Marine organisms cannot grow and reproduce without proper metabolic regulation.Within a metabolic network,problems with a given link will affect the normal life activities of the organism.Many metabolic mechanisms ass...Marine organisms cannot grow and reproduce without proper metabolic regulation.Within a metabolic network,problems with a given link will affect the normal life activities of the organism.Many metabolic mechanisms associated with behaviors of Am-phioctopus fangsiao are still unclear.Moreover,as a factor affecting the normal growth of A.fangsiao,egg protection has rarely been considered in previous behavioral studies.In this research,we analyzed the transcriptome profile of gene expression in A.fangsiao egg-unprotected larvae and egg-protected larvae,and identified 818 differentially expressed genes(DEGs).We used GO and KEGG enrichment analyses to search for metabolism-related DEGs.Protein-protein interaction networks were constructed to examine the interactions between metabolism-related genes.Twenty hub genes with multiple protein-protein interaction relationships or that were involved in multiple KEGG signaling pathways were obtained and verified by quantitative RT-PCR.We first studied the effects of egg protection on the metabolism of A.fangsiao larvae by means of protein-protein interaction networks,and the results provide va-luable gene resources for understanding the metabolism of invertebrate larvae.The data serve as a foundation for further research on the egg-protecting behavior of invertebrates.展开更多
Alpha-synuclein plays an important role in Parkinson's disease(PD).The current study of alpha-synuclein mainly concentrates at the gene level.However, it is found that the study at the protein level has special si...Alpha-synuclein plays an important role in Parkinson's disease(PD).The current study of alpha-synuclein mainly concentrates at the gene level.However, it is found that the study at the protein level has special significance.Meanwhile, there is free information on the Internet, such as databases and algorithms of protein-protein interactions(PPIs).In this paper, a novel method which integrates distributed heterogeneous data sources and algorithms to predict PPIs for alpha-synuclein in silico is proposed.The PPIs generated by the method take advantage of various experimental data, and indicate new information about PPIs for alpha-synuclein.In the end of this paper, the result illustrates that the method is practical.It is hoped that the prediction result obtained by this method can provide guidance for biological experiments of PPIs for alpha-synuclein to reveal possible mechanisms of PD.展开更多
Duplication and divergence have been widely recognized as the two domi- nant evolutionary forces in shaping biological networks, e.g., gene regulatory networks and protein-protein interaction （PPI） networks. It has ...Duplication and divergence have been widely recognized as the two domi- nant evolutionary forces in shaping biological networks, e.g., gene regulatory networks and protein-protein interaction （PPI） networks. It has been shown that the network growth models constructed on the principle of duplication and divergence can recapture the topo- logical properties of real PPI networks. However, such network models only consider the evolution processes. How to select the model parameters with the real biological experi- mental data has not been presented. Therefore, based on the real PPI network statistical data, a yeast PPI network model is constructed. The simulation results indicate that the topological characteristics of the constructed network model are well consistent with those of real PPI networks, especially on sparseness, scale-free, small-world, hierarchical modularity, and disassortativity.展开更多
Searching the maximum bicliques or bipartite subgraphs in a graph is a tough question. We proposed a new and efficient method, Searching Quasi-Bicliques (SQB) algorithm, to detect maximum quasi-bicliques from protein-...Searching the maximum bicliques or bipartite subgraphs in a graph is a tough question. We proposed a new and efficient method, Searching Quasi-Bicliques (SQB) algorithm, to detect maximum quasi-bicliques from protein-protein interaction network. As a Divide-and-Conquer method, SQB consists of three steps: first, it divides the protein-protein interaction network into a number of Distance-2-Subgraphs;second, by combining top-down and branch-and-bound methods, SQB seeks quasi-bicliques from every Distance-2-Subgraph;third, all the redundant results are removed. We successfully applied our method on the Saccharomyces cerevisiae dataset and obtained 2754 distinct quasi-bicliques.展开更多
Domain-domain interactions are important clues to inferring protein-protein interactions. Although about 8 000 domain-domain interactions are discovered so far,they are just the tip of the iceberg. Because domains are...Domain-domain interactions are important clues to inferring protein-protein interactions. Although about 8 000 domain-domain interactions are discovered so far,they are just the tip of the iceberg. Because domains are conservative and commonplace in proteins,domain-domain interactions are discovered based on pairs of domains which significantly co-exist in proteins. Meanwhile,it is realized that:( 1) domain-domain interactions may exist within the same proteins or across different proteins;( 2) only the domain-domain interactions across different proteins can mediate interactions between proteins;( 3) domains have biases to interact with other domains. And then,a novel method is put forward to construct protein-protein interaction network by using domain-domain interactions. The method is validated by experiments and compared with the state- of-art methods in the field. The experimental results suggest that the method is reasonable and effectiveness on constructing Protein-protein interactions network.展开更多
To explore the molecular mechanism of Ind-igo Naturalis in intervening chronic myelocytic leukemia （CML） under the guidance of protein-protein interaction network, the molecular docking technique and in vitro c...To explore the molecular mechanism of Ind-igo Naturalis in intervening chronic myelocytic leukemia （CML） under the guidance of protein-protein interaction network, the molecular docking technique and in vitro cell experiment were chosen. CML-related genes were obtained from the online mendelian inheritance in man database （OMIM）, then String 10. 0 was used for text mining and constructing the CML protein-protein interaction network. The interaction data were input in Cytoscape 3. 4. 0 software. Plug-in CentiScaPe 2. 1 was used for implement topology analysis. Small active substances of Indigo Naturalis were obtained from a third-party database, which were optimized by Chemoffice 8. 0 and Sybyl 8. 1, then small molecular ligand library was obtained. The molecular docking was carried out by Surflex-Dock module, the key target was received after scoring. Protein-protein interaction network of CML was constructed, which was consisted of 425 nodes （ proteins） and 2 799 sides （ interactions）. The key gene J.AK2 was got. CML is a polygenic disease and JAK2 is likely to be a key node.展开更多
Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autoph...Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autophagy is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors.In contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic targets.Meanwhile,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after intersection.Colony formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related PPIs.Our network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified proteins.Notably,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results.Subsequently,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 cells.Conclusions:This study not only enhances our understanding of autophagy regulation in TNBC but also identifies the Beclin 2-Ubiquilin 1 axis as a promising target for precision therapy.These findings open new avenues for drug discovery and offer inspiration for more effective treatments for this aggressive cancer subtype.展开更多
Achieving a reduction in global greenhouse gas(GHG)emissions requires collaborative efforts from the international community;however,a comprehensive understanding of the spatiotemporal characteristics(i.e.,complex emi...Achieving a reduction in global greenhouse gas(GHG)emissions requires collaborative efforts from the international community;however,a comprehensive understanding of the spatiotemporal characteristics(i.e.,complex emission networks and driver patterns)and the mutual influence of gross domestic product(GDP)and GHG emissions remains limited at a global level in the 21st century,which is not conducive to forming a consensus in global climate change negotiations and formulating relevant policies.To fill these gaps,this study comprehensively analyzes the complex network and driver pattern of GHG emissions,as well as the corresponding mutual influence with GDP for 185 countries during 2000-2021,based on social network analysis,the logarithmic Divisia decomposition approach,and panel vector autoregression model at global and regional levels.The results indicate that significant heterogeneity and inequality exist in terms of GHG emissions among regions and countries in different geographical areas and economic income levels.Additionally,GDP per capita and GHG emission intensity are the largest positive and negative drivers,respectively,affecting the increase in global GHG emissions.Furthermore,key countries,such as Germany and Canada,that could serve as coordinating bridges to strengthen collaboration in the global emission network are identified.This study highlights the need to encourage key participants in the emission network and foster international cooperation in governance,energy technology,and economic investment to address climate change.展开更多
With the increasing importance of multimodal data in emotional expression on social media,mainstream methods for sentiment analysis have shifted from unimodal to multimodal approaches.However,the challenges of extract...With the increasing importance of multimodal data in emotional expression on social media,mainstream methods for sentiment analysis have shifted from unimodal to multimodal approaches.However,the challenges of extracting high-quality emotional features and achieving effective interaction between different modalities remain two major obstacles in multimodal sentiment analysis.To address these challenges,this paper proposes a Text-Gated Interaction Network with Inter-Sample Commonality Perception(TGICP).Specifically,we utilize a Inter-sample Commonality Perception(ICP)module to extract common features from similar samples within the same modality,and use these common features to enhance the original features of each modality,thereby obtaining a richer and more complete multimodal sentiment representation.Subsequently,in the cross-modal interaction stage,we design a Text-Gated Interaction(TGI)module,which is text-driven.By calculating the mutual information difference between the text modality and nonverbal modalities,the TGI module dynamically adjusts the influence of emotional information from the text modality on nonverbal modalities.This helps to reduce modality information asymmetry while enabling full cross-modal interaction.Experimental results show that the proposed model achieves outstanding performance on both the CMU-MOSI and CMU-MOSEI baseline multimodal sentiment analysis datasets,validating its effectiveness in emotion recognition tasks.展开更多
Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies....Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies. The precise determination of the specific composition of protein complexes, especially using scalable and high-throughput methods, represents a systematic approach toward revealing particular cellular biological functions. In this regard, the direct profiling protein-protein interactions (PPIs) represent an efficient way to dissect functional pathways for revealing novel protein functions. In this review, we illustrate the technological evolution for the large-scale and precise identification of PPIs toward higher physiologically relevant accuracy. These techniques aim at improving the efficiency of complex pull-down, the signal specificity and accuracy in distinguishing specific PPIs, and the accuracy of identifying physiological relevant PPIs. A newly developed streamline proteomic approach for mapping the binary relationship of PPIs in a protein complex is introduced.展开更多
In the current information society, the dissemination mechanisms and evolution laws of individual or collective opinions and their behaviors are the research hot topics in the field of opinion dynamics. First, in this...In the current information society, the dissemination mechanisms and evolution laws of individual or collective opinions and their behaviors are the research hot topics in the field of opinion dynamics. First, in this paper, a two-layer network consisting of an individual-opinion layer and a collective-opinion layer is constructed, and a dissemination model of opinions incorporating higher-order interactions(i.e. OIHOI dissemination model) is proposed. Furthermore, the dynamic equations of opinion dissemination for both individuals and groups are presented. Using Lyapunov's first method,two equilibrium points, including the negative consensus point and positive consensus point, and the dynamic equations obtained for opinion dissemination, are analyzed theoretically. In addition, for individual opinions and collective opinions,some conditions for reaching negative consensus and positive consensus as well as the theoretical expression for the dissemination threshold are put forward. Numerical simulations are carried to verify the feasibility and effectiveness of the proposed theoretical results, as well as the influence of the intra-structure, inter-connections, and higher-order interactions on the dissemination and evolution of individual opinions. The main results are as follows.(i) When the intra-structure of the collective-opinion layer meets certain characteristics, then a negative or positive consensus is easier to reach for individuals.(ii) Both negative consensus and positive consensus perform best in mixed type of inter-connections in the two-layer network.(iii) Higher-order interactions can quickly eliminate differences in individual opinions, thereby enabling individuals to reach consensus faster.展开更多
