AlzGPS: a genome-wide positioning systems platform to catalyze multi-omics for Alzheimer's drug discovery.
AlzGPS: a genome-wide positioning systems platform to catalyze multi-omics for Alzheimer's drug discovery.
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AlzGPS：一个全基因组定位系统平台，用于催化阿尔茨海默病药物发现的多组学。
DOI：
10.1186/s13195-020-00760-w
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发表时间：
2021-01-13
期刊：
影响因子：
--
通讯作者：
Cheng F
中科院分区：
文献类型：
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作者：
Zhou Y;Fang J;Bekris LM;Kim YH;Pieper AA;Leverenz JB;Cummings J;Cheng F
最近的DNA/RNA测序和其他多组学技术促进了对AD生物学和病理生理学的理解，但仍缺乏针对AD的疾病修饰治疗。在药物发现和开发过程中整合基因组、转录组、蛋白质组和人类互动组的新方法对这一努力至关重要。在这项研究中，我们开发了用于阿尔茨海默病药物发现的全基因组定位系统平台，https://alzgps.lerner.ccf.org)，是一个综合的系统生物学工具，可以搜索、可视化和分析多组学、各种类型的异质生物网络和临床数据库，用于靶标识别和开发有效的AD预防和治疗。通过阿尔茨GPS：(1)我们收集了100多个AD多组学数据集，这些数据集捕获了AD发病机制的基因、核糖核酸、蛋白质和小分子图谱(例如，早期与晚期以及tau或淀粉样蛋白的内表型)；(2)我们结合多组学研究结果和人类蛋白质-蛋白质相互作用网络构建了内表型疾病模型；(3)我们使用最先进的网络邻近分析提供了~ 3000FDA批准的/研究中的AD药物的可能治疗信息；(4)我们为高可信的候选药物收集了近300篇文献参考文献；(5)我们纳入了1,000多项 AD临床试验的信息，注明了药物的作用机制和主要药物靶点，并将它们链接到我们针对靶点的集成多组学视图和药物的网络分析结果；(6)我们实现了用于数据库浏览和网络可视化的高度交互的Web界面。由阿尔茨GPS实现的网络可视化包括针对感兴趣基因的大脑特定邻域网络、针对感兴趣组学的内表型疾病模块网络以及针对疾病模块的药物的作用机制网络。通过结合系统药理学和基于网络的多组学数据综合分析，阿尔茨GPS为加速AD治疗开发提供了可行的系统生物学工具。网上版载有补充材料，可在10.1186/s13195-020-00760-w查阅。
Recent DNA/RNA sequencing and other multi-omics technologies have advanced the understanding of the biology and pathophysiology of AD, yet there is still a lack of disease-modifying treatments for AD. A new approach to integration of the genome, transcriptome, proteome, and human interactome in the drug discovery and development process is essential for this endeavor. In this study, we developed AlzGPS (Genome-wide Positioning Systems platform for Alzheimer’s Drug Discovery, https://alzgps.lerner.ccf.org), a comprehensive systems biology tool to enable searching, visualizing, and analyzing multi-omics, various types of heterogeneous biological networks, and clinical databases for target identification and development of effective prevention and treatment for AD. Via AlzGPS: (1) we curated more than 100 AD multi-omics data sets capturing DNA, RNA, protein, and small molecule profiles underlying AD pathogenesis (e.g., early vs. late stage and tau or amyloid endophenotype); (2) we constructed endophenotype disease modules by incorporating multi-omics findings and human protein-protein interactome networks; (3) we provided possible treatment information from ~ 3000 FDA approved/investigational drugs for AD using state-of-the-art network proximity analyses; (4) we curated nearly 300 literature references for high-confidence drug candidates; (5) we included information from over 1000 AD clinical trials noting drug’s mechanisms-of-action and primary drug targets, and linking them to our integrated multi-omics view for targets and network analysis results for the drugs; (6) we implemented a highly interactive web interface for database browsing and network visualization. Network visualization enabled by AlzGPS includes brain-specific neighborhood networks for genes-of-interest, endophenotype disease module networks for omics-of-interest, and mechanism-of-action networks for drugs targeting disease modules. By virtue of combining systems pharmacology and network-based integrative analysis of multi-omics data, AlzGPS offers actionable systems biology tools for accelerating therapeutic development in AD. The online version contains supplementary material available at 10.1186/s13195-020-00760-w.
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影响因子：
16.6
作者：
Cheng F;Desai RJ;Handy DE;Wang R;Schneeweiss S;Barabási AL;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
16.2
作者：
Bai, Bing;Wang, Xusheng;Peng, Junmin
通讯作者：
Peng, Junmin
DOI：
10.1073/pnas.85.11.4051
发表时间：
1988-06-01
影响因子：
11.1
作者：
GOEDERT, M;WISCHIK, CM;KLUG, A
通讯作者：
KLUG, A
影响因子：
14
作者：
通讯作者：
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