Organ system heterogeneity DB: a database for the visualization of phenotypes at the organ system level.

Deepthi Mannil,Ingo Vogt,Jeanette Prinz,Monica Campillos

doi:10.1093/nar/gku948

Abstract

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.

Highlights

Human diseases, drug treatments and genetically modified mouse models are perturbations in mammalian organisms with observable phenotypes
Side effect similarity has been employed to identify new drug targets [1] and functional relations between disease genes have been found among diseases that share symptoms [2,3]
The comparison of phenotypes of human diseases and drugs with those of genetically modified mouse models has been exploited for gene prioritization in diseases [4,5,6] and to predict novel drug–target interactions [7], respectively

Summary

Introduction

Drug treatments and genetically modified mouse models are perturbations in mammalian organisms with observable phenotypes. This database provides the organ system level impact of disease symptoms, drug side effects and phenotypes of genetically modified mouse models.

Results

Conclusion