Population migration data derived from location-based services has often been used to delineate population flows between cities or construct intercity relationship networks to reveal and explore the complex interactio...Population migration data derived from location-based services has often been used to delineate population flows between cities or construct intercity relationship networks to reveal and explore the complex interaction patterns underlying human activities.Nevertheless,the inherent heterogeneity in multimodal migration big data has been ignored.This study conducts an in-depth comparison and quantitative analysis through a comprehensive lens of spatial association.Initially,the intercity interactive networks in China were constructed,utilizing migration data from Baidu and AutoNavi collected during the same time period.Subsequently,the characteristics and spatial structure similarities of the two types of intercity interactive networks were quantitatively assessed and analyzed from overall(network)and local(node)perspectives.Furthermore,the precision of these networks at the local scale is corroborated by constructing an intercity network from mobile phone(MP)data.Results indicate that the intercity interactive networks in China,as delineated by Baidu and AutoNavi migration flows,exhibit a high degree of structure equivalence.The correlation coefficient between these two networks is 0.874.Both networks exhibit a pronounced spatial polarization trend and hierarchical structure.This is evident in their distinct core and peripheral structures,as well as in the varying importance and influence of different nodes within the networks.Nevertheless,there are notable differences worthy of attention.Baidu intercity interactive network exhibits pronounced cross-regional effects,and its high-level interactions are characterized by a“rich-club”phenomenon.The AutoNavi intercity interactive network presents a more significant distance attenuation effect,and the high-level interactions display a gradient distribution pattern.Notably,there exists a substantial correlation between the AutoNavi and MP networks at the local scale,evidenced by a high correlation coefficient of 0.954.Furthermore,the“spatial dislocations”phenomenon was observed within the spatial structures at different levels,extracted from the Baidu and AutoNavi intercity networks.However,the measured results of network spatial structure similarity from three dimensions,namely,node location,node size,and local structure,indicate a relatively high similarity and consistency between the two networks.展开更多
Drug development remains a critical issue in the field of biomedicine.With the rapid advancement of information technologies such as artificial intelligence(AI)and the advent of the big data era,AI-assisted drug devel...Drug development remains a critical issue in the field of biomedicine.With the rapid advancement of information technologies such as artificial intelligence(AI)and the advent of the big data era,AI-assisted drug development has become a new trend,particularly in predicting drug-target associations.To address the challenge of drug-target prediction,AI-driven models have emerged as powerful tools,offering innovative solutions by effectively extracting features from complex biological data,accurately modeling molecular interactions,and precisely predicting potential drug-target outcomes.Traditional machine learning(ML),network-based,and advanced deep learning architectures such as convolutional neural networks(CNNs),graph convolutional networks(GCNs),and transformers play a pivotal role.This review systematically compiles and evaluates AI algorithms for drug-and drug combination-target predictions,highlighting their theoretical frameworks,strengths,and limitations.CNNs effectively identify spatial patterns and molecular features critical for drug-target interactions.GCNs provide deep insights into molecular interactions via relational data,whereas transformers increase prediction accuracy by capturing complex dependencies within biological sequences.Network-based models offer a systematic perspective by integrating diverse data sources,and traditional ML efficiently handles large datasets to improve overall predictive accuracy.Collectively,these AI-driven methods are transforming drug-target predictions and advancing the development of personalized therapy.This review summarizes the application of AI in drug development,particularly in drug-target prediction,and offers recommendations on models and algorithms for researchers engaged in biomedical research.It also provides typical cases to better illustrate how AI can further accelerate development in the fields of biomedicine and drug discovery.展开更多
Tree interactions are essential for the structure,dynamics,and function of forest ecosystems,but variations in the architecture of life-stage interaction networks(LSINs)across forests is unclear.Here,we constructed 16...Tree interactions are essential for the structure,dynamics,and function of forest ecosystems,but variations in the architecture of life-stage interaction networks(LSINs)across forests is unclear.Here,we constructed 16 LSINs in the mountainous forests of northwest Hebei,China based on crown overlap from four mixed forests with two dominant tree species.Our results show that LSINs decrease the complexity of stand densities and basal areas due to the interaction cluster differentiation.In addition,we found that mature trees and saplings play different roles,the first acting as“hub”life stages with high connectivity and the second,as“bridges”controlling information flow with high centrality.Across the forests,life stages with higher importance showed better parameter stability within LSINs.These results reveal that the structure of tree interactions among life stages is highly related to stand variables.Our efforts contribute to the understanding of LSIN complexity and provide a basis for further research on tree interactions in complex forest communities.展开更多
We investigate the impact of pairwise and group interactions on the spread of epidemics through an activity-driven model based on time-dependent networks.The effects of pairwise/group interaction proportion and pairwi...We investigate the impact of pairwise and group interactions on the spread of epidemics through an activity-driven model based on time-dependent networks.The effects of pairwise/group interaction proportion and pairwise/group interaction intensity are explored by extensive simulation and theoretical analysis.It is demonstrated that altering the group interaction proportion can either hinder or enhance the spread of epidemics,depending on the relative social intensity of group and pairwise interactions.As the group interaction proportion decreases,the impact of reducing group social intensity diminishes.The ratio of group and pairwise social intensity can affect the effect of group interaction proportion on the scale of infection.A weak heterogeneous activity distribution can raise the epidemic threshold,and reduce the scale of infection.These results benefit the design of epidemic control strategy.展开更多
