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Multi-omics prediction of immune-related adverse events during checkpoint immunotherapy

Ying Jing, Jin Liu, Youqiong Ye, Lei Pan, Hui Deng, Yushu Wang, Yang Yang, Lixia Diao, Steven H. Lin, Gordon B. Mills, Guanglei Zhuang, Xinying Xue, Leng Han

2020Nature Communications208 citationsDOIOpen Access PDF

Abstract

Immune-related adverse events (irAEs), caused by anti-PD-1/PD-L1 antibodies, can lead to fulminant and even fatal consequences and thus require early detection and aggressive management. However, a comprehensive approach to identify biomarkers of irAE is lacking. Here, we utilize a strategy that combines pharmacovigilance data and omics data, and evaluate associations between multi-omics factors and irAE reporting odds ratio across different cancer types. We identify a bivariate regression model of LCP1 and ADPGK that can accurately predict irAE. We further validate LCP1 and ADPGK as biomarkers in an independent patient-level cohort. Our approach provides a method for identifying potential biomarkers of irAE in cancer immunotherapy using both pharmacovigilance data and multi-omics data.

Topics & Concepts

OmicsPharmacovigilanceBivariate analysisAdverse effectImmunotherapyMedicineCohortCancerBioinformaticsOncologyComputer scienceInternal medicineMachine learningBiologyCancer Immunotherapy and BiomarkersComputational Drug Discovery MethodsColorectal Cancer Treatments and Studies
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