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Human pathways in animal models: possibilities and limitations

机译:动物模型中的人途径:可能性和限制

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摘要

Animal models are crucial for advancing our knowledge about the molecular pathways involved in human diseases. However, it remains unclear to what extent tissue expression of pathways in healthy individuals is conserved between species. In addition, organism-specific information on pathways in animal models is often lacking. Within these limitations, we explore the possibilities that arise from publicly available data for the animal models mouse, rat, and pig. We approximate the animal pathways activity by integrating the human counterparts of curated pathways with tissue expression data from the models. Specifically, we compare whether the animal orthologs of the human genes are expressed in the same tissue. This is complicated by the lower coverage and worse quality of data in rat and pig as compared to mouse. Despite that, from 203 human KEGG pathways and the seven tissues with best experimental coverage, we identify 95 distinct pathways, for which the tissue expression in one animal model agrees better with human than the others. Our systematic pathway-tissue comparison between human and three animal modes points to specific similarities with human and to distinct differences among the animal models, thereby suggesting the most suitable organism for modeling a human pathway or tissue.
机译:动物模型对于推进有关涉及人类疾病的分子途径的知识至关重要。然而,它仍然尚不清楚健康个体途径的组织表达在多大程度上在物种之间保守。此外,往往缺乏动物模型中途径的有机体特异性信息。在这些限制内,我们探讨了从动物模型小鼠,大鼠和猪的公开可用数据产生的可能性。通过将策致途径的人对应物与模型的组织表达数据集成,我们近似动物途径活性。具体地,我们比较人类基因的动物直向同时在同一组织中表达。与小鼠相比,这与大鼠和猪中数据的较低覆盖率和更差的质量复杂化。尽管如此,来自203个人Kegg途径和七种组织,具有最佳实验覆盖率,我们鉴定了95个不同的途径,其中一个动物模型中的组织表达与人类更好地同意。我们的系统和三种动物模式之间的系统和三种动物模式的组织比较点与动物模型中的特定相似性和不同的差异,从而表明最合适的生物体用于建模人途径或组织。

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