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

项目摘要 先兆子痫是一种以妊娠妇女高血压和蛋白尿为特征的医学病症。它 发生在5%至8%的所有怀孕（常见的乳腺癌），是发病的主要原因， 母亲和胎儿的死亡率。令人惊讶的是，流行病学研究表明， 有证据表明，与先兆子痫妊娠相关的妇女乳腺癌发生率几乎降低了50%， 几十年后的癌症然而，由于伦理和实践的原因，长期随访的直接证据 人类缺乏。此外，解释持续影响的潜在机制 先兆子痫仍然是未知的。在这里，我们提出了一种替代和综合组学方法来调查 先兆子痫和以后患乳腺癌风险之间的分子联系。我们将进行一个嵌套的案例 对照研究，以研究胎盘中的表观基因组、RNA-Seq转录组和蛋白质组学差异 以及与先兆子痫相关的母亲血液DNA样本去识别样本将被 通过夏威夷生物资源库（HiBR）收集，它们反映了夏威夷独特的多种族人口， 夏威夷。我们将构建生物信息学管道，分别分析所有三种类型的组学数据， 为组学数据整合开发新的计算方法。我们将确定连贯的基因，模块和 生物学途径作为先兆子痫的生物标志物。此外，我们会将我们的数据与DNA进行比较， 乳腺癌样本的甲基化组、RNA-Seq转录组和蛋白质组学数据 基因组图谱。通过这种比较，我们将揭示与癌症相关的基因、模块和生物学特性。 先兆子痫样本中的信号通路这将提供直接的分子水平的证据， 先兆子痫和乳腺癌的风险在以后的生活中，这实际上是不可能使用的方法， 人口后续行动。它还将在孩子出生时就确定乳腺癌易感性的生物标志物， 预防癌症的目的。

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.