GNPS_Nobel_twin_study
Ontology highlight
ABSTRACT:
INSTRUMENT(S): maXis
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Rohit Loomba
PROVIDER: MSV000082374 | GNPS | Fri May 18 12:02:00 BST 2018
REPOSITORIES: GNPS
Similar Datasets
Project description:Liver biopsy is currently the only reliable method to establish non‐alcoholic fatty liver disease (NAFLD) severity. However, this technique is invasive and occasionally associated with severe complications. Thus, non‐invasive diagnostic markers for NAFLD are needed. Former studies have postulated 18 different serum biomarker microRNAs with altered levels in NAFLD patients. In this study, we have re‐examined the predictive value of these serum microRNAs and found that only 6 of them (miR‐34a, ‐192, ‐27b, ‐122, ‐197 and ‐30c) are validated in our independent cohort as biomarkers associated with NAFLD severity. Among them, miR‐192, ‐27b and ‐122 are abundantly expressed in liver and confidently detected in serum, and display strong correlations with transaminases. The classification performance of validated miRNAs (and their ratios) for patients with non‐alcoholic steatohepatitis (NASH) is similar to that reached by AST, whereas for advanced fibrosis prediction, the miR‐27b/‐197 ratio demonstrated a good performance and an excellent sensitivity and, along with the FIB‐4 index, may constitute a potent non‐invasive predictive tool.
2018-07-19 | GSE114923 | GEO
Project description:Background & Aims: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting non-invasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression. Methods: We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0?1 (mild) and F3?4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome. Results: Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P<.05). Methylation at FGFR2, MAT1A, and CASP1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, whereas genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and under-expressed. Conclusions: Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD. Three technical replicates were included for quality control along with 35 mild NAFLD (33 unique samples) and 24 advanced NAFLD (23 unique sample). One sample per technical duplication was randomly included for a total of 56 NAFLD samples used for study.
2013-08-30 | E-GEOD-49542 | biostudies-arrayexpress
Project description:Non-alcoholic fatty liver disease (NAFLD) is estimated to affect 25% of the world’s population and its prevalence is increasing with the rise in obesity. The evolution of this disease includes different pathological stages: steatosis, inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy stands as the gold standard for NAFLD assessment despite its invasive nature and limited performance. Liver fibrosis is the most important clinical parameter, as it is closely related to mortality, and biopsies are only considered when advanced fibrosis is suspected. This scenario makes the finding of a non-invasive and reliable biomarker an urgent need for an accurate diagnosis. To this end, we first performed a discovery study on 159 plasma samples from histologically characterised NAFLD patients using mass spectrometry (MS)-based quantitative proteomics. Insulin-like growth factor-binding protein complex acid labile (ALS, P35858) and Galectin-3-binding protein (LG3BP, Q08380) were selected for a verification by enzyme-linked immunosorbent assay (ELISA) in the same cohort and finally validated in an independent NAFLD cohort of 200 plasma samples.ALS and LG3BP were validated as advanced liver fibrosis biomarkers and successfully included in a panel with FibroTest variables. ELISA kits availability would allow to achieve relatively fast clinical translation if further investigations in larger cohorts confirm these results.
2024-05-22 | PXD043340 | Pride
Project description:Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are the hepatic manifestations of metabolic syndrome. Histological assessment of liver biopsies is the gold standard for diagnosis of NASH. A Liver biopsy is resource heavy and can lead to complications such as bleeding and, moreover, does not fully capture the tissue heterogeneity of the fibrotic liver. Therefore, non-invasive biomarkers that can reflect an integrated state of the liver is highly needed to improve diagnosis and sampling bias. Hepatic stellate cells (HSCs) are central in development of hepatic fibrosis, a hallmark of NASH. Secreted HSC-specific proteins may, therefore, reflect disease state in the NASH liver and thereby serve as non-invasive diagnostic biomarkers. We performed RNA-sequencing on liver biopsies from a discovery cohort (n = 30) of histological characterised obese patients (body mass index > 35 kg/m2) to identify and evaluate HSC-specific genes encoding secreted proteins. Bioinformatical analysis was used to identify potential biomarkers and their expression at single-cell resolution. We validated our findings by single-molecule fluorescence in situ hybridization (smFISH) and ELISA to detect mRNA in liver tissue and protein levels in plasma, respectively. Hepatic expression of SPARC-related modular calcium-binding protein 2 (SMOC2) was increased in NASH (steatosis ≥ 1, lobular inflammation ≥ 1, and hepatocyte ballooning ≥ 1) compared no-NAFLD (p.adj < 0.001). Single-cell RNA-sequencing data indicated SMOC2 expression by HSCs, which was validated using smFISH. Moreover, plasma SMOC2 was elevated in NASH compared to no-NAFLD (p < 0.001) with a predictive accuracy of AUROC 0.88. In conclusion, we propose increased SMOC2 in plasma reflects HSC activation, a key cellular event associated with NASH progression, and may serve as a non-invasive biomarker of NASH.