In industrial wireless networks,data transmitted from source to destination are highly repetitive.This often leads to the queuing of the data,and poor management of the queued data results in excessive delays,increase...In industrial wireless networks,data transmitted from source to destination are highly repetitive.This often leads to the queuing of the data,and poor management of the queued data results in excessive delays,increased energy consumption,and packet loss.Therefore,a nature-inspired-based Dragonfly Interaction Optimization Algorithm(DMOA)is proposed for optimization of the queue delay in industrial wireless networks.The term“interaction”herein used is the characterization of the“flying movement”of the dragonfly towards damselflies(female dragonflies)for mating.As a result,interaction is represented as the flow of transmitted data packets,or traffic,from the source to the base station.This includes each and every feature of dragonfly movement as well as awareness of the rival dragonflies,predators,and damselflies for the desired optimization of the queue delay.These features are juxtaposed as noise and interference,which are further used in the calculation of industrial wireless metrics:latency,error rate(reliability),throughput,energy efficiency,and fairness for the optimization of the queue delay.Statistical analysis,convergence analysis,the Wilcoxon test,the Friedman test,and the classical as well as the 2014 IEEE Congress of Evolutionary Computation(CEC)on the benchmark functions are also used for the evaluation of DMOA in terms of its robustness and efficiency.The results demonstrate the robustness of the proposed algorithm for both classical and benchmarking functions of the IEEE CEC 2014.Furthermore,the accuracy and efficacy of DMOA were demonstrated by means of the convergence rate,Wilcoxon testing,and ANOVA.Moreover,fairness using Jain’s index in queue delay optimization in terms of throughput and latency,along with computational complexity,is also evaluated and compared with other algorithms.Simulation results show that DMOA exceeds other bio-inspired optimization algorithms in terms of fairness in queue delay management and average packet loss.The proposed algorithm is also evaluated for the conflicting objectives at Pareto Front,and its analysis reveals that DMOA finds a compromising solution between the objectives,thereby optimizing queue delay.In addition,DMOA on the Pareto front delivers much greater performance when it comes to optimizing the queuing delay for industry wireless networks.展开更多
E3 ubiquitin ligases are participated in numerous processes, regulating the response to biotic and abiotic stresses. Botrytis susceptible1 interactor (BOI) is a RING (Really Interesting New Gene)-type E3 ligase that m...E3 ubiquitin ligases are participated in numerous processes, regulating the response to biotic and abiotic stresses. Botrytis susceptible1 interactor (BOI) is a RING (Really Interesting New Gene)-type E3 ligase that mediates the ubiquitination of BOS1 (Botrytis susceptible1), a transcription factor involved in stress and pathogen responses. Although BOI is an E3 ligase, there are reports to show that BOI interacts with target proteins such as DELLAs or CONSTANS to repress gibberellin responses and flowering without the degradation of the target proteins. In this article, we utilize diversified methods to comprehensively analyze the expression pattern, interaction network and function of BOI gene. Firstly, 1800 bp upstream region of BOI gene from Arabidopsis thaliana (Arabidopsis) genome was isolated, and fused GUS reporter gene. The resulting expression cassette was introduced into wild-type Arabidopsis through Agrobacterium-mediated transformation. The result demonstrated that BOI gene was expressed predominantly in leaves, siliques, young roots, and flowering tissues, indicating that BOI gene may be involved in multiple processes in plant growth and development in Arabidopsis. Besides, eight candidate interacting proteins were obtained from the Arabidopsis cDNA library via yeast two-hybrid technology, including EXO70E2 (AT5G61010), WRKY7 (AT4G24240), WRKY11 (AT4G31550), WRKY17 (AT2G24570), UBP20 (AT4G17895), L5 (AT1G12290), SAUR9 (AT4G36110) and TCP21 (AT5G08330). Functional analysis of these candidate interacting proteins manifested that they related to multiple pathways, including biological and abiotic stress, programmed cell death, protein degradation, material metabolism and transcriptional regulation. In addition, the results of the transient assay proclaimed that BOI protein affects the protein stability of EXO70E2 and L5 through its E3 ubiquitin ligase activity. Our results provide novel clues for a better understanding of molecular mechanisms underlying BOI-mediated regulations.展开更多
BACKGROUND Studies show that the antifibrotic mechanism of taurine may involve its inhibition of the activation and proliferation of hepatic stellate cells(HSCs). Since the molecular mechanism of taurine-mediated anti...BACKGROUND Studies show that the antifibrotic mechanism of taurine may involve its inhibition of the activation and proliferation of hepatic stellate cells(HSCs). Since the molecular mechanism of taurine-mediated antifibrotic activity has not been fully unveiled and is little studied, it is imperative to use "omics" methods to systematically investigate the molecular mechanism by which taurine inhibits liver fibrosis.AIM To establish a network including transcriptomic and protein-protein interaction data to elucidate the molecular mechanism of taurine-induced HSC apoptosis.METHODS We used microarrays, bioinformatics, protein-protein interaction(PPI) network,and sub-modules to investigate taurine-induced changes in gene expression in human HSCs(LX-2). Subsequently, all of the differentially expressed genes(DEGs) were subjected to gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Furthermore, the interactions of DEGs were explored in a human PPI network, and sub-modules of the DEGs interaction network were analyzed using Cytoscape software.RESULTS A total of 635 DEGs were identified in taurine-treated HSCs when compared with the controls. Of these, 304 genes were statistically significantly up-regulated, and 331 down-regulated. Most of these DEGs were mainly located on the membrane and extracellular region, and are involved in the biological processes of signal transduction, cell proliferation, positive regulation of extracellular regulated protein kinases 1(ERK1) and ERK2 cascade, extrinsic apoptotic signaling pathway and so on. Fifteen significantly enriched pathways with DEGs were identified, including mitogen-activated protein kinase(MAPK) signaling pathway, peroxisome proliferators-activated receptor signaling pathway,estrogen signaling pathway, Th1 and Th2 cell differentiation, cyclic adenosine monophosphate signaling pathway and so on. By integrating the transcriptomics and human PPI data, nine critical genes, including MMP2, MMP9, MMP21,TIMP3, KLF10, CX3CR1, TGFB1, VEGFB, and EGF, were identified in the PPI network analysis.CONCLUSION Taurine promotes the apoptosis of HSCs via up-regulating TGFB1 and then activating the p38 MAPK-JNK-Caspase9/8/3 pathway. These findings enhance the understanding of the molecular mechanism of taurine-induced HSC apoptosis and provide references for liver disorder therapy.展开更多
Proteins carry out their functions by interacting with other proteins and small molecules, forming a complex interaction network. In this review, we briefly introduce classical graph theory based protein-protein inter...Proteins carry out their functions by interacting with other proteins and small molecules, forming a complex interaction network. In this review, we briefly introduce classical graph theory based protein-protein interaction networks. We also describe the commonly used experimental methods to construct these networks, and the insights that can be gained from these networks. We then discuss the recent transition from graph theory based networks to structure based protein-protein interaction networks and the advantages of the latter over the former, using two networks as examples. We further discuss the usefulness of structure based protein-protein interaction networks for drug discovery, with a special emphasis on drug repositioning.展开更多
基金supported by the earmarked fund for the Modern Agro-industry Technology Research System(No.CARS-49)the Natural Science Foundation of Shan-dong Province(No.ZR2019BC052)the National Natural Science Foundation of China(No.42006077).
