Integrative network-based analysis of multi-omics data to elucidate the molecular connection between asthma and COPD
基于多组学数据的综合网络分析,阐明哮喘和慢性阻塞性肺病之间的分子联系
基本信息
- 批准号:10219832
- 负责人:
- 金额:$ 18.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-18 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAdvisory CommitteesAlgorithmsAreaAsthmaAwardBig DataBioinformaticsBiologicalBiologyBloodBlood specimenCD4 Positive T LymphocytesCatalogsChildhoodChildhood AsthmaChronic Obstructive Airway DiseaseComplexComputing MethodologiesConfidence IntervalsDNA MethylationDataDevelopmentDiseaseDisease ProgressionDisease modelEducational workshopEnvironmentEpidemiologyEpigenetic ProcessEtiologyFetal LungGene ExpressionGenesGeneticGenetic RiskGenetic TranscriptionGenomeGenomicsImpairmentLifeLinkLungLung diseasesMediatingMediator of activation proteinMedical InformaticsMedicineMentorsMessenger RNAMethodologyMethodsMethylationMicroRNAsModelingMolecularMultiomic DataNetwork-basedPathway interactionsPatternPeripheral Blood Mononuclear CellPhenotypePhysicsPlayPopulationProteomePublic HealthResearchRoleSNP genotypingSamplingSignal TransductionSiteSmokeStandardizationStructure of parenchyma of lungSystemSystems BiologyTeaching HospitalsTestingTimeTissue MicroarrayTissuesTrainingTraining ProgramsTranscription ProcessWhole Bloodairway obstructionasthmaticbasechronic airflow obstructionclinical translationcohortcomputing resourcesepigenetic regulationepigenomicsfetal smoke exposurehigh riskhuman dataimprovedin uteroinsightlung developmentmedical schoolsmeetingsmemberprecision medicineprenatalrisk variantskillstranscriptomics
项目摘要
Project Summary/Abstract
Growing evidence suggests an etiological link between asthma and chronic obstructive pulmonary disease
(COPD) wherein mild-to-moderate persistent asthmatics are susceptible to persistent airflow obstruction, putting
them at a higher risk for developing COPD. Furthermore, epigenetic modulation due to in utero smoke (IUS)
exposure during fetal lung development may play a role in asthma and COPD. These and other data suggest a
lifelong trajectory of lung impairment from prenatal lung development to childhood asthma to COPD in adulthood.
Longitudinal and carefully phenotyped multi-omic data offer the opportunity to understand the molecular
determinants of this disease trajectory. Systems and network biology methods hold the potential to effectively
integrate, analyze and interpret multi-omics data. Multilayer networks, in particular, offer a feasible first step to
model disease perturbations jointly across multiple molecular levels, from the genome to the proteome. In this
application, we will simultaneously analyze the rich multi-omics data (SNP genotyping, DNA methylation, mRNA
and miRNA expression) collected as part of long-standing asthma and COPD cohorts using multilayer network
methods. We will first integrate IUS exposure, asthma and COPD multi-omics data into networks and develop
their statistical framework to facilitate subsequent bioinformatics analyses. We will then track the developmental
origins of asthma by the integrated temporal analysis of fetal lung and childhood asthma multi-omics data. Finally,
we will identify key molecules and pathways of the phenotypic transition from asthma in early life to COPD in
adulthood using multilayer networks. Dr. Halu’s training in statistical physics and complex networks has prepared
him well for his proposed research. However, understanding the molecular basis connecting complex lung
diseases such as asthma and COPD through the analysis of multi-omics data is a formidable task that will require
further training in specific areas. Dr. Halu will leverage the excellent intellectual environment of Harvard Medical
School (HMS) and its teaching hospitals, and will have access to extensive computational resources through the
Channing Division of Network Medicine and HMS. Through formal coursework and workshops, and with the help
of a mentoring and advisory team with complementary expertise, Dr. Halu will immerse himself in a training
program focusing on statistical genetics, epigenetics, and omics integration, big data in medical informatics, and
the biology of pulmonary diseases and clinical translation. Dr. Halu will also participate in regular meetings with
his mentors and advisory board members, which will allow him to share his progress. Altogether, Dr. Halu’s
training and research plan will enable him to expand his current skill set to include the ability to address the
challenges of analyzing the complex genomic and epigenomic data of large epidemiological cohorts, identify
open questions in the systems biology of asthma and COPD, and ultimately contribute to the precision medicine
of lung disease.
