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A blood-based multi-omic landscape for the molecular characterization of Kidney Stone Disease

ABSTRACT: We adopted high-throughput sequencing and mass spectrometry (MS) techniques in this study and carried out an integrative analysis of exosome proteome and DNA methylation data from blood samples of normal and Kidney stone disease patients to screen biomarkers.

ORGANISM(S): Homo Sapiens

SUBMITTER: Rui Wang

PROVIDER: PXD044503 | iProX | Thu Aug 10 00:00:00 BST 2023

REPOSITORIES: iProX

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A Blood-based Multi-omic Landscape for the molecular characterization of Kidney Stone Disease

Project description:Kidney stone disease (KSD, also named renal calculi, nephrolithiasis, or urolithiasis) is a common urological disease entailing the formation of minerals and salts that form inside the urinary tract, frequently caused by diabetes and high blood pressure, hypertension, and monogenetic components in most patients. 10% of adults worldwide are affected by KSD, which incidence continues to be highly prevalent and increasing. For the identification of novel therapeutic targets in KSD to deal with this situation, we adopted high-throughput sequencing and mass spectrometry (MS) techniques in this study and carried out an integrative analysis of exosome proteome and DNA methylation data from blood samples of normal and KSD patients. Our study described the profiling of serum exosome and DNA methylation in blood from both normal individuals and those with Kidney Stone Disease (KSD), finding the overexpressed proteins and the demethylated DNA genes in KSD samples are related to immune reactions. The consistency of the results in proteomics and epigenetics supports the feasibility of the comprehensive strategy. Our understanding of the molecular landscape of KSD provides an opportunity for more information on the pathogenic mechanism, precise diagnosis, and treatment for KSD.

2024-01-01 | GSE240640 | GEO

Multi-omic brain and behavioral correlates of cell-free fetal DNA methylation in macaque maternal obesity models

Project description:Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. We conclude that in this model, maternal obesity was associated with changes in the infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic factors.

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Highly sensitive MLH1 methylation analysis in blood allows the identification of low-level epigenetic mosaicism

Project description:Constitutional MLH1 epimutations are a rare cause of Lynch syndrome. Low methylation levels (≤10%) have been occasionally described. The aim of this study was the identification of patients with low levels of epigenetic mosaicism in MLH1 gene. Eighteen patients with MLH1 hypermethylated tumors and undetectable methylation in blood as assessed by Methylation-Specific Multiplex Ligation-Dependent Probe Amplification were included (MS-MLPA). Highly sensitive MS-Melting Curve Analysis (MS-MCA) at MLH1 promoter was used to screen for epigenetic mosaicism. Constitutional methylation was confirmed by other methods. Mutational analysis of hereditary cancer genes including MLH1 was performed. MS-MCA analysis identified one case (5.6%) with low levels of methylation (1-2%) in blood DNA. The patient had developed 3 gastrointestinal tumors at ages 22, 24 and 25, sharing MLH1 promoter hypermethylation and loss of heterozygosity associated with c.655A allele. The presence of low MLH1 methylation levels was confirmed by clonal bisulfite sequencing, evidencing the association with c.-93G allele (in phase with c.655G). The extension of the hypermethylated region overlaps with the reported in constitutional MLH1 epimutation carriers. No rare germline variants were identified. The use of highly sensitive techniques such as MS-MCA has demonstrated to be useful for the detection of low MLH1 methylation levels in blood.

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Amplicon-based bisulfite sequencing of promoter regions for selected tumour supressor genes in DNA from white blood cells.

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2022-07-07 | GSE201688 | GEO

Multi-omic landscape of rheumatoid arthritis: re-evaluation of drug adverse effects.

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An integrative analysis of the age-associated multi-omic landscape across cancers.

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TMT proteomic analysis of thyroid cancer tissue sample

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2021-12-14 | PXD027538 | Pride

Revealing the transitory and local effect of the demethylation agent zebularine on plant development and proteome dynamics of Salix purpurea

Project description:DNA methylation plays major roles in the epigenetic regulation of gene expression, transposon and transcriptional silencing, and DNA repair, with implications in developmental processes and phenotypic plasticity. Relevantly for arboreal species, DNA methylation constitute a regulative layer in cell wall dynamics associated with xylogenesis. The use of methyltransferase and/or demethylase inhibitors has been proven informative to shed light on the methylome dynamics behind the regulation of these processes. The present work employs the cytidine analog zebularine to inhibit DNA methyltransferases and induce DNA hypomethylation in Salix purpurea plantlets grown in vitro and in soil. An integrative approach has been adopted to highlight the effects of hypomethylation on proteomic dynamics, exposing the age-specific (three weeks of in vitro culture and one month of growth in soil) and tissue-specific (shoot and root) effects following exposure to zebularine. Significant proteomic shifts were revealed in the development from in vitro to in-soil culture and, whereas zebularine treatment decreased methylation in three-weeks roots, a functionally heterogeneous subset of protein entries was differentially accumulated in shoot samples, including entries associated with cell wall dynamics, tissue morphogenesis, and hormonal regulation. The identification of tissue-specific proteomic hallmarks in combination with hypomethylating agents provides new insights into the role of DNA methylation in early plant development in willow species.

2024-01-08 | PXD045653 | Pride

DNA methylation landscape of ocular tissue relative to matched peripheral blood

Project description:The principal aim of this work was to investigate the methylation profiles of specific ocular tissues, and compare this profile to matched peripheral blood. Matched human blood and eye tissue were obtained post-mortem (n=8) and DNA methylation profiling performed on blood, neurosensory retina, retinal pigment epithelium (RPE)/choroid and optic nerve tissue using the Illumina Infinium HumanMethylation450 platform.

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Altered Biogenesis and MicroRNA Content of Hippocampal Exosomes Following Experimental Status Epilepticus

Project description:Here, we characterised the effects of experimental status epilepticus on the expression of exosome biosynthesis components and analysed microRNA content in exosome-enriched fractions prepared from the mouse hippocampus. Status epilepticus induced by unilateral intra-amygdala kainic acid resulted in acute subfield-specific, bi-directional changes in transcripts associated with exosome biosynthesis including up-regulation of ESCRT–dependent and –independent pathways. Increased expression of exosome components including Alix were detectable in samples obtained two weeks after status epilepticus and changes occurred in both the ipsilateral and contralateral hippocampus. Small RNAseq analysis of exosome-enriched fractions prepared using two different techniques detected a rich diversity of conserved microRNAs and determined status epilepticus selectively alters microRNA contents, including upregulation of the glia-enriched miR-21a-3p. We also characterized editing sites of the exosome-enriched miRNAs and found six exosome-enriched miRNAs that were Adenosine-to-Inosine (ADAR) edited with the majority of the editing events predicted to occur within miRNA seed regions. However, the prevalence of these editing events was not altered by status epilepticus. These studies demonstrate status epilepticus alters the exosome pathway and its microRNA content, but not editing patterns.

2019-12-12 | GSE136695 | GEO

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