An Integrative Omics Approach to Identify Biomarkers Related to Preeclampsia and Breast Cancer Risks

识别与先兆子痫和乳腺癌风险相关的生物标志物的综合组学方法

• 批准号: 9162127
• 负责人: Lana X Garmire
• 金额: $ 63.66万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-19 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9162127
• 关键词: AFP gene; Accounting; Adult; Big Data; Bioinformatics; Biological; Biological Markers; Birth; Blood; Blood specimen; Child; Chronic Disease; Classification; Computing Methodologies; DNA; DNA Methylation; Data; Data Analyses; Disease; Environment; Epidemiologic Studies; Epigenetic Process; Ethics; Etiology; Female; Genes; Genomics; Goals; Hawaii; Hormones; Human; Hypertension; Intervention; Level of Evidence; Life; Link; Malignant Neoplasms; Mediator of activation protein; Medical; Modeling; Molecular; Morbidity - disease rate; Mothers; Nested Case-Control Study; Pathway interactions; Physical Exercise; Pilot Projects; Placenta; Play; Population; Pre-Eclampsia; Predisposition; Pregnancy; Pregnant Women; Prevention; Progesterone; Proteinuria; Proteome; Proteomics; Research Personnel; Role; Sampling; Tamoxifen; Testing; The Cancer Genome Atlas; Tissues; Umbilical Cord Blood; Universities; Woman; biobank; cancer prevention; cancer risk; case control; cohort; data integration; epigenetic regulation; epigenome; epigenomics; follow-up; genetic signature; genome-wide; improved; in utero; malignant breast neoplasm; medical schools; methylome; mortality; novel; offspring; peripheral blood; pregnant; protective effect; repository; research study; secretory protein; targeted treatment; theories; therapeutic biomarker; therapeutic target; tool; transcriptome; transcriptome sequencing; unborn child

PROJECT SUMMARY Preeclampsia is the medical condition characterized by hypertension and proteinuria in pregnant women. It occurs in 5 to 8% of all pregnancies (as common as breast cancer) and is the leading cause of morbidity and mortality for both the mother and the unborn child. Surprisingly, epidemiological studies have shown strong evidence that women associated with preeclamptic pregnancies have almost 50% reduced rate of breast cancers decades later. However, due to ethical and practical reasons, direct evidence from long-term follow up in human population is lacking. Moreover, the underlying mechanism to explain the lasting effect of preeclampsia remains unknown. Here we propose an alternative and integrative omics approach to investigate the molecular links between preeclampsia and breast cancer risks later in life. We will conduct a nested case control study to investigate the epigenome, RNA-Seq transcriptome and proteomics differences in the placenta and matched maternal blood DNA samples associated with preeclampsia. The de-identified samples will be collected through the Hawaii Biorepository (HiBR), and they reflect the unique multi-ethnic population of Hawaii. We will construct bioinformatics pipelines to analyze all three types of omics data individually, and develop new computational methods for omics data integration. We will identify coherent genes, modules and biological pathways as the biomarkers of preeclampsia. Moreover, we will compare our data with the DNA methylome, RNA-Seq transcriptome, and proteomics data of the breast cancer samples from The Cancer Genome Atlas. Through such comparison, we will uncover the cancer-related genes, modules and biological pathways within the preeclampsia samples. This will provide direct molecular-level evidence to link preeclampsia and breast cancer risks later in life, which is practically impossible using the approach of population follow-up. It will also identify biomarkers of breast cancer susceptibility as early as a child's birth, for the purpose of cancer prevention.

项目摘要 子痫前期是孕妇高血压和蛋白尿的特征。它 发生在所有妊娠的5％至8％（与乳腺癌一样常见）中，是发病率和 母亲和未出生的孩子的死亡率。令人惊讶的是，流行病学研究表明 证据表明，与先兆妊娠有关的妇女的乳房率降低了近50％ 几十年后的癌症。但是，由于道德和实际原因，长期随访的直接证据 缺乏人口。此外，解释持久作用的基本机制 子痫前期仍然未知。在这里，我们提出了一种替代性和综合的OMIC方法来调查 子痫前期和乳腺癌之间的分子联系以后有可能。我们将进行嵌套箱 对照研究研究表观基因组，RNA-SEQ转录组和蛋白质组学的差异 并匹配与先兆子痫相关的母体血液DNA样品。取消识别的样本将是 通过夏威夷生物座席（Hibr）收集，它们反映了独特的多种族人口 夏威夷。我们将构建生物信息学管道，以分别分析所有三种类型的OMIC数据，并 开发用于OMIC数据集成的新计算方法。我们将确定连贯的基因，模块和 生物学途径是先兆子痫的生物标志物。此外，我们将将数据与DNA进行比较 甲基甲基，RNA-SEQ转录组和乳腺癌样品的蛋白质组学数据 基因组地图集。通过这种比较，我们将发现与癌症相关的基因，模块和生物学 子痫样品中的途径。这将提供直接的分子级证据以链接 子痫前期和乳腺癌后期的风险，这实际上是不可能的 人口随访。它还将在儿童出生时识别出乳腺癌敏感性的生物标志物，因为 预防癌症的目的。