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Blood DNA Methylation Biomarkers of Post AcuteSequelae of SARS CoV 2 Infection (PASC)

SARS CoV 2 感染后急性后遗症的血液 DNA 甲基化生物标志物 (PASC)

基本信息

批准号：
10730452
负责人：
Reid Spencer Alisch
金额：
$ 81.24万
依托单位：
ALBANY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-05 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10730452
关键词：
2019-nCoV Acute Acute respiratory failure Age Factors Blood Blood specimen COVID-19 COVID-19 impact COVID-19 patient COVID-19 severity COVID-19 survivors Cell Separation Cells Cessation of life Chemicals Classification Clinical Cognitive Critical Illness DNA DNA Maintenance DNA Methylation DNA methylation profiling DNA sequencing Data Development Dimensions Dyspnea Environmental Risk Factor Epigenetic Process Exhibits Functional disorder Future Gene Expression Gene Expression Regulation Genomics Hospitalization Hospitals Immune Individual Inflammatory Integration Host Factors Leukocytes Long COVID Lymphoid Lymphoid Cell Magnetism Measures Methylation Mission Modification Molecular Muscle Weakness Myelogenous Myeloid Cells National Heart, Lung, and Blood Institute Nature Outcome Participant Patients Pattern Phenotype Population Positioning Attribute Post-Acute Sequelae of SARS-CoV-2 Infection Predisposition Process Public Health Publishing RNA RNA Sequences Recovery Regulation Reporting Research Resolution SARS-CoV-2 infection Sampling Sensitivity and Specificity Severity of illness Sleep Disorders Subgroup Testing Time Tissues Transcript United States National Institutes of Health Untranslated RNA acute infection chromatin modification clinical phenotype disorder control epigenetic regulation genome-wide histone modification individual response infection burden inorganic phosphate instrument long-term sequelae longitudinal analysis machine learning classification methylation biomarker methylome multiple omics novel post SARS-CoV-2 infection post-COVID-19 transcriptome transcriptome sequencing whole genome

项目摘要

Project Summary: DNA 5'-C-phosphate-G-3' (CpG) methylation is a covalent epigenetic modification that regulates gene expression and is highly sensitive to age and environmental factors. Critically ill patients exhibit altered circulating blood DNA methylation profiles. We have recently reported a large scale methylome analysis of COVID-19 in association with clinical outcomes, which suggests an epigenetic regulation of genes controlling disease severity. Recent evidence indicates that many surviving COVID-19 patients develop long term dysfunctions and the NIH-NHLBI has recently launched an initiative to elucidate the nature of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). It is currently unknown if the rapid methylome regulation evoked by acute illness persist after SARS-CoV-2 resolution. Such persistence could underpin long term sequela associated with this condition. Because DNA methylation is a relatively stable DNA chemical modification that could influence long-term gene expression profiles and given that we recently found that multiple regions developed during acute illness persist differentially methylated one year after hospital discharge, we hypothesize that COVID-19 infection leads to enduring DNA methylation abnormalities that remain after resolution of acute illness in association with the post-COVID-19 clinical profile. In this application, we plan to conduct whole genome DNA methylation and RNA sequencing of circulating leucocytes to establish sub phenotypes of PASC, predict future PASC development in the acute COVID-19, and determine which circulating leucocyte lineage contributes to that enduring methylome.

项目概述：DNA 5 '-C-磷酸-G-3'（CpG）甲基化是一种共价表观遗传修饰，调节基因表达，对年龄和环境因素高度敏感。重症患者表现出改变循环血液DNA甲基化谱。我们最近报道了一个大规模的甲基化分析 COVID-19与临床结果相关，这表明基因控制的表观遗传调节疾病严重程度。最近的证据表明，许多幸存的COVID-19患者功能障碍和NIH-NHLBI最近发起了一项倡议，以阐明急性后 SARS-CoV-2感染后遗症（PASC）。目前尚不清楚，是否快速甲基化调控引起的急性疾病在SARS-CoV-2消退后持续存在。这种持续性可能会导致长期后遗症与这种情况有关。因为DNA甲基化是一种相对稳定的DNA化学修饰，可能会影响长期的基因表达谱，鉴于我们最近发现，在急性疾病期间发生的持续差异甲基化在出院后一年，我们假设COVID-19感染导致持续的DNA甲基化异常，解决与COVID-19后临床特征相关的急性疾病。在本申请中，我们计划进行循环白细胞的全基因组DNA甲基化和RNA测序，以建立亚组DNA甲基化和RNA测序。 PASC的表型，预测未来PASC在急性COVID-19中的发展，并确定白细胞谱系有助于持久的甲基化。