Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Integrated ordination of miRNA and mRNA expression profiles [mRNA]

ABSTRACT: Several studies have shown that negative and positive miRNA-mRNA correlations are symmetrically distributed. While negative correlations are consistent with a faster degradation of miRNA targets, the presence of positive correlations suggests bidirectional interactions between the two classes of molecules. However, a comprehensive study of miRNA and mRNA correlations is lacking. A homogeneous map of miRNA and mRNA relationships was obtained by multidimensional scaling (MDS) applied to a single matrix including both heterologous (miRNA-mRNA) and homologous (miRNA-miRNA and mRNA-mRNA) correlations. Liver samples were obtained from 4 patients with HBV-associated acute liver failure (ALF), 10 liver donors and 7 subjects who underwent hepatic resection for liver angioma. This dataset is part of the TransQST collection.

ORGANISM(S): Homo sapiens

SUBMITTER: Giacomo Diaz

PROVIDER: E-GEOD-62029 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Integrated ordination of miRNA and mRNA expression profiles.

Diaz Giacomo G Zamboni Fausto F Tice Ashley A Farci Patrizia P

BMC genomics 20151012

<h4>Background</h4>Several studies have investigated miRNA and mRNA co-expression to identify regulatory networks at the transcriptional level. A typical finding of these studies is the presence of both negative and positive miRNA-mRNA correlations. Negative correlations are consistent with the expected, faster degradation of target mRNAs, whereas positive correlations denote the existence of feed-forward regulations mediated by transcription factors. Both mechanisms have been characterized at t ...[more]

PMID: 26459852

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Project description:Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms whereby HBV induces ALF are unknown. We used gene expression profiling to establish a molecular definition of hepatitis B virus (HBV)-associated ALF. Two patients who underwent liver transplantation for HBV-associated ALF were studied. Gene expression profiling was performed on 8 liver specimens obtained from the two patients with ALF (4 samples per liver) and individual liver specimens from 8 liver donors and normal livers from 11 patients who underwent resection for angioma. Statistical analyses were used to identify the signature genes of HBV-associated ALF. Multivariate permutation analysis identified 1,368 transcripts that were differentially expressed in ALF; 709 were up-regulated and 659 down-regulated. The most represented up-regulated transcripts were those involved in the immune response, whereas the most abundant down-regulated transcripts were those involved in metabolism and hepatic synthesis. ALF was characterized by overriding B-cell signature comprising genes related to mature B cells and plasma cells with abundant polyclonal expression of immunoglobulin genes. By contrast, there was a limited T-cell signature and up-regulation of several inhibitors of T-cell activation. Immunohistochemical analysis confirmed the prominent B-cell signature showing diffuse liver infiltration by plasma blasts and plasma cells with strong cytoplasmic staining for IgM and IgG, associated with a significant deposition of complement factors. Using phage display technology, we demonstrated that the molecular target of the massive intrahepatic antibody response is the hepatitis B core antigen (HBcAg). These data suggest that the humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF. Liver samples were obtained from explanted livers of two patients with HBV-associated ALF (4 samples per liver), 8 normal liver donors and 11 patients who underwent resection for angioma. Gene expression profiling was used to establish a molecular definition of ALF. Patient data derived from associated publication Table S2. This dataset is part of the TransQST collection.

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Project description:Background: microRNAs (miRNAs) are approximately 21 nucleotide non-coding transcripts capable of regulating gene expression. The most widely studied mechanism of regulation involves binding of the miRNA to a target mRNA, usually in its 3’ untranslated region (UTR). As a result, translation of the target mRNA is inhibited and sometimes the mRNA itself can be de-stabilized. The inhibitory effects of miRNAs have been linked to many diverse cellular processes including malignant proliferation and apoptosis, development and differentiation, metabolic processes and neural plasticity. We asked whether endogenous fluctuations in a set of mRNA and miRNA profiles contain correlated changes that are statistically distinguishable from the many other fluctuations in the data set. Methodology/Principal Findings: Biopsies from 12 human primary brain tumors were used to extract RNA. These samples were used to determine genome-wide mRNA expression levels by microarray analysis and a miRNA profile by real-time reverse transcription PCR (RT-PCR). Correlation coefficients were determined for all possible mRNA-miRNA pairs and the distribution of these correlations compared to the random distribution. An excess of high positive and negative correlation pairs were observed at the tails of these distributions. Most of these highest correlation pairs do not contain sufficiently complementary sequences to predict a target relationship; nor do they lie in physical proximity to each other. However, by examining pairs in which the significance of the correlation coefficients is modestly relaxed, negative correlations do tend to predict targets and positive correlations do tend to predict physically proximate pairs. A subset of high correlation pairs were experimentally validated by over-expressing or suppressing a miRNA and measuring the correlated mRNAs. Conclusions/Significance: Sufficient information exists within a set of tumor samples to detect endogenous correlations between miRNA and mRNA levels. Based on the validations of the correlations the causal arrow for these correlations is likely to be directed from the miRNAs to the mRNAs. From these data sets, we inferred and validated a tumor suppression pathway linked to miR-181c. Keywords: cell type comparison

Dataset Information

Integrated ordination of miRNA and mRNA expression profiles [mRNA]

Publications

Integrated ordination of miRNA and mRNA expression profiles.

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