Biological entities are involved in complicated and complex connections;hence,discovering biological information using network biology ideas is critical.In the past few years,network biology has emerged as an integrat...Biological entities are involved in complicated and complex connections;hence,discovering biological information using network biology ideas is critical.In the past few years,network biology has emerged as an integrative and systems-level approach for understanding and interpreting these complex interactions.Biological network analysis is one method for reducing enormous data sets to clinically useful knowledge for disease diagnosis,prognosis,and treatment.The network of biological entities can help us predict drug targets for several diseases.The drug targets identified through the systems biology approach help in targeting the essential biological pathways that contribute to the progression and development of the disease.The novel strategical approach of system biologyassisted pharmacology coupled with computer-aided drug discovery(CADD)can help drugs fight multifactorial diseases efficiently.In the present review,we have summarized the role and application of network biology for not only unfolding the mechanism of complex neurodevelopmental disorders but also identifying important drug targets for diseases like ADHD,Autism,Epilepsy,and Intellectual Disability.Systems biology has emerged as a promising approach to identifying drug targets and aiming for targeted drug discovery for the precise treatment of neurodevelopmental disorders.展开更多
BACKGROUND Human Wharton’s jelly-derived mesenchymal stromal/stem cells(hWJ-MSCs)have gained considerable attention in their applications in cell-based therapy due to several advantages offered by them.Recently,we re...BACKGROUND Human Wharton’s jelly-derived mesenchymal stromal/stem cells(hWJ-MSCs)have gained considerable attention in their applications in cell-based therapy due to several advantages offered by them.Recently,we reported that hWJ-MSCs and their conditioned medium have significant therapeutic radioprotective potential.This finding raised an obvious question to identify unique features of hWJ-MSCs over other sources of stem cells for a better understanding of its radioprotective mechanism.AIM To understand the radioprotective mechanism of soluble factors secreted by hWJMSCs and identification of their unique genes.METHODS Propidium iodide staining,endogenous spleen colony-forming assay,and survival study were carried out for radioprotection studies.Homeostasis-driven proliferation assay was performed for in vivo lymphocyte proliferation.Analysis of RNAseq data was performed to find the unique genes of WJ-MSCs by comparing them with bone marrow mesenchymal stem cells,embryonic stem cells,and human fibroblasts.Gene enrichment analysis and protein-protein interaction network were used for pathway analysis.RESULTS Co-culture of irradiated murine splenic lymphocytes with WJ-MSCs offered significant radioprotection to lymphocytes.WJ-MSC transplantation increased the homeostasis-driven proliferation of the lymphocytes.Neutralization of WJ-MSC conditioned medium with granulocyte-colony stimulating factor antibody abolished therapeutic radioprotection.Transcriptome analysis showed that WJ-MSCs share several common genes with bone marrow MSCs and embryonic stem cells and express high levels of unique genes such as interleukin(IL)1-α,IL1-β,IL-6,CXCL3,CXCL5,CXCL8,CXCL2,CCL2,FLT-1,and IL-33.It was also observed that WJ-MSCs preferentially modulate several cellular pathways and processes that handle the repair and regeneration of damaged tissues compared to stem cells from other sources.Cytokine-based network analysis showed that most of the radiosensitive tissues have a more complex network for the elevated cytokines.CONCLUSION Systemic infusion of WJ-MSC conditioned media will have significant potential for treating accidental radiation exposed victims。展开更多
Background:Yanhusuo powder,also known as Xuanhusuo powder,is a long-standing Chinese herbal formula mainly used in the treatment of osteoarthritis.Although the clinical effectiveness of Yanhusuo powder has long been a...Background:Yanhusuo powder,also known as Xuanhusuo powder,is a long-standing Chinese herbal formula mainly used in the treatment of osteoarthritis.Although the clinical effectiveness of Yanhusuo powder has long been acknowledged,its mechanism of action and bioactive components remain unknown.Methods:A novel analytical method combining the use of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultra-performance liquid chromatography-triple quadrupole mass spectrometry was applied to profile the formula and absorbed prototype components in plasma after oral administration of Yanhusuo powder.Then,the absorbed constituents were subjected to network pharmacology to predict targets and pathways.AutoDock software was then used for molecular docking studies to screen for potential pharmacodynamic substances.Results:A total of 34 in vitro formula components and 20 in vivo prototype compounds from the various relevant species were successfully separated and identified for the first time.Compound-target-pathway analysis revealed that 20 absorbed constituents,42 target genes and 42 pathways are probably related to the efficacy of Yanhusuo powder against osteoarthritis.The efficacy of Yanhusuo powder mainly involves AKT1,fibronectin 1 and matrix metalloproteinase 9 targets and apoptosis,as well as PI3K-AKT and mitogen-activated protein kinases signaling pathways.According to the results of the molecular docking studies,it can be preliminarily judged that protopine,dehydrocorybulbine and angelicin may be the pharmacologically active substances of Yanhusuo powder.Conclusion:The results provide a scientific basis for understanding the bioactive compounds and the pharmacological mechanism of Yanhusuo powder.展开更多
