Integrative Dynamic Omics Profiling: A First Step Towards Personalized Medicine

可用组学技术的快速进步预计将极大地帮助发展和 应用个性化、精准化、预防性医学。特别是，人们期待着新的医学见解。 通过全球监测分子的变化来整合基因组信息 与监测相结合的组成部分，如转录、蛋白质组和代谢组信息 不同的生理状态。这就需要开发新的方法和工具来处理 分析和整合多个基因组数据，以期实现医学上的适用性。拟议的研究 这项为期4年的K99/R00计划将在迈克尔·斯奈德博士的实验室开始，他是一位著名的 遗传学和多重组学，他将在K99年的整个K99年中担任George Mias博士的导师 获奖。这项提议的首要内容是开发一个框架，以整合从 监控多个时间点上的多个组信息。创新的方法包括 开发统计工具来分析不同的组学技术，包括原始数据处理， 组合个体基因组数据，将数据分类为医学上相关的类别，并确定 通过通路分析的生物学意义。考虑因素包括数据抽样不均匀、缺乏 在K99期间，将解决从患者获取样本所固有的重复和噪声问题。 此外，多个组学组件之间的相互作用将通过以下变化进行推断 表达式和时变网络将被定义，可以被分析以详细解释转变 在生理状态之间。为了发展计算方法，高精度的实验 将通过监测基因、蛋白质和代谢物在多个时间点的表达来执行 刺激的B细胞[K99期的淋巴母细胞和R00期的原代B细胞]，重点放在 和复杂核因子-kappaB(NF-�-B)信号通路。此外，开发了工具、算法 并将在R00期间向科学界传播数据。建议的学习活动 K99/R00奖将允许Mias博士调整他的研究方法，以实现跨多个 平台，并为独立调查获得必要的实验背景。独一无二的 斯奈德博士�S实验室的性质，将为米亚斯博士提供密切互动和合作的机会 处于遗传学组学研究前沿的实验专家。此外，实验室�S Mias博士随时可以获得的大量资源将极大地促进他的研究和学术努力。 K99/R00奖项将使Mias博士能够顺利过渡到独立的教员职位 R00阶段，并在自己的实验室中成功地领导了新颖的研究。

The rapid advancement in available -omics technologies is expected to greatly aid the development and application of personalized, precise and preventive medicine. In particular, novel medical insights are expected through the integration of genomic information through the global monitoring of changes in molecular components, such as trancriptomic, proteomic and metabolomic information in conjunction with monitoring varying physiological states. This necessitates the development of new methodology and tools to handle the analysis and integration of multiple omic data with a view towards medical applicability. The proposed research of this 4-year K99/R00 proposal will begin at the laboratory of Dr. Michael Snyder, a renowned expert in genetics and multiple omics, who will act as the mentor for Dr. George Mias throughout the K99 year of the award. Foremost in this proposal is the development of a framework to integrate dynamic data obtained from monitoring multible omic information over multiple time points. The innovative methodology involves the development of statistical tools to analyze different omics technologies, including raw data processing, combining the individual omic data, categorizing the data in medically relevant categories, and ascertaining biological significance through pathway analyses. Considerations such as uneven sampling of data, lack of replicates and noise, inherent in obtaining samples from patients will be addressed during the K99 period. Additionally, the interactions between multiple omics components will be inferred through changes in expression, and time-varying networks will be defined that can be analyzed for detail explanation of transitions between physiological states. In order to develop the computational methodology, highly precise experiments will be performed, by monitoring gene, protein and metabolite expression over multiple time points in stimulated B-cells[lymphoblasts in K99 period and primary B cells in R00 period], with focus on the important and complex Nuclear Factor kappa B (NF�B) signaling pathways. Furthermore, developed tools, algorithms and data will be disseminated to the scientific community in the R00 period. The proposed learning activities of the K99/R00 award will allow Dr. Mias to adapt his research approaches to omics integration across multiple platforms, and acquire the necessary experimental background for independent investigations. The unique nature of Dr. Snyder�s lab, will provide Dr. Mias the opportunity to closely interact and collaborate with experimental experts conducting research at the forefront of omics research in genetics. Moreover, the lab�s extensive resources readily available to Dr. Mias will greatly facilitate his research and academic endeavors. The K99/R00 award will enable Dr. Mias to to smoothly transition into an independent faculty position in the R00 phase and successfully lead novel investigations in his own laboratory.