Understanding the Molecular Drivers of Disease Heterogeneity in Crohn's Disease Using Multi-omic Data Integration and Network Analysis.
CD4+ T cells
Crohn’s disease
blood
clinical phenotypes
data integration
drug repurposing
drug targets
gene expression
genetics
heterogeneity
hubs
monocytes
networks
systems biology
Journal
Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162
Informations de publication
Date de publication:
17 05 2021
17 05 2021
Historique:
received:
10
03
2020
pubmed:
15
12
2020
medline:
9
2
2022
entrez:
14
12
2020
Statut:
ppublish
Résumé
Crohn's disease (CD), a form of inflammatory bowel disease (IBD), is characterized by heterogeneity along multiple clinical axes, which in turn impacts disease progression and treatment modalities. Using advanced data integration approaches and systems biology tools, we studied the contribution of CD susceptibility variants and gene expression in distinct peripheral immune cell subsets (CD14+ monocytes and CD4+ T cells) to relevant clinical traits. Our analyses revealed that most clinical traits capturing CD heterogeneity could be associated with CD14+ and CD4+ gene expression rather than disease susceptibility variants. By disentangling the sources of variation, we identified molecular features that could potentially be driving the heterogeneity of various clinical traits of CD patients. Further downstream analyses identified contextual hub proteins such as genes encoding barrier functions, antimicrobial peptides, chemokines, and their receptors, which are either targeted by drugs used in CD or other inflammatory diseases or are relevant to the biological functions implicated in disease pathology. These hubs could be used as cell type-specific targets to treat specific subtypes of CD patients in a more individualized approach based on the underlying biology driving their disease subtypes. Our study highlights the importance of data integration and systems approaches to investigate complex and heterogeneous diseases such as IBD.
Identifiants
pubmed: 33313682
pii: 6032729
doi: 10.1093/ibd/izaa281
pmc: PMC8128416
doi:
Substances chimiques
Antimicrobial Peptides
0
Chemokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
870-886Subventions
Organisme : European Research Council
ID : 694679
Pays : International
Informations de copyright
© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.
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