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NOGEA: A Network-oriented Gene Entropy Approach for Dissecting disease comorbidity and Drug Repositioning

Genomics, Proteomics & Bioinformatics 2021年第4期19卷 549-564页

作者： Zihu Guo Yingxue Fu Chao Huang Chunli Zheng Ziyin Wu Xuetong Chen Shuo Gao Yaohua Ma Mohamed Shahen Yan Li Pengfei Tu Jingbo Zhu Zhenzhong Wang Wei Xiao Yonghua Wang College of Life Science Northwest UniversityXi'an 710069China College of Life Science Northwest A&F UniversityYangling 712100China Zoology Department Faculty of ScienceTanta UniversityTanta 31527Egypt Key Laboratory of Industrial Ecology and Environmental Engineering(Ministry of Education) Faculty of ChemicalEnvironmental and Biological Science and TechnologyDalian University of TechnologyDalian 116024China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China School of Food Science and Technology Dalian Polytechnic UniversityDalian 116034China State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process Lianyungang 222001China

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes(DAGs),which are important for understanding disease initiation and developing precision ***,DAGs often contain large amounts of redundant or false positive information,leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human *** this study,a networkoriented gene entropy approach(NOGEA)is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene *** addition,we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression *** genes may also be used to extract the underlying information of different diseases,thus revealing mechanisms of disease *** importantly,approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network,which provides a new way for predicting drug-disease *** this method,11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro ***,the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence,thus providing a valuable strategy for drug efficacy screening and *** codes are publicly available at https://***/guozihuaa/NOGEA.

关键词： Systems pharmacology Gene entropy disease gene network disease comorbidity Drug repositioning

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