文摘Marine organisms cannot grow and reproduce without proper metabolic regulation.Within a metabolic network,problems with a given link will affect the normal life activities of the organism.Many metabolic mechanisms associated with behaviors of Am-phioctopus fangsiao are still unclear.Moreover,as a factor affecting the normal growth of A.fangsiao,egg protection has rarely been considered in previous behavioral studies.In this research,we analyzed the transcriptome profile of gene expression in A.fangsiao egg-unprotected larvae and egg-protected larvae,and identified 818 differentially expressed genes(DEGs).We used GO and KEGG enrichment analyses to search for metabolism-related DEGs.Protein-protein interaction networks were constructed to examine the interactions between metabolism-related genes.Twenty hub genes with multiple protein-protein interaction relationships or that were involved in multiple KEGG signaling pathways were obtained and verified by quantitative RT-PCR.We first studied the effects of egg protection on the metabolism of A.fangsiao larvae by means of protein-protein interaction networks,and the results provide va-luable gene resources for understanding the metabolism of invertebrate larvae.The data serve as a foundation for further research on the egg-protecting behavior of invertebrates.
基金supported by the National Basic Research Program of China (Grant No.2006CB500702)the Shanghai Lead-ing Academic Discipline Project (Grant No.J50103)Shanghai University Systems Biology Reasearch Funding (GrantNo.SBR08001)
文摘Alpha-synuclein plays an important role in Parkinson's disease(PD).The current study of alpha-synuclein mainly concentrates at the gene level.However, it is found that the study at the protein level has special significance.Meanwhile, there is free information on the Internet, such as databases and algorithms of protein-protein interactions(PPIs).In this paper, a novel method which integrates distributed heterogeneous data sources and algorithms to predict PPIs for alpha-synuclein in silico is proposed.The PPIs generated by the method take advantage of various experimental data, and indicate new information about PPIs for alpha-synuclein.In the end of this paper, the result illustrates that the method is practical.It is hoped that the prediction result obtained by this method can provide guidance for biological experiments of PPIs for alpha-synuclein to reveal possible mechanisms of PD.
基金Project supported by the National Natural Science Foundation of China(No.11172158)
文摘Duplication and divergence have been widely recognized as the two domi- nant evolutionary forces in shaping biological networks, e.g., gene regulatory networks and protein-protein interaction （PPI） networks. It has been shown that the network growth models constructed on the principle of duplication and divergence can recapture the topo- logical properties of real PPI networks. However, such network models only consider the evolution processes. How to select the model parameters with the real biological experi- mental data has not been presented. Therefore, based on the real PPI network statistical data, a yeast PPI network model is constructed. The simulation results indicate that the topological characteristics of the constructed network model are well consistent with those of real PPI networks, especially on sparseness, scale-free, small-world, hierarchical modularity, and disassortativity.
文摘Searching the maximum bicliques or bipartite subgraphs in a graph is a tough question. We proposed a new and efficient method, Searching Quasi-Bicliques (SQB) algorithm, to detect maximum quasi-bicliques from protein-protein interaction network. As a Divide-and-Conquer method, SQB consists of three steps: first, it divides the protein-protein interaction network into a number of Distance-2-Subgraphs;second, by combining top-down and branch-and-bound methods, SQB seeks quasi-bicliques from every Distance-2-Subgraph;third, all the redundant results are removed. We successfully applied our method on the Saccharomyces cerevisiae dataset and obtained 2754 distinct quasi-bicliques.
基金Sponsored by the National Natural Science Foundation of China(Grant No.61271346,61571163,61532014,91335112 and 61402132)the Fundamental Research Funds for the Central Universities(Grant No.DB13AB02)
文摘Domain-domain interactions are important clues to inferring protein-protein interactions. Although about 8 000 domain-domain interactions are discovered so far,they are just the tip of the iceberg. Because domains are conservative and commonplace in proteins,domain-domain interactions are discovered based on pairs of domains which significantly co-exist in proteins. Meanwhile,it is realized that:( 1) domain-domain interactions may exist within the same proteins or across different proteins;( 2) only the domain-domain interactions across different proteins can mediate interactions between proteins;( 3) domains have biases to interact with other domains. And then,a novel method is put forward to construct protein-protein interaction network by using domain-domain interactions. The method is validated by experiments and compared with the state- of-art methods in the field. The experimental results suggest that the method is reasonable and effectiveness on constructing Protein-protein interactions network.
文摘To explore the molecular mechanism of Ind-igo Naturalis in intervening chronic myelocytic leukemia （CML） under the guidance of protein-protein interaction network, the molecular docking technique and in vitro cell experiment were chosen. CML-related genes were obtained from the online mendelian inheritance in man database （OMIM）, then String 10. 0 was used for text mining and constructing the CML protein-protein interaction network. The interaction data were input in Cytoscape 3. 4. 0 software. Plug-in CentiScaPe 2. 1 was used for implement topology analysis. Small active substances of Indigo Naturalis were obtained from a third-party database, which were optimized by Chemoffice 8. 0 and Sybyl 8. 1, then small molecular ligand library was obtained. The molecular docking was carried out by Surflex-Dock module, the key target was received after scoring. Protein-protein interaction network of CML was constructed, which was consisted of 425 nodes （ proteins） and 2 799 sides （ interactions）. The key gene J.AK2 was got. CML is a polygenic disease and JAK2 is likely to be a key node.
基金the National Natural Science Foundation of China(Nos.22307009,82374155,82073997,82104376)the Sichuan Science and Technology Program(Nos.2023NSFSC1108,2024NSFTD0023)+1 种基金the Postdoctoral Research Project of Sichuan Provincethe Xinglin Scholar Research Promotion Project of Chengdu University of TCM.
文摘Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional therapies.Autophagy is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of tumors.In contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference pathways.Methods:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic targets.Meanwhile,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after intersection.Colony formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate PPI.Results:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related PPIs.Our network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified proteins.Notably,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay results.Subsequently,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 cells.Conclusions:This study not only enhances our understanding of autophagy regulation in TNBC but also identifies the Beclin 2-Ubiquilin 1 axis as a promising target for precision therapy.These findings open new avenues for drug discovery and offer inspiration for more effective treatments for this aggressive cancer subtype.
基金supported by the Humanities and Social Sciences Youth Foundation,Ministry of Education of China[Grant No.24YJC630248]Sichuan Office of Philosophy and Social Science,China[Grant No.SCJJ24ND299].