Traditional Chinese medicine (TCM) has developed over thousands of years and has accumulated abundant clinical experience, forming a comprehensive and unique medical system. Emerging evidence has begun to illustrate...Traditional Chinese medicine (TCM) has developed over thousands of years and has accumulated abundant clinical experience, forming a comprehensive and unique medical system. Emerging evidence has begun to illustrate TCM as an area of important medical rediscoveries. This review article briefly introduced the concept, significance, and technology of network pharmacology based on network biology and systems biology. It focused on the theoretical system and potential prospect of TCM network applied in TCM research and development including predicting new drug targets, action mechanism, new drug discovery; evaluating pharmacodynamics, pharmacokinetics, safety, toxicology, quality control, and bioinformatics of drugs. We also discussed the opportunities and challenges in the development and application of network pharmacology in the modernization of TCM research.展开更多
Network toxicology that is an important branch of the network pharmacology emerges on the basis of network biology. It refers to study on the toxicological features of a constructed network model which is used to anal...Network toxicology that is an important branch of the network pharmacology emerges on the basis of network biology. It refers to study on the toxicological features of a constructed network model which is used to analyze toxic substances and their interaction and regulation in biological systems, particularly investigate the toxic effects of drugs and/or compatibility of medicines on body, and clarify the mechanism of toxicity. Network toxicology currently develops rapidly in safety prediction of Chinese materia medica (CMM). The application of network toxicology to safety and toxicology study on CMM is extremely beneficial to identify the toxic components and potential incompatibility of CMM. Since CMM is a complex system with multi-components, multi-targets, and multi-interactions, the network toxicology in safety prediction of CMM faces three great challenges, including integration studies of bioinformatics, innovation of methods, and tools and risk assessment in future development of the network toxicology in CMM research. In this paper, relevant database, approaches and tools that network toxicology utilized in the safety study of CMM were carefully reviewed. Based on the progress made, the scientific development and modernization of CMM will be greatly enhanced.展开更多
Objective: To investigate the mechanisms of Panax notoginseng saponins(PNS) in treating coronary heart disease(CHD) by integrating gene interaction network and functional enrichment analysis. Methods: Text minin...Objective: To investigate the mechanisms of Panax notoginseng saponins(PNS) in treating coronary heart disease(CHD) by integrating gene interaction network and functional enrichment analysis. Methods: Text mining was used to get CHD and PNS associated genes. Gene–gene interaction networks of CHD and PNS were built by the Gene MANIA Cytoscape plugin. Advanced Network Merge Cytoscape plugin was used to analyze the two networks. Their functions were analyzed by gene functional enrichment analysis via DAVID Bioinformatics. Joint subnetwork of CHD network and PNS network was identified by network analysis. Results: The 11 genes of the joint subnetwork were the direct targets of PNS in CHD network and enriched in cytokine-cytokine receptor interaction pathway. PNS could affect other 85 genes by the gene–gene interaction of joint subnetwork and these genes were enriched in other 7 pathways. The direct mechanisms of PNS in treating CHD by targeting cytokines to relieve the inflammation and the indirect mechanisms of PNS in treating CHD by affecting other 7 pathways through the interaction of joint subnetwork of PNS and CHD network. The genes in the 7 pathways could be potential targets for the immunologic adjuvant, anticoagulant, hypolipidemic, anti-platelet and anti-hypertrophic activities of PNS. Conclusion: The key mechanisms of PNS in treating CHD could be anticoagulant and hypolipidemic which are indicated by analyzing biological functions of hubs in the merged network.展开更多
Background: Module detection is widely used to analyze and visualize biological networks. A number of methods and tools have been developed to achieve it. Meanwhile, bipartite module detection is also very useful for...Background: Module detection is widely used to analyze and visualize biological networks. A number of methods and tools have been developed to achieve it. Meanwhile, bipartite module detection is also very useful for mining and analyzing bipartite biological networks and a few methods have been developed for it. However, there is few user- friendly toolkit for this task. Methods: To this end, we develop an online web toolkit BMTK, which implements seven existing methods. Results: BMTK provides a uniform operation platform and visualization function, standardizes input and output format, and improves algorithmic structure to enhance computing speed. We also apply this toolkit onto a drug-target bipartite network to demonstrate its effectiveness. Conclusions: BMTK will be a powerful tool for detecting bipartite modules in diverse bipartite biological networks. Availability: The web application is freely accessible at http://www.zhanglabtools.net/BMTK.展开更多
A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network(interactome) indicates that, at ...A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network(interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy(IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field.展开更多
