Department of Informatics and Telecommunications, University of Athens, 15784, Ilissia Athens, Greece.
Center of Systems Biology, Biomedical Research Foundation, Academy of Athens, Soranou Ephessiou 4, 115 27, Athens, Greece.
Sci Rep. 2017 Oct 3;7(1):12569. doi: 10.1038/s41598-017-12849-8.
Idiopathic Pulmonary Fibrosis (IPF) is a rare disease of the respiratory system in which the lungs stiffen and get scarred, resulting in breathing weakness and eventually leading to death. Drug repurposing is a process that provides evidence for existing drugs that may also be effective in different diseases. In this study, we present a computational pipeline having as input a number of gene expression datasets from early and advanced stages of IPF and as output lists of repurposed drugs ranked with a novel composite score. We have devised and used a scoring formula in order to rank the repurposed drugs, consolidating the standard repurposing score with structural, functional and side effects' scores for each drug per stage of IPF. The whole pipeline involves the selection of proper gene expression datasets, data preprocessing and statistical analysis, selection of the most important genes related to the disease, analysis of biological pathways, investigation of related molecular mechanisms, identification of fibrosis-related microRNAs, drug repurposing, structural and literature-based analysis of the repurposed drugs.
特发性肺纤维化（IPF）是一种罕见的呼吸系统疾病，其特征是肺部变硬和结疤，导致呼吸无力，最终导致死亡。药物再利用是一个提供现有药物证据的过程，这些药物可能对不同的疾病也有效。在这项研究中，我们提出了一个计算管道，其输入是来自 IPF 早期和晚期的多个基因表达数据集，输出是按新型综合评分排序的再利用药物列表。我们设计并使用了一种评分公式，以便对再利用药物进行排名，为每个阶段的 IPF 中的每种药物整合了标准的再利用评分以及结构、功能和副作用评分。整个管道涉及选择适当的基因表达数据集、数据预处理和统计分析、选择与疾病相关的最重要的基因、分析生物途径、研究相关的分子机制、鉴定纤维化相关的 microRNAs、药物再利用、再利用药物的结构和文献分析。
