Systems Analysis of Biliary Atresia Through Integration of High-Throughput Biological Data.
biliary atresia
integrative method
network reconstruction
omics analysis
systems biology
Journal
Frontiers in physiology
ISSN: 1664-042X
Titre abrégé: Front Physiol
Pays: Switzerland
ID NLM: 101549006
Informations de publication
Date de publication:
2020
2020
Historique:
received:
02
03
2020
accepted:
15
07
2020
entrez:
28
8
2020
pubmed:
28
8
2020
medline:
28
8
2020
Statut:
epublish
Résumé
Biliary atresia (BA), blockage of the proper bile flow due to loss of extrahepatic bile ducts, is a rare, complex disease of the liver and the bile ducts with unknown etiology. Despite ongoing investigations to understand its complex pathogenesis, BA remains the most common cause of liver failure requiring liver transplantation in children. To elucidate underlying mechanisms, we analyzed the different types of high-throughput genomic and transcriptomic data collected from the blood and liver tissue samples of children suffering from BA. Through use of a novel integrative approach, we identified potential biomarkers and over-represented biological functions and pathways to derive a comprehensive network showing the dysfunctional mechanisms associated with BA. One of the pathways highlighted in the integrative network was hypoxia signaling. Perturbation with hypoxia inducible factor activator, dimethyloxalylglycine, induced the biliary defects of BA in a zebrafish model, serving as a validation for our studies. Our approach enables a systems-level understanding of human BA biology that is highlighted by the interaction between key biological functions such as fibrosis, inflammation, immunity, hypoxia, and development.
Identifiants
pubmed: 32848883
doi: 10.3389/fphys.2020.00966
pmc: PMC7426509
doi:
Types de publication
Journal Article
Langues
eng
Pagination
966Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK109365
Pays : United States
Informations de copyright
Copyright © 2020 Min, Ningappa, So, Shin, Sindhi and Subramaniam.
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