2,577 results on '"Regulatory networks"'
Search Results
2. Mining key genes associated with phosphorus deficiency through genome-wide identification and characterization of cucumber SPX family genes.
- Author
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Li, Jialin, Hu, Linyue, Luan, Qianqian, Zhang, Jingdan, Feng, Xueru, Li, Hongmei, Wang, Zenghui, and He, Wenxing
- Subjects
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CULTIVARS , *GENE families , *CUCUMBERS , *CHROMOSOME duplication , *PROMOTERS (Genetics) , *GENE expression profiling , *GENES - Abstract
Background: Proteins harboring the SPX domain are crucial for the regulation of phosphate (Pi) homeostasis in plants. This study aimed to identify and analyze the entire SPX gene family within the cucumber genome. Results: The cucumber genome encompassed 16 SPX domain-containing genes, which were distributed across six chromosomes and categorized into four distinct subfamilies: SPX, SPX-MFS, SPX-EXS and SPX-RING, based on their structure characteristics. Additionally, gene duplications and synteny analysis were conducted for CsSPXs, revealing that their promoter regions were enriched with a variety of hormone-responsive, biotic/abiotic stress and typical P1BS-related elements. Tissue expression profiling of CsSPX genes revealed that certain members were specifically expressed in particular organs, suggesting essential roles in cucumber growth and development. Under low Pi stress, CsSPX1 and CsSPX2 exhibited a particularly strong response to Pi starvation. It was observed that the cucumber cultivar Xintaimici displayed greater tolerance to low Pi compared to black-spined cucumber under low Pi stress conditions. Protein interaction networks for the 16 CsSPX proteins were predicted, and yeast two-hybrid assay revealed that CsPHR1 interacted with CsSPX2, CsSPX3, CsSPX4 and CsSPX5, implying their involvement in the Pi signaling pathway in conjunction with CsPHR1. Conclusion: This research lays the foundation for further exploration of the function of the CsSPX genes in response to low Pi stress and for elucidating the underlying mechanism. [ABSTRACT FROM AUTHOR]
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- 2024
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- View/download PDF
3. CACIMAR: cross-species analysis of cell identities, markers, regulations, and interactions using single-cell RNA sequencing data.
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Jiang, Junyao, Li, Jinlian, Huang, Sunan, Jiang, Fan, Liang, Yanran, Xu, Xueli, and Wang, Jie
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RNA sequencing , *CELL analysis , *GENETIC regulation , *GENE regulatory networks - Abstract
Transcriptomic analysis across species is increasingly used to reveal conserved gene regulations which implicate crucial regulators. Cross-species analysis of single-cell RNA sequencing (scRNA-seq) data provides new opportunities to identify the cellular and molecular conservations, especially for cell types and cell type-specific gene regulations. However, few methods have been developed to analyze cross-species scRNA-seq data to uncover both molecular and cellular conservations. Here, we built a tool called CACIMAR, which can perform cross-species analysis of cell identities, markers, regulations, and interactions using scRNA-seq profiles. Based on the weighted sum models of the conserved features, we developed different conservation scores to measure the conservation of cell types, regulatory networks, and intercellular interactions. Using publicly available scRNA-seq data on retinal regeneration in mice, zebrafish, and chick, we demonstrated four main functions of CACIMAR. First, CACIMAR allows to identify conserved cell types even in evolutionarily distant species. Second, the tool facilitates the identification of evolutionarily conserved or species-specific marker genes. Third, CACIMAR enables the identification of conserved intracellular regulations, including cell type-specific regulatory subnetworks and regulators. Lastly, CACIMAR provides a unique feature for identifying conserved intercellular interactions. Overall, CACIMAR facilitates the identification of evolutionarily conserved cell types, marker genes, intracellular regulations, and intercellular interactions, providing insights into the cellular and molecular mechanisms of species evolution. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
4. Single-nucleus multi-omics of Parkinson's disease reveals a glutamatergic neuronal subtype susceptible to gene dysregulation via alteration of transcriptional networks.