文摘Achieving a reduction in global greenhouse gas(GHG)emissions requires collaborative efforts from the international community;however,a comprehensive understanding of the spatiotemporal characteristics(i.e.,complex emission networks and driver patterns)and the mutual influence of gross domestic product(GDP)and GHG emissions remains limited at a global level in the 21st century,which is not conducive to forming a consensus in global climate change negotiations and formulating relevant policies.To fill these gaps,this study comprehensively analyzes the complex network and driver pattern of GHG emissions,as well as the corresponding mutual influence with GDP for 185 countries during 2000-2021,based on social network analysis,the logarithmic Divisia decomposition approach,and panel vector autoregression model at global and regional levels.The results indicate that significant heterogeneity and inequality exist in terms of GHG emissions among regions and countries in different geographical areas and economic income levels.Additionally,GDP per capita and GHG emission intensity are the largest positive and negative drivers,respectively,affecting the increase in global GHG emissions.Furthermore,key countries,such as Germany and Canada,that could serve as coordinating bridges to strengthen collaboration in the global emission network are identified.This study highlights the need to encourage key participants in the emission network and foster international cooperation in governance,energy technology,and economic investment to address climate change.
基金supported by the Natural Science Foundation of Henan under Grant 242300421220the Henan Provincial Science and Technology Research Project under Grants 252102211047 and 252102211062+3 种基金the Jiangsu Provincial Scheme Double Initiative Plan JSS-CBS20230474the XJTLU RDF-21-02-008the Science and Technology Innovation Project of Zhengzhou University of Light Industry under Grant 23XNKJTD0205the Higher Education Teaching Reform Research and Practice Project of Henan Province under Grant 2024SJGLX0126.
文摘With the increasing importance of multimodal data in emotional expression on social media,mainstream methods for sentiment analysis have shifted from unimodal to multimodal approaches.However,the challenges of extracting high-quality emotional features and achieving effective interaction between different modalities remain two major obstacles in multimodal sentiment analysis.To address these challenges,this paper proposes a Text-Gated Interaction Network with Inter-Sample Commonality Perception(TGICP).Specifically,we utilize a Inter-sample Commonality Perception(ICP)module to extract common features from similar samples within the same modality,and use these common features to enhance the original features of each modality,thereby obtaining a richer and more complete multimodal sentiment representation.Subsequently,in the cross-modal interaction stage,we design a Text-Gated Interaction(TGI)module,which is text-driven.By calculating the mutual information difference between the text modality and nonverbal modalities,the TGI module dynamically adjusts the influence of emotional information from the text modality on nonverbal modalities.This helps to reduce modality information asymmetry while enabling full cross-modal interaction.Experimental results show that the proposed model achieves outstanding performance on both the CMU-MOSI and CMU-MOSEI baseline multimodal sentiment analysis datasets,validating its effectiveness in emotion recognition tasks.
基金support from the Shanghai Science and Technology Development Program (Grant Nos. 03DZ14024 & 07ZR14010)the 863 High Technology Foundation of China (Grant No. 2006AA02A310)+1 种基金US NIH 1R01AI064806-01A2, 5R21DK082706U.S. Department of Energy, the Office of Science (BER) (Grant No. DE-FG02- 07ER64422)
文摘Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies. The precise determination of the specific composition of protein complexes, especially using scalable and high-throughput methods, represents a systematic approach toward revealing particular cellular biological functions. In this regard, the direct profiling protein-protein interactions (PPIs) represent an efficient way to dissect functional pathways for revealing novel protein functions. In this review, we illustrate the technological evolution for the large-scale and precise identification of PPIs toward higher physiologically relevant accuracy. These techniques aim at improving the efficiency of complex pull-down, the signal specificity and accuracy in distinguishing specific PPIs, and the accuracy of identifying physiological relevant PPIs. A newly developed streamline proteomic approach for mapping the binary relationship of PPIs in a protein complex is introduced.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.72031009 and 61473338)。
文摘In the current information society, the dissemination mechanisms and evolution laws of individual or collective opinions and their behaviors are the research hot topics in the field of opinion dynamics. First, in this paper, a two-layer network consisting of an individual-opinion layer and a collective-opinion layer is constructed, and a dissemination model of opinions incorporating higher-order interactions(i.e. OIHOI dissemination model) is proposed. Furthermore, the dynamic equations of opinion dissemination for both individuals and groups are presented. Using Lyapunov's first method,two equilibrium points, including the negative consensus point and positive consensus point, and the dynamic equations obtained for opinion dissemination, are analyzed theoretically. In addition, for individual opinions and collective opinions,some conditions for reaching negative consensus and positive consensus as well as the theoretical expression for the dissemination threshold are put forward. Numerical simulations are carried to verify the feasibility and effectiveness of the proposed theoretical results, as well as the influence of the intra-structure, inter-connections, and higher-order interactions on the dissemination and evolution of individual opinions. The main results are as follows.(i) When the intra-structure of the collective-opinion layer meets certain characteristics, then a negative or positive consensus is easier to reach for individuals.(ii) Both negative consensus and positive consensus perform best in mixed type of inter-connections in the two-layer network.(iii) Higher-order interactions can quickly eliminate differences in individual opinions, thereby enabling individuals to reach consensus faster.
