PDF(Pubmed)
Abstract：
Understudied or dark proteins have the potential to shed light on as-yet undiscovered molecular mechanisms that underlie phenotypes and suggest innovative therapeutic approaches for many diseases. The Reactome-IDG (Illuminating the Druggable Genome) project aims to place dark proteins in the context of manually curated, highly reliable pathways in Reactome, the most comprehensive, open-source biological pathway knowledgebase, facilitating the understanding functions and predicting therapeutic potentials of dark proteins. The Reactome-IDG web portal, deployed at https://idg.reactome.org, provides a simple, interactive web page for users to search pathways that may functionally interact with dark proteins, enabling the prediction of functions of dark proteins in the context of Reactome pathways. Enhanced visualization features implemented at the portal allow users to investigate the functional contexts for dark proteins based on tissue-specific gene or protein expression, drug-target interactions, or protein or gene pairwise relationships in the original Reactome\'s systems biology graph notation (SBGN) diagrams or the new simplified functional interaction (FI) network view of pathways. The protocols in this chapter describe step-by-step procedures to use the web portal to learn biological functions of dark proteins in the context of Reactome pathways. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Search for interacting pathways of a protein Support Protocol: Interacting pathway results for an annotated protein Alternate Protocol: Use individual pairwise relationships to predict interacting pathways of a protein Basic Protocol 2: Using the IDG pathway browser to study interacting pathways Basic Protocol 3: Overlaying tissue-specific expression data Basic Protocol 4: Overlaying protein/gene pairwise relationships in the pathway context Basic Protocol 5: Visualizing drug/target interactions.
摘要：
研究不足的或暗蛋白有可能揭示尚未发现的表型基础的分子机制，并为许多疾病提出创新的治疗方法。Reactome-IDG（照亮药物基因组）项目旨在将暗蛋白置于手动策划的背景下，在反应组中高度可靠的途径，最全面的,开源生物通路知识库，有助于理解暗蛋白的功能和预测治疗潜力。Reactome-IDG门户网站，部署在https://idg。reactome.org,提供了一个简单的，交互式网页，供用户搜索可能在功能上与暗蛋白相互作用的途径，在反应组途径的背景下，能够预测暗蛋白的功能。在门户上实现的增强的可视化功能允许用户基于组织特异性基因或蛋白质表达调查暗蛋白质的功能上下文。药物-靶标相互作用，原始Reactome系统生物学图表示法（SBGN）图中的蛋白质或基因成对关系或新的简化功能相互作用（FI）网络路径视图。本章中的协议描述了使用门户网站在Reactome途径的背景下学习暗蛋白的生物学功能的逐步程序。©2023威利期刊有限责任公司。基本方案1：搜索蛋白质支持方案的相互作用途径：注释蛋白质的相互作用途径结果替代方案：使用个体成对关系预测蛋白质的相互作用途径基本方案2：使用IDG途径浏览器研究相互作用途径基本方案3：叠加组织特异性表达数据基本方案4：在途径中叠加蛋白质/基因成对关系基本方案5：可视化药物/靶标相互作用。
