Hybrid phenotype mining method for investigating off-target protein and underlying side effects of anti-tumor immunotherapy.
Background: It is of utmost importance to investigate novel therapies for cancer, as it is a major cause of death. In recent years, immunotherapies, especially those against immune checkpoints, have been developed and brought significant improvement in cancer management. However, on the other hand,...
| Publicado en: | BMC Medical Informatics & Decision Making Vol. 20; pp. 1 - 12 |
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| Autores principales: | , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
7/9/2020 Supplement 3
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=144473169&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 144473169 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14726947 1CI0 jtl: BMC Medical Informatics & Decision Making issn: 14726947 maglogo: N pubinfo: dt: 7/9/2020 Supplement 3 vid: 20 pid: 24147 pub: BioMed Central artinfo: ui: 144473169 144473169 NLM32646421 144473169 10.1186/s12911-020-1105-4 NLM32646421 144473169 ppf: 1 ppct: 11 formats: tig: atl: Hybrid phenotype mining method for investigating off-target protein and underlying side effects of anti-tumor immunotherapy. aug: au: Zheng, Yuyu Meng, Xiangyu Zweigenbaum, Pierre Chen, Lingling Xia, Jingbo affil: Hubei Key Lab of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, 430070, Wuhan, China sug: subj: Neoplasms Drug Therapy Adverse Drug Event Neoplasms Human Proteins Immunotherapy Adverse Effects Phenotype Validation Studies Comparative Studies Evaluation Research Multicenter Studies ab: Background: It is of utmost importance to investigate novel therapies for cancer, as it is a major cause of death. In recent years, immunotherapies, especially those against immune checkpoints, have been developed and brought significant improvement in cancer management. However, on the other hand, immune checkpoints blockade (ICB) by monoclonal antiboties may cause common and severe adverse reactions (ADRs), the cause of which remains largely undetermined. We hypothesize that ICB-agents may induce adverse reactions through off-target protein interactions, similar to the ADR-causing off-target effects of small molecules. In this study, we propose a hybrid phenotype mining approach which integrates molecular level information and provides new mechanistic insights for ICB-associated ADRs.Methods: We trained a conditional random fields model on the TAC 2017 benchmark training data, then used it to extract all drug-centric phenotypes for the five anti-PD-1/PD-L1 drugs from the drug labels of the DailyMed database. Proteins with structure similar to the drugs were obtained by using BlastP, and the gene targets of drugs were obtained from the STRING database. The target-centric phenotypes were extracted from the human phenotype ontology database. Finally, a screening module was designed to investigate off-target proteins, by making use of gene ontology analysis and pathway analysis.Results: Eventually, through the cross-analysis of the drug and target gene phenotypes, the off-target effect caused by the mutation of gene BTK was found, and the candidate side-effect off-target site was analyzed.Conclusions: This research provided a hybrid method of biomedical natural language processing and bioinformatics to investigate the off-target-based mechanism of ICB treatment. The method can also be applied for the investigation of ADRs related to other large molecule drugs. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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