Mannil Deepthi, Vogt Ingo, Prinz Jeanette, Campillos Monica
German Center for Diabetes Research, Neuherberg 85764, Germany Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
German Center for Diabetes Research, Neuherberg 85764, Germany Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg 85764, Germany
Nucleic Acids Res. 2015 Jan;43(Database issue):D900-6. doi: 10.1093/nar/gku948. Epub 2014 Oct 13.
Perturbations of mammalian organisms including diseases, drug treatments and gene perturbations in mice affect organ systems differently. Some perturbations impair relatively few organ systems while others lead to highly heterogeneous or systemic effects. Organ System Heterogeneity DB (http://mips.helmholtz-muenchen.de/Organ_System_Heterogeneity/) provides information on the phenotypic effects of 4865 human diseases, 1667 drugs and 5361 genetically modified mouse models on 26 different organ systems. Disease symptoms, drug side effects and mouse phenotypes are mapped to the System Organ Class (SOC) level of the Medical Dictionary of Regulatory Activities (MedDRA). Then, the organ system heterogeneity value, a measurement of the systemic impact of a perturbation, is calculated from the relative frequency of phenotypic features across all SOCs. For perturbations of interest, the database displays the distribution of phenotypic effects across organ systems along with the heterogeneity value and the distance between organ system distributions. In this way, it allows, in an easy and comprehensible fashion, the comparison of the phenotypic organ system distributions of diseases, drugs and their corresponding genetically modified mouse models of associated disease genes and drug targets. The Organ System Heterogeneity DB is thus a platform for the visualization and comparison of organ system level phenotypic effects of drugs, diseases and genes.
包括疾病、药物治疗和小鼠基因扰动在内的哺乳动物机体扰动对器官系统的影响各不相同。一些扰动仅损害相对较少的器官系统,而另一些则会导致高度异质性或全身性影响。器官系统异质性数据库(http://mips.helmholtz-muenchen.de/Organ_System_Heterogeneity/)提供了4865种人类疾病、1667种药物和5361种基因改造小鼠模型对26种不同器官系统的表型效应信息。疾病症状、药物副作用和小鼠表型被映射到《监管活动医学词典》(MedDRA)的系统器官分类(SOC)级别。然后,根据所有SOC中表型特征的相对频率计算器官系统异质性值,该值用于衡量扰动的全身性影响。对于感兴趣的扰动,数据库会显示表型效应在各器官系统中的分布情况,以及异质性值和器官系统分布之间的距离。通过这种方式,它能够以简单易懂的方式比较疾病、药物及其相关疾病基因和药物靶点的相应基因改造小鼠模型的表型器官系统分布。因此,器官系统异质性数据库是一个用于可视化和比较药物、疾病和基因在器官系统水平上的表型效应的平台。