Background:Many studies have examined the role of genes,proteins,andmicroribonucleic acids(miRNAs)in colorectal cancer(CRC).However,these studies did not establish the regulatory relationships among multi-omics,and on...Background:Many studies have examined the role of genes,proteins,andmicroribonucleic acids(miRNAs)in colorectal cancer(CRC).However,these studies did not establish the regulatory relationships among multi-omics,and only a few have investigated the key genes involved in the transition from colorectal adenoma to CRC.In this study,we established regulatory networks of target gene-miRNA-transcription factors(TFs)to elucidate the pathogenesis of CRC.Methods:Data from 70 patients with CRC were obtained from the Gene Expression Omnibus database.Bioinformatics analyses were used to identify the hub genes involved in the colorectal adenoma-carcinoma sequence.We conducted prognostic evaluations,analyzed gene co-expression patterns,assessed immune cell infiltration,and performed Mendelian randomization.A gene-miRNA-TF network was constructed and further analyzed.Results:Periostin(POSTN),thrombospondin 2(THBS2),collagen alpha-2 type I(COL1A2),and other molecules were found to interact and play key roles in the colorectal adenoma-carcinoma sequence.The 3 genes-11 miRNAs-6 TFs regulatory network we constructed was involved in this process through various pathways and interactions with immune cells.Several molecules in this network affected the final prognosis of patients with CRC.THBS2 showed a causal genetic relationship with neutrophils(p=0.035,odds ratio=1.020[95% confidence interval=1.001-1.039]).Therefore,bleomycin and other drugs may potentially improve the prognosis of patients with CRC.Conclusions:The 3 genes-11 miRNAs-6 TFs regulatory network may provide valuable insights into the pathogenesis of CRC.Additionally,some of these molecules may affect patient prognosis,serving as biomarkers or therapeutic targets.THBS2 may promote neutrophil infiltration into CRC tissues by increasing neutrophil levels in the blood.展开更多
Primordial germ cells(PGCs)are the precursors of germline that are specified at the embryonic stage.Recent studies reveal that humans employ different mechanisms for PGC specification compared with model organisms suc...Primordial germ cells(PGCs)are the precursors of germline that are specified at the embryonic stage.Recent studies reveal that humans employ different mechanisms for PGC specification compared with model organisms such as mice.Moreover,the specific regulatory machinery remains largely unexplored,mainly due to the inaccessible nature of this complex biological process in humans.Here,we curate and integrate multi-omics data,including 581 RNA-seq,54 ATAC-seq,45 ChIP-seq,and 69 single-cell RNA-seq samples from different stages of human PGC development to recapitulate the precisely controlled and stepwise process,presenting an atlas in the human PGC database(hPGCdb).With these uniformly processed data and integrated analyses,we characterize the potential key transcription factors and regulatory networks governing human germ cell fate.We validate the important roles of some of the key factors in germ cell development by CRISPRi knockdown.We also identify the soma-germline interaction network and discover the involvement of SDC2 and LAMA4 for PGC development,as well as soma-derived NOTCH2 signaling for germ cell differentiation.Taken together,we have built a database for human PGCs(http://43.131.248.15:6882)and demonstrate that hPGCdb enables the identification of the missing pieces of mechanisms governing germline development,including both intrinsic and extrinsic regulatory programs.展开更多
BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new ...BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis(UC).METHODS We obtained gene expression profiles of circRNAs,miRNAs,and mRNAs in UC from the Gene Expression Omnibus dataset.The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions.Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs.We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram,whose efficacy was tested with the C-index,receiver operating characteristic curve(ROC),and decision curve analysis(DCA).RESULTS A circRNA-miRNA-mRNA regulatory network was obtained,containing 12 circRNAs,three miRNAs,and 38 mRNAs.Two optimal prognostic-related differentially expressed circRNAs,hsa_circ_0085323 and hsa_circ_0036906,were included to construct a predictive nomogram.The model showed good discrimination,with a C-index of 1(>0.9,high accuracy).ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC.The circRNa-miRNA-mRNA network in UC could be more clinically significant.展开更多
Mesenchymal stem cells(MSCs)have been proposed in regenerative medicine,especially for angiogenic purposes,due to their potential to self-renew,differentiate,and regulate the microenvironment.Peripheral vascular disea...Mesenchymal stem cells(MSCs)have been proposed in regenerative medicine,especially for angiogenic purposes,due to their potential to self-renew,differentiate,and regulate the microenvironment.Peripheral vascular diseases,which are associated with reduced blood supply,have been treated but not cured.An effective therapy is to recover blood supply via vessel regeneration in the affected area,and MSCs appear to be promising for such conditions.Several studies aimed to explore the role of MSCs in performing angiogenesis and have revealed numerous potential methods to enhance MSC capacity in vessel formation.Efforts have been made to modify standard MSCs to optimize their prospective characteristics.Thus,understanding the mechanism underlying MSC angiogenic potential,and learning how to control their effect in the in vivo environment is critical for success in clinical settings.This review covers the angiogenesis process and discusses the role of some of the key angiogenic regulators.Possible techniques to enhance the angiogenic capacity of MSCs are also mentioned to suggest potential methods for therapeutic application.展开更多
Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we...Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we introduced a comprehensive single-cell transcriptomic atlas of Arabidopsis seedlings.This atlas is the result of meticulous integration of 63 previously published scRNA-seq datasets,addressing batch effects and conserving biological variance.This integration spans a broad spectrum of tissues,including both below-and above-ground parts.Utilizing a rigorous approach for cell type annotation,we identified 47 distinct cell types or states,largely expanding our current view of plant cell compositions.We systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordinated manner to control cell-type specific gene expression.Taken together,our study not only offers extensive plant cell atlas exploration that serves as a valuable resource,but also provides molecular insights into gene-regulatory programs that varies from different cell types.展开更多
Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer...Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.展开更多
The complexity of unknown scenarios and the dynamics involved in target entrapment make designing control strategies for swarm robots a formidable task,which in turn impacts their efficiency in complex and dynamic set...The complexity of unknown scenarios and the dynamics involved in target entrapment make designing control strategies for swarm robots a formidable task,which in turn impacts their efficiency in complex and dynamic settings.To address these challenges,this paper introduces an adaptive swarm robot entrapment control model grounded in the transformation of gene regulatory networks(AT-GRN).This innovative model enables swarm robots to dynamically adjust entrap-ment strategies by assessing current environmental conditions via real-time sensory data.Further-more,an improved motion control model for swarm robots is designed to dynamically shape the for-mation generated by the AT-GRN.Through two sets of rigorous experimental environments,the proposed model significantly enhances the trapping performance of swarm robots in complex envi-ronments,demonstrating remarkable adaptability and stability.展开更多
Based on a model of network encoding and dynamics called the artificial genome, we propose a segmental duplication and divergence model for evolving artificial regulatory networks. We find that this class of networks ...Based on a model of network encoding and dynamics called the artificial genome, we propose a segmental duplication and divergence model for evolving artificial regulatory networks. We find that this class of networks share structural properties with natural transcriptional regulatory networks. Specifically, these networks can display scale-free and small-world structures. We also find that these networks have a higher probability to operate in the ordered regimen, and a lower probability to operate in the chaotic regimen. That is, the dynamics of these networks is similar to that of natural networks. The results show that the structure and dynamics inherent in natural networks may be in part due to their method of generation rather than being exclusively shaped by subsequent evolution under natural selection.展开更多
The feed forward loop （FFL）, wherein a gene X can regulate target gene Z alone or cooperatively with gene Y, is one of the most important motifs in gene regulatory networks. Gene expression often involves a small nu...The feed forward loop （FFL）, wherein a gene X can regulate target gene Z alone or cooperatively with gene Y, is one of the most important motifs in gene regulatory networks. Gene expression often involves a small number of reactant molecules and thus internal molecular fluctuation is considerable. Here we studied how an FFL responds to small external signal inputs at gene X, with particular attention paid to the fluctuation resonance （FR） phenomenon of gene Z. We found that for all coherent FFLs, where the sign of the direct regulation path from X to Z is the same as the overall sign of the indirect path via Y, the FR shows a regular single peak, while for incoherent FFLs, the FR exhibits distinct bimodal shapes. The results indicate that one could use small external signals to help identify the regulatory structure of an unknown FFL in complex gene networks.展开更多
MicroRNAs （miRNAs） are endogenous -22 nucleotide noncoding RNAs that regulate the expression of complementary messenger RNAs （mRNAs）. Thousands of miRNA genes have been found in diverse species, and many of them a...MicroRNAs （miRNAs） are endogenous -22 nucleotide noncoding RNAs that regulate the expression of complementary messenger RNAs （mRNAs）. Thousands of miRNA genes have been found in diverse species, and many of them are highly conserved. With the miRNA roles identified in nearly all aspects of biological processes, evidence is mounting that miRNAs could represent a new layer of regulatory network, and their regulatory effect might be much more pervasive than previously suspected. Here we focus on the posttranscriptional level gene regulation of miRNAs in animals and review how the miRNAs act to sustain and shape up the expression profiles of specific cell types; how the miRNAs integrate into the existing gene regulatory networks; and how the miRNAs influence the evolution of 3＇UTR of mammalian mRNAs.展开更多
Gene regulatory networks play pivotal roles in our understanding of biological processes/mechanisms at the molecular level.Many studies have developed sample-specific or cell-type-specific gene regulatory networks fro...Gene regulatory networks play pivotal roles in our understanding of biological processes/mechanisms at the molecular level.Many studies have developed sample-specific or cell-type-specific gene regulatory networks from single-cell transcriptomic data based on a large amount of cell samples.Here,we review the state-of-the-art computational algorithms and describe various applications of gene regulatory networks in biological studies.展开更多
