Global Omics and Viromics Initiative on Pregnancy

GLO VIP项目的长期目标是确定女性生殖道的病毒组 纵向怀孕前，怀孕期间和怀孕后，并评估其与早产（PTB）和其他 不良妊娠结局。本研究将采用我们先前研究中生成的三个现有队列： 1)一组约1000名孕妇参加了我们的阴道人类微生物组项目（VaHMP） 该研究从约6500名患者中收集了超过60，000份横断面样本（宫颈，阴道，口腔，肛周，血液）， VCU健康中心女性诊所的访客; 2）约1000名孕妇参与的队列 在我们的多细胞微生物组研究妊娠倡议（MOMS PI）中， 妇女诊所、分娩和分娩、NICU和新生儿诊所;以及3）约500名孕妇的队列 参与MOMS PI，但在亚基马瑞典医院的妇女诊所纵向取样 总医院和华盛顿大学健康中心。约15万个纵向样本 （宫颈、阴道、口腔、直肠、血液、尿液、胎盘、脐带、脐带血、胎粪和首次粪便） 用于RNA、DNA、蛋白质组、代谢组和免疫蛋白质组分析。略高于30%的 这些组群中的每一个中的妇女都经历了复杂的妊娠;例如，10-15% PTB，约10%早产 胎膜破裂（PROM）或早产胎膜早破（PPROM），约20%高血压，约10%妊娠糖尿病， 和5%的先兆子痫。我们从VaHMP中确定了约250例受试者（约150例有不良结局） 队列和MOMS PI的VCU队列的约240例（约200例有不良结局），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 女性生殖道病毒组的研究及其与不良妊娠关系的探讨 结果，并将细菌微生物组，病毒组和健康之间的关系联系起来。样品 来自MOMS PI西雅图队列的受试者（约100例不良结局）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、第一次排便） 并复制我们在项目发现阶段的结果。此外，我们将描述 通过代谢物和细胞因子的代谢组学和免疫蛋白质组学分析选定样品中的宿主应答 参与者和新生儿的血液和其他相关组织中的水平， 项目的阶段。 我们的研究结果将提供一个全面的概述病毒组的女性生殖道和其 对妊娠的影响，以及病毒组在不良妊娠结局中作用的迹象。

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.