Project 003 - VICI

项目003 - VICI

• 批准号: 10602745
• 负责人: VICTOR GERARD DEGRUTTOLA
• 金额: $ 33.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10602745
• 关键词: Address; Algorithms; Automobile Driving; Biological; Blood; Cells; Characteristics; Classification; Clinical; Complex; Data; Data Set; Development; Dimensions; Environment; Environmental Risk Factor; Epigenetic Process; Future; Gene Expression; Generations; Genes; Genome; Gifts; Goals; HIV; Heterogeneity; Human body; Immune; Immunologics; Integration Host Factors; Knowledge; Linear Models; Measures; Mediating; Mediation; Medicine; Methods; Modeling; Movement; Network-based; Organ; Participant; Pathway interactions; Pattern; Perfusion; Persons; Phenotype; Population; Predisposition; Reproducibility; Research; Research Personnel; Research Project Grants; Resources; Satellite Viruses; Statistical Methods; Structure; System; Talents; Technology; Testing; Tissue Sample; Tissues; Validation; Viral; Viremia; Virion; analytical method; antiretroviral therapy; biological systems; cohort; complex data; data integration; demographics; diverse data; gene regulatory network; high dimensionality; innovation; insight; integration site; migration; multidimensional data; network models; new technology; novel; participant enrollment; programs; trait

PROJECT 3. Viral, Immunologic and Cellular data Integration (VICI) Research Project - ABSTRACT For 40 years, research has advanced HIV medicine to the point where persons with HIV (PWH) can live normal and healthy lives if they have access to antiretroviral therapy (ART). Nevertheless, HIV cannot be readily cured. Curing HIV requires further advances in approaches to investigating biological systems at multiple scales, from interactions among genes within a cell to migration of HIV between tissues. Innovative methods are needed to characterize HIV dynamics more fully in settings where ART is and is not stopped. These methods are urgently needed to address the challenges that arise in proof-of-concept studies with a small number of participants. The VICI Research Project (RP) proposes development and validation of methods for analyzing large and complex datasets generated by the other RPs (VENI and VIDI) from 20 well-characterize participants enrolled in the innovative Last Gift cohort. As reproducible scientific results depend as much on development of novel analytical methods to address the challenges posed by these datasets as on their generation, we propose to devote considerable resources and talent to the proposed VICI RP. Throughout this VICI RP, we describe development, statistical validation, and application of models that integrate high-dimensional, single-cell and single-genome data with clinical and other low-dimensional covariates. Proposed methods use a ‘systems’ approach that incorporates connections among complex and distinct entities (e.g., gene expression, integration site, epigenetic marks, tissue types) or elucidates relationships among predictors to integrate the totality of the data. Aims 1 and 2 focus on novel statistical methods to (1) combine novel network methods with the discrete trait analyses (described in the VENI RP) to infer viral migration networks and its predictors, and (2) identify cell phenotypes based on classes of gene regulatory networks identified through a novel form of recursive partitioning. These methods will be directly applied to analyze HIV activation and repopulation of tissues. Aim 3 uses mediation analysis⸺including novel tests for heterogeneity in mediation effects⸺to assess mechanisms that drive HIV persistence in the body. These complementary aims share the same overarching goal of providing a system-based framework that facilitates analysis of large, complex, and high dimensional datasets. To illustrate the study framework and guide reviewers, we describe the application of the proposed innovative methods on the study-defined reservoir states of HIV leaving, coming, and staying HOME on and off ART.

项目3。病毒，免疫学和细胞数据整合（VICI）研究项目 - 摘要 40年来，研究已将艾滋病毒医学提高到艾滋病毒（PWH）可以正常生活的地步 如果他们可以接受抗逆转录病毒疗法（ART），那么他们的生活。然而，艾滋病毒不能轻易治愈。 治愈艾滋病毒需要进一步的进步，以在多个尺度上研究生物系统的方法 细胞中基因之间的相互作用与组织之间HIV的迁移。需要创新的方法 在艺术所在的环境中，更充分地表征HIV动力学。 迫切需要这些方法来应对概念证明研究所带来的挑战 参与者数量。 VICI研究项目（RP）提议开发和验证方法 分析来自20个特色的其他RP（Veni和Vidi）生成的大型和复杂的数据集 参与者参加了创新的最后礼物队列。由于可重复的科学结果很大程度上取决于 开发新的分析方法，以应对这些数据集所带来的挑战 这一代人建议将考虑资源和人才投入到拟议的VICI RP上。 通过此VICI RP，我们描述了整合的开发，统计验证和应用 具有临床和其他低维协变量的高维，单细胞和单基因组数据。 提议的方法使用一种“系统”方法，该方法结合了复杂和不同实体之间的连接 （例如，基因表达，整合位点，表观遗传标记，组织类型）或阐明之间的关系 预测数据集成数据的总体。 目标1和2关注新颖的统计方法（1）将新型网络方法与离散性状相结合 分析（在Veni RP中描述）以推断病毒迁移网络及其预测因子，以及（2）识别细胞 基于基因调节网络类别的表型通过新颖的递归形式识别 分区。这些方法将直接应用于分析组织的HIV激活和重生。 AIM 3使用调解分析⸺包括调解效应中异质性的新型测试⸺进行评估 驱动体内艾滋病毒持久性的机制。 这些完成的目标共享相同的总体目标，即提供一个基于系统的框架 促进对大，复杂和高维数据集的分析。说明学习框架和指南 审稿人，我们描述了拟议的创新方法在研究定义的储层国家中的应用 艾滋病毒离开，来和呆在家里。