In the post-genomic biology era,the reconstruction of gene regulatory networks from microarray gene expression data is very important to understand the underlying biological system,and it has been a challenging task i...In the post-genomic biology era,the reconstruction of gene regulatory networks from microarray gene expression data is very important to understand the underlying biological system,and it has been a challenging task in bioinformatics.The Bayesian network model has been used in reconstructing the gene regulatory network for its advantages,but how to determine the network structure and parameters is still important to be explored.This paper proposes a two-stage structure learning algorithm which integrates immune evolution algorithm to build a Bayesian network.The new algorithm is evaluated with the use of both simulated and yeast cell cycle data.The experimental results indicate that the proposed algorithm can find many of the known real regulatory relationships from literature and predict the others unknown with high validity and accuracy.展开更多
Long noncoding RNAs(lncRNAs)participate in a variety of biological processes and diseases.However,the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed.In this study of righ...Long noncoding RNAs(lncRNAs)participate in a variety of biological processes and diseases.However,the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed.In this study of right side hemisection of the spinal cord at T10,we detected the expression of lncRNAs in the proximal tissue of T10 lamina at different time points and found 445 lncRNAs and 6522 mRNA were differentially expressed.We divided the differentially expressed lncRNAs into 26 expression trends and analyzed Profile 25 and Profile 2,the two expression trends with the most significant difference.Our results showed that the expression of 68 lncRNAs in Profile 25 rose first and remained high 3 days post-injury.There were 387 mRNAs co-expressed with the 68 lncRNAs in Profile 25.The co-expression network showed that the co-expressed genes were mainly enriched in cell division,inflammatory response,FcγR-mediated cell phagocytosis signaling pathway,cell cycle and apoptosis.The expression of 56 lncRNAs in Profile2 first declined and remained low after 3 days post-injury.There were 387 mRNAs co-expressed with the 56 lncRNAs in Profile 2.The co-expression network showed that the co-expressed genes were mainly enriched in the chemical synaptic transmission process and in the signaling pathway of neuroactive ligand-receptor interaction.The results provided the expression and regulatory network of the main lncRNAs after spinal cord injury and clarified their co-expressed gene enriched biological processes and signaling pathways.These findings provide a new direction for the clinical treatment of spinal cord injury.展开更多
During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial struc...During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial structures,such as tooth and palate.However,the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated.Here,we perform single-cell RNA-Seq to comprehensively characterize the transcriptional dynamics during mouse maxillary development from embryonic day(E)10.5eE14.5.Our single-cell transcriptome atlas of~28,000 cells uncovers mesenchymal cell populations representing distinct differentiating states and reveals their developmental trajectory,suggesting that the segregation of dental from the palatal mesenchyme occurs at E11.5.Moreover,we identify a series of key transcription factors(TFs)associated with mesenchymal fate transitions and deduce the gene regulatory networks directed by these TFs.Collectively,our study provides important resources and insights for achieving a systems-level understanding of craniofacial morphogenesis and abnormality.展开更多
Plants have an ability to flower under optimal seasonal conditions to ensure reproductive success.Photoperiod and temperature are two important season-dependent factors of plant flowering.The floral transition of plan...Plants have an ability to flower under optimal seasonal conditions to ensure reproductive success.Photoperiod and temperature are two important season-dependent factors of plant flowering.The floral transition of plants depends on accurate measurement of changes in photoperiod and temperature.Recent advances in molecular biology and genetics on Arabidopsis and rice reveals that the regulation of plant flowering by photoperiod and temperature are involved in a complicated gene network with different regulatory pathways,and new evidence and understanding were provided in the regulation of rice flowering.Here,we summarize and analyze different flowering regulatory pathways in detail in rice based on previous studies and our results,including short-day promotion,long-day suppression,long-day induction of flowering,night break,different light-quality and temperature regulation pathways.展开更多
Inferring gene regulatory networks from large-scale expression data is an important topic in both cellular systems and computational biology. The inference of regulators might be the core factor for understanding actu...Inferring gene regulatory networks from large-scale expression data is an important topic in both cellular systems and computational biology. The inference of regulators might be the core factor for understanding actual regulatory conditions in gene regulatory networks, especially when strong regulators do work significantly. In this paper, we propose a novel approach based on combining neuro-fu^zy network models with biological knowledge to infer strong regulators and interrelated fuzzy rules. The hybrid neuro-fuzzy architecture can not only infer the fuzzy rules, which are suitable for describing the regulatory conditions in regulatory nctworks＋ but also explain the meaning of nodes and weight value in the neural network. It can get useful rules automatically without lhctitious judgments. At the same time, it does not add recursive layers to the model, and the model can also strengthen the relationships among genes and reduce calculation. We use the proposed approach to reconstruct a partial gene regulatory network of yeast, The results show that this approach can work effectively.展开更多
