Exploring the mechanism of Guizhi decoction’s“Jun-Chen-Zuo-Shi”in treating plant nervous disorders based on weighted network pharmacology and molecular docking techniques

Objective:To explore the mechanism of Guizhi decoction’s“Jun-Chen-Zuo-Shi”in treating plant nervous disorders based on network pharmacology and molecular docking methods.Methods:The main active ingredients of Guizhi decoction were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and plant nervous disorder-related targets were screened from the Gene Cards database,OMIM database,and PharmGKB database.The intersection of the two was obtained.The intersection targets were used to draw a protein interaction network and a“Traditional Chinese Medicine-active ingredient-target”network using the STRING database and Cytoscape 3.9.1.The nodes in the“Traditional Chinese Medicine-active ingredient-target”network were weighted according to the“Jun-Chen-Zuo-Shi”principle.Kyoto Encyclopedia of Genes and Genomes,and gene ontology enrichment analysis were performed on the intersection targets.Molecular docking was used to verify the affinity between core targets and key ingredients.Results:A total of 225 effective components of Guizhi decoction were screened,among which 127 components could bind to 160 common targets and play a therapeutic role.The common targets were mainly enriched in 2785 gene ontology entries and 189 Kyoto Encyclopedia of Genes and Genomes pathways.Molecular docking confirmed that core targets could spontaneously bind to key ingredients.Conclusion:The key targets for the treatment of plant nervous disorders by Guizhi decoction are MAPK1,TP53,RB1,STAT3,MAPK3,MAPK14,etc.,which reflect the characteristics of the synergistic mechanism of traditional Chinese medicine with multiple components,targets,and pathways through the regulation of inflammatory signal pathways and oxidative stress processes.

Entropy-based link prediction in weighted networks

Information entropy has been proved to be an effective tool to quantify the structural importance of complex networks.In a previous work [Xu et al. Physica A, 456 294（2016）], we measure the contribution of a path in link prediction with information entropy. In this paper, we further quantify the contribution of a path with both path entropy and path weight,and propose a weighted prediction index based on the contributions of paths, namely weighted path entropy（WPE）, to improve the prediction accuracy in weighted networks. Empirical experiments on six weighted real-world networks show that WPE achieves higher prediction accuracy than three other typical weighted indices.

Weighted Networks Model Based on Traffic Dynamics with Local Perturbation

In the study of weighted complex networks, the interplay between traffic and topology have been paid much attention. However, the variation of topology and weight brought by new added vertices or edges should also be considered. In this paper, an evolution model of weighted networks driven by traffic dynamics with local perturbation is proposed. The model gives power-law distribution of degree, weight and strength, as confirmed by empirical measurements. By choosing appropriate parameters W and δ, the exponents of various power law distributions can be adjusted to meet real world networks. Nontrivial clustering coefficient C, degree assortativity coefficient r, and strength-degree correlation are also considered. What should be emphasized is that, with the consideration of local perturbation, one can adjust the exponent of strength-degree correlation more effectively. It makes our model more general than previous ones and may help reproducing real world networks more appropriately. PACS numbers： 87.23.Kg, 89.75.Da, 89.75.Fb, 89.75.Hc.

Detecting and describing the modular structures of weighted networks

In the functional properties of complex networks, modules play a central role. In this paper, we propose a new method to detect and describe the modular structures of weighted networks. In order to test the proposed method, as an example, we use our method to analyse the structural properties of the Chinese railway network. Here, the stations are regarded as the nodes and the track sections are regarded as the links. Rigorous analysis of the existing data shows that using the proposed algorithm, the nodes of network can be classified naturally. Moreover, there are several core nodes in each module. Remarkably, we introduce the correlation function Grs, and use it to distinguish the different modules in weighted networks.

Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning

Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).

