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Research Paper|Volume 12, Issue 21|pp 21504—21517

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

Xinmiao Yan1, Yiyan Yang1, Zikun Chen1, Zuojing Yin1, Zeliang Deng1, Tianyi Qiu2, Kailin Tang1, Zhiwei Cao1
  • 1Department of Gastroenterology, Shanghai Tenth People’s Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
  • 2Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China
Received: March 14, 2020Accepted: July 30, 2020Published: November 10, 2020
https://doi.org/10.18632/aging.103925

Copyright: © 2020 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.