WRKY transcription factors(TFs)have been identified as important core regulators in the responses of plants to biotic and abiotic stresses.Cultivated peanut(Arachis hypogaea)is an important oil and protein crop.Previo...WRKY transcription factors(TFs)have been identified as important core regulators in the responses of plants to biotic and abiotic stresses.Cultivated peanut(Arachis hypogaea)is an important oil and protein crop.Previous studies have identified hundreds of WRKY TFs in peanut.However,their functions and regulatory networks remain unclear.Simultaneously,the AdWRKY40 TF is involved in drought tolerance in Arachis duranensis and has an orthologous relationship with the AhTWRKY24 TF,which has a homoeologous relationship with AhTWRKY106 TF in A.hypogaea cv.Tifrunner.To reveal how the homoeologous AhTWRKY24 and AhTWRKY106 TFs regulate the downstream genes,DNA affinity purification sequencing(DAP-seq)was performed to detect the binding sites of TFs at the genome-wide level.A total of 3486 downstream genes were identified that were collectively regulated by the AhTWRKY24 and AhTWRKY106 TFs.The results revealed that W-box elements were the binding sites for regulation of the downstream genes by AhTWRKY24 and AhTWRKY106 TFs.A gene ontology enrichment analysis indicated that these downstream genes were enriched in protein modification and reproduction in the biological process.In addition,RNA-seq data showed that the AhTWRKY24 and AhTWRKY106 TFs regulate differentially expressed genes involved in the response to drought stress.The AhTWRKY24 and AhTWRKY106 TFs can specifically regulate downstream genes,and they nearly equal the numbers of downstream genes from the two A.hypogaea cv.Tifrunner subgenomes.These results provide a theoretical basis to study the functions and regulatory networks of AhTWRKY24 and AhTWRKY106 TFs.展开更多
Recently, self-sustained oscillatory genetic regulatory networks （GRNs） have attracted significant attention in the biological field. Given a GRN, it is important to anticipate whether the network could generate osc...Recently, self-sustained oscillatory genetic regulatory networks （GRNs） have attracted significant attention in the biological field. Given a GRN, it is important to anticipate whether the network could generate oscillation with proper parameters, and what the key ingredients for the oscillation are. In this paper the ranges of some function-related parameters which are favorable to sustained oscillations are considered. In particular, some oscillatory motifs appearing with high-frequency in most of the oscillatory GRNs are observed. Moreover, there are some anti-oscillatory motifs which have a strong oscillation repressing effect. Some conclusions analyzing these motif effects and constructing oscillatory GRNs are provided.展开更多
To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer （HRPC）, we investigated the transcriptional circuitry and signaling in a...To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer （HRPC）, we investigated the transcriptional circuitry and signaling in androgen-dependent 22Rvl and MDA PCa 2b cells, androgen- and estrogen-dependent LNCaP cells, and androgen-independent DU 145 and PC-3 prostate cancer （PCa） cell lines. We used microarray analyses, quantitative real-time PCR, pathway prediction analyses, and determination of Transcription Factor Binding Site （TFBS） signatures to dissect HRPC regulatory networks. We generated graphical representations of global topology and local network motifs that might be important in prostate carcinogenesis. Many important putative biomarker ＇target hubs＇ were identified in the current study including AP-1, NF-KB, EGFR, ERK1/2, JNK, p38 MAPK, TGF beta, VEGF, PDGF, CD44, Akt, PI3K, NOTCH1, CASP1, MMP2 and AR. Our results suggest that complex cellular events including autoregulation, feedback loops and cross-talk might govern progression from early lesion to clinically diagnosed PCa, as well as metastatic potential of pre-existent high-grade prostate intraepithelial neoplasia （HG-PIN） and/or advancement to HRPC. The identification of TFBS signatures for TCF/LEF, SOX9 and ELK1 in the regulatory elements suggests additional biomarkers for the potential development of chemopreventive/therapeutic strategies against PCa. Taken together, in this study, we have identified putative biomarker ＇target hubs＇ in the architecture of PCa signaling networks, and investigated TFBS signatures that might enhance our understanding of key regulatory nodes in the progression and pathogenesis of HRPC.展开更多
文摘Background:Many studies have examined the role of genes,proteins,andmicroribonucleic acids(miRNAs)in colorectal cancer(CRC).However,these studies did not establish the regulatory relationships among multi-omics,and only a few have investigated the key genes involved in the transition from colorectal adenoma to CRC.In this study,we established regulatory networks of target gene-miRNA-transcription factors(TFs)to elucidate the pathogenesis of CRC.Methods:Data from 70 patients with CRC were obtained from the Gene Expression Omnibus database.Bioinformatics analyses were used to identify the hub genes involved in the colorectal adenoma-carcinoma sequence.We conducted prognostic evaluations,analyzed gene co-expression patterns,assessed immune cell infiltration,and performed Mendelian randomization.A gene-miRNA-TF network was constructed and further analyzed.Results:Periostin(POSTN),thrombospondin 2(THBS2),collagen alpha-2 type I(COL1A2),and other molecules were found to interact and play key roles in the colorectal adenoma-carcinoma sequence.The 3 genes-11 miRNAs-6 TFs regulatory network we constructed was involved in this process through various pathways and interactions with immune cells.Several molecules in this network affected the final prognosis of patients with CRC.THBS2 showed a causal genetic relationship with neutrophils(p=0.035,odds ratio=1.020[95% confidence interval=1.001-1.039]).Therefore,bleomycin and other drugs may potentially improve the prognosis of patients with CRC.Conclusions:The 3 genes-11 miRNAs-6 TFs regulatory network may provide valuable insights into the pathogenesis of CRC.Additionally,some of these molecules may affect patient prognosis,serving as biomarkers or therapeutic targets.THBS2 may promote neutrophil infiltration into CRC tissues by increasing neutrophil levels in the blood.
