Exploring pharmacological active ingredients of traditional Chinese medicine by pharmacotranscriptomic map in ITCM
Exploring pharmacological active ingredients of traditional Chinese medicine by pharmacotranscriptomic map in ITCM
复制标题
应用ITCM中的药物转录组图谱探索中药的药理活性成分
DOI：
10.1093/bib/bbad027
复制
发表时间：
2023-03-19
影响因子：
9.5
通讯作者：
Zhang，Weidong
中科院分区：
文献类型：
--
作者：
Tian，Saisai;Zhang，Jinbo;Zhang，Weidong
随着高通量技术的出现，基于基因表达谱的计算筛选已成为药物发现的最有效方法之一。更重要的是，基于特征的方法显着提高了新的药物-疾病对发现，而不依赖于药物或疾病特异性的先验知识，这已被广泛应用于现代医学。然而，由于缺乏足够的药物转录组学数据，基于谱的中药活性成分的系统筛选很少进行。在此，我们开发了迄今为止最大的基于中药活性成分的在线药物转录组学平台--中药整合平台（ITCM），用于有效成分的筛选。首先，我们进行了统一的高通量实验，并构建了496种代表性活性成分的最大数据库，这是我们团队之前构建的数据库的五倍。基于转录组的多尺度分析也被用来阐明它们的机制。然后，我们开发了六种最先进的签名搜索方法来筛选活性成分，并确定所有方法的最佳签名大小。此外，我们将它们整合到筛选策略TCM-Query中，以识别特殊疾病的潜在活性成分。此外，还通过文献挖掘，全面收集了中医药相关资源。最后，我们将ITCM应用于一种活性成分巴瓦奇宁和两种疾病，包括前列腺癌和COVID-19，以证明药物发现的力量。国际中医药大会旨在全面发掘中药有效成分，促进中药药理作用研究和新药开发。ITCM可在http://itcm.biotcm.net上获得。
With the emergence of high-throughput technologies, computational screening based on gene expression profiles has become one of the most effective methods for drug discovery. More importantly, profile-based approaches remarkably enhance novel drug–disease pair discovery without relying on drug- or disease-specific prior knowledge, which has been widely used in modern medicine. However, profile-based systematic screening of active ingredients of traditional Chinese medicine (TCM) has been scarcely performed due to inadequate pharmacotranscriptomic data. Here, we develop the largest-to-date online TCM active ingredients-based pharmacotranscriptomic platform integrated traditional Chinese medicine (ITCM) for the effective screening of active ingredients. First, we performed unified high-throughput experiments and constructed the largest data repository of 496 representative active ingredients, which was five times larger than the previous one built by our team. The transcriptome-based multi-scale analysis was also performed to elucidate their mechanism. Then, we developed six state-of-art signature search methods to screen active ingredients and determine the optimal signature size for all methods. Moreover, we integrated them into a screening strategy, TCM-Query, to identify the potential active ingredients for the special disease. In addition, we also comprehensively collected the TCM-related resource by literature mining. Finally, we applied ITCM to an active ingredient bavachinin, and two diseases, including prostate cancer and COVID-19, to demonstrate the power of drug discovery. ITCM was aimed to comprehensively explore the active ingredients of TCM and boost studies of pharmacological action and drug discovery. ITCM is available at http://itcm.biotcm.net.