H-RACS:一种用于对癌症协同药物进行排序的便捷工具。

H-RACS: a handy tool to rank anti-cancer synergistic drugs.

机构信息

Department of Gastroenterology, Shanghai Tenth People's Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.

Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China.

出版信息

Aging (Albany NY). 2020 Nov 10;12(21):21504-21517. doi: 10.18632/aging.103925.

Abstract

Though promising, identifying synergistic combinations from a large pool of candidate drugs remains challenging for cancer treatment. Due to unclear mechanism and limited confirmed cases, only a few computational algorithms are able to predict drug synergy. Yet they normally require the drug-cell treatment results as an essential input, thus exclude the possibility to pre-screen those unexplored drugs without cell treatment profiling. Based on the largest dataset of 33,574 combinational scenarios, we proposed a handy webserver, H-RACS, to overcome the above problems. Being loaded with chemical structures and target information, H-RACS can recommend potential synergistic pairs between candidate drugs on 928 cell lines of 24 prevalent cancer types. A high model performance was achieved with AUC of 0.89 on independent combinational scenarios. On the second independent validation of DREAM dataset, H-RACS obtained precision of 67% among its top 5% ranking list. When being tested on new combinations and new cell lines, H-RACS showed strong extendibility with AUC of 0.84 and 0.81 respectively. As the first online server freely accessible at http://www.badd-cao.net/h-racs, H-RACS may promote the pre-screening of synergistic combinations for new chemical drugs on unexplored cancers.

摘要

尽管很有前景,但从大量候选药物中确定协同组合对于癌症治疗仍然具有挑战性。由于机制不明确和确认案例有限,只有少数计算算法能够预测药物协同作用。然而,它们通常需要药物-细胞处理结果作为必要的输入,因此排除了在没有细胞处理分析的情况下预先筛选那些未探索药物的可能性。基于 33574 个组合场景的最大数据集,我们提出了一个方便的网络服务器 H-RACS,以克服上述问题。H-RACS 加载了化学结构和目标信息,可以在 24 种常见癌症类型的 928 种细胞系上推荐候选药物之间的潜在协同对。在独立组合场景上,该模型的 AUC 达到了 0.89,性能很高。在 DREAM 数据集的第二个独立验证中,H-RACS 在其排名前 5%的列表中获得了 67%的精度。在对新组合和新细胞系进行测试时,H-RACS 分别表现出了 0.84 和 0.81 的 AUC,具有很强的可扩展性。作为第一个可在 http://www.badd-cao.net/h-racs 上免费访问的在线服务器,H-RACS 可能会促进对未探索癌症的新化学药物的协同组合的预筛选。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1112/7695372/40192e4d36dd/aging-12-103925-g001.jpg

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