基金supported by the National Natural Science Foundation of China awarded to D.C.(32270835)Zhejiang Natural Science Foundation awarded to D.C.(Z22C129553)Dr.Li Dak Sum&Yip Yio Chin Development Fund for Regenerative Medicine,Zhejiang University,awarded to D.C.
文摘Primordial germ cells(PGCs)are the precursors of germline that are specified at the embryonic stage.Recent studies reveal that humans employ different mechanisms for PGC specification compared with model organisms such as mice.Moreover,the specific regulatory machinery remains largely unexplored,mainly due to the inaccessible nature of this complex biological process in humans.Here,we curate and integrate multi-omics data,including 581 RNA-seq,54 ATAC-seq,45 ChIP-seq,and 69 single-cell RNA-seq samples from different stages of human PGC development to recapitulate the precisely controlled and stepwise process,presenting an atlas in the human PGC database(hPGCdb).With these uniformly processed data and integrated analyses,we characterize the potential key transcription factors and regulatory networks governing human germ cell fate.We validate the important roles of some of the key factors in germ cell development by CRISPRi knockdown.We also identify the soma-germline interaction network and discover the involvement of SDC2 and LAMA4 for PGC development,as well as soma-derived NOTCH2 signaling for germ cell differentiation.Taken together,we have built a database for human PGCs(http://43.131.248.15:6882)and demonstrate that hPGCdb enables the identification of the missing pieces of mechanisms governing germline development,including both intrinsic and extrinsic regulatory programs.
基金Supported by the National Natural Science Foundation of China,No.81774093,No.81904009,No.81974546 and No.82174182Key R&D Project of Hubei Province,No.2020BCB001.
文摘BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis(UC).METHODS We obtained gene expression profiles of circRNAs,miRNAs,and mRNAs in UC from the Gene Expression Omnibus dataset.The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions.Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs.We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram,whose efficacy was tested with the C-index,receiver operating characteristic curve(ROC),and decision curve analysis(DCA).RESULTS A circRNA-miRNA-mRNA regulatory network was obtained,containing 12 circRNAs,three miRNAs,and 38 mRNAs.Two optimal prognostic-related differentially expressed circRNAs,hsa_circ_0085323 and hsa_circ_0036906,were included to construct a predictive nomogram.The model showed good discrimination,with a C-index of 1(>0.9,high accuracy).ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC.The circRNa-miRNA-mRNA network in UC could be more clinically significant.
文摘Mesenchymal stem cells(MSCs)have been proposed in regenerative medicine,especially for angiogenic purposes,due to their potential to self-renew,differentiate,and regulate the microenvironment.Peripheral vascular diseases,which are associated with reduced blood supply,have been treated but not cured.An effective therapy is to recover blood supply via vessel regeneration in the affected area,and MSCs appear to be promising for such conditions.Several studies aimed to explore the role of MSCs in performing angiogenesis and have revealed numerous potential methods to enhance MSC capacity in vessel formation.Efforts have been made to modify standard MSCs to optimize their prospective characteristics.Thus,understanding the mechanism underlying MSC angiogenic potential,and learning how to control their effect in the in vivo environment is critical for success in clinical settings.This review covers the angiogenesis process and discusses the role of some of the key angiogenic regulators.Possible techniques to enhance the angiogenic capacity of MSCs are also mentioned to suggest potential methods for therapeutic application.
基金supported by the National Natural Science Foundation of China (No.32070656)the Nanjing University Deng Feng Scholars Program+1 种基金the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions,China Postdoctoral Science Foundation funded project (No.2022M711563)Jiangsu Funding Program for Excellent Postdoctoral Talent (No.2022ZB50)
文摘Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we introduced a comprehensive single-cell transcriptomic atlas of Arabidopsis seedlings.This atlas is the result of meticulous integration of 63 previously published scRNA-seq datasets,addressing batch effects and conserving biological variance.This integration spans a broad spectrum of tissues,including both below-and above-ground parts.Utilizing a rigorous approach for cell type annotation,we identified 47 distinct cell types or states,largely expanding our current view of plant cell compositions.We systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordinated manner to control cell-type specific gene expression.Taken together,our study not only offers extensive plant cell atlas exploration that serves as a valuable resource,but also provides molecular insights into gene-regulatory programs that varies from different cell types.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82172723)the Natural Science Foundation of Sichuan(Grant Nos.2023NSFSC1828 and 2022NSFSC1289)+2 种基金the“Xinglin Scholar”Scientific Research Promotion Plan of Chengdu University of Transitional Chinese Medicine(Grant No.BSH2021003)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.ZYYCXTD-D-202209)the Research Funding of Department of Science and Technology of Qinghai Province(Grant No.2023-ZJ-729)。
文摘Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.
