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使用ReactomeFIViz在通路和网络背景下可视化药物靶点相互作用。

Visualization of drug target interactions in the contexts of pathways and networks with ReactomeFIViz.

作者信息

Blucher Aurora S, McWeeney Shannon K, Stein Lincoln, Wu Guanming

机构信息

Knight Cancer Institute, Oregon Health & Science University, Portland, OR, 97239, USA.

Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, 97239, USA.

出版信息

F1000Res. 2019 Jun 20;8:908. doi: 10.12688/f1000research.19592.1. eCollection 2019.

Abstract

The precision medicine paradigm is centered on therapies targeted to particular molecular entities that will elicit an anticipated and controlled therapeutic response. However, genetic alterations in the drug targets themselves or in genes whose products interact with the targets can affect how well a drug actually works for an individual patient. To better understand the effects of targeted therapies in patients, we need software tools capable of simultaneously visualizing patient-specific variations and drug targets in their biological context. This context can be provided using pathways, which are process-oriented representations of biological reactions, or biological networks, which represent pathway-spanning interactions among genes, proteins, and other biological entities. To address this need, we have recently enhanced the Reactome Cytoscape app, ReactomeFIViz, to assist researchers in visualizing and modeling drug and target interactions. ReactomeFIViz integrates drug-target interaction information with high quality manually curated pathways and a genome-wide human functional interaction network. Both the pathways and the functional interaction network are provided by Reactome, the most comprehensive open source biological pathway knowledgebase. We describe several examples demonstrating the application of these new features to the visualization of drugs in the contexts of pathways and networks. Complementing previous features in ReactomeFIViz, these new features enable researchers to ask focused questions about targeted therapies, such as drug sensitivity for patients with different mutation profiles, using a pathway or network perspective.

摘要

精准医学范式以针对特定分子实体的疗法为核心,这些疗法将引发预期且可控的治疗反应。然而,药物靶点自身或其产物与靶点相互作用的基因中的基因改变,会影响药物对个体患者的实际疗效。为了更好地理解靶向疗法对患者的影响,我们需要能够在生物学背景下同时可视化患者特异性变异和药物靶点的软件工具。这种背景可以通过通路(生物学反应的面向过程的表示)或生物网络(代表基因、蛋白质和其他生物实体之间跨通路的相互作用)来提供。为满足这一需求,我们最近增强了Reactome Cytoscape应用程序ReactomeFIViz,以协助研究人员可视化和建模药物与靶点的相互作用。ReactomeFIViz将药物-靶点相互作用信息与高质量的人工策划通路以及全基因组人类功能相互作用网络整合在一起。通路和功能相互作用网络均由Reactome提供,Reactome是最全面的开源生物通路知识库。我们描述了几个示例,展示了这些新功能在通路和网络背景下药物可视化中的应用。作为对ReactomeFIViz先前功能的补充,这些新功能使研究人员能够从通路或网络的角度,针对靶向疗法提出有针对性的问题,例如不同突变谱患者的药物敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e757/6644836/935bb8e66363/f1000research-8-21482-g0002.jpg

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