Barcelona Supercomputing Center, Barcelona, Spain.
Department of Computer Science, University College London, London, WC1E 6BT, UK.
Sci Rep. 2021 Sep 23;11(1):18985. doi: 10.1038/s41598-021-98289-x.
The COVID-19 pandemic is raging. It revealed the importance of rapid scientific advancement towards understanding and treating new diseases. To address this challenge, we adapt an explainable artificial intelligence algorithm for data fusion and utilize it on new omics data on viral-host interactions, human protein interactions, and drugs to better understand SARS-CoV-2 infection mechanisms and predict new drug-target interactions for COVID-19. We discover that in the human interactome, the human proteins targeted by SARS-CoV-2 proteins and the genes that are differentially expressed after the infection have common neighbors central in the interactome that may be key to the disease mechanisms. We uncover 185 new drug-target interactions targeting 49 of these key genes and suggest re-purposing of 149 FDA-approved drugs, including drugs targeting VEGF and nitric oxide signaling, whose pathways coincide with the observed COVID-19 symptoms. Our integrative methodology is universal and can enable insight into this and other serious diseases.
COVID-19 大流行肆虐。它揭示了快速推进科学发展以理解和治疗新疾病的重要性。为了应对这一挑战,我们采用了一种可解释的人工智能算法进行数据融合,并将其应用于新的病毒-宿主相互作用、人类蛋白质相互作用和药物的组学数据上,以更好地了解 SARS-CoV-2 感染机制,并预测 COVID-19 的新药物-靶标相互作用。我们发现,在人类相互作用组中,SARS-CoV-2 蛋白靶向的人类蛋白和感染后差异表达的基因在相互作用组中有共同的邻居,这些邻居可能是疾病机制的关键。我们发现了 185 种针对这些关键基因中 49 种的新的药物-靶标相互作用,并提出了重新利用 149 种 FDA 批准药物的建议,包括针对 VEGF 和一氧化氮信号的药物,其途径与观察到的 COVID-19 症状一致。我们的综合方法具有普遍性,可以为理解这种疾病和其他严重疾病提供洞见。