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.

青少年广泛使用电子烟（e-cigs）是美国和美国的一个重大公共卫生问题 迄今为止，在世界许多地区，电子烟的使用对这一弱势群体的长期健康影响很大。 电子烟蒸汽中存在的许多有毒物质和致癌物质通过表观遗传发挥其生物效应。 可能导致疾病相关基因失调的变化是关键。 健康和疾病状态下基因表达的表观遗传调节剂。 方法：研究 lncRNA 介导的基因调控及其与疾病发展的关系 青少年电子烟用户，我们将对青少年电子烟用户的细胞和组织进行RNA测序和基于网络的分析 与非用户相比，目标 1a：使用系统生物学方法，我们将检测异常的 lncRNA 和 他们的相互作用网络导致青少年电子烟使用者的基因失调。检测到的控制lncRNA。 青少年电子烟使用者的基因失调可以作为电子烟暴露和影响的新生物标志物。 1b：应用先进的预测方法，我们将确定哪些疾病与异常相关 在青少年电子烟用户中检测到的与特定相关的异常 lncRNA。 疾病可用于电子烟的风险评估 目标 2：使用计算模型，我们将找到 异常 lncRNA 与吸电子烟的强度和持续时间（即剂量）之间的关联 青少年使用的电子烟产品的特征 识别影响 lncRNA 的产品特征。 青少年电子烟使用者介导的基因失调可以告知 FDA 对烟草产品的监管，以保护 青年和促进公共卫生。 对 RFA-OD-21-004 的响应：该提案将最大限度地利用我们现有的生物样本 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 TCORS，由 FDA|CTP 赞助，这是来自代表的独特生物样本集合。 南加州的人口样本在美国没有公开的存储库提供类似的标本。 我们将生成有关青少年使用电子烟的健康风险的科学证据。 告知 FDA 对烟草产品的监管，以保护这一弱势群体并促进公众 我们将采用创新方法来解决本次 RFA 中的两个科学兴趣领域，包括 评估 (1) 接触情况；以及 (2) 青少年（他们是特殊群体）的潜在危害 通过阐明青少年使用电子烟所造成的生物学后果的分子变化， 我们将开发新的暴露和影响的生物标志物，这些生物标志物将具有重要的用途。 通过确定电子烟剂量和产品，评估该弱势群体使用电子烟的健康风险。 特征可以调节青少年电子烟使用者引起的生物效应，我们将提供急需的 数据为 FDA 对烟草产品的监管提供信息，以保护青少年和促进公众健康。