Systems analysis of biliary atresia through integration of high-throughput biological data
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ABSTRACT:
PROVIDER: PRJNA561789 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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
2020-08-31 | GSE136270 | GEO
Project description:Background: RNASeq was performed on organoids derived from livers of normal healthy donors and patients with biliary atresia to characterize transcriptomic signatures. Methods: Organoids generated from livers of normal healthy donors and patients with biliary atresia were cultured either in expansion (undifferentiated: 3 NCOs and 11 BACOs) or differentiation medium (differentiated: 3 BACOs). Liver tissues obtained from deceased-donor subjects served as normal controls (N=3). Total RNA was isolated from organoids and liver biopsy tissue specimens. Results: Organoids from patients with biliary atresia showed abnormal cell polarity, loss of tight junctions, increased permeability and decreased expression of genes related to epidermal growth factor (EGF)- and fibroblast growth factor 2 (FGF2)-signaling. When treated with EGF+FGF2, biliary atresia organoids expressed differentiation and functional markers with restored cell polarity. Conclusion: Organoids from biliary atresia are viable and have evidence of halted epithelial development. The induction of developmental markers, improved cell‐cell junction, and decreased epithelial permeability by EGF and FGF2 identifies potential strategies to promote epithelial maturation and function.
2021-10-25 | GSE186444 | GEO
Project description:We report label-free quantification of xenobiotic metabolizing enzymes (XME), transporters, redox enzymes, proteases and nucleases in 25 human liver microsomal samples, taken from patients with biliary atresia. Nearly 3500 proteins were identified and quantified. These data can be used in physiologically based pharmacokinetic models to predict appropriate drug doses drugs used in biliary atresia patients.
2021-09-09 | PXD020974 | Pride
Project description: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.
| S-EPMC7426509 | biostudies-literature
Project description:Gene expression profile of biliary atresia at time of Kasai portoenterostomy was evaluated by comparing gene expression profile in biliary atresia and controls (choledochocyst).
2023-08-29 | GSE200517 | GEO
Project description:To investigate gene expression profile of human liver MAIT cells from patients with biliary atresia, we isolated human liver MAIT cells from liver tissues of patients with biliary atresia and from adjacent non-tumor liver tissues of hepatoblastoma patients (as control) at the time of diagnosis, and subjected for bulk RNA sequencing.
2024-05-15 | GSE217466 | GEO
Project description:Mapping Disease Pathways for Biliary Atresia
| PRJNA1032978 | ENA
Project description:Mapping Disease Pathways for Biliary Atresia
| PRJNA1032979 | ENA
Project description:We investigated bile-acid induced gene expression patterns in regulatory T-cells, and applied those gene sets to gene expression profiles of liver samples obtained from children with biliary atresia and intrahepatic cholestasis. Patient subgroups identified using the regulatory T-cell gene sets were then assessed for association with two-year outcome in patients with biliary atresia.
2022-12-20 | GSE221346 | GEO
Project description:BACKGROUND: Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis. METHODS: We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years. RESULTS: Fourteen of 47 livers displayed prominent features of inflammation (N=9) or fibrosis (N=5), with the remainder showing similar levels of both simultaneously. Differential profiling of gene expression of the 14 livers displayed a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates. The groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, while those with a fibrosis signature had decreased transplant-free survival. CONCLUSION: Molecular profiling at diagnosis of biliary atresia uncovers a signature of inflammation or fibrosis in most livers. This signature may relate to staging of disease at diagnosis and has implications to clinical outcomes. Clinical and laboratory data and liver biopies were obtained from 47 infants at diagnosis of biliary atresia and every 3-6 month intervals until 2 years of age as part of a prospective, observational study of the Biliary Atresia Research Consortium. Liver biopsies underwent histological scoring and those specimens classified as inflammation or fibrosis were used to generate a group-specific gene expression profile. The profile was used to assign a molecular stages of inflammation or fibrosis to the entire cohort. Molecular groups were tested for biological plausibility using immunostaining to quantify hepatic inflammatory cells, and quantitative PCR to reproduce the expression of gene groups and the expression of collagen genes. They were also tested for clinical relevance by testing of association with indicators of liver function, complications of disease, and clinical outcome. This dataset is part of the TransQST collection.
2010-08-31 | E-GEOD-15235 | biostudies-arrayexpress