Genome-wide association studies (GWASs) have identified thousands of genes and genetic variants (mainly SNPs) that contribute to complex diseases in humans. Functional characterization and mechanistic elucidation ...Genome-wide association studies (GWASs) have identified thousands of genes and genetic variants (mainly SNPs) that contribute to complex diseases in humans. Functional characterization and mechanistic elucidation of these SNPs and genes action are the next major challenge. It has been well established that SNPs altering the amino acids of protein-coding genes can drastically impact protein function, and play an important role in molecular pathogenesis. Functions of regulatory SNPs can be complex and elusive, and involve gene expression regulation through the effect on RNA splicing, transcription factor binding, DNA metbylation and miRNA recruitment. In the present review, we summarize the recent progress in our understanding of functional consequences of GWAS-associated non-coding regulatory SNPs, and discuss the application of systems genetics and network biology in the interpretation of GWAS findings.展开更多
For multicellular organisms,cell-cell communication is essential to numerous biological processes.Drawing upon the latest development of single-cell RNA-sequencing(scRNA-seq),high-resolution transcriptomic data have d...For multicellular organisms,cell-cell communication is essential to numerous biological processes.Drawing upon the latest development of single-cell RNA-sequencing(scRNA-seq),high-resolution transcriptomic data have deepened our understanding of cellular phenotype heterogeneity and composition of complex tissues,which enables systematic cell-cell communication studies at a single-cell level.We first summarize a common workflow of cell-cell communication study using scRNA-seq data,which often includes data preparation,construction of communication networks,and result validation.Two common strategies taken to uncover cell-cell communications are reviewed,e.g.,physically vicinal structure-based and ligand-receptor interaction-based one.To conclude,challenges and current applications of cell-cell communication studies at a single-cell resolution are discussed in details and future perspectives are proposed.展开更多
文摘Biological entities are involved in complicated and complex connections;hence,discovering biological information using network biology ideas is critical.In the past few years,network biology has emerged as an integrative and systems-level approach for understanding and interpreting these complex interactions.Biological network analysis is one method for reducing enormous data sets to clinically useful knowledge for disease diagnosis,prognosis,and treatment.The network of biological entities can help us predict drug targets for several diseases.The drug targets identified through the systems biology approach help in targeting the essential biological pathways that contribute to the progression and development of the disease.The novel strategical approach of system biologyassisted pharmacology coupled with computer-aided drug discovery(CADD)can help drugs fight multifactorial diseases efficiently.In the present review,we have summarized the role and application of network biology for not only unfolding the mechanism of complex neurodevelopmental disorders but also identifying important drug targets for diseases like ADHD,Autism,Epilepsy,and Intellectual Disability.Systems biology has emerged as a promising approach to identifying drug targets and aiming for targeted drug discovery for the precise treatment of neurodevelopmental disorders.
文摘BACKGROUND Human Wharton’s jelly-derived mesenchymal stromal/stem cells(hWJ-MSCs)have gained considerable attention in their applications in cell-based therapy due to several advantages offered by them.Recently,we reported that hWJ-MSCs and their conditioned medium have significant therapeutic radioprotective potential.This finding raised an obvious question to identify unique features of hWJ-MSCs over other sources of stem cells for a better understanding of its radioprotective mechanism.AIM To understand the radioprotective mechanism of soluble factors secreted by hWJMSCs and identification of their unique genes.METHODS Propidium iodide staining,endogenous spleen colony-forming assay,and survival study were carried out for radioprotection studies.Homeostasis-driven proliferation assay was performed for in vivo lymphocyte proliferation.Analysis of RNAseq data was performed to find the unique genes of WJ-MSCs by comparing them with bone marrow mesenchymal stem cells,embryonic stem cells,and human fibroblasts.Gene enrichment analysis and protein-protein interaction network were used for pathway analysis.RESULTS Co-culture of irradiated murine splenic lymphocytes with WJ-MSCs offered significant radioprotection to lymphocytes.WJ-MSC transplantation increased the homeostasis-driven proliferation of the lymphocytes.Neutralization of WJ-MSC conditioned medium with granulocyte-colony stimulating factor antibody abolished therapeutic radioprotection.Transcriptome analysis showed that WJ-MSCs share several common genes with bone marrow MSCs and embryonic stem cells and express high levels of unique genes such as interleukin(IL)1-α,IL1-β,IL-6,CXCL3,CXCL5,CXCL8,CXCL2,CCL2,FLT-1,and IL-33.It was also observed that WJ-MSCs preferentially modulate several cellular pathways and processes that handle the repair and regeneration of damaged tissues compared to stem cells from other sources.Cytokine-based network analysis showed that most of the radiosensitive tissues have a more complex network for the elevated cytokines.CONCLUSION Systemic infusion of WJ-MSC conditioned media will have significant potential for treating accidental radiation exposed victims。
基金The work was supported by the National Natural Science Foundation of China(No.81373942)the Key Science and Technology Research Projects of Tibet Autonomous Region of China(No.XZ201801-GA-16).
