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 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.

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.

Malicious Code Modeling and Analysis in Weighted Scale-Free Networks

We study the detailed malicious code propagating process in scale-free networks with link weights that denotes traffic between two nodes. It is found that the propagating velocity reaches a peak rapidly then decays in a power-law form, which is different from the well-known result in unweighted network case. Simulation results show that the nodes with larger strength are preferential to be infected, but the hierarchical dynamics are not clearly found. The simulation results also show that larger dispersion of weight of networks leads to slower propagating, which indicates that malicious code propagates more quickly in unweighted scale-free networks than in weighted scale-free networks under the same condition. These results show that not only the topology of networks but also the link weights affect the malicious propagating process.

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.

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.

Synchronization Stability in Weighted Complex Networks with Coupling Delays

Realistic networks display not only a complex topological structure, but also a heterogeneous distribution of weights in connection strengths. In addition, the information spreading through a complex network is often associated with time delays due to the finite speed of signal transmission over a distance. Hence, the weighted complex network with coupling delays have meaningful implications in real world, and resultantly gains increasing attention in various fields of science and engineering. Based on the theory of asymptotic stability of linear time-delay systems, synchronization stability of the weighted complex dynamical network with coupling delays is investigated, and simple criteria are obtained for both delay-independent and delay-dependent stabilities of synchronization states. The obtained criteria in this paper encompass the established results in the literature as special cases. Some examples are given to illustrate the theoretical results.

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.

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.

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.

Modeling Evolution of Weighted Clique Networks

We propose a weighted clique network evolution model, which expands continuously by the addition of a new clique （maximal complete sub-graph） at. each time step. And the cliques in the network overlap with each other. The structural expansion of the weighted clique network is combined with the edges＇ weight and vertices＇ strengths dynamical evolution. The model is based on a weight-driven dynamics and a weights＇ enhancement mechanism combining with the network growth. We study the network properties, which include the distribution of vertices＇ strength and the distribution o~ edges＇ weight, and find that both the distributions follow the scale-free distribution. At the same time, we also find that the relationship between strength and degree of a vertex are linear correlation during the growth of the network. On the basis of mean-field theory, we study the weighted network model and prove that both vertices＇ strength and edges＇ weight of this model follow the scale-free distribution. And we exploit an algorithm to forecast the network dynamics, which can be used to reckon the distributions and the corresponding scaling exponents. Furthermore, we observe that mean-field based theoretic results are consistent with the statistical data of the model, which denotes the theoretical result in this paper is effective.

Modeling Topology and Nonlinear Dynamical Behavior of the Weighted Scale-Free Networks

An improved weighted scale-free network, which has two evolution mechanisms： topological growth and strength dynamics, has been introduced. The topology structure of the model will be explored in details in this work. The evolution driven mechanism of Olami-Feder Christensen （OFC） model is added to our model to study the self-organlzed criticality and the dynamical behavior. We also.consider attack mechanism and the study of the model with attack is also investigated in this paper. We tlnd there are differences between the model with attack and without attack.

Hash function construction using weighted complex dynamical networks

A novel scheme to construct a hash function based on a weighted complex dynamical network （WCDN） generated from an original message is proposed in this paper. First, the original message is divided into blocks. Then, each block is divided into components, and the nodes and weighted edges are well defined from these components and their relations. Namely, the WCDN closely related to the original message is established. Furthermore, the node dynamics of the WCDN are chosen as a chaotic map. After chaotic iterations, quantization and exclusive-or operations, the fixed-length hash value is obtained. This scheme has the property that any tiny change in message can be diffused rapidly through the WCDN, leading to very different hash values. Analysis and simulation show that the scheme possesses good statistical properties, excellent confusion and diffusion, strong collision resistance and high efficiency.

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.

Scaling of weighted spectral distribution in weighted small-world networks

Many real-world systems can be modeled by weighted small-world networks with high clustering coefficients. Recent studies for rigorously analyzing the weighted spectral distribution（W SD） have focused on unweighted networks with low clustering coefficients. In this paper, we rigorously analyze the W SD in a deterministic weighted scale-free small-world network model and find that the W SD grows sublinearly with increasing network order（i.e., the number of nodes） and provides a sensitive discrimination for each input of this model. This study demonstrates that the scaling feature of the W SD exists in the weighted network model which has high and order-independent clustering coefficients and reasonable power-law exponents.

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.

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.

Identification of key genes regulating the synthesis of quercetin derivatives in Rosa roxburghii through integrated transcriptomics and metabolomics

Rosa roxburghii fruit is rich in flavonoids, but little is known about their biosynthetic pathways. In this study, we employed transcriptomics and metabolomics to study changes related to the flavonoids at five different stages of R. roxburghii fruit development. Flavonoids and the genes related to their biosynthesis were found to undergo significant changes in abundance across different developmental stages, and numerous quercetin derivatives were identified. We found three gene expression modules that were significantly associated with the abundances of the different flavonoids in R. roxburghii and identified three structural UDP-glycosyltransferase genes directly involved in the synthesis of quercetin derivatives within these modules. In addition, we found that RrBEH4, RrLBD1 and RrPIF8could significantly increase the expression of downstream quercetin derivative biosynthesis genes. Taken together,these results provide new insights into the metabolism of flavonoids and the accumulation of quercetin derivatives in R. roxburghii.

Physiological and transcriptome analyses of Chinese cabbage in response to drought stress

Chinese cabbage is an important leafy vegetable crop with high water demand and susceptibility to drought stress.To explore the molecular mechanisms underlying the response to drought,we performed a transcriptome analysis of drought-tolerant and-sensitive Chinese cabbage genotypes under drought stress,and uncovered core drought-responsive genes and key signaling pathways.A co-expression network was constructed by a weighted gene coexpression network analysis(WGCNA)and candidate hub genes involved in drought tolerance were identified.Furthermore,abscisic acid(ABA)biosynthesis and signaling pathways and their drought responses in Chinese cabbage leaves were systemically explored.We also found that drought treatment increased the antioxidant enzyme activities and glucosinolate contents significantly.These results substantially enhance our understanding of the molecular mechanisms underlying drought responses in Chinese cabbage.

Transcriptome analysis reveals the genetic basis of crest cushion formation in duck

The Chinese crested duck is a unique duck breed having a bulbous feather shape on its duck head.However,the mechanisms involved in its formation and development are unclear.In the present study,RNA sequencing analysis was performed on the crested tissues of 6 Chinese crested ducks and the scalp tissues of 6 cherry valley ducks(CVs)from 2 developmental stages.This study identified 261 differentially expressed genes(DEGs),122 upregulated and 139 downregulated,in the E28 stage and 361 DEGs,154 upregulated and 207 downregulated in the D42 stage between CC and CV ducks.The subsequent results of weighted gene co-expression network analysis(WGCNA)revealed that the turquoise and cyan modules were associated with the crest trait in the D42 stage,meanwhile,the green,brown,and pink modules were associated with the crest trait in the E28 stage.Venn analysis of the DEGs and WGCNA showed that 145 and 45 genes are associated between the D42 and E28 stages,respectively.The expression of WNT16,BMP2,SLC35F2,SLC6A15,APOBEC2,ABHD6,TNNC2,MYL1,and TNNI2 were verified by real-time quantitative PCR.This study provides an approach to reveal the molecular mechanisms underlying the crested trait development.