基金supported in part by the National Science and Technol-ogy Major Project(No.2021ZD0111502)the National Nat-ural Science Foundation of China(Nos.62176147,62476163)+2 种基金the Science and Technology Planning Project of Guangdong Province of China(Nos.2022A1515110660,2021JC06X549)the STU Scientific Research Foundation for Talents(No.NTF21001)Guangdong Basic and Applied Basic Research Foundation(No.2023B1515120020)。
文摘The complexity of unknown scenarios and the dynamics involved in target entrapment make designing control strategies for swarm robots a formidable task,which in turn impacts their efficiency in complex and dynamic settings.To address these challenges,this paper introduces an adaptive swarm robot entrapment control model grounded in the transformation of gene regulatory networks(AT-GRN).This innovative model enables swarm robots to dynamically adjust entrap-ment strategies by assessing current environmental conditions via real-time sensory data.Further-more,an improved motion control model for swarm robots is designed to dynamically shape the for-mation generated by the AT-GRN.Through two sets of rigorous experimental environments,the proposed model significantly enhances the trapping performance of swarm robots in complex envi-ronments,demonstrating remarkable adaptability and stability.
文摘Based on a model of network encoding and dynamics called the artificial genome, we propose a segmental duplication and divergence model for evolving artificial regulatory networks. We find that this class of networks share structural properties with natural transcriptional regulatory networks. Specifically, these networks can display scale-free and small-world structures. We also find that these networks have a higher probability to operate in the ordered regimen, and a lower probability to operate in the chaotic regimen. That is, the dynamics of these networks is similar to that of natural networks. The results show that the structure and dynamics inherent in natural networks may be in part due to their method of generation rather than being exclusively shaped by subsequent evolution under natural selection.
基金ACKNOWLEDGMENT This work was supported by the National Natural Science Foundation of China （No.20673106）.
文摘The feed forward loop （FFL）, wherein a gene X can regulate target gene Z alone or cooperatively with gene Y, is one of the most important motifs in gene regulatory networks. Gene expression often involves a small number of reactant molecules and thus internal molecular fluctuation is considerable. Here we studied how an FFL responds to small external signal inputs at gene X, with particular attention paid to the fluctuation resonance （FR） phenomenon of gene Z. We found that for all coherent FFLs, where the sign of the direct regulation path from X to Z is the same as the overall sign of the indirect path via Y, the FR shows a regular single peak, while for incoherent FFLs, the FR exhibits distinct bimodal shapes. The results indicate that one could use small external signals to help identify the regulatory structure of an unknown FFL in complex gene networks.
基金supported by the National Basic Research Program of China (973 Program) (No. 2006CB701506 and 2007CB815705)the Chinese Academy of Sciences (No. KSCX1-YW-R-34)+1 种基金the National Natural Science Foundation of China (No. 30525028, 30630013 and 30871343)the Natural Science Foundation of Yunnan Province of China.
文摘MicroRNAs （miRNAs） are endogenous -22 nucleotide noncoding RNAs that regulate the expression of complementary messenger RNAs （mRNAs）. Thousands of miRNA genes have been found in diverse species, and many of them are highly conserved. With the miRNA roles identified in nearly all aspects of biological processes, evidence is mounting that miRNAs could represent a new layer of regulatory network, and their regulatory effect might be much more pervasive than previously suspected. Here we focus on the posttranscriptional level gene regulation of miRNAs in animals and review how the miRNAs act to sustain and shape up the expression profiles of specific cell types; how the miRNAs integrate into the existing gene regulatory networks; and how the miRNAs influence the evolution of 3＇UTR of mammalian mRNAs.
基金supported by the National Key Research and Development Program of China(2017YFA0505500)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38040400)+1 种基金National Science Foundation of China(31771476 and 31930022)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)。
文摘Gene regulatory networks play pivotal roles in our understanding of biological processes/mechanisms at the molecular level.Many studies have developed sample-specific or cell-type-specific gene regulatory networks from single-cell transcriptomic data based on a large amount of cell samples.Here,we review the state-of-the-art computational algorithms and describe various applications of gene regulatory networks in biological studies.
基金supported by National Natural Science Foundation of China (Grant Nos. 60433020, 60175024 and 60773095)European Commission under grant No. TH/Asia Link/010 (111084)the Key Science-Technology Project of the National Education Ministry of China (Grant No. 02090),and the Key Laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, Jilin University, P. R. China
文摘In the post-genomic biology era,the reconstruction of gene regulatory networks from microarray gene expression data is very important to understand the underlying biological system,and it has been a challenging task in bioinformatics.The Bayesian network model has been used in reconstructing the gene regulatory network for its advantages,but how to determine the network structure and parameters is still important to be explored.This paper proposes a two-stage structure learning algorithm which integrates immune evolution algorithm to build a Bayesian network.The new algorithm is evaluated with the use of both simulated and yeast cell cycle data.The experimental results indicate that the proposed algorithm can find many of the known real regulatory relationships from literature and predict the others unknown with high validity and accuracy.