Weighted gene co-expression network analysis reveals similarities and differences of molecular features between dilated and ischemic cardiomyopathies

Cardiomyopathies represent the most common clinical and genetic heterogeneous group of diseases that affect the heart function.Though progress has been made to elucidate the process,molecular mechanisms of different classes of cardiomyopathies remain elusive.This paper aims to describe the similarities and differences in molecular features of dilated cardiomyopathy(DCM)and ischemic cardiomyopathy(ICM).We firstly detected the co-expressed modules using the weighted gene co-expression network analysis(WGCNA).Significant modules associated with DCM/ICM were identified by the Pearson correlation coefficient(PCC)between the modules and the phenotype of DCM/ICM.The differentially expressed genes in the modules were selected to perform functional enrichment.The potential transcription factors(TFs)prediction was conducted for transcription regulation of hub genes.Apoptosis and cardiac conduction were perturbed in DCM and ICM,respectively.TFs demonstrated that the biomarkers and the transcription regulations in DCM and ICM were different,which helps make more accurate discrimination between them at molecular levels.In conclusion,comprehensive analyses of the molecular features may advance our understanding of DCM and ICM causes and progression.Thus,this understanding may promote the development of innovative diagnoses and treatments.

Identification of key genes underlying clinical features of hepatocellular carcinoma based on weighted gene co‑expression network analysis and bioinformatics analysis

Objective: To identify module genes that are closely related to clinical features of hepatocellular carcinoma (HCC) by weighted gene co‑expression network analysis, and to provide a reference for early clinical diagnosis and treatment. Methods: GSE84598 chip data were downloaded from the GEO database, and module genes closely related to the clinical features of HCC were extracted by comprehensive weighted gene co‑expression network analysis. Hub genes were identified through protein interaction network analysis by the maximum clique centrality (MCC) algorithm;Finally, the expression of hub genes was validated by TCGA database and the Kaplan Meier plotter online database was used to evaluate the prognostic relationship between hub genes and HCC patients. Results: By comparing the gene expression data between HCC tissue samples and normal liver tissue samples, a total of 6 262 differentially expressed genes were obtained, of which 2 207 were upregulated and 4 055 were downregulated. Weighted gene co‑expression network analysis was applied to identify 120 genes of key modules. By intersecting with the differentially expressed genes, 115 candidate hub genes were obtained. The results of enrichment analysis showed that the candidate hub genes were closely related to cell mitosis, p53 signaling pathway and so on. Further application of the MCC algorithm to the protein interaction network of 115 candidate hub genes identified five hub genes, namely NUF2, RRM2, UBE2C, CDC20 and MAD2L1. Validation of hub genes by TCGA database revealed that all five hub genes were significantly upregulated in HCC tissues compared to normal liver tissues;Moreover, survival analysis revealed that high expression of hub genes was closely associated with poor prognosis in HCC patients. Conclusions: This study identifies five hub genes by combining multiple databases, which may provide directions for the clinical diagnosis and treatment of HCC.

Generalized chaos synchronization of a weighted complex network with different nodes

This paper proposes a method of realizing generalized chaos synchronization of a weighted complex network with different nodes. Chaotic systems with diverse structures are taken as the nodes of the complex dynamical network, the nonlinear terms of the systems are taken as coupling functions, and the relations among the nodes are built through weighted connections. The structure of the coupling functions between the connected nodes is obtained based on Lyapunov stability theory. A complex network with nodes of Lorenz system, Coullet system, RSssler system and the New system is taken as an example for simulation study and the results show that generalized chaos synchronization exists in the whole weighted complex network with different nodes when the coupling strength among the nodes is given with any weight value. The method can be used in realizing generalized chaos synchronization of a weighted complex network with different nodes. Furthermore, both the weight value of the coupling strength among the nodes and the number of the nodes have no effect on the stability of synchronization in the whole complex network.

Weighted Evolving Networks with Self-organized Communities

In order to describe the self-organization of communities in the evolution of weighted networks, we propose a new evolving model for weighted community-structured networks with the preferential mechanisms functioned in different levels according to community sizes and node strengths, respectively. Theoretical analyses and numerical simulations show that our model captures power-law distributions of community sizes, node strengths, and link weights, with tunable exponents of v ≥ 1, γ 〉 2, and α 〉 2, respectively, sharing large clustering coefficients and scaling clustering spectra, and covering the range from disassortative networks to assortative networks. Finally, we apply our new model to the scientific co-authorship networks with both their weighted and unweighted datasets to verify its effectiveness.

