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Human stool proteome analysis from patients with biliary atresia

ABSTRACT: Stool samples from four patients with Biliary atresia (BA) and three patients with neonatal cholestasis of other etiologies (non-BA) were analyzed by overlapping DIA-MS.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Jun Fujishiro

PROVIDER: PXD022391 | JPOST Repository | Sat Nov 06 00:00:00 GMT 2021

REPOSITORIES: jPOST

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			Action	DRS
	BA-1.raw	Raw
	BA-2.raw	Raw
	BA-3.raw	Raw
	BA-4.raw	Raw
	BA-nonBA.sdia	Other

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1 - 5 of 8

Publications

Discovery of Candidate Stool Biomarker Proteins for Biliary Atresia Using Proteome Analysis by Data-Independent Acquisition Mass Spectrometry.

Watanabe Eiichiro E Kawashima Yusuke Y Suda Wataru W Kakihara Tomo T Takazawa Shinya S Nakajima Daisuke D Nakamura Ren R Nishi Akira A Suzuki Kan K Ohara Osamu O Fujishiro Jun J

Proteomes 20201127 4

Biliary atresia (BA) is a destructive inflammatory obliterative cholangiopathy of the neonate that affects various parts of the bile duct. If early diagnosis followed by Kasai portoenterostomy is not performed, progressive liver cirrhosis frequently leads to liver transplantation in the early stage of life. Therefore, prompt diagnosis is necessary for the rescue of BA patients. However, the prompt diagnosis of BA remains challenging because specific and reliable biomarkers for BA are currently u ...[more]

PMID: 33260872

Similar Datasets

Identification of stool biomarkers for biliary atresia by proteome analysis targeting host-derived proteins.

Project description:Stool samples from three patients with Biliary atresia (BA), two patients with neonatal cholestasis of other etiologies (non-BA), and four healthy infants (H) were analyzed by overlapping DIA-MS.

2020-08-22 | PXD021051 | JPOST Repository

Stool Proteome analysis of biliary atresia after Kasai portoenterostomy

Project description:Stool samples from three patients with biliary atresia after Kasai portoenterostomy (BA-KPE) and four non-BA healthy controls (non-BA) were analyzed by overlapping DIA-MS.

2023-02-02 | PXD031394 | JPOST Repository

Proteomics defines plasma biomarkers for the early diagnosis of biliary atresia

Project description:Early diagnosis of biliary atresia (BA) is crucial for improving the chances of survival and preserving the liver function of children with BA. To explore potential biomarkers for early diagnosis of BA with other non-BA jaundice cases, we performed proteomic analysis with data-independent acquisition (DIA) and parallel reaction monitoring (PRM). With this approach we were able to detect and validate differential protein expression in plasma of patients. Bioinformatics analysis revealed the enrichment biological processes, characteristic of BA by identifying differential expression of specific proteins of which with 10 were up- and 23 down-regulated. Signaling pathway analysis demonstrated changes in protein expression associated with an alteration in immunoglobins levels, which is indicative immune dysfunction in BA. When polymeric immunoglobulin receptor (pIgR) expression was combined with an immunoglobulin lambda variable chain (IGL c2225_light_IGLV1-47_IGLJ2), revealed by machine learning, they provided a useful early diagnostic model for BA, which had a sensitivity of 0.8, specificity of 1, accuracy of 0.89, and AUC value of 0.944. Our study not only identified a possible effective plasma biomarker for the early diagnosis of BA but may also help to further elucidate the underlying mechanisms of BA.

2024-06-22 | PXD048938 | Pride

Methylation microarray studies highlight PDGFA expression as a factor in biliary atresia

2015-06-18 | GSE69948 | GEO

Methylation microarray studies highlight PDGFA expression as a factor in biliary atresia

Project description:Biliary atresia (BA) is a progressive fibro-inflammatory disorder that is the leading indication for liver transplantation in children. Although there is evidence implicating genetic, infectious, environmental, and inflammatory causes, the etiology of BA remains unknown. We have recently reported that cholangiocytes from BA patients showed decreased DNA methylation relative to disease- and non-disease controls, supporting a potential role for DNA hypomethylation in BA etiopathogenesis. In the current study, we examined the methylation status of specific genes in human BA livers using methylation microarray technology. We found global DNA hypomethylation in BA samples as compared to disease- and non-disease controls at specific genetic loci. Hedgehog pathway members, SHH and GLI2, known to be upregulated in BA, were both hypomethylated, validating this approach as an investigative tool. Another region near the PDGFA locus was the most significantly hypomethylated in BA, suggesting potential aberrant expression. Validation assays confirmed increased transcriptional and protein expression of PDGFA in BA livers. We also show that PDGF-A protein is specifically localized to cholangiocytes in human liver samples. Injection of PDGF-AA protein dimer into zebrafish larvae caused biliary developmental and functional defects. In addition, activation of the Hedgehog pathway caused increased expression of PDGF-A in zebrafish larvae, providing a previously unrecognized link between PDGF and the Hedgehog pathway. DNA hypomethylation appears to be a specific factor in mediating overexpression of genes associated with BA. Our findings validate the role of Hedgehog pathway signaling and implicate PDGF as a new candidate for a role in BA pathogenesis.

