Identification and Interpretation of Chromatin Changes Associated with the Aging of Human Immune Cells

与人类免疫细胞衰老相关的染色质变化的鉴定和解释

• 批准号: 9753292
• 负责人: Duygu Ucar
• 金额: $ 46.82万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753292
• 关键词: Address; Affect; Age; Aging; Algorithms; Area; Biology of Aging; Blood; Cell physiology; Cells; Chromatin; Clinical; Collaborations; Complex; Connecticut; Data; Disease; Elderly; Functional disorder; Generations; Genetic Transcription; Genomic medicine; Genomics; Goals; Health; Human; Immune; Immune response; Immune system; Immunobiology; Immunologic Markers; Immunologist; Individual; Infection; Laboratories; Machine Learning; Mining; Principal Investigator; Public Health; Regulatory Element; Research; Sampling; Scientist; Source; The Jackson Laboratory; Training; Universities; Woman; Work; combat; computer science; computerized tools; computing resources; data integration; epigenomics; genomic data; genomic signature; healthy aging; immune health; informatics tool; learning network; men; next generation sequence data; novel; programs; therapy design; tool

PROJECT SUMMARY/ABSTRACT This research program aims to bridge the gap between genomics data generation from clinical samples and our ability to infer and interpret intricate regulatory programs that underpin cell function and dysfunction in human cells. The Ucar laboratory develops and applies computational solutions to uncover complex regulatory programs in human cells and address previously inaccessible questions related to how disruptions in these programs affect human health and disease. The goal is to create computational tools that are versatile, easy to use and in keeping with the ever-increasing sophistication and complexity of NGS data. The current focus on the immunobiology of aging leverages the Principal Investigator's extensive training in computer science, epigenomics, and aging biology. Ongoing work with collaborators at The Jackson Laboratory and The University of Connecticut Health Center has led to multiple discoveries related to the genomic signatures of human immune aging, and has yielded numerous questions that form the basis for the proposed research program, including: 1) Which regulatory programs and regulatory interactions are disrupted with aging in which immune cells? 2) How do men and women age differently? 3) What are the putative genomic/clinical/immunological markers of healthy aging? To address these questions, this research program will focus on developing machine learning and network mining algorithms that enable integration of data from diverse sources, since complex regulatory interactions and diverse regulatory elements cannot be inferred from a single data type. Fueled by these tools, it will investigate the dynamics of regulatory programs in blood- derived human immune cells associated with aging through collaborations with clinicians, immunologists, and chromatin scientists. This research will advance our understanding of how immune responses are transcriptionally regulated, will facilitate the design of interventions to boost immune health in elderly and diseased individuals, and will yield computational resources useful to diverse areas of genomic medicine.

项目摘要/摘要 该研究计划旨在弥合基因组数据生成从临床样本和 我们推断和解释基于细胞功能和功能障碍的复杂调节程序的能力 人类细胞。 UCAR实验室开发并应用计算解决方案来发现复杂的调节 人类细胞中的程序并解决了以前无法访问的问题与这些问题有关 计划影响人类健康和疾病。目标是创建通用，易于的计算工具 使用并与NGS数据的复杂性和复杂性不断增加。当前关注 衰老的免疫生物学利用了主要研究者在计算机科学方面的广泛培训， 表观基因组学和衰老生物学。与杰克逊实验室的合作者和合作者正在进行的工作 康涅狄格大学健康中心已导致与基因组签名有关的多个发现 人类免疫衰老，并提出了许多构成拟议研究基础的问题 计划，包括：1）哪些监管计划和监管互动都被衰老中断了 免疫细胞？ 2）男人和女人的年龄有何不同？ 3）假定是什么 健康衰老的基因组/临床/免疫标记？为了解决这些问题，该研究计划 将着重于开发机器学习和网络挖掘算法，这些算法能够从 各种来源，由于无法推断出复杂的监管互动和多种监管要素 来自单个数据类型。在这些工具的推动下，它将研究血液中调节计划的动态 通过与临床医生，免疫学家和 染色质科学家。这项研究将提高我们对免疫反应的理解 受转录管制的，将有助于设计干预措施，以增强老年人的免疫健康和 患病的个体，并将产生对基因组医学不同领域有用的计算资源。