Generating weighted community networks based on local events

Many realistic networks have community structures, namely, a network consists of groups of nodes within which links are dense but among which links are sparse. This paper proposes a growing network model based on local processes, the addition of new nodes intra-community and new links intra- or inter-community. Also, it utilizes the preferential attachment for building connections determined by nodes＇ strengths, which evolves dynamically during the growth of the system. The resulting network reflects the intrinsic community structure with generalized power-law distributions of nodes＇ degrees and strengths.

A Weighted Evolving Network with Community Size Preferential Attachment

Community structure is an important characteristic in real complex network.It is a network consists ofgroups of nodes within which links are dense but among which links are sparse.In this paper, the evolving network includenode, link and community growth and we apply the community size preferential attachment and strength preferentialattachment to a growing weighted network model and utilize weight assigning mechanism from BBV model.Theresulting network reflects the intrinsic community structure with generalized power-law distributions of nodes'degreesand strengths.

A Mixed Mechanism of Weighted-Driven and Inner Selection in Networks

For most networks, the weight of connection is changing with their attachment and inner affinity. By introducing a mixed mechanism of weighted-driven and inner selection, the model exhibits wide range power-law distributions of node strength and edge weight, and the exponent can be adjusted by not only the parameter δ but also the probability q. Furthermore, we investigate the weighted average shortest distance, clustering coefficient, and the correlation of our network. In addition, the weighted assortativity coefficient which characterizes important information of weighted topological networks has been discussed, but the variation of coefficients is much smaller than the former researches.

A weighted network evolving model with capacity constraints

Most of existing works on complex network assumed that the nodes and edges were uncapacitated during the evolving process,and displayed "rich club" phenomenon.Here we will show that the "rich club" could be changed to "common rich" if we consider the node capacity.In this paper,we define the node and edge attractive index with node capacity,and propose a new evolving model on the base of BBV model,with evolving simulations of the networks.In the new model,an entering node is linked with an existing node according to the preferential attachment mechanism defined with the attractive index of the existing node.We give the theoretical approximation and simulation solutions.If node capacity is finite,the rich node may not be richer further when the node strength approaches or gets to the node capacity.This is confirmed by analyzing the passenger traffic and routes of Chinese main airports.Due to node strength being function of time t,we can use the theoretical approximation solution to forecast how node strength changes and the time when node strength reaches its maximum value.

A novel weighted evolving network model based on clique overlapping growth

A novel weighted evolving network model based on the clique overlapping growth was proposed.The model shows different network characteristics under two different selection mechanisms that are preferential selection and random selection.On the basis of mean-field theory,this model under the two different selection mechanisms was analyzed.The analytic equations of distributions of the number of cliques that a vertex joins and the vertex strength of the model were given.It is proved that both distributions follow the scale-free power-law distribution in preferential selection mechanism and the exponential distribution in random selection mechanism,respectively.The analytic expressions of exponents of corresponding distributions were obtained.The agreement between the simulations and analytical results indicates the validity of the theoretical analysis.Finally,three real transport bus networks(BTNs) of Beijing,Shanghai and Hangzhou in China were studied.By analyzing their network properties,it is discovered that these real BTNs belong to a kind of weighted evolving network model with clique overlapping growth and random selection mechanism that was proposed in this context.

Projective synchronization of spatiotemporal chaos in a weighted complex network

Projective synchronization of a weighted complex network is studied in which nodes are spatiotemporal chaos systems and all nodes are coupled not with the nonlinear terms of the system but through a weighted connection. The range of the linear coefficient matrix of separated configuration, when the synchronization is implemented, is determined according to Lyapunov stability theory. It is found that projective synchronization can be realized for unidirectional star-connection even if the coupling strength between the nodes is a given arbitrary weight value. The Gray-Scott models having spatiotemporal Chaos behaviours are taken as nodes in the weighted complex network, and simulation results of spatiotemporal synchronization show the effectiveness of the method.

