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基于大规模药物诱导基因表达谱的因子特异性生成模式。

Factor-specific generative pattern from large-scale drug-induced gene expression profile.

机构信息

Department of Biomedical Sciences, Seoul National University Biomedical Informatics (SNUBI), Seoul National University College of Medicine, Seoul, Republic of Korea.

Division of Biomedical Informatics, Seoul National University Biomedical Informatics (SNUBI), Seoul National University College of Medicine, Seoul, Republic of Korea.

出版信息

Sci Rep. 2023 Apr 18;13(1):6339. doi: 10.1038/s41598-023-33061-x.

Abstract

Drug discovery is a complex and interdisciplinary field that requires the identification of potential drug targets for specific diseases. In this study, we present FacPat, a novel approach that identifies the optimal factor-specific pattern explaining the drug-induced gene expression profile. FacPat uses a genetic algorithm based on pattern distance to mine the optimal factor-specific pattern for each gene in the LINCS L1000 dataset. We applied Benjamini-Hochberg correction to control the false discovery rate and identified significant and interpretable factor-specific patterns consisting of 480 genes, 7 chemical compounds, and 38 human cell lines. Using our approach, we identified genes that show context-specific effects related to chemical compounds and/or human cell lines. Furthermore, we performed functional enrichment analysis to characterize biological features. We demonstrate that FacPat can be used to reveal novel relationships among drugs, diseases, and genes.

摘要

药物发现是一个复杂的跨学科领域,需要确定针对特定疾病的潜在药物靶点。在这项研究中,我们提出了 FacPat,这是一种新颖的方法,可确定最佳的特定于因子的模式,以解释药物诱导的基因表达谱。FacPat 使用基于模式距离的遗传算法来挖掘 LINCS L1000 数据集每个基因的最佳特定于因子的模式。我们应用了 Benjamini-Hochberg 校正来控制错误发现率,并确定了由 480 个基因、7 种化学化合物和 38 个人类细胞系组成的具有显著意义且可解释的特定于因子的模式。使用我们的方法,我们确定了与化学化合物和/或人类细胞系相关的表现出特定于上下文的效应的基因。此外,我们进行了功能富集分析以描述生物学特征。我们证明 FacPat 可用于揭示药物、疾病和基因之间的新关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25ab/10113368/190eefd89a87/41598_2023_33061_Fig1_HTML.jpg

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