Department of Bioinformatics, Smart Health Big Data Analysis and Location Services Engineering Lab of Jiangsu Province, School of Geographic and Biologic Information, Nanjing University of Posts and Telecommunications, No. 9, Wenyuan Road, Qixia District, Nanjing, Jiangsu 210023, China.
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, No. 1, Wenyuan Road, Qixia District, Nanjing, Jiangsu 210023, China.
Database (Oxford). 2022 Aug 27;2022. doi: 10.1093/database/baac075.
Synthetic lethality has been widely concerned because of its potential role in cancer treatment, which can be harnessed to selectively kill cancer cells via identifying inactive genes in a specific cancer type and further targeting the corresponding synthetic lethal partners. Herein, to obtain cancer-specific synthetic lethal interactions, we aimed to predict genetic interactions via a pan-cancer analysis from multiple molecular levels using random forest and then develop a user-friendly database. First, based on collected public gene pairs with synthetic lethal interactions, candidate gene pairs were analyzed via integrating multi-omics data, mainly including DNA mutation, copy number variation, methylation and mRNA expression data. Then, integrated features were used to predict cancer-specific synthetic lethal interactions using random forest. Finally, SLOAD (http://www.tmliang.cn/SLOAD) was constructed via integrating these findings, which was a user-friendly database for data searching, browsing, downloading and analyzing. These results can provide candidate cancer-specific synthetic lethal interactions, which will contribute to drug designing in cancer treatment that can promote therapy strategies based on the principle of synthetic lethality. Database URL http://www.tmliang.cn/SLOAD/.
合成致死性因其在癌症治疗中的潜在作用而受到广泛关注,它可以通过识别特定癌症类型中失活的基因,并进一步靶向相应的合成致死伙伴,从而选择性地杀死癌细胞。为此,我们旨在通过随机森林从多个分子水平对泛癌症分析进行预测,从而获得癌症特异性的合成致死相互作用,并进一步开发一个用户友好的数据库。首先,基于收集到的具有合成致死相互作用的公共基因对,通过整合多组学数据(主要包括 DNA 突变、拷贝数变异、甲基化和 mRNA 表达数据)来分析候选基因对。然后,使用随机森林来预测癌症特异性的合成致死相互作用。最后,通过整合这些发现构建了 SLOAD(http://www.tmliang.cn/SLOAD),这是一个用于数据搜索、浏览、下载和分析的用户友好型数据库。这些结果可以提供候选的癌症特异性合成致死相互作用,这将有助于癌症治疗中的药物设计,促进基于合成致死原理的治疗策略。数据库 URL:http://www.tmliang.cn/SLOAD/。