Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA.
Nucleic Acids Res. 2019 Jan 8;47(D1):D573-D580. doi: 10.1093/nar/gky1126.
Human gene networks have proven useful in many aspects of disease research, with numerous network-based strategies developed for generating hypotheses about gene-disease-drug associations. The ability to predict and organize genes most relevant to a specific disease has proven especially important. We previously developed a human functional gene network, HumanNet, by integrating diverse types of omics data using Bayesian statistics framework and demonstrated its ability to retrieve disease genes. Here, we present HumanNet v2 (http://www.inetbio.org/humannet), a database of human gene networks, which was updated by incorporating new data types, extending data sources and improving network inference algorithms. HumanNet now comprises a hierarchy of human gene networks, allowing for more flexible incorporation of network information into studies. HumanNet performs well in ranking disease-linked gene sets with minimal literature-dependent biases. We observe that incorporating model organisms' protein-protein interactions does not markedly improve disease gene predictions, suggesting that many of the disease gene associations are now captured directly in human-derived datasets. With an improved interactive user interface for disease network analysis, we expect HumanNet will be a useful resource for network medicine.
人类基因网络在疾病研究的许多方面都证明是有用的,已经开发了许多基于网络的策略来生成关于基因-疾病-药物关联的假设。预测和组织与特定疾病最相关的基因的能力被证明尤为重要。我们之前通过使用贝叶斯统计学框架整合多种类型的组学数据开发了人类功能基因网络 HumanNet,并证明了它检索疾病基因的能力。在这里,我们介绍了 HumanNet v2(http://www.inetbio.org/humannet),这是一个人类基因网络数据库,通过纳入新的数据类型、扩展数据源和改进网络推断算法进行了更新。HumanNet 现在包含一个人类基因网络层次结构,允许更灵活地将网络信息纳入研究中。HumanNet 在对疾病相关基因集进行排名时表现良好,几乎没有文献依赖性偏差。我们观察到,纳入模式生物的蛋白质-蛋白质相互作用并没有显著改善疾病基因预测,这表明许多疾病基因关联现在已经直接在源自人类的数据集。通过改进用于疾病网络分析的交互式用户界面,我们预计 HumanNet 将成为网络医学的有用资源。