Global Omics and Viromics Initiative on Pregnancy

全球妊娠组学和病毒组学倡议

• 批准号: 10006017
• 负责人: Gregory Allen Buck
• 金额: $ 64.82万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10006017
• 关键词: Adverse event; Archives; Bacterial Vaginosis; Birth; Blood; Cervical; Clinic; Complex; DNA; DNA Viruses; Data; Disease; Environment; Evolution; Feces; Female; First Pregnancy Trimester; General Hospitals; Genetic; Gestational Diabetes; Goals; HIV; Health; Hospitals; Human; Human Microbiome; Human Papillomavirus; Hypertension; Immune response; Individual; Infection; Meconium; Medical Records; Membrane; Metagenomics; Neonatal; Newborn Infant; Nucleic Acids; Outcome; Participant; Pathogenesis; Pathologic; Penetration; Phase; Placenta; Plasma; Pre-Eclampsia; Predisposition; Pregnancy; Pregnancy Outcome; Pregnancy Trimesters; Pregnant Women; Premature Birth; Premature Rupture Fetal Membranes; Proteome; RNA; RNA Viruses; Recording of previous events; Reporting; Reproductive Health; Ribosomal RNA; Role; Sampling; Second Pregnancy Trimester; Simplexvirus; Site; Skin; Surveys; Swab; Third Pregnancy Trimester; Tissues; Umbilical Cord Blood; United States National Institutes of Health; Universities; Urine; Vagina; Validation; Viral; Viral Physiology; Virus; Virus Diseases; Washington; Whole Blood; Woman; Women' s Health; Zika Virus; adverse outcome; adverse pregnancy outcome; bacteriome; cohort; cytokine; experience; fetal; improved; innovative technologies; insight; interest; metabolome; metabolomics; metagenomic sequencing; metatranscriptome; microbiome; microbiome alteration; microbiome research; multiple omics; neonatal outcome; neonate; novel strategies; pathogenic virus; pregnant; preterm premature rupture of membranes; racial and ethnic; rectal; reproductive tract; transcriptome sequencing; transmission process; vaginal microbiome; vaginal microbiota; virome

The long-term objectives of the GLO VIP project are to define the virome of the female reproductive tract longitudinally before, during and after pregnancy, and to assess its relationship to preterm birth (PTB) and other adverse pregnancy outcomes. The study will employ three extant cohorts generated from our previous studies: 1) a cohort of ~1000 pregnant women who participated in our Vaginal Human Microbiome Project (VaHMP) which collected over 60,000 cross-sectional samples (cervical, vaginal, buccal, perianal, blood) from ~6500 visitors to our women’s clinics at the VCU Health Center; 2) a cohort of ~1000 pregnant women who participated in our Multi Omic Microbiome Study Pregnancy Initiative (MOMS PI) and were sampled longitudinally in VCU’s women’s clinics, Labor & Delivery, NICU, and Newborn Baby Clinic; and 3) a cohort of ~500 pregnant women who participated in MOMS PI but were sampled longitudinally at women’s clinics at Swedish Hospital, Yakima General Hospital, and the University of Washington Health Center. Approximately 150,000 longitudinal samples (cervical, vaginal, buccal, rectal, blood, urine, placenta, cord, cord blood, meconium and first stool) have been prepared for RNA, DNA, proteome, metabolome, and immunoproteome analyses. Slightly over 30% of the women in each of these cohorts experienced complicated pregnancies; e.g., 10-15% PTB, ~10% premature rupture of membranes (PROM) or preterm PROM (PPROM), ~20% hypertension, ~10% gestational diabetes, and ~5% pre-eclampsia. We have identified ~250 subjects (~150 with adverse outcomes) from the VaHMP cohort and ~240 (~200 with adverse outcomes) from the VCU cohort of MOMS PI for the discovery phase of this project, in which we will employ Whole Metagenome Sequencing (WMGS) and Whole Metatranscriptome Sequencing (WMTS) to characterize the DNA and RNA viromes, including both known and previously unknown viruses, of the female reproductive tract and probe for relationships between the virome and adverse pregnancy outcomes, and correlate the relationship between the bacterial microbiome, the virome, and health. Samples from participants (~100 with adverse outcomes) from the Seattle cohort of MOMS PI will be used in the validation phase of the study in which we will examine birth products and neonatal samples (meconium, buccal, first stool) for viral activity and replicate our results from the discovery phase of the project. In addition, we will characterize host responses in selected samples by metabolomics and immunoproteomic analysis of metabolyte and cytokine levels in blood and other relevant tissues from participants and neonates identified as of interest in the discovery phase of the project. Our results will provide both a comprehensive overview of the virome of the female reproductive tract and its impact on pregnancy, and indications of the role(s) of the virome in adverse pregnancy outcomes.

GLO VIP 项目的长期目标是定义女性生殖道的病毒组 纵向研究怀孕前、怀孕期间和怀孕后的情况，并评估其与早产 (PTB) 和其他疾病的关系 不良妊娠结局。该研究将采用我们之前研究中产生的三个现有队列： 1) 参与我们的阴道人类微生物组项目 (VaHMP) 的约 1000 名孕妇组成的队列 收集了约 6500 名患者的 60,000 多个横截面样本（宫颈、阴道、口腔、肛周、血液） 弗吉尼亚联邦大学 (VCU) 健康中心女性诊所的访客； 2) 约 1000 名孕妇参与的队列 在我们的多组学微生物组研究妊娠计划 (MOMS PI) 中，并在 VCU 中纵向采样 妇女诊所、分娩、新生儿重症监护室和新生儿诊所； 3) 约 500 名孕妇组成的队列 参加 MOMS PI，但在亚基马瑞典医院的妇女诊所进行纵向抽样 综合医院和华盛顿大学健康中心。大约 150,000 个纵向样本 （宫颈、阴道、口腔、直肠、血液、尿液、胎盘、脐带、脐带血、胎便和初便） 用于 RNA、DNA、蛋白质组、代谢组和免疫蛋白质组分析。略高于30% 每个队列中的女性都经历过复杂的怀孕过程；例如，10-15% PTB，~10% 过早 胎膜破裂 (PROM) 或早产 PROM (PPROM)、~20% 高血压、~10% 妊娠期糖尿病、 约 5% 患有先兆子痫。我们已从 VaHMP 中识别出约 250 名受试者（约 150 名出现不良结果） 队列和约 240 名来自 MOMS PI 的 VCU 队列的约 240 名（约 200 名不良结果），用于本研究的发现阶段 项目，其中我们将采用全宏基因组测序（WMGS）和全元转录组 测序 (WMTS) 用于表征 DNA 和 RNA 病毒组，包括已知和以前未知的病毒组 女性生殖道病毒并探讨病毒组与不良妊娠之间的关系 结果，并将细菌微生物组、病毒组和健康之间的关系关联起来。样品 来自 MOMS PI 西雅图队列的参与者（约 100 名出现不良结果）将用于验证 研究阶段，我们将检查出生产品和新生儿样本（胎便、口腔、第一次粪便） 病毒活性并复制我们在项目发现阶段的结果。此外，我们将表征 通过代谢组学和代谢物和细胞因子的免疫蛋白质组学分析选定样品中的宿主反应 参与者和新生儿的血液和其他相关组织中的水平被确定为该发现感兴趣的 项目的阶段。 我们的研究结果将提供女性生殖道病毒组的全面概述及其 对妊娠的影响，以及病毒组在不良妊娠结局中的作用的迹象。