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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

基本信息

批准号：
10076552
负责人：
Lana X Garmire
金额：
$ 49.88万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-19 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10076552
关键词：
AFP gene Adult Big Data Bioinformatics Biological Biological Markers Birth Blood Blood specimen Breast Cancer Risk Factor Childbirth Chronic Disease Classification Computing Methodologies DNA DNA Methylation Data Data Analyses Disease Environment Epigenetic Process Ethics Etiology Female Genes Genomics Goals Hawaii Hormones Human Hypertension Individual Intervention Level of Evidence Life Link Longterm Follow-up 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 Pregnancy Complications Pregnant Women Prevention Progesterone Proteinuria Proteome Proteomics Research Personnel Role Sampling Tamoxifen Testing The Cancer Genome Atlas Tissues Umbilical Cord Blood Universities Woman anti-cancer biobank bioinformatics pipeline cancer prevention case control cohort data integration epidemiology study epigenetic regulation epigenome epigenomics experimental study follow-up genetic signature genome-wide improved in utero malignant breast neoplasm medical schools methylome mortality novel offspring peripheral blood protective effect secretory protein targeted biomarker theories therapeutic target tool transcriptome transcriptome sequencing unborn child

项目摘要

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.

项目概要先兆子痫是一种以孕妇高血压和蛋白尿为特征的疾病。它发生在所有妊娠中的 5% 至 8%（与乳腺癌一样常见），是发病率和死亡率的主要原因母亲和未出生婴儿的死亡率。令人惊讶的是，流行病学研究表明，有证据表明，患有先兆子痫的女性的乳房发育率会降低近 50% 几十年后癌症。然而，由于伦理和实践原因，长期随访的直接证据人口中缺乏。此外，解释持久效应的根本机制先兆子痫仍然未知。在这里，我们提出了一种替代和综合组学方法来研究先兆子痫与晚年乳腺癌风险之间的分子联系。我们将进行嵌套案例对照研究探讨胎盘表观基因组、RNA-Seq 转录组和蛋白质组差异并匹配与先兆子痫相关的母体血液 DNA 样本。去识别化后的样本将通过夏威夷生物储存库 (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来单独分析所有三种类型的组学数据，并且开发组学数据集成的新计算方法。我们将识别连贯的基因、模块和生物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 The Cancer 乳腺癌样本的甲基化组、RNA-Seq 转录组和蛋白质组数据基因组图谱。通过这样的比较，我们将揭示与癌症相关的基因、模块和生物学特性。先兆子痫样本中的通路。这将为链接提供直接的分子水平证据先兆子痫和乳腺癌在以后的生活中存在风险，而使用以下方法实际上是不可能的人口跟踪。它还将在孩子出生时就识别出乳腺癌易感性的生物标志物，达到预防癌症的目的。