Organ system heterogeneity DB: a database for the visualization of phenotypes at the organ system level.
Bottom Line: Some perturbations impair relatively few organ systems while others lead to highly heterogeneous or systemic effects.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.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.
Affiliation: German Center for Diabetes Research, Neuherberg 85764, Germany Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg 85764, Germany.Show MeSH
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Mentions: Besides, the analysis of organismal phenotypes has evidenced the great variability of the phenotypic impact of mammalian perturbations. While some perturbations exert local effects impairing predominantly few organ systems, others cause heterogeneous effects across many organ systems, leading to a systemic harm of the organism (9,10). In a recent study (9), we analyzed the systemic impact of a large number of human diseases, drugs and genetic perturbations in mice by using the organ system heterogeneity, a measurement of the spread of phenotypic effects across multiple mammalian organ systems. We discovered a close relationship of gene properties, such as subcellular localization of the gene products, tissue expression, essentiality and the number of genes, involved in a perturbation with its systemic impact (9). This finding highlights the relevance of the analysis of phenotypic data at the organ system level for the understanding of the molecular causes linked to systemic effects of perturbations. Towards this aim, we have developed the Organ System Heterogeneity DB. This database provides the organ system level impact of disease symptoms, drug side effects and phenotypes of genetically modified mouse models. In particular, it allows the visualization of the phenotypic effects of 4865 diseases, 1667 drugs and 5361 genes (Figure 1) on 26 different organ system categories (as defined by the Medical Dictionary of Regulatory Activities (MedDRA)).
Affiliation: German Center for Diabetes Research, Neuherberg 85764, Germany Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg 85764, Germany.