Data of methylome and transcriptome derived from human dilated cardiomyopathy

AbstractAlterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM). Differentially methylated probes (DMPs) and differentially expressed genes (DEGs) were identified between the left ventricle (LV, a pathological locus for DCM) and the right ventricle (RV, a proxy for normal hearts). The data in this DiB are for supporting our report entitled “Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy” (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016) [1]

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Initiation Timing of Continuous Interscalene Brachial Plexus Blocks in Patients Undergoing Shoulder Arthroplasty: A Retrospective Before-and-After Study

A continuous interscalene brachial plexus block (CIBPB) is usually administered before surgery in awake patients. However, the use of CIBPB before surgery could hinder the identification of nerve injuries after total shoulder arthroplasty (TSA). This study aimed to compare the analgesic effects of preoperatively and postoperatively initiated CIBPBs in patients undergoing TSA. The medical records of patients who underwent TSA between January 2016 and August 2020 were retrospectively reviewed. The following analgesic phases were used: intravenous (IV) patient-controlled analgesia (PCA) phase (IV PCA group, n = 40), preoperative block phase (PreBlock group, n = 44), and postoperative block phase (PostBlock group, n = 33). The postoperative initiation of CIBPB after a neurologic exam provided better analgesia than IV PCA and had no differences with the preoperative initiation of CIBPB, except for the worst pain at the postanesthetic care unit. Opioid consumption was significantly greater in the IV PCA group, but there were no differences between the PreBlock and PostBlock groups on operation day after the transfer to the general ward. The initiation of CIBPB after a patient’s emergence from general anesthesia had comparable analgesic efficacy with preoperative CIBPB but offered the chance of a postoperative neurologic exam

Canonical pathways enriched in the T2D and ΔhiGlu60 subgroups by Ingenuity Pathway Analysis (IPA).

<p>The bar graphs showed 39 pathways in the T2D and 26 pathways in the ΔhiGlu60 subgroups with the enriched percentage and p values. The percentages indicate the number of differentially methylated genes that map to each pathway divided by the total number of genes that map to the canonical pathway. The total number of gene was indicated at the top of bar. The p value (–log10 <i>P</i>) is the probability that each biological function assigned to that data set was assigned by chance.</p

Correlations of the degree of DNA methylation of <i>MSI2</i> (chr17:55484635) with six related traits.

<p>Correlations between DNA methylation at cg23586172 and Glu0 (A), HbA1c (B), BMI (C), Ins0 (D), HOMA-IR (E) and <i>QUICKI</i> (F) were present in the T2D group (n = 440). Glu0, fasting blood glucose level; HbA1, glycosylated hemoglobin level; BMI, body mass index; and Ins0, fasting blood insulin level. HOMA-IR, Ins0(μU/mL) × Glu0 (mg/mL)/405): <i>QUICKI</i>, 1 / (log(Ins0 μU/mL) + log(Glu0 mg/dL).</p

Differential DNA methylation of <i>MSI2</i> and its correlation with diabetic traits

<div><p>Differential DNA methylation with hyperglycemia is significantly associated with Type 2 Diabetes (T2D). Longtime extended exposure to high blood glucose levels can affect the epigenetic signatures in all organs. However, the relevance of the differential DNA methylation changes with hyperglycemia in blood with pancreatic islets remains unclear. We investigated differential DNA methylation in relation to glucose homeostasis based on the Oral Glucose Tolerance Test (OGTT) in a population-based cohort. We found a total of 382 differential methylation sites from blood DNA in hyperglycemia and type 2 diabetes subgroups using a longitudinal and cross-sectional approach. Among them, three CpG sites were overlapped; they were mapped to the <i>MSI2</i> and <i>CXXC4</i> genes. In a DNA methylation replication study done by pyrosequencing (n = 440), the CpG site of <i>MSI2</i> were shown to have strong associations with the T2D group (p value = 2.20E-16). The differential methylation of <i>MSI2</i> at chr17:55484635 was associated with diabetes-related traits, in particular with insulin sensitivity (<i>QUICKI</i>, p value = 2.20E-16) and resistance (HOMA-IR, p value = 1.177E-07). In human pancreatic islets, at the single-base resolution (using whole-genome bisulfite sequencing), the 292 CpG sites in the ±5kb at chr17:55484635 were found to be significantly hypo-methylated in donors with T2D (average decrease = 13.91%, 95% confidence interval (CI) = 4.18~ 17.06) as compared to controls, and methylation patterns differed by sex (-9.57%, CI = -16.76~ -6.89) and age (0.12%, CI = -11.17~ 3.77). Differential methylation of the <i>MSI2</i> gene (chr17:55484635) in blood and islet cells is strongly related to hyperglycemia. Our findings suggest that epigenetic perturbation on the target site of <i>MSI2</i> gene in circulating blood and pancreatic islets should represent or affect hyperglycemia.</p></div

Linear regression of target CpG methylations with six diabetes-related traits.

<p>Linear regression of target CpG methylations with six diabetes-related traits.</p