文摘Background:Yanhusuo powder,also known as Xuanhusuo powder,is a long-standing Chinese herbal formula mainly used in the treatment of osteoarthritis.Although the clinical effectiveness of Yanhusuo powder has long been acknowledged,its mechanism of action and bioactive components remain unknown.Methods:A novel analytical method combining the use of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultra-performance liquid chromatography-triple quadrupole mass spectrometry was applied to profile the formula and absorbed prototype components in plasma after oral administration of Yanhusuo powder.Then,the absorbed constituents were subjected to network pharmacology to predict targets and pathways.AutoDock software was then used for molecular docking studies to screen for potential pharmacodynamic substances.Results:A total of 34 in vitro formula components and 20 in vivo prototype compounds from the various relevant species were successfully separated and identified for the first time.Compound-target-pathway analysis revealed that 20 absorbed constituents,42 target genes and 42 pathways are probably related to the efficacy of Yanhusuo powder against osteoarthritis.The efficacy of Yanhusuo powder mainly involves AKT1,fibronectin 1 and matrix metalloproteinase 9 targets and apoptosis,as well as PI3K-AKT and mitogen-activated protein kinases signaling pathways.According to the results of the molecular docking studies,it can be preliminarily judged that protopine,dehydrocorybulbine and angelicin may be the pharmacologically active substances of Yanhusuo powder.Conclusion:The results provide a scientific basis for understanding the bioactive compounds and the pharmacological mechanism of Yanhusuo powder.
基金National Natural Science Foundation of China(81430096)China Drug Innovation Plan(2014ZX09507005,2014ZX09507005-003,2012ZX09304002,2012ZX09505001)
文摘Traditional Chinese medicine (TCM) has developed over thousands of years and has accumulated abundant clinical experience, forming a comprehensive and unique medical system. Emerging evidence has begun to illustrate TCM as an area of important medical rediscoveries. This review article briefly introduced the concept, significance, and technology of network pharmacology based on network biology and systems biology. It focused on the theoretical system and potential prospect of TCM network applied in TCM research and development including predicting new drug targets, action mechanism, new drug discovery; evaluating pharmacodynamics, pharmacokinetics, safety, toxicology, quality control, and bioinformatics of drugs. We also discussed the opportunities and challenges in the development and application of network pharmacology in the modernization of TCM research.
基金National Natural Science Foundation of China(81430096)China Drug Innovation Plan(2014ZX09507005,2014ZX09507005-003,2012ZX09304002,2012ZX09505001)
文摘Network toxicology that is an important branch of the network pharmacology emerges on the basis of network biology. It refers to study on the toxicological features of a constructed network model which is used to analyze toxic substances and their interaction and regulation in biological systems, particularly investigate the toxic effects of drugs and/or compatibility of medicines on body, and clarify the mechanism of toxicity. Network toxicology currently develops rapidly in safety prediction of Chinese materia medica (CMM). The application of network toxicology to safety and toxicology study on CMM is extremely beneficial to identify the toxic components and potential incompatibility of CMM. Since CMM is a complex system with multi-components, multi-targets, and multi-interactions, the network toxicology in safety prediction of CMM faces three great challenges, including integration studies of bioinformatics, innovation of methods, and tools and risk assessment in future development of the network toxicology in CMM research. In this paper, relevant database, approaches and tools that network toxicology utilized in the safety study of CMM were carefully reviewed. Based on the progress made, the scientific development and modernization of CMM will be greatly enhanced.
基金Supported by the National Natural Science Foundation of China(No.81173116)
文摘Objective: To investigate the mechanisms of Panax notoginseng saponins(PNS) in treating coronary heart disease(CHD) by integrating gene interaction network and functional enrichment analysis. Methods: Text mining was used to get CHD and PNS associated genes. Gene–gene interaction networks of CHD and PNS were built by the Gene MANIA Cytoscape plugin. Advanced Network Merge Cytoscape plugin was used to analyze the two networks. Their functions were analyzed by gene functional enrichment analysis via DAVID Bioinformatics. Joint subnetwork of CHD network and PNS network was identified by network analysis. Results: The 11 genes of the joint subnetwork were the direct targets of PNS in CHD network and enriched in cytokine-cytokine receptor interaction pathway. PNS could affect other 85 genes by the gene–gene interaction of joint subnetwork and these genes were enriched in other 7 pathways. The direct mechanisms of PNS in treating CHD by targeting cytokines to relieve the inflammation and the indirect mechanisms of PNS in treating CHD by affecting other 7 pathways through the interaction of joint subnetwork of PNS and CHD network. The genes in the 7 pathways could be potential targets for the immunologic adjuvant, anticoagulant, hypolipidemic, anti-platelet and anti-hypertrophic activities of PNS. Conclusion: The key mechanisms of PNS in treating CHD could be anticoagulant and hypolipidemic which are indicated by analyzing biological functions of hubs in the merged network.
基金This work has been supported by the National Natural Science Foundation of China (Nos. 61621003, 61422309, 61379092 and 11661141019), the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB13040600) and CAS Frontier Science Research Key Project for Top Young Scientist (QYZDB-SSW-SYS008).
文摘Background: Module detection is widely used to analyze and visualize biological networks. A number of methods and tools have been developed to achieve it. Meanwhile, bipartite module detection is also very useful for mining and analyzing bipartite biological networks and a few methods have been developed for it. However, there is few user- friendly toolkit for this task. Methods: To this end, we develop an online web toolkit BMTK, which implements seven existing methods. Results: BMTK provides a uniform operation platform and visualization function, standardizes input and output format, and improves algorithmic structure to enhance computing speed. We also apply this toolkit onto a drug-target bipartite network to demonstrate its effectiveness. Conclusions: BMTK will be a powerful tool for detecting bipartite modules in diverse bipartite biological networks. Availability: The web application is freely accessible at http://www.zhanglabtools.net/BMTK.
基金funded by the National Plan for Science,Technology and Innovation program (NSTIP/KACST, No.11-BIO2072-20 to D.C.)
文摘A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network(interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy(IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field.
基金supported by the National Natural Science Foundation of China (Nos. 31371275 and 30971635)the National Basic Research Program of China (973 Program) (No. 2011CB504004)self-determined research funds of CCNU from the colleges’ basic research and operation of MOE (No. CCNU14Z01003)
文摘Genome-wide association studies (GWASs) have identified thousands of genes and genetic variants (mainly SNPs) that contribute to complex diseases in humans. Functional characterization and mechanistic elucidation of these SNPs and genes action are the next major challenge. It has been well established that SNPs altering the amino acids of protein-coding genes can drastically impact protein function, and play an important role in molecular pathogenesis. Functions of regulatory SNPs can be complex and elusive, and involve gene expression regulation through the effect on RNA splicing, transcription factor binding, DNA metbylation and miRNA recruitment. In the present review, we summarize the recent progress in our understanding of functional consequences of GWAS-associated non-coding regulatory SNPs, and discuss the application of systems genetics and network biology in the interpretation of GWAS findings.
基金This study was supported by the National Natural Science Foundation of China(Grant Nos.81774153 and 81973701)the Natural Science Foundation of Zhejiang Province(LZ20H290002)the National Youth Top-notch Talent Support Program(W02070098).
文摘For multicellular organisms,cell-cell communication is essential to numerous biological processes.Drawing upon the latest development of single-cell RNA-sequencing(scRNA-seq),high-resolution transcriptomic data have deepened our understanding of cellular phenotype heterogeneity and composition of complex tissues,which enables systematic cell-cell communication studies at a single-cell level.We first summarize a common workflow of cell-cell communication study using scRNA-seq data,which often includes data preparation,construction of communication networks,and result validation.Two common strategies taken to uncover cell-cell communications are reviewed,e.g.,physically vicinal structure-based and ligand-receptor interaction-based one.To conclude,challenges and current applications of cell-cell communication studies at a single-cell resolution are discussed in details and future perspectives are proposed.