文摘Long noncoding RNAs(lncRNAs)participate in a variety of biological processes and diseases.However,the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed.In this study of right side hemisection of the spinal cord at T10,we detected the expression of lncRNAs in the proximal tissue of T10 lamina at different time points and found 445 lncRNAs and 6522 mRNA were differentially expressed.We divided the differentially expressed lncRNAs into 26 expression trends and analyzed Profile 25 and Profile 2,the two expression trends with the most significant difference.Our results showed that the expression of 68 lncRNAs in Profile 25 rose first and remained high 3 days post-injury.There were 387 mRNAs co-expressed with the 68 lncRNAs in Profile 25.The co-expression network showed that the co-expressed genes were mainly enriched in cell division,inflammatory response,FcγR-mediated cell phagocytosis signaling pathway,cell cycle and apoptosis.The expression of 56 lncRNAs in Profile2 first declined and remained low after 3 days post-injury.There were 387 mRNAs co-expressed with the 56 lncRNAs in Profile 2.The co-expression network showed that the co-expressed genes were mainly enriched in the chemical synaptic transmission process and in the signaling pathway of neuroactive ligand-receptor interaction.The results provided the expression and regulatory network of the main lncRNAs after spinal cord injury and clarified their co-expressed gene enriched biological processes and signaling pathways.These findings provide a new direction for the clinical treatment of spinal cord injury.
基金supported by the National Natural Science Foundation of China(82071096 to X.W,31970585,32170544,and 31801056 to Q.B.)the National Key Research and Development Program of China(2017YFC1001800 to X.W.,2018YFC1004703 to Q.B),the Fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine(JYZZ179 to J.S.)+1 种基金the Innovative research team of high-level local universities in Shanghai(SHSMU-ZLCX20211700)the SHIPM-pi fund No.JY201803 from Shanghai Institute of Precision Medicine,Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine.
文摘During vertebrate embryonic development,neural crest-derived ectomesenchyme within the maxillary prominences undergoes precisely coordinated proliferation and differentiation to give rise to diverse craniofacial structures,such as tooth and palate.However,the transcriptional regulatory networks underpinning such an intricate process have not been fully elucidated.Here,we perform single-cell RNA-Seq to comprehensively characterize the transcriptional dynamics during mouse maxillary development from embryonic day(E)10.5eE14.5.Our single-cell transcriptome atlas of~28,000 cells uncovers mesenchymal cell populations representing distinct differentiating states and reveals their developmental trajectory,suggesting that the segregation of dental from the palatal mesenchyme occurs at E11.5.Moreover,we identify a series of key transcription factors(TFs)associated with mesenchymal fate transitions and deduce the gene regulatory networks directed by these TFs.Collectively,our study provides important resources and insights for achieving a systems-level understanding of craniofacial morphogenesis and abnormality.
基金supported by the National Natural Science Foundation of China(Grant Nos.31171515 and 30871328)the Tianjin Natural Science Foundation of China(Grant No.11JCZDJC17900)+1 种基金the Program of Tianjin Municipal Education Commission,China(Grant No.20090609)the Knowledge Innovation Program of Tianjin Normal University,China(Grant No.52X09039)
文摘Plants have an ability to flower under optimal seasonal conditions to ensure reproductive success.Photoperiod and temperature are two important season-dependent factors of plant flowering.The floral transition of plants depends on accurate measurement of changes in photoperiod and temperature.Recent advances in molecular biology and genetics on Arabidopsis and rice reveals that the regulation of plant flowering by photoperiod and temperature are involved in a complicated gene network with different regulatory pathways,and new evidence and understanding were provided in the regulation of rice flowering.Here,we summarize and analyze different flowering regulatory pathways in detail in rice based on previous studies and our results,including short-day promotion,long-day suppression,long-day induction of flowering,night break,different light-quality and temperature regulation pathways.
基金Acknowledgement This paper is supported by National Natural Science Foundation of China （Grant No. 60973092 and No. 60873146）, the National High Technology Research and Development Program of China （Grant No.2009 AA02Z307）, the ＂211 Project＂ of Jilin University, the Key Laboratory for Symbol Computation and Knowledge Engineering （Ministry of Education, China）, and the Key Laboratory for New Technology of Biological Recognition of Jilin Province （No. 20082209）.
文摘Inferring gene regulatory networks from large-scale expression data is an important topic in both cellular systems and computational biology. The inference of regulators might be the core factor for understanding actual regulatory conditions in gene regulatory networks, especially when strong regulators do work significantly. In this paper, we propose a novel approach based on combining neuro-fu^zy network models with biological knowledge to infer strong regulators and interrelated fuzzy rules. The hybrid neuro-fuzzy architecture can not only infer the fuzzy rules, which are suitable for describing the regulatory conditions in regulatory nctworks＋ but also explain the meaning of nodes and weight value in the neural network. It can get useful rules automatically without lhctitious judgments. At the same time, it does not add recursive layers to the model, and the model can also strengthen the relationships among genes and reduce calculation. We use the proposed approach to reconstruct a partial gene regulatory network of yeast, The results show that this approach can work effectively.
基金funded by the Start-up Foundation for High Talents of Qingdao Agricultural University(No.665/1120012)the Natural Science Foundation of Shandong Province,China(ZR2019QC017)+4 种基金the National Key Research and Development Program,China(2022YFD2300101-1)the Key Research and Development Program of Shandong Province,China(2021LZGC003 and 2021LZGC026-03)Peanut Seed Industry Project in Shandong Province,China(2022LZGC007)the Science&Technology Specific Projects in Agricultural High-tech Industrial Demonstration Area of the Yellow River Delta,China(2022SZX18)the Graduate Student Innovation Program of Qingdao Agricultural University(QNYCX23001).
文摘WRKY transcription factors(TFs)have been identified as important core regulators in the responses of plants to biotic and abiotic stresses.Cultivated peanut(Arachis hypogaea)is an important oil and protein crop.Previous studies have identified hundreds of WRKY TFs in peanut.However,their functions and regulatory networks remain unclear.Simultaneously,the AdWRKY40 TF is involved in drought tolerance in Arachis duranensis and has an orthologous relationship with the AhTWRKY24 TF,which has a homoeologous relationship with AhTWRKY106 TF in A.hypogaea cv.Tifrunner.To reveal how the homoeologous AhTWRKY24 and AhTWRKY106 TFs regulate the downstream genes,DNA affinity purification sequencing(DAP-seq)was performed to detect the binding sites of TFs at the genome-wide level.A total of 3486 downstream genes were identified that were collectively regulated by the AhTWRKY24 and AhTWRKY106 TFs.The results revealed that W-box elements were the binding sites for regulation of the downstream genes by AhTWRKY24 and AhTWRKY106 TFs.A gene ontology enrichment analysis indicated that these downstream genes were enriched in protein modification and reproduction in the biological process.In addition,RNA-seq data showed that the AhTWRKY24 and AhTWRKY106 TFs regulate differentially expressed genes involved in the response to drought stress.The AhTWRKY24 and AhTWRKY106 TFs can specifically regulate downstream genes,and they nearly equal the numbers of downstream genes from the two A.hypogaea cv.Tifrunner subgenomes.These results provide a theoretical basis to study the functions and regulatory networks of AhTWRKY24 and AhTWRKY106 TFs.
基金Project supported by the National Natural Science Foundation of China (Grant No. 10975015)the National Basic Research Program of China (Grant No. 2007CB814800)
文摘Recently, self-sustained oscillatory genetic regulatory networks （GRNs） have attracted significant attention in the biological field. Given a GRN, it is important to anticipate whether the network could generate oscillation with proper parameters, and what the key ingredients for the oscillation are. In this paper the ranges of some function-related parameters which are favorable to sustained oscillations are considered. In particular, some oscillatory motifs appearing with high-frequency in most of the oscillatory GRNs are observed. Moreover, there are some anti-oscillatory motifs which have a strong oscillation repressing effect. Some conclusions analyzing these motif effects and constructing oscillatory GRNs are provided.
基金National Institutes of Health(Grant No.RO1 CA118947 and RO1 CA152826 to Ah-Ng Tony Kong and R21 CA133675 to Li Cai)
文摘To understand the organization of the biological networks that might potentially govern the pathogenesis of hormone refractory prostate cancer （HRPC）, we investigated the transcriptional circuitry and signaling in androgen-dependent 22Rvl and MDA PCa 2b cells, androgen- and estrogen-dependent LNCaP cells, and androgen-independent DU 145 and PC-3 prostate cancer （PCa） cell lines. We used microarray analyses, quantitative real-time PCR, pathway prediction analyses, and determination of Transcription Factor Binding Site （TFBS） signatures to dissect HRPC regulatory networks. We generated graphical representations of global topology and local network motifs that might be important in prostate carcinogenesis. Many important putative biomarker ＇target hubs＇ were identified in the current study including AP-1, NF-KB, EGFR, ERK1/2, JNK, p38 MAPK, TGF beta, VEGF, PDGF, CD44, Akt, PI3K, NOTCH1, CASP1, MMP2 and AR. Our results suggest that complex cellular events including autoregulation, feedback loops and cross-talk might govern progression from early lesion to clinically diagnosed PCa, as well as metastatic potential of pre-existent high-grade prostate intraepithelial neoplasia （HG-PIN） and/or advancement to HRPC. The identification of TFBS signatures for TCF/LEF, SOX9 and ELK1 in the regulatory elements suggests additional biomarkers for the potential development of chemopreventive/therapeutic strategies against PCa. Taken together, in this study, we have identified putative biomarker ＇target hubs＇ in the architecture of PCa signaling networks, and investigated TFBS signatures that might enhance our understanding of key regulatory nodes in the progression and pathogenesis of HRPC.
