A Saliva Based Epigenetic Assay for Assessing Vitamin B9 and B12 Status

用于评估维生素 B9 和 B12 状态的基于唾液的表观遗传测定

• 批准号: 10541702
• 负责人: Robert A Philibert
• 金额: $ 28.14万
• 依托单位: BEHAVIORAL DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10541702
• 关键词: Acute; African American; African American population; Aging; Athletic; Behavioral; Biocompatible Materials; Biological Assay; Biometry; Blood; Chronic; Chronic Disease; Clinical; Complex; Coronary heart disease; DNA; Data; Dementia; Detection; Diabetes Mellitus; Diagnostic; Diet; Dietary intake; Digestive System Disorders; Disease; Epigenetic Process; Ethnic Origin; Folic Acid; Future; Genes; Genetic; Genetic Variation; Genomics; Genotype; Grant; Health; Healthcare; Heart Diseases; Home; Human Development; Individual; Intake; Intervention; Lead; Legal patent; Lipids; Machine Learning; Malignant Neoplasms; Medical; Metabolism; Methods; Methylation; Micronutrients; Modeling; Monitor; Nicotinamide adenine dinucleotide; Nutraceutical; Nutrient; Nutritional; Nutritional status; Outcome; Painless; Patients; Performance; Population; Population Heterogeneity; Premature aging syndrome; Preventive; Research Personnel; Risk; Risk Factors; Saliva; Serology; Serology test; Serum; Surveys; Techniques; Technology; Telemedicine; Testing; Thiamine; Translating; United States Department of Agriculture; United States National Institutes of Health; Vision; Vitamin A; Vitamins; Whole Blood; Work; base; biosignature; chemotherapy; clinically relevant; cohort; dietary; dietary supplements; digital; effectiveness testing; epigenetic marker; genome-wide; healing; healthy aging; improved; individualized prevention; innovation; machine learning model; methylation biomarker; methylomics; modifiable risk; novel; nutrition; nutritional genomics; nutritional supplementation; personalized approach; personalized intervention; personalized medicine; precision nutrition; predictive marker; response; saliva diagnostic

Gene-diet interactions can have major effects on human development, aging and response to medical therapy. In particular, this is true for key nutrients such as Vitamin A, D, B9 and B12. Unfortunately, the current “one size fits all” approaches for determining whether an individual has adequate levels of these and other micronutrients relies on older studies that use serum assays that only capture recent intake that do not capture the health care challenges incurred by our now aging, more diverse population We believe that integrated genetic-epigenetic assessments of saliva DNA can better capture cellular micronutrient status and serve as a cornerstone of future Precision NutriEpigenomic therapies. Our method, which does not require drawing blood, will be robust against day-to-day dietary intake fluctuations and can be conducted using remote, telemedicine type approaches. This more functionally oriented method could find widespread use in a variety of both medical and non-medical nutraceutical settings in optimizing athletic performance, facilitating healthy aging and monitoring nutritional supplemental of both chronic (e.g., digestive disease) and acute (e.g., chemotherapy) patients. For example, the method is generalized for the assessments targeting the use of common supplements such as Nicotinamide Adenine Dinucleotide (NAD+). We hypothesize that integrated genetic-epigenetic signatures of saliva DNA will robustly predict serum B9 and B12 levels. To test that hypothesis, we will use data from a cohort of 450 African Americans for whom we already have serum, genome wide genetic, and genome wide epigenetic data from whole blood DNA. We will use machine learning to first mine the most predictive biosignature for serum B9 and B12 levels. Next, using our patent-pending, proprietary techniques, we will translate that whole blood (WB) DNA based signature into a saliva-based signature. Then, we will transform the test into an easy to perform set of methylation sensitive digital PCR assays. If successful, the project will have high impact because it could lead to painless, at-home nutraceutical testing. It is significant because certain nutrients are thought to be protective against cancer or premature aging. Our plan is highly feasible because the large body of prior work, abundant biomaterials, and our expertise in both epigenetics and machine learning. It is innovative because saliva diagnostics have not yet been introduced to the nutraceutical market. The BD team is well qualified. The project will led by Dr. Rob Philibert, an expert in epigenetic diagnostics. He will be assisted by a team of co-investigators that includes experts in nutrition (Dr. Ruth Grossman) and biostatistics (Dr. Jeff Long). If successful, this R43 will serve as the basis for an R44 that develop a battery of saliva based nutritional assays.

基因-饮食相互作用对人类发育、衰老和对药物的反应有重大影响。 疗法特别是对于维生素A，D，B 9和B12等关键营养素来说，情况尤其如此。可惜现在的 “一刀切”的方法来确定一个人是否有足够的水平，这些和其他 微量营养素依赖于较早的研究，这些研究使用血清测定法，仅捕获最近的摄入量， 我们现在老龄化，更多样化的人口所带来的医疗保健挑战 我们相信，唾液DNA的综合遗传-表观遗传评估可以更好地捕获细胞内的 微量营养素的状态，并作为未来精确营养表观基因组疗法的基石。我们的方法， 不需要抽血，对日常饮食摄入量的波动具有鲁棒性， 使用远程、远程医疗类型的方法进行。这种更注重功能的方法可以找到 广泛用于各种医疗和非医疗营养品环境中，以优化运动 性能，促进健康老龄化和监测慢性（例如，消化 疾病）和急性（例如，化疗）患者。例如，该方法被推广用于评估 目标是使用常见的补充剂，如烟酰胺腺嘌呤二核苷酸（NAD+）。 我们假设唾液DNA的综合遗传-表观遗传特征将有力地预测血清B 9 B12水平。为了验证这一假设，我们将使用450名非裔美国人的数据， 已经有血清、全基因组遗传和来自全血DNA的全基因组表观遗传数据。我们将 使用机器学习首先挖掘血清B 9和B12水平的最具预测性的生物特征。接下来，使用我们的 正在申请专利的专有技术，我们将把基于全血（WB）DNA的签名翻译成 基于唾液的签名。然后，我们将把测试转化为一个易于执行的甲基化敏感的 数字PCR分析。 如果成功，该项目将产生很大的影响，因为它可能导致无痛，在家里的营养品 试验.这是重要的，因为某些营养素被认为是预防癌症或早产儿 衰老我们的计划是高度可行的，因为大量的前期工作，丰富的生物材料，以及我们的 表观遗传学和机器学习方面的专业知识。它是创新的，因为唾液诊断还没有 被引入营养品市场。BD团队是合格的。该项目将由罗布博士领导 Philibert是表观遗传学诊断专家。他将得到一个合作调查小组的协助， 营养学专家（Ruth Grossman博士）和生物统计学专家（Jeff Long博士）。如果成功，这台R43将作为 这是R44的基础，它开发了一系列基于唾液的营养测定。