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体 在怀孕前、怀孕期间和怀孕后进行纵向研究，并评估其与早产(PTB)和其他 不良妊娠结局。这项研究将采用我们以前的研究产生的三个现有的队列： 1)参加我们的阴道人类微生物组计划(VaHMP)的约1000名孕妇队列 它从6500人中收集了超过6万份横断面样本(宫颈、阴道、口腔、肛周、血液) VCU健康中心妇女诊所的访客；2)参加的约1000名孕妇队列 在我们的多组微生物组研究中，妊娠倡议(Moms PI)和VCU的纵向样本 妇女诊所、分娩、NICU和新生儿诊所；以及3)约500名孕妇的队列 他们参加了母亲派，但在亚基马瑞典医院的妇女诊所进行了纵向抽样 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、胎粪和第一便) 准备用于RNA、DNA、蛋白质组、代谢组和免疫蛋白质组分析。略高于30%的 这些队列中的每一位妇女都经历了复杂的怀孕；例如，10%-15%的肺结核，约10%的早产 胎膜破裂(PROM)或早产(PPROM)，~20%的高血压，~10%的妊娠期糖尿病， 和~5%的先兆子痫。我们已经从VaHMP中确定了约250名受试者(约150名有不良后果) 母亲PI的VCU队列中的~240人(~200人，有不良后果)，用于本研究的发现阶段 项目，在该项目中，我们将使用全元基因组测序(WMGS)和全元翻译组 对DNA和RNA病毒体进行测序(WMTS)，包括已知和以前未知的 女性生殖道病毒及其与不良妊娠关系的探查 结果，并将细菌微生物群、病毒体和健康之间的关系联系起来。样本 来自西雅图母亲PI队列的参与者(约100名有不良后果)将用于验证 研究阶段，我们将检查分娩产品和新生儿样本(胎粪、口腔、第一次粪便) 用于病毒活性，并复制我们在项目发现阶段的结果。此外，我们还将描述 代谢物和细胞因子的代谢组学和免疫蛋白质组学分析在选定样本中的宿主反应 参与者和被确认为对发现感兴趣的新生儿的血液和其他相关组织的水平 项目的各个阶段。 我们的结果将全面概述女性生殖道的病毒体及其 对妊娠的影响，以及病毒在不良妊娠结局中的作用的适应症(S)。

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.