项目概要/摘要
越来越多的证据表明哮喘和慢性阻塞性肺疾病之间存在病因学联系
(慢性阻塞性肺病)患有轻度至中度持续性哮喘的患者容易受到持续性气流阻塞的影响,
此外,由于宫内烟雾(IUS)导致的表观遗传调节,她们患慢性阻塞性肺病的风险更高。
这些和其他数据表明,胎儿肺部发育期间的暴露可能在哮喘和慢性阻塞性肺病中发挥作用。
从产前肺部发育到儿童哮喘再到成年慢性阻塞性肺病,肺损伤的终生轨迹。
纵向和仔细表型的多组学数据提供了了解分子生物学的机会
这种疾病轨迹的决定因素 系统和网络生物学方法有可能有效地
整合、分析和解释多组学数据尤其提供了可行的第一步。
从基因组到蛋白质组,共同构建多个分子水平的疾病扰动模型。
应用程序,我们将同时分析丰富的多组学数据(SNP基因分型、DNA甲基化、mRNA
和 miRNA 表达)使用多层网络收集作为长期哮喘和慢性阻塞性肺病队列的一部分
我们将首先将 IUS 暴露、哮喘和 COPD 多组学数据整合到网络中并开发。
他们的统计框架以促进后续的生物信息学分析。
通过对胎儿肺和儿童哮喘多组学数据的综合时间分析来确定哮喘的起源。
我们将确定从早期哮喘到慢性阻塞性肺病的表型转变的关键分子和途径
Halu 博士在统计物理和复杂网络方面的培训为成年后使用多层网络做好了准备。
然而,他很好地理解了连接复杂肺的分子基础。
通过多组学数据分析来研究哮喘和慢性阻塞性肺病等疾病是一项艰巨的任务,需要
Halu 博士将利用哈佛医学院优良的智力环境进行特定领域的进一步培训。
学校(HMS)及其教学医院,并将通过
网络医学和 HMS 的钱宁部门通过正式的课程和研讨会,并在帮助下。
Halu 博士拥有一支具有互补专业知识的指导和咨询团队,他将沉浸在培训中
重点关注统计遗传学、表观遗传学和组学整合、医学信息学中的大数据以及
Halu 博士还将参加肺部疾病生物学和临床翻译的定期会议。
他的导师和顾问委员会成员,这将使他能够分享哈鲁博士的总体进展。
培训和研究计划将使他能够扩展他目前的技能,包括解决以下问题的能力:
分析大型流行病学队列的复杂基因组和表观基因组数据的挑战,确定
哮喘和慢性阻塞性肺病系统生物学中的开放性问题,最终有助于精准医疗
肺部疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Arda Halu其他文献
Arda Halu的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Arda Halu', 18)}}的其他基金
Integrative network-based analysis of multi-omics data to elucidate the molecular connection between asthma and COPD
基于多组学数据的综合网络分析,阐明哮喘和慢性阻塞性肺病之间的分子联系
- 批准号:
10656319 - 财政年份:2020
- 资助金额:
$ 18.9万 - 项目类别:
Integrative network-based analysis of multi-omics data to elucidate the molecular connection between asthma and COPD
基于多组学数据的综合网络分析,阐明哮喘和慢性阻塞性肺病之间的分子联系
- 批准号:
10434711 - 财政年份:2020
- 资助金额:
$ 18.9万 - 项目类别:
Integrative network-based analysis of multi-omics data to elucidate the molecular connection between asthma and COPD
基于多组学数据的综合网络分析,阐明哮喘和慢性阻塞性肺病之间的分子联系
- 批准号:
10055406 - 财政年份:2020
- 资助金额:
$ 18.9万 - 项目类别:
相似国自然基金
基于动态信息的深度学习辅助设计成人脊柱畸形手术方案的研究
- 批准号:82372499
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
SMC4/FoxO3a介导的CD38+HLA-DR+CD8+T细胞增殖在成人斯蒂尔病MAS发病中的作用研究
- 批准号:82302025
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
单核细胞产生S100A8/A9放大中性粒细胞炎症反应调控成人Still病发病及病情演变的机制研究
- 批准号:82373465
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
SERPINF1/SRSF6/B7-H3信号通路在成人B-ALL免疫逃逸中的作用及机制研究
- 批准号:82300208
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
MRI融合多组学特征量化高级别成人型弥漫性脑胶质瘤免疫微环境并预测术后复发风险的研究
- 批准号:82302160
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
相似海外基金
Characterizing the genetic etiology of delayed puberty with integrative genomic techniques
利用综合基因组技术表征青春期延迟的遗传病因
- 批准号:
10663605 - 财政年份:2023
- 资助金额:
$ 18.9万 - 项目类别:
Implementing SafeCare Kenya to Reduce Noncommunicable Disease Burden: Building Community Health Workers' Capacity to Support Parents with Young Children
实施 SafeCare Kenya 以减少非传染性疾病负担:建设社区卫生工作者支持有幼儿的父母的能力
- 批准号:
10672785 - 财政年份:2023
- 资助金额:
$ 18.9万 - 项目类别:
A cloud-based digital health navigation program for colorectal cancer screening
基于云的结直肠癌筛查数字健康导航程序
- 批准号:
10697474 - 财政年份:2023
- 资助金额:
$ 18.9万 - 项目类别:
Center for Harmonizing and Improving Interventions to Prevent Suicide (CHIIPS)
协调和改进预防自杀干预措施中心 (CHIIPS)
- 批准号:
10662785 - 财政年份:2023
- 资助金额:
$ 18.9万 - 项目类别:
Sex, Physiological State, and Genetic Background Dependent Molecular Characterization of CircuitsGoverning Parental Behavior
控制父母行为的回路的性别、生理状态和遗传背景依赖性分子特征
- 批准号:
10661884 - 财政年份:2023
- 资助金额:
$ 18.9万 - 项目类别: