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基于基因表达谱的药物-疾病关联在不同类别药物和疾病中的表现。

The Performance of Gene Expression Signature-Guided Drug-Disease Association in Different Categories of Drugs and Diseases.

机构信息

Department of Pharmaceutical Sciences, Computational Chemical Genomics Screening Center, University of Pittsburgh School of Pharmacy, 3501 Terrace St Pittsburgh, PA 15261, USA.

Department of Biological Sciences, University of Pittsburgh School of Arts & Sciences, Pittsburgh, PA 15260, USA.

出版信息

Molecules. 2020 Jun 16;25(12):2776. doi: 10.3390/molecules25122776.

Abstract

A gene expression signature (GES) is a group of genes that shows a unique expression profile as a result of perturbations by drugs, genetic modification or diseases on the transcriptional machinery. The comparisons between GES profiles have been used to investigate the relationships between drugs, their targets and diseases with quite a few successful cases reported. Especially in the study of GES-guided drugs-disease associations, researchers believe that if a GES induced by a drug is opposite to a GES induced by a disease, the drug may have potential as a treatment of that disease. In this study, we data-mined the crowd extracted expression of differential signatures (CREEDS) database to evaluate the similarity between GES profiles from drugs and their indicated diseases. Our study aims to explore the application domains of GES-guided drug-disease associations through the analysis of the similarity of GES profiles on known pairs of drug-disease associations, thereby identifying subgroups of drugs/diseases that are suitable for GES-guided drug repositioning approaches. Our results supported our hypothesis that the GES-guided drug-disease association method is better suited for some subgroups or pathways such as drugs and diseases associated with the immune system, diseases of the nervous system, non-chemotherapy drugs or the mTOR signaling pathway.

摘要

基因表达特征(GES)是一组基因,由于药物、遗传修饰或疾病对转录机制的干扰,表现出独特的表达谱。GES 谱之间的比较被用于研究药物、其靶标和疾病之间的关系,已有相当多的成功案例报道。特别是在 GES 指导的药物-疾病关联研究中,研究人员认为,如果一种药物诱导的 GES 与一种疾病诱导的 GES 相反,那么该药物可能具有治疗该疾病的潜力。在这项研究中,我们对人群提取的差异表达特征(CREEDS)数据库进行了数据挖掘,以评估药物和其指示疾病的 GES 谱之间的相似性。我们的研究旨在通过分析已知药物-疾病关联对的 GES 谱的相似性,探索 GES 指导的药物-疾病关联的应用领域,从而确定适合 GES 指导的药物重定位方法的药物/疾病亚组。我们的结果支持了我们的假设,即 GES 指导的药物-疾病关联方法更适合某些亚组或途径,如与免疫系统、神经系统疾病、非化疗药物或 mTOR 信号通路相关的药物和疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c43/7357095/b719e67c5e10/molecules-25-02776-g001.jpg

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