AUTHOR=Li Bing , Wang Ying , Gu Hao , Yu Yanan , Wang Pengqian , Liu Jun , Zhang Yingying , Chen Yinying , Niu Qikai , Wang Bo , Liu Qiong , Guan Shuang , Li Yanda , Zhang Huamin , Wang Zhong 

TITLE=Modular Screening Reveals Driver Induced Additive Mechanisms of Baicalin and Jasminoidin on Cerebral Ischemia Therapy

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.813983

DOI=10.3389/fcvm.2022.813983

ISSN=2297-055X

ABSTRACT=Combination therapy with increased efficacy and reduced toxicity plays a crucial role in treating complex diseases including stroke, but it remains an insurmountable barrier to elucidate the mechanisms of synergistic effects. Here we present a Driver induced Modular Screening (DiMS) strategy integrated synergistic module and driver gene identification to elucidate the additive mechanisms of Baicalin (BA) and Jasminoidin (JA) on cerebral ischemia therapy. Based on anti-ischemia genomic networks BA, JA and their combination (BJ), we obtained 4, 3 and 9 On-modules of BA, JA and BJ by modular similarity analysis. Compared with the monotherapy groups, four additive modules (Add-module, BJ_Mod-4, 7, 9, 13) and 15 driver genes of BJ were identified by modular similarity and network control methods, seven driver proteins (PAQR8, RhoA, EMC10, GGA2, VIPR1, FAM120A, SEMA3F) were validated by animal experiments. Functional analysis found neuroprotective roles of the Add-modules and driver genes, such as the Neurotrophin signaling pathway, FoxO signaling pathway, which may reflects the additive mechanisms of BJ. Moreover, such a DiMS paradigm provides a new angle to explore the synergistic mechanisms of combination therapy and screen multi-targeted drugs for complex diseases.