Integrative Network Biology Approaches to Identify, Characterize and Validate Molecular Subtypes in Alzheimer's Disease

识别、表征和验证阿尔茨海默病分子亚型的综合网络生物学方法

• 批准号: 10517122
• 负责人: Minghui Wang
• 金额: $ 41.92万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10517122
• 关键词: Administrative Supplement; Alzheimer' s Disease; Automobile Driving; Biology; Cell Nucleus; Cells; Comparative Study; Complex; Data; Data Set; Disease; Essential Genes; FDA approved; Genetic; Goals; Immune response; Inflammation; Inflammatory; Malignant Neoplasms; Molecular; Molecular Profiling; Multiomic Data; Non-Insulin-Dependent Diabetes Mellitus; Pathway Analysis; Pathway interactions; Pharmaceutical Preparations; Proteins; Quantitative Trait Loci; Rheumatoid Arthritis; Source; Therapeutic; Tissues; United States National Institutes of Health; cohort; gene network; human disease; mRNA Expression; molecular subtypes; multiple omics; network models; novel; programs; targeted treatment

Dysregulated inflammation/immune response has been identified as a key factor driving major human diseases such as cancer, Rheumatoid Arthritis (RA), Type 2 diabetes (T2D) and Alzheimer's disease (AD). However, there lacks a comprehensive comparative study of the inflammation/immune response components (inflammatome) in those diseases for identifying more effective targets and therapeutics against multiple inflammation driven diseases. This concept proposal aims to systematically investigate the uniqueness and commonality of inflammation related pathways in major human diseases using state-of-the-art multiscale molecular network modeling approaches to integrate large-scale multi-Omics datasets generated by NIH's AMP Programs and other sources. This project will identify not only data driven signatures, networks and key drivers of inflammation conserved across multiple diseases, but also FDA approved drugs that are potentially effective in treating multiple inflammatory diseases. The proposed study is truly transformative in discovering both novel mechanisms and therapeutics for major human diseases which involve dysregulated inflammation and immune response.

炎症/免疫反应失调已被确定为驱动主要人类疾病的关键因素 如癌症、风湿性关节炎（RA）、2型糖尿病（T2 D）和阿尔茨海默病（AD）。但 缺乏对炎症/免疫反应组分（炎性组）的全面比较研究 在这些疾病中，用于鉴定针对多种炎症驱动的更有效的靶标和治疗剂， 疾病这一概念提案旨在系统地研究 使用最先进的多尺度分子网络研究人类主要疾病中的炎症相关通路 整合NIH AMP计划生成的大规模多组学数据集的建模方法， 其他来源该项目不仅将确定数据驱动的签名，网络和炎症的关键驱动因素， 在多种疾病中保守，但也有FDA批准的药物， 多种炎症性疾病。这项拟议中的研究在发现这两种新颖性方面确实具有变革性 涉及炎症和免疫调节失调的主要人类疾病的机制和治疗方法 反应

项目成果

Microglial TYROBP/DAP12 in Alzheimer's disease: Transduction of physiological and pathological signals across TREM2.

• DOI: 10.1186/s13024-022-00552-w
• 发表时间: 2022-08-24
• 期刊: Molecular neurodegeneration
• 影响因子: 15.1

Integrative gene network analysis identifies key signatures, intrinsic networks and host factors for influenza virus A infections.

• DOI: 10.1038/s41540-017-0036-x
• 发表时间: 2017
• 期刊: NPJ systems biology and applications
• 影响因子: 4
• 作者: Forst CV;Zhou B;Wang M;Chou TW;Mason G;Song WM;Schadt E;Ghedin E;Zhang B
• 通讯作者: Zhang B

Inter-tissue coexpression network analysis reveals DPP4 as an important gene in heart to blood communication.

• DOI: 10.1186/s13073-016-0268-1
• 发表时间: 2016-02-09
• 期刊: Genome medicine
• 影响因子: 12.3
• 作者: Long Q;Argmann C;Houten SM;Huang T;Peng S;Zhao Y;Tu Z;GTEx Consortium;Zhu J
• 通讯作者: Zhu J

EPRS is a critical regulator of cell proliferation and estrogen signaling in ER+ breast cancer.

• DOI: 10.18632/oncotarget.11870
• 发表时间: 2016-10-25
• 期刊: Oncotarget
• 作者: Katsyv I;Wang M;Song WM;Zhou X;Zhao Y;Park S;Zhu J;Zhang B;Irie HY
• 通讯作者: Irie HY

The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer's disease.

• DOI: 10.1038/sdata.2018.185
• 发表时间: 2018-09-11
• 期刊: Scientific data
• 影响因子: 9.8
• 作者: Wang M;Beckmann ND;Roussos P;Wang E;Zhou X;Wang Q;Ming C;Neff R;Ma W;Fullard JF;Hauberg ME;Bendl J;Peters MA;Logsdon B;Wang P;Mahajan M;Mangravite LM;Dammer EB;Duong DM;Lah JJ;Seyfried NT;Levey AI;Buxbaum JD;Ehrlich M;Gandy S;Katsel P;Haroutunian V;Schadt E;Zhang B
• 通讯作者: Zhang B