Large-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets

Abstract Identifying the occurrence mechanism of drug-induced side effects (SEs) is critical for design of drug target and new drug development. The expression of genes in biological processes is regulated by transcription factors(TFs) and/or microRNAs. Most of previous studies were focused on a sin...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Xiaodong Jia, Qing Jin, Xiangqiong Liu, Xiusen Bian, Yunfeng Wang, Lei Liu, Hongzhe Ma, Fujian Tan, Mingliang Gu, Xiujie Chen
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
R
Q
Acceso en línea:https://doaj.org/article/239946725e554e61914fbcd41eb0f1d1
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:239946725e554e61914fbcd41eb0f1d1
record_format dspace
spelling oai:doaj.org-article:239946725e554e61914fbcd41eb0f1d12021-12-02T15:04:58ZLarge-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets10.1038/s41598-017-06083-52045-2322https://doaj.org/article/239946725e554e61914fbcd41eb0f1d12017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06083-5https://doaj.org/toc/2045-2322Abstract Identifying the occurrence mechanism of drug-induced side effects (SEs) is critical for design of drug target and new drug development. The expression of genes in biological processes is regulated by transcription factors(TFs) and/or microRNAs. Most of previous studies were focused on a single level of gene or gene sets, while studies about regulatory relationships of TFs, miRNAs and biological processes are very rare. Discovering the complex regulating relations among TFs, gene sets and miRNAs will be helpful for researchers to get a more comprehensive understanding about the mechanism of side reaction. In this study, a framework was proposed to construct the relationship network of gene sets, miRNAs and TFs involved in side effects. Through the construction of this network, the potential complex regulatory relationship in the occurrence process of the side effects was reproduced. The SE-gene set network was employed to characterize the significant regulatory SE-gene set interaction and molecular basis of accompanied side effects. A total of 117 side effects complex modules including four types of regulating patterns were obtained from the SE-gene sets-miRNA/TF complex regulatory network. In addition, two cases were used to validate the complex regulatory modules which could more comprehensively interpret occurrence mechanism of side effects.Xiaodong JiaQing JinXiangqiong LiuXiusen BianYunfeng WangLei LiuHongzhe MaFujian TanMingliang GuXiujie ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Xiaodong Jia
Qing Jin
Xiangqiong Liu
Xiusen Bian
Yunfeng Wang
Lei Liu
Hongzhe Ma
Fujian Tan
Mingliang Gu
Xiujie Chen
Large-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets
description Abstract Identifying the occurrence mechanism of drug-induced side effects (SEs) is critical for design of drug target and new drug development. The expression of genes in biological processes is regulated by transcription factors(TFs) and/or microRNAs. Most of previous studies were focused on a single level of gene or gene sets, while studies about regulatory relationships of TFs, miRNAs and biological processes are very rare. Discovering the complex regulating relations among TFs, gene sets and miRNAs will be helpful for researchers to get a more comprehensive understanding about the mechanism of side reaction. In this study, a framework was proposed to construct the relationship network of gene sets, miRNAs and TFs involved in side effects. Through the construction of this network, the potential complex regulatory relationship in the occurrence process of the side effects was reproduced. The SE-gene set network was employed to characterize the significant regulatory SE-gene set interaction and molecular basis of accompanied side effects. A total of 117 side effects complex modules including four types of regulating patterns were obtained from the SE-gene sets-miRNA/TF complex regulatory network. In addition, two cases were used to validate the complex regulatory modules which could more comprehensively interpret occurrence mechanism of side effects.
format article
author Xiaodong Jia
Qing Jin
Xiangqiong Liu
Xiusen Bian
Yunfeng Wang
Lei Liu
Hongzhe Ma
Fujian Tan
Mingliang Gu
Xiujie Chen
author_facet Xiaodong Jia
Qing Jin
Xiangqiong Liu
Xiusen Bian
Yunfeng Wang
Lei Liu
Hongzhe Ma
Fujian Tan
Mingliang Gu
Xiujie Chen
author_sort Xiaodong Jia
title Large-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets
title_short Large-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets
title_full Large-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets
title_fullStr Large-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets
title_full_unstemmed Large-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets
title_sort large-scale analysis of drug side effects via complex regulatory modules composed of micrornas, transcription factors and gene sets
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/239946725e554e61914fbcd41eb0f1d1
work_keys_str_mv AT xiaodongjia largescaleanalysisofdrugsideeffectsviacomplexregulatorymodulescomposedofmicrornastranscriptionfactorsandgenesets
AT qingjin largescaleanalysisofdrugsideeffectsviacomplexregulatorymodulescomposedofmicrornastranscriptionfactorsandgenesets
AT xiangqiongliu largescaleanalysisofdrugsideeffectsviacomplexregulatorymodulescomposedofmicrornastranscriptionfactorsandgenesets
AT xiusenbian largescaleanalysisofdrugsideeffectsviacomplexregulatorymodulescomposedofmicrornastranscriptionfactorsandgenesets
AT yunfengwang largescaleanalysisofdrugsideeffectsviacomplexregulatorymodulescomposedofmicrornastranscriptionfactorsandgenesets
AT leiliu largescaleanalysisofdrugsideeffectsviacomplexregulatorymodulescomposedofmicrornastranscriptionfactorsandgenesets
AT hongzhema largescaleanalysisofdrugsideeffectsviacomplexregulatorymodulescomposedofmicrornastranscriptionfactorsandgenesets
AT fujiantan largescaleanalysisofdrugsideeffectsviacomplexregulatorymodulescomposedofmicrornastranscriptionfactorsandgenesets
AT minglianggu largescaleanalysisofdrugsideeffectsviacomplexregulatorymodulescomposedofmicrornastranscriptionfactorsandgenesets
AT xiujiechen largescaleanalysisofdrugsideeffectsviacomplexregulatorymodulescomposedofmicrornastranscriptionfactorsandgenesets
_version_ 1718388942607220736