基金National Natural Science Foundation of China,No.42361040。
文摘Population migration data derived from location-based services has often been used to delineate population flows between cities or construct intercity relationship networks to reveal and explore the complex interaction patterns underlying human activities.Nevertheless,the inherent heterogeneity in multimodal migration big data has been ignored.This study conducts an in-depth comparison and quantitative analysis through a comprehensive lens of spatial association.Initially,the intercity interactive networks in China were constructed,utilizing migration data from Baidu and AutoNavi collected during the same time period.Subsequently,the characteristics and spatial structure similarities of the two types of intercity interactive networks were quantitatively assessed and analyzed from overall(network)and local(node)perspectives.Furthermore,the precision of these networks at the local scale is corroborated by constructing an intercity network from mobile phone(MP)data.Results indicate that the intercity interactive networks in China,as delineated by Baidu and AutoNavi migration flows,exhibit a high degree of structure equivalence.The correlation coefficient between these two networks is 0.874.Both networks exhibit a pronounced spatial polarization trend and hierarchical structure.This is evident in their distinct core and peripheral structures,as well as in the varying importance and influence of different nodes within the networks.Nevertheless,there are notable differences worthy of attention.Baidu intercity interactive network exhibits pronounced cross-regional effects,and its high-level interactions are characterized by a“rich-club”phenomenon.The AutoNavi intercity interactive network presents a more significant distance attenuation effect,and the high-level interactions display a gradient distribution pattern.Notably,there exists a substantial correlation between the AutoNavi and MP networks at the local scale,evidenced by a high correlation coefficient of 0.954.Furthermore,the“spatial dislocations”phenomenon was observed within the spatial structures at different levels,extracted from the Baidu and AutoNavi intercity networks.However,the measured results of network spatial structure similarity from three dimensions,namely,node location,node size,and local structure,indicate a relatively high similarity and consistency between the two networks.
基金supported by grants from the National Natural Science Foundation of China(Grant No.:T2341008)Intelligent and Precise Research on TCM for Spleen and Stomach Diseases(20233930063).
文摘Drug development remains a critical issue in the field of biomedicine.With the rapid advancement of information technologies such as artificial intelligence(AI)and the advent of the big data era,AI-assisted drug development has become a new trend,particularly in predicting drug-target associations.To address the challenge of drug-target prediction,AI-driven models have emerged as powerful tools,offering innovative solutions by effectively extracting features from complex biological data,accurately modeling molecular interactions,and precisely predicting potential drug-target outcomes.Traditional machine learning(ML),network-based,and advanced deep learning architectures such as convolutional neural networks(CNNs),graph convolutional networks(GCNs),and transformers play a pivotal role.This review systematically compiles and evaluates AI algorithms for drug-and drug combination-target predictions,highlighting their theoretical frameworks,strengths,and limitations.CNNs effectively identify spatial patterns and molecular features critical for drug-target interactions.GCNs provide deep insights into molecular interactions via relational data,whereas transformers increase prediction accuracy by capturing complex dependencies within biological sequences.Network-based models offer a systematic perspective by integrating diverse data sources,and traditional ML efficiently handles large datasets to improve overall predictive accuracy.Collectively,these AI-driven methods are transforming drug-target predictions and advancing the development of personalized therapy.This review summarizes the application of AI in drug development,particularly in drug-target prediction,and offers recommendations on models and algorithms for researchers engaged in biomedical research.It also provides typical cases to better illustrate how AI can further accelerate development in the fields of biomedicine and drug discovery.
基金This study was supported by the National Water Pollution Control and Treatment Science and Technology Major Project(2017ZX07101-002).
文摘Tree interactions are essential for the structure,dynamics,and function of forest ecosystems,but variations in the architecture of life-stage interaction networks(LSINs)across forests is unclear.Here,we constructed 16 LSINs in the mountainous forests of northwest Hebei,China based on crown overlap from four mixed forests with two dominant tree species.Our results show that LSINs decrease the complexity of stand densities and basal areas due to the interaction cluster differentiation.In addition,we found that mature trees and saplings play different roles,the first acting as“hub”life stages with high connectivity and the second,as“bridges”controlling information flow with high centrality.Across the forests,life stages with higher importance showed better parameter stability within LSINs.These results reveal that the structure of tree interactions among life stages is highly related to stand variables.Our efforts contribute to the understanding of LSIN complexity and provide a basis for further research on tree interactions in complex forest communities.
基金This work was supported by the National Natural Science Foundation of China(Grant No.12072340)the China Postdoctoral Science Foundation(Grant No.2022M720727)the Jiangsu Funding Program for Excellent Postdoctoral Talent(Grant No.2022ZB130).
文摘We investigate the impact of pairwise and group interactions on the spread of epidemics through an activity-driven model based on time-dependent networks.The effects of pairwise/group interaction proportion and pairwise/group interaction intensity are explored by extensive simulation and theoretical analysis.It is demonstrated that altering the group interaction proportion can either hinder or enhance the spread of epidemics,depending on the relative social intensity of group and pairwise interactions.As the group interaction proportion decreases,the impact of reducing group social intensity diminishes.The ratio of group and pairwise social intensity can affect the effect of group interaction proportion on the scale of infection.A weak heterogeneous activity distribution can raise the epidemic threshold,and reduce the scale of infection.These results benefit the design of epidemic control strategy.
基金supported by Priority Research Centers Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(2018R1A6A1A03024003)the MSIT(Ministry of Science and ICT),Korea,under the Innovative Human Resource Development for Local Intellectualization support program(IITP-2023-2020-0-01612)supervised by the IITP(Institute for Information&communications TechnologyPlanning&Evaluation).
文摘In industrial wireless networks,data transmitted from source to destination are highly repetitive.This often leads to the queuing of the data,and poor management of the queued data results in excessive delays,increased energy consumption,and packet loss.Therefore,a nature-inspired-based Dragonfly Interaction Optimization Algorithm(DMOA)is proposed for optimization of the queue delay in industrial wireless networks.The term“interaction”herein used is the characterization of the“flying movement”of the dragonfly towards damselflies(female dragonflies)for mating.As a result,interaction is represented as the flow of transmitted data packets,or traffic,from the source to the base station.This includes each and every feature of dragonfly movement as well as awareness of the rival dragonflies,predators,and damselflies for the desired optimization of the queue delay.These features are juxtaposed as noise and interference,which are further used in the calculation of industrial wireless metrics:latency,error rate(reliability),throughput,energy efficiency,and fairness for the optimization of the queue delay.Statistical analysis,convergence analysis,the Wilcoxon test,the Friedman test,and the classical as well as the 2014 IEEE Congress of Evolutionary Computation(CEC)on the benchmark functions are also used for the evaluation of DMOA in terms of its robustness and efficiency.The results demonstrate the robustness of the proposed algorithm for both classical and benchmarking functions of the IEEE CEC 2014.Furthermore,the accuracy and efficacy of DMOA were demonstrated by means of the convergence rate,Wilcoxon testing,and ANOVA.Moreover,fairness using Jain’s index in queue delay optimization in terms of throughput and latency,along with computational complexity,is also evaluated and compared with other algorithms.Simulation results show that DMOA exceeds other bio-inspired optimization algorithms in terms of fairness in queue delay management and average packet loss.The proposed algorithm is also evaluated for the conflicting objectives at Pareto Front,and its analysis reveals that DMOA finds a compromising solution between the objectives,thereby optimizing queue delay.In addition,DMOA on the Pareto front delivers much greater performance when it comes to optimizing the queuing delay for industry wireless networks.
