Network-based analysis of disease-associated epigenetic changes in youth electronic cigarette users

基于网络的青少年电子烟使用者疾病相关表观遗传变化分析

• 批准号: 10680306
• 负责人: AHMAD BESARATINIA
• 金额: $ 24.84万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680306
• 关键词: Address; Algorithms; Area; Biochemical; Biological; Biological Markers; Biological Specimen Banks; California; Carcinogens; Cells; Characteristics; Collaborations; Collection; Computer Models; Data; Data Set; Development; Devices; Diet; Disease; Dose; Electronic cigarette; Epidemic; Epigenetic Process; Funding; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Generations; Genes; Genetic Transcription; Health; Laboratories; Leukocytes; Life Style; Link; Marketing; Measurement; Measures; Mediating; Methods; Modeling; Molecular; National Institute of Dental and Craniofacial Research; Network-based; Nicotine; Oral; Pathway Analysis; Population; Process; Public Health; Regulation; Regulator Genes; Risk; Risk Assessment; Sampling; Smoking Status; Source; Special Population; Specimen; Study Subject; Systems Biology; Tissue-Specific Gene Expression; Tissues; Untranslated RNA; Vulnerable Populations; Walking; Youth; demographics; disorder risk; e-cigarette aerosols; electronic cigarette use; electronic cigarette user; electronic liquid; health assessment; innovation; interest; manufacture; novel marker; peripheral blood; preservation; public health relevance; public repository; recruit; tobacco products; tobacco regulation; toxicant; transcriptome sequencing; vaper; vaping

The widespread use of electronic cigarettes (e-cigs) by youth is a significant public health problem in the US and many parts of the world. To date, the long-term health effects of e-cig use in this vulnerable population are largely unknown. Many toxicants and carcinogens present in e-cig vapor exert their biological effects through epigenetic changes that can cause dysregulation of disease-related genes. Long non-coding RNAs (lncRNAs) are key epigenetic regulators of gene expression in health and disease states. Approach: To investigate lncRNA-mediated gene regulation and its association with disease development in youth vapers, we will perform RNA-seq and network-based analyses on cells and tissues of youth e-cig users as compared to non-users. Aim 1a: Using a systems biology approach, we will detect aberrant lncRNAs and their interaction networks that drive gene dysregulation in youth e-cig users. The detected lncRNAs that govern gene dysregulation in youth e-cig users can serve as novel biomarkers of exposure and effects for vaping. Aim 1b: Applying advanced prediction methods, we will identify which diseases are associated with the aberrant lncRNAs detected in youth e-cig users. Aberrant lncRNAs in youth e-cig users that are associated with specific diseases can be used for risk assessment of vaping. Aim 2: Using computational modeling, we will find the associations between aberrant lncRNAs and the intensity and duration of vaping (i.e., dose) and the characteristics of vaping products used by youth. Identifying product characteristics that influence the lncRNA- mediated gene dysregulation in youth e-cig users can inform the FDA’s regulation of tobacco products to protect youth and promote public health. Responsiveness to RFA-OD-21-004: This proposal will maximize the use of existing biospecimens from our recently completed NIDCR-funded project whose study subjects were recruited through collaboration with USC- TCORS, which is sponsored by the FDA|CTP. This is a unique collection of biospecimens from a representative sample of population in Southern California. No publicly available repository in the US offers similar specimens needed for this proposal. We will generate scientific evidence on the health risks of e-cig use in youth, thus informing the FDA’s regulation of tobacco products to protect this vulnerable population and promote public health. We will use an innovative approach to address two scientific interest areas in this RFA, including assessment of (1) exposure; and (2) potential harm from vaping in youth, who are a population of special relevance. By elucidating the molecular changes that underlie the biological consequences of e-cig use in youth, we will develop novel biomarkers of exposure and effects. These biomarkers will have significant utility for assessing the health risks of e-cig use in this vulnerable population. By determining how vaping dose and product characteristics can modulate the induced biological effects in youth e-cig users, we will provide urgently needed data to inform the FDA’s regulation of tobacco products to protect youth and promote public health.

青年对电子烟（电子烟）的广泛使用是美国的一个重大公共卫生问题， 世界许多地方。迄今 未知。 E-CIG蒸气中存在的许多毒物和致癌物通过表观遗传学作用 可能导致疾病相关基因失调的变化。长非编码RNA（lncrNA）是关键 健康和疾病状态中基因表达的表观遗传调节剂。 方法：研究lncRNA介导的基因调节及其与疾病发展的关联 青年Vapers，我们将对青年电子烟使用者的细胞和组织进行RNA-Seq和基于网络的分析 与非用户相比。 AIM 1A：使用系统生物学方法，我们将检测到异常的lncrnas和 他们的相互作用网络会驱动青年电子烟使用者中基因失调的基因失调。统治的检测到的lncrnas 青年电子烟使用者中的基因失调可以作为暴露和vaping影响的新型生物标志物。目的 1B：应用高级预测方法，我们将确定哪些疾病与异常相关 在青年电子烟的使用者中检测到的lncRNA。与特定相关的青年电子烟使用者中的异常lncrnas 疾病可用于风险评估vaping。目标2：使用计算建模，我们将找到 异常的lncrNA与烟的强度和持续时间之间的关联（即剂量）和 青年使用的烟产品的特征。识别影响lncRNA-的产品特性 青年电子烟使用者中介导的基因失调可以告知FDA对烟草产品的监管以保护 青年并促进公共卫生。 对RFA-OD-21-004的响应能力：该提案将最大程度地利用我们的现有生物测量。 最近完成了NIDCR资助的项目，其研究对象是通过与USC-合作招募的 TCOR，由FDA | CTP赞助。这是代表的独特生物测量集 南加州人口样本。美国没有公开可用的存储库提供类似的标本 该提议需要。我们将获得有关年轻人使用电子烟的健康风险的科学证据，因此 告知FDA对烟草产品的监管，以保护这一脆弱人群并促进公众 健康。我们将使用一种创新的方法来解决此RFA的两个科学兴趣领域，包括 评估（1）暴露； （2）青年人的烟雾可能受到的潜在伤害，这是一个特殊人群 关联。通过阐明年轻人使用电子烟的生物学后果的分子变化， 我们将开发出新颖的暴露和影响生物标志物。这些生物标志物将具有重要的实用性 评估在这一脆弱人群中使用电子烟的健康风险。通过确定烟剂量和产品如何 特征可以调节青年电子烟使用者的诱导生物学效应，我们将急需提供 数据以告知FDA对烟草产品的监管，以保护青年并促进公共卫生。