2015-06-18 | E-GEOD-69948 | biostudies-arrayexpress

Single Cell Sequencing of a Novel Model of Neonatal Bile Duct Ligation in Mice Identifies Etiology-Specific Macrophage Function Compared to Murine Biliary Atresia

Project description:Background & Aims: Macrophages (MF) play a role in neonatal etiologies of obstructive cholestasis, however, the role for precise MF subsets remains poorly defined. We developed a neonatal murine model of bile duct ligation (BDL) to characterize etiology-specific differences in neonatal cholestatic MF polarization. Approach & Results: Neonatal BDL surgery was performed on female BALB/c mice at 10 days of life (DOL) with sham laparotomy as controls. Comparison was made to the Rhesus Rotavirus (RRV)-induced murine model of biliary atresia (BA). Evaluation of changes at day 7 after surgery (BDL and sham groups) and murine BA (DOL14) included laboratory data, histology (H&E, anti-CD45 and anti-CK19 staining), flow cytometry of MF subsets by MHCII and Ly6c expression, and single cell RNA-sequencing (scRNA-seq) analysis. Neonatal BDL achieved a 90% survival rate; mice had elevated bile acids, bilirubin, and alanine aminotransferase (ALT) versus controls (p < 0.05 for all). Histology demonstrated hepatocellular injury, CD45+ portal infiltrate, and CK19+ bile duct proliferation in neonatal BDL. Comparison to murine BA showed increased ALT in neonatal BDL despite no difference in histology Ishak score. Neonatal BDL had significantly lower MHCII-Ly6c+ MF versus murine BA, however, scRNA-seq identified greater etiology-specific MF heterogeneity with increased endocytosis in neonatal BDL MF versus cellular killing in murine BA MF. Conclusions: We generated an innovative murine model of neonatal obstructive cholestasis with low mortality. This model enabled comparison to murine BA to define etiology-specific cholestatic MF function. Further comparisons to human data may enable development of immune modulatory therapies to improve patient outcomes.

2023-09-06 | GSE228996 | GEO

Non-invasive urinary metabolomic profiles discriminate biliary atresia from infantile hepatitis syndrome

Project description:<div><b>INTRODUCTION:</b> Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring in the first 3 months of life. The most common causes of neonatal cholestasis are infantile hepatitis syndrome (IHS) and biliary atresia (BA). The clinical manifestations of the two diseases are too similar to distinguish them. However, early detection is very important in improving the clinical outcome of BA. Currently, a liver biopsy is the only proven and effective method used to differentially diagnose these two similar diseases in the clinic. However, this method is invasive. Therefore, sensitive and non-invasive biomarkers are needed to effectively differentiate between BA and IHS. We hypothesized that urinary metabolomics can produce unique metabolite profiles for BA and IHS.</div><div><b>OBJECTIVES:</b> The aim of this study was to characterize urinary metabolomic profiles in infants with BA and IHS, and to identify differences among infants with BA, IHS, and normal controls (NC).</div><div><b>METHODS:</b> Urine samples along with patient characteristics were obtained from 25 BA, 38 IHS, and 38 NC infants. A non-targeted gas chromatography-mass spectrometry (GC-MS) metabolomics method was used in conjunction with orthogonal partial least squares discriminant analysis (OPLS-DA) to explore the metabolomic profiles of BA, IHS, and NC infants.</div><div><b>RESULTS:</b> In total, 41 differentially expressed metabolites between BA vs. NC, IHS vs. NC, and BA vs. IHS were identified. N-acetyl-D-mannosamine and alpha-aminoadipic acid were found to be highly accurate at distinguishing between BA and IHS.</div><div><b>CONCLUSIONS:</b> BA and IHS infants have specific urinary metabolomic profiles. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be used to discriminate BA from IHS.</div>

2019-06-25 | MTBLS689 | MetaboLights

Gene expression profile of human liver MAIT cells from patients with biliary atresia

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

Biomarker for diagnosis in post-Kasai portoenterostomy of biliary atresia by shotgun proteomics analysis

Project description:Biliary atresia (BA) causes neonatal cholestasis jaundice. The primary therapeutic treatment for BA is the Kasai portoenterostomy, a surgical procedure creating a new bile duct to restore bile flow. However, current diagnostic approaches for BA are imprecise and time-consuming, making early diagnosis crucial for successful treatment outcomes. The present study was aimed to analyze proteins from peripheral blood mononuclear cells (PBMCs) obtained from children with biliary atresia compared with healthy children as potential biomarkers for diagnostic tests.

2023-10-14 | PXD043181 | JPOST Repository

Systems analysis of biliary atresia through integration of high-throughput biological data

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

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