system in mucosal homeostasis

AU - Benis, Nirupama

AU - Wells, Jerry M.

AU - Smits, Mari A.

AU - Kar, Soumya Kanti

AU - van der Hee, Bart

AU - Martins dos Santos, Vitor A.P.

AU - Suarez-Diez, Maria

AU - Schokker, Dirkjan

PY - 2019/12/30

Y1 - 2019/12/30

N2 - Background: The mammalian intestine is a complex biological system that exhibits functional plasticity in its response to diverse stimuli to maintain homeostasis. To improve our understanding of this plasticity, we performed a high-level data integration of 14 whole-genome transcriptomics datasets from samples of intestinal mouse mucosa. We used the tool Centrality based Pathway Analysis (CePa), along with information from the Reactome database. Results: The results show an integrated response of the mouse intestinal mucosa to challenges with agents introduced orally that were expected to perturb homeostasis. We observed that a common set of pathways respond to different stimuli, of which the most reactive was the Regulation of Complement Cascade pathway. Altered expression of the Regulation of Complement Cascade pathway was verified in mouse organoids challenged with different stimuli in vitro. Conclusions: Results of the integrated transcriptomics analysis and data driven experiment suggest an important role of epithelial production of complement and host complement defence factors in the maintenance of homeostasis.

AB - Background: The mammalian intestine is a complex biological system that exhibits functional plasticity in its response to diverse stimuli to maintain homeostasis. To improve our understanding of this plasticity, we performed a high-level data integration of 14 whole-genome transcriptomics datasets from samples of intestinal mouse mucosa. We used the tool Centrality based Pathway Analysis (CePa), along with information from the Reactome database. Results: The results show an integrated response of the mouse intestinal mucosa to challenges with agents introduced orally that were expected to perturb homeostasis. We observed that a common set of pathways respond to different stimuli, of which the most reactive was the Regulation of Complement Cascade pathway. Altered expression of the Regulation of Complement Cascade pathway was verified in mouse organoids challenged with different stimuli in vitro. Conclusions: Results of the integrated transcriptomics analysis and data driven experiment suggest an important role of epithelial production of complement and host complement defence factors in the maintenance of homeostasis.

KW - Complement pathway

KW - Data integration

KW - Homeostasis

KW - Intestine

KW - Pathway analysis

KW - Transcriptomics

U2 - 10.1186/s12864-019-6390-x

DO - 10.1186/s12864-019-6390-x

M3 - Article

VL - 20

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

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