2022-11-02 | GSE207310 | GEO
Project description:Non-invasive prediction of NAFLD severity: a comprehensive, independent validation of previously postulate serum microRNA biomarkers
| PRJNA473134 | ENA
Project description:The availability of disease-modifying therapies and newborn screening programs for spinal muscular atrophy (SMA) has generated an urgent need to identify reliable biomarkers to monitor disease progression, therapeutic response and classify patients according to disease severity. Objectives of this study were to identify potential biomarkers for disease severity, and to describe changes in the proteomic profile after 302 days of nusinersen administration (T302). In this multicenter retrospective longitudinal study, we employed an untargeted non-targeted mass spectrometry-based proteomic approach (LC-MS) on cerebrospinal fluid (CSF) samples collected from 61 SMA patients treated with nusinersen (SMA1 n=19, SMA2 n=19, SMA3 n=23) at baseline and T302. A machine learning classifier approach (Random Forest, RF) was applied to exploit proteins able to stratify disease severity at baseline. Bioinformatics analysis was performed to investigate Gene Ontology (GO) functional annotation of differentially expressed proteins (DEPs) at T302. The RF algorithm identified CNTN1 and NRXN3 as new potential biomarkers of disease severity based on their expression at baseline. Analysis of changes in proteomic profiles identified 147 DEPs after nusinersen treatment in SMA1, 135 in SMA2, and 289 in SMA3. Overall, Nusinersen-induced changes on proteomic profile were consistent with i) common effects observed in all SMA types (i.e. regulation of axonogenesis), and ii) disease severity-specific changes, namely regulation of glucose metabolism in SMA1, of coagulation processes in SMA2, and of complement cascade in SMA3. By analyzing a large cohort of CSF samples from SMA patients, and applying cutting-edge bioinformatic analysis and artifical intelligence alghorithms, this study has identified new potential biomarkers of disease severity, and provided new insights on biological processes modulation after 302 days of nusinersen treatment.
2024-10-02 | PXD047529 | Pride
Project description:Background & Aims: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting non-invasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression. Methods: We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0?1 (mild) and F3?4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome. Results: Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P<.05). Methylation at FGFR2, MAT1A, and CASP1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, whereas genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and under-expressed. Conclusions: Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD.
2013-08-30 | GSE49542 | GEO
Project description:Background & Aims: Although non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, aspects of its molecular pathogenesis are unknown and clinical biomarkers for early diagnosis and accurate disease staging remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of NAFLD and explore the utility of novel candidate biomarkers in NAFLD patients. Methods: Liver protein fractions were analyzed in a relative quantitative proteomic approach utilizing isobaric tags for relative and absolute quantitation (iTRAQ) labeling combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential expression was confirmed independently by western blotting and immunohistochemistry, first in mouse sections and then in biopsies from paediatric NAFLD patients. Candidate serum biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling we identified decreased expression of hepatic glyoxalase 1 (GLO1) in an animal model of NAFLD. GLO1 protein levels were also found reduced in tissue biopsies from pediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid-loading in hepatocytes, GLO1 is first hyper-acetylated then ubiquitinylated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 62 biopsy-confirmed adult NAFLD patients serum levels of the primary methylglyoxal-derived advanced glycated endproduct, hydroimidazolone (MG-H1) were found strongly correlated with body mass index (r=0.619, p<0.0001). Conclusions: We characterize, for the first time, the post-translational modification and regulation of GLO1 expression in response to hepatic lipid loading with functional consequences in NAFLD patients.
2018-02-16 | PXD001442 | Pride
Project description:High-calorie diets lead hepatic steatosis and to the development of non-alcoholic fatty liver disease (NAFLD), which can evolve over many years into the inflammatory form non-alcoholic steatohepatits (NASH) posing a risk for the development of hepatocellular carcinoma (HCC). Due to the diet and the liver alteration, the axis between liver and gut is disturbed, resulting in gut microbiome alterations. Consequently, detecting these gut microbiome alterations repre-sents a promising strategy for early NASH and HCC detection. We analyzed medical parame-ters and the fecal metaproteome of 19 healthy controls, 32 NASH, and 29 HCC patients target-ing the discovery of diagnostic biomarkers. Here, NASH and HCC resulted in increased in-flammation status and shifts within the composition of the gut microbiome. Increased abun-dance of kielin/chordin, E3 ubiquitin ligase, and nucleophosmin 1 represented valuable fecal biomarkers indicating disease-related changes in the liver. Whereas a single biomarker failed to separate NASH and HCC, machine learning-based classification algorithms provided 0.86% accuracy in distinguishing between controls, NASH, and HCC. Conclusion: Fecal metaproteomics enables early detection of NASH and HCC by providing single biomarkers and ma-chine learning-based metaprotein panels.
2022-10-13 | PXD034175 | Pride
Project description:To identify urinary RNA as non-invasive biomarkers for progression of chronic kidney disease
2018-10-31 | GSE121978 | GEO