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Shwab, E. Keats, Gingerich, Daniel C., Man, Zhaohui, Gamache, Julia, Garrett, Melanie E., Crawford, Gregory E., Ashley-Koch, Allison E., Serrano, Geidy E., Beach, Thomas G., Lutz, Michael W., and Chiba-Falek, Ornit
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PARKINSON'S disease , *TRANSCRIPTION factors , *MULTIOMICS , *GENOME-wide association studies , *GENE expression , *CALCIUM channels , *GENE regulatory networks - Abstract
The genetic architecture of Parkinson's disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precision level. Using parallel single-nucleus (sn)RNA-seq and snATAC-seq analyses we simultaneously profiled the transcriptomic and chromatin accessibility landscapes in temporal cortex tissues from 12 PD compared to 12 control subjects at a granular single cell resolution. An integrative bioinformatic pipeline was developed and applied for the analyses of these snMulti-omics datasets. The results identified a subpopulation of cortical glutamatergic excitatory neurons with remarkably altered gene expression in PD, including differentially-expressed genes within PD risk loci identified in genome-wide association studies (GWAS). This was the only neuronal subtype showing significant and robust overexpression of SNCA. Further characterization of this neuronal-subpopulation showed upregulation of specific pathways related to axon guidance, neurite outgrowth and post-synaptic structure, and downregulated pathways involved in presynaptic organization and calcium response. Additionally, we characterized the roles of three molecular mechanisms in governing PD-associated cell subtype-specific dysregulation of gene expression: (1) changes in cis-regulatory element accessibility to transcriptional machinery; (2) changes in the abundance of master transcriptional regulators, including YY1, SP3, and KLF16; (3) candidate regulatory variants in high linkage disequilibrium with PD-GWAS genomic variants impacting transcription factor binding affinities. To our knowledge, this study is the first and the most comprehensive interrogation of the multi-omics landscape of PD at a cell-subtype resolution. Our findings provide new insights into a precise glutamatergic neuronal cell subtype, causal genes, and non-coding regulatory variants underlying the neuropathological progression of PD, paving the way for the development of cell- and gene-targeted therapeutics to halt disease progression as well as genetic biomarkers for early preclinical diagnosis. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
5. Mining key genes associated with phosphorus deficiency through genome-wide identification and characterization of cucumber SPX family genes
- Author
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Jialin Li, Linyue Hu, Qianqian Luan, Jingdan Zhang, Xueru Feng, Hongmei Li, Zenghui Wang, and Wenxing He
- Subjects
Cucumber ,SPX family ,Pi starvation ,PHR1 ,Regulatory networks ,Botany ,QK1-989 - Abstract
Abstract Background Proteins harboring the SPX domain are crucial for the regulation of phosphate (Pi) homeostasis in plants. This study aimed to identify and analyze the entire SPX gene family within the cucumber genome. Results The cucumber genome encompassed 16 SPX domain-containing genes, which were distributed across six chromosomes and categorized into four distinct subfamilies: SPX, SPX-MFS, SPX-EXS and SPX-RING, based on their structure characteristics. Additionally, gene duplications and synteny analysis were conducted for CsSPXs, revealing that their promoter regions were enriched with a variety of hormone-responsive, biotic/abiotic stress and typical P1BS-related elements. Tissue expression profiling of CsSPX genes revealed that certain members were specifically expressed in particular organs, suggesting essential roles in cucumber growth and development. Under low Pi stress, CsSPX1 and CsSPX2 exhibited a particularly strong response to Pi starvation. It was observed that the cucumber cultivar Xintaimici displayed greater tolerance to low Pi compared to black-spined cucumber under low Pi stress conditions. Protein interaction networks for the 16 CsSPX proteins were predicted, and yeast two-hybrid assay revealed that CsPHR1 interacted with CsSPX2, CsSPX3, CsSPX4 and CsSPX5, implying their involvement in the Pi signaling pathway in conjunction with CsPHR1. Conclusion This research lays the foundation for further exploration of the function of the CsSPX genes in response to low Pi stress and for elucidating the underlying mechanism.