文摘E3 ubiquitin ligases are participated in numerous processes, regulating the response to biotic and abiotic stresses. Botrytis susceptible1 interactor (BOI) is a RING (Really Interesting New Gene)-type E3 ligase that mediates the ubiquitination of BOS1 (Botrytis susceptible1), a transcription factor involved in stress and pathogen responses. Although BOI is an E3 ligase, there are reports to show that BOI interacts with target proteins such as DELLAs or CONSTANS to repress gibberellin responses and flowering without the degradation of the target proteins. In this article, we utilize diversified methods to comprehensively analyze the expression pattern, interaction network and function of BOI gene. Firstly, 1800 bp upstream region of BOI gene from Arabidopsis thaliana (Arabidopsis) genome was isolated, and fused GUS reporter gene. The resulting expression cassette was introduced into wild-type Arabidopsis through Agrobacterium-mediated transformation. The result demonstrated that BOI gene was expressed predominantly in leaves, siliques, young roots, and flowering tissues, indicating that BOI gene may be involved in multiple processes in plant growth and development in Arabidopsis. Besides, eight candidate interacting proteins were obtained from the Arabidopsis cDNA library via yeast two-hybrid technology, including EXO70E2 (AT5G61010), WRKY7 (AT4G24240), WRKY11 (AT4G31550), WRKY17 (AT2G24570), UBP20 (AT4G17895), L5 (AT1G12290), SAUR9 (AT4G36110) and TCP21 (AT5G08330). Functional analysis of these candidate interacting proteins manifested that they related to multiple pathways, including biological and abiotic stress, programmed cell death, protein degradation, material metabolism and transcriptional regulation. In addition, the results of the transient assay proclaimed that BOI protein affects the protein stability of EXO70E2 and L5 through its E3 ubiquitin ligase activity. Our results provide novel clues for a better understanding of molecular mechanisms underlying BOI-mediated regulations.
基金the National Natural Science Foundation of China,No.81360595 and No.81860790Guangxi Natural Science Foundation Program,No.KJT13066+2 种基金the Bagui Scholars Foundation Program of Guangxithe Special-term Experts Foundation Program of Guangxithe Project of Guangxi Young Teacher Fundamental Ability Promotion,No.2017KY0298
文摘BACKGROUND Studies show that the antifibrotic mechanism of taurine may involve its inhibition of the activation and proliferation of hepatic stellate cells(HSCs). Since the molecular mechanism of taurine-mediated antifibrotic activity has not been fully unveiled and is little studied, it is imperative to use "omics" methods to systematically investigate the molecular mechanism by which taurine inhibits liver fibrosis.AIM To establish a network including transcriptomic and protein-protein interaction data to elucidate the molecular mechanism of taurine-induced HSC apoptosis.METHODS We used microarrays, bioinformatics, protein-protein interaction(PPI) network,and sub-modules to investigate taurine-induced changes in gene expression in human HSCs(LX-2). Subsequently, all of the differentially expressed genes(DEGs) were subjected to gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Furthermore, the interactions of DEGs were explored in a human PPI network, and sub-modules of the DEGs interaction network were analyzed using Cytoscape software.RESULTS A total of 635 DEGs were identified in taurine-treated HSCs when compared with the controls. Of these, 304 genes were statistically significantly up-regulated, and 331 down-regulated. Most of these DEGs were mainly located on the membrane and extracellular region, and are involved in the biological processes of signal transduction, cell proliferation, positive regulation of extracellular regulated protein kinases 1(ERK1) and ERK2 cascade, extrinsic apoptotic signaling pathway and so on. Fifteen significantly enriched pathways with DEGs were identified, including mitogen-activated protein kinase(MAPK) signaling pathway, peroxisome proliferators-activated receptor signaling pathway,estrogen signaling pathway, Th1 and Th2 cell differentiation, cyclic adenosine monophosphate signaling pathway and so on. By integrating the transcriptomics and human PPI data, nine critical genes, including MMP2, MMP9, MMP21,TIMP3, KLF10, CX3CR1, TGFB1, VEGFB, and EGF, were identified in the PPI network analysis.CONCLUSION Taurine promotes the apoptosis of HSCs via up-regulating TGFB1 and then activating the p38 MAPK-JNK-Caspase9/8/3 pathway. These findings enhance the understanding of the molecular mechanism of taurine-induced HSC apoptosis and provide references for liver disorder therapy.
基金This work was funded by grants from the National Natural Science Foundation of China （NSFC） （Grant No. 31210103916 and 91019019）, Chinese Ministry of Science and Technology （Grant No. 2011CB504206） and Chinese Academy of Sciences （CAS） （Grant Nos. KSCX2-EW-R-02 and KSCX2-EW-J-15） and stem cell leading project XDA01010303 to J.D.J.H.H.N. was supported by the Chinese Academy of Sciences Fellow- ship for Young International Scientist [Grant No. 2012Y1SB0006] and the National Natural Science Foundation of China [Grant No. 31250110524]. The authors thank Dr. Jerome Boyd-Kirkup for extensive editing and Hamna Anwar for proofreading the manu- script.
文摘Proteins carry out their functions by interacting with other proteins and small molecules, forming a complex interaction network. In this review, we briefly introduce classical graph theory based protein-protein interaction networks. We also describe the commonly used experimental methods to construct these networks, and the insights that can be gained from these networks. We then discuss the recent transition from graph theory based networks to structure based protein-protein interaction networks and the advantages of the latter over the former, using two networks as examples. We further discuss the usefulness of structure based protein-protein interaction networks for drug discovery, with a special emphasis on drug repositioning.
