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
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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:The pathophysiological mechanisms that drive non-alcoholic fatty liver disease (NAFLD) progression remain poorly understood. This multicenter study characterized the transcriptional changes that occur as liver disease progresses. 216 snap frozen liver biopsies, comprising 206 NAFLD cases with different fibrosis stages and 10 controls were studied. Samples underwent high-throughput RNA sequencing. This study provides novel insights into transcriptional changes during liver disease evolution and progression as well as proof of principle that transcriptomic changes reveal potentially tractable biomarkers for NAFLD fibrosis.
2020-12-03 | GSE135251 | 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: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:The objective of this study was to identify gene expression markers of disease severity in a cohort of RSV infected children Respiratory syncytial virus (RSV) is the number one pathogen causing lower respiratory tract infection that leads to hospitalization in young children. Despite growing insights in the disease pathogenesis, the clinical presentation in these children is highly variable and heterogeneous, and reliable markers predictive of disease progression are lacking. We characterized the host response to acute RSV infection to identify biomarkers associated with RSV disease and disease severity. Whole genome transcriptome was analysed early on the disease course in blood samples from otherwise healthy children <2 years of age, who were either hospitalized (n = 110) or evaluated as outpatients (n = 37) due to RSV infection. Age-matched non-RSV-infected healthy children (n = 51) were analysed in parallel. A clustering approach on the transcriptome data revealed biologically meaningful biomarkers associated with progression to severe RSV disease. Overall, the whole blood transcriptome pointed to alterations in frequency of specific immune cell types (neutrophils, T- and B-lymphocytes, NK cells, monocytes) in RSV-infected children. In addition, a cluster enriched for neutrophil degranulation genes, was highly correlated with clinical disease severity. The driver genes of this cluster (OLFM4, ELANE, MMP8, BPI, CEACAM8, LCN2, LTF and MPO) were selected and validated in independent existing transcriptomics datasets. We identified a set of genes involved in neutrophil degranulation as markers for RSV disease severity. Additional prospective studies using these markers are required to further confirm their value as predictive tool in routine clinical care.
2022-01-21 | GSE188427 | GEO
Project description:Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Yet clinically, distinguishing between NAFLD patients with average CV risk from those at elevated risk is not easily achieved by traditional CV risk factors and clinically-based scoring systems. Here we hypothesize that in-depth analysis of circulating miRNAs can identify strong putative biomarkers for the degree of CV risk among patients with NAFLD
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Project description:Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with NAFLD and its progression. Microarrays were used to identify hepatic gene expression changes in each of these models. The goal is to identify a predictor of different NAFLD progressions. Non-alcoholic fatty liver disease (NAFLD) is recognized as a low-grade systemic inflammatory state with both hepatic and extra-hepatic manifestations. We aimed to identify common key regulators and adaptive pathways in different NAFLD phenotypes. NAFL, NASH and NAFL+T2DM rat models were used to represent simple fatty liver, fatty liver with severe hepatic manifestations, and fatty liver with severe metabolic manifestations, respectively. We applied microarray analysis to characterize the key regulators and adaptive pathways in different NAFLD phenotypes. There are 12 samples in our study which belonged to 4 groups, and each group contains 3 different samples.
2015-01-23 | E-GEOD-65220 | biostudies-arrayexpress
Project description:Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading cause of chronic liver disease in the United States and developed countries. In humans, genetic factors greatly influence individual susceptibility to NAFLD. The goals of this study were to compare the magnitude of interindividual differences in the severity of liver injury induced by methyl-donor deficiency among individual inbred strains of mice and to investigate the underlying mechanisms associated with the variability. Feeding mice a choline- and folate-deficient diet for 12 wk caused liver injury similar to NAFLD. The magnitude of liver injury varied among the strains, with the order of sensitivity being A/J M-bM-^IM-^H C57BL/6J M-bM-^IM-^H C3H/HeJ < 129S1/SvImJ M-bM-^IM-^H CAST/EiJ < PWK/PhJ < WSB/EiJ. The interstrain variability in severity of NAFLD liver damage was associated with dysregulation of genes involved in lipid metabolism, primarily with a down-regulation of the peroxisome proliferator receptor M-NM-1 (PPARM-NM-1)-regulated lipid catabolic pathway genes. Markers of oxidative stress and oxidative stress-induced DNA damage were also elevated in the livers but were not correlated with severity of liver damage. These findings suggest that the PPARM-NM-1-regulated metabolism network is one of the key mechanisms determining interstrain susceptibility and severity of NAFLD in mice. Male A/J, C3H/HeJ and WSB/EiJ inbred mice were maintained on either control or choline- and folate-deficient (CFD) diets for 12 weeks. Gene expression profiles in the livers from control mice and mice fed a CFD-diet were investigated.
2014-10-16 | E-GEOD-62362 | biostudies-arrayexpress