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- 2024
- Full Text
- View/download PDF
6. Single-nucleus multi-omics of Parkinson’s disease reveals a glutamatergic neuronal subtype susceptible to gene dysregulation via alteration of transcriptional networks
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E. Keats Shwab, Daniel C. Gingerich, Zhaohui Man, Julia Gamache, Melanie E. Garrett, Gregory E. Crawford, Allison E. Ashley-Koch, Geidy E. Serrano, Thomas G. Beach, Michael W. Lutz, and Ornit Chiba-Falek
- Subjects
Parkinson’s disease ,Single-nucleus (sn)RNA-seq ,snATAC-seq ,Candidate cis regulatory element (cCRE) ,Regulatory networks ,Glutamatergic neurons ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract The genetic architecture of Parkinson’s disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precision level. Using parallel single-nucleus (sn)RNA-seq and snATAC-seq analyses we simultaneously profiled the transcriptomic and chromatin accessibility landscapes in temporal cortex tissues from 12 PD compared to 12 control subjects at a granular single cell resolution. An integrative bioinformatic pipeline was developed and applied for the analyses of these snMulti-omics datasets. The results identified a subpopulation of cortical glutamatergic excitatory neurons with remarkably altered gene expression in PD, including differentially-expressed genes within PD risk loci identified in genome-wide association studies (GWAS). This was the only neuronal subtype showing significant and robust overexpression of SNCA. Further characterization of this neuronal-subpopulation showed upregulation of specific pathways related to axon guidance, neurite outgrowth and post-synaptic structure, and downregulated pathways involved in presynaptic organization and calcium response. Additionally, we characterized the roles of three molecular mechanisms in governing PD-associated cell subtype-specific dysregulation of gene expression: (1) changes in cis-regulatory element accessibility to transcriptional machinery; (2) changes in the abundance of master transcriptional regulators, including YY1, SP3, and KLF16; (3) candidate regulatory variants in high linkage disequilibrium with PD-GWAS genomic variants impacting transcription factor binding affinities. To our knowledge, this study is the first and the most comprehensive interrogation of the multi-omics landscape of PD at a cell-subtype resolution. Our findings provide new insights into a precise glutamatergic neuronal cell subtype, causal genes, and non-coding regulatory variants underlying the neuropathological progression of PD, paving the way for the development of cell- and gene-targeted therapeutics to halt disease progression as well as genetic biomarkers for early preclinical diagnosis.
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- 2024
- Full Text
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7. On the Detection of Significant Pairwise Interactions in Complex Systems
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Fini, Giada, D’Addese, Gianluca, La Rocca, Luca, Villani, Marco, Filipe, Joaquim, Editorial Board Member, Ghosh, Ashish, Editorial Board Member, Prates, Raquel Oliveira, Editorial Board Member, Zhou, Lizhu, Editorial Board Member, Villani, Marco, editor, Cagnoni, Stefano, editor, and Serra, Roberto, editor
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- 2024
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8. Multimodal Methods for Knowledge Discovery from Bulk and Single-Cell Multi-Omics Data
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Li, Yue, Fonseca, Gregory, Ding, Jun, Alkhateeb, Abedalrhman, editor, and Rueda, Luis, editor
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- 2024
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9. Biomarker potential of competing endogenous RNA networks in Polycystic Ovary Syndrome (PCOS)
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Roozbeh Heidarzadehpilehrood and Maryam Pirhoushiaran
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Polycystic ovary syndrome ,Competing endogenous RNA (ceRNA) ,Long noncoding RNA ,MicroRNAs ,Circular RNAs ,Regulatory networks ,Genetics ,QH426-470 - Abstract
Polycystic ovary syndrome (PCOS) is the most common condition affecting women of reproductive age globally. PCOS continues to be the largest contributing factor to female infertility despite significant progress in our knowledge of the molecular underpinnings and treatment of the condition. The fact that PCOS is a very diverse condition makes it one of the key reasons why we haven't been able to overcome it. Non-coding RNAs (ncRNAs) are implicated in the development of PCOS, according to growing evidence. However, it is unclear how the complex regulatory relationships between the many ncRNA types contribute to the growth of this malignancy. Competing endogenous RNA (ceRNA), a recently identified mechanism in the RNA world, suggests regulatory interactions between various RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). Recent studies on PCOS have shown that dysregulation of multiple ceRNA networks (ceRNETs) between these ncRNAs plays crucial roles in developing the defining characteristics of PCOS development. And it is believed that such a finding may open a new door for a deeper comprehension of PCOS's unexplored facets. In addition, it may be able to provide fresh biomarkers and effective therapy targets for PCOS. This review will go over the body of information that exists about the primary roles of ceRNETs before highlighting the developing involvement of several newly found ceRNETs in a number of PCOS characteristics.
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- 2024
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10. Characterization of PANoptosis-related genes in Crohn’s disease by integrated bioinformatics, machine learning and experiments
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Yang Yang, Alphonse Houssou Hounye, Yiqian Chen, Zhuqing Liu, Guanzhong Shi, and Ying Xiao
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PANoptosis ,Crohn’s disease ,Bioinformatics ,Machine learning ,Regulatory networks ,Medicine ,Science - Abstract
Abstract Currently, the biological understanding of Crohn’s disease (CD) remains limited. