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

基因-饮食相互作用可能对人类发育、衰老和对医学的反应产生重大影响 心理治疗。尤其是对维生素A、D、B9和B12等关键营养素而言，情况更是如此。不幸的是，目前的情况 “一刀切”的方法来确定一个人是否有足够的这样或那样的水平 微量营养素依赖于较旧的研究，这些研究使用的血清分析只记录了最近的摄入量，而不是 我们现在老龄化、更加多样化的人口带来的医疗保健挑战 我们相信对唾液DNA的综合遗传-表观遗传学评估可以更好地捕捉细胞 微量营养素的地位，并作为未来精密营养表观基因组疗法的基石。我们的方法， 它不需要抽血，对日常饮食摄入量的波动有很强的抵抗力，而且可以 使用远程、远程医疗类型的方法进行。这个更面向函数的方法可以找到 在各种医疗和非医疗保健环境中广泛使用，以优化运动 性能，促进健康老龄化和监测慢性(如消化)的营养补充 疾病)和急性(如化疗)患者。例如，该方法被推广到评估中 针对常见补充剂的使用，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B9 和B12水平。为了验证这一假设，我们将使用450名非洲裔美国人的数据，我们为他们 已经有全血DNA的血清、全基因组遗传和全基因组表观遗传学数据。我们会 使用机器学习首先挖掘对血清B9和B12水平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的签名转换为 基于唾液的签名。然后，我们将测试转化为一组易于执行的甲基化敏感 数字聚合酶链式反应分析。 如果成功，该项目将产生很大影响，因为它可能导致无痛、在家营养食品 测试。这一研究意义重大，因为人们认为某些营养素可以预防癌症或早产儿。 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 在表观遗传学和机器学习方面的专业知识。这是创新的，因为唾液诊断还没有 已被引入营养食品市场。BD团队很有资格。该项目将由Rob博士领导 一位表观遗传学诊断专家。他将得到一个联合调查小组的协助，该小组包括 营养专家(Ruth Grossman博士)和生物统计学专家(Jeff Long博士)。如果成功，这款R43将作为 R44的基础，它开发了一系列基于唾液的营养分析。

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.