Empirical investigation of topological and weighted properties of a bus transport network from China

Many bus transport networks （BTNs） have evolved into directed networks. A new representation model for BTNs is proposed, called directed-space P. The bus transport network of Harbin （BTN-H） is described as a directed and weighted complex network by the proposed representation model and by giving each node weights. The topological and weighted properties are revealed in detail. In-degree and out-degree distributions, in-weight and out-weight distributions are presented as an exponential law, respectively. There is a strong relation between in-weight and in-degree （also between out-weight and out-degree）, which can be fitted by a power function. Degree-degree and weight-weight correlations are investigated to reveal that BTN-H has a disassortative behavior as the nodes have relatively high degree （or weight）. The disparity distributions of out-degree and in-degree follow an approximate power-law. Besides, the node degree shows a near linear increase with the number of routes that connect to the corresponding station. These properties revealed in this paper can help public transport planners to analyze the status quo of the BTN in nature.

Predictive Characteristics of Co-authorship Networks: Comparing the Unweighted, Weighted, and Bipartite Cases

Purpose： This study aims to answer the question to what extent different types of networks can be used to predict future co-authorship among authors.Design/methodology/approach： We compare three types ot networks： unwelgntea networks, in which a link represents a past collaboration; weighted networks, in which links are weighted by the number of joint publications; and bipartite author-publication networks. The analysis investigates their relation to positive stability, as well as their potential in predicting links in future versions of the co-authorship network. Several hypotheses are tested.Findings： Among other results, we find that weighted networks do not automatically lead to better predictions. Bipartite networks, however, outperform unweighted networks in almost all cases. Research limitations： Only two relatively small case studies are considered Practical implications： The study suggests that future link prediction studies on networks should consider using the bipartite network as a training network. Originality/value： This is the first systematic comparison of unweighted, weighted, and bipartite training networks in link prediction.

Integrating Local Closure Coefficient into Weighted Networks for Link Prediction

Triadic closure is a simple and fundamental kind of link formulation mechanism in network.Local closure coefficient(LCC),a new network property,is to measure the triadic closure with respect to the fraction of length-2 paths for link prediction.In this paper,a weighted format of LCC(WLCC)is introduced to measure the weighted strength of local triadic structure,and a statistic similari-ty-based link prediction metric is proposed to incorporate the definition of WLCC.To prove the metrics effectiveness and scalability,the WLCC formula-tion was further investigated under weighted local Naive Bayes(WLNB)link prediction framework.Finally,extensive experimental studies was conducted with weighted baseline metrics on various public network datasets.The results demonstrate the merits of the proposed metrics in comparison with the weighted baselines.

Analysis of epidemic spreading with feedback mechanism in weighted networks

In this paper, we investigate a new model with a generalized feedback mechanism in weighted networks. Compare to previous models, we consider the initiative response of people and the important impact of nodes with different edges on transmission rate as epidemics prevail. Furthermore, by constructing Lyapunov function, we prove that the disease-free equilibrium E^0 is globally asymptotically stable as the epidemic threshold R^＊〈 1. When R^＊ 〉 1, we obtain the permanence of epidemic and the local stability of endemic equilibrium E＊. Finally, one can find a good agreement between numerical simulations and our analytical results.

Identification of key genes involved in axon regeneration and Wallerian degeneration by weighted gene co-expression network analysis

Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration.Therefore,investigating how axon regeneration and degeneration work together to repair peripheral nerve injury may uncover the molecular mechanisms and signal cascades underlying peripheral nerve repair and provide potential strategies for improving the low axon regeneration capacity of the central nervous system.In this study,we applied weighted gene co-expression network analysis to identify differentially expressed genes in proximal and distal sciatic nerve segments from rats with sciatic nerve injury.We identified 31 and 15 co-expression modules from the proximal and distal sciatic nerve segments,respectively.Functional enrichment analysis revealed that the differentially expressed genes in proximal modules promoted regeneration,while the differentially expressed genes in distal modules promoted neurodegeneration.Next,we constructed hub gene networks for selected modules and identified a key hub gene,Kif22,which was up-regulated in both nerve segments.In vitro experiments confirmed that Kif22 knockdown inhibited proliferation and migration of Schwann cells by modulating the activity of the extracellular signal-regulated kinase signaling pathway.Collectively,our findings provide a comparative framework of gene modules that are co-expressed in injured proximal and distal sciatic nerve segments,and identify Kif22 as a potential therapeutic target for promoting peripheral nerve injury repair via Schwann cell proliferation and migration.All animal experiments were approved by the Institutional Animal Ethics Committee of Nantong University,China(approval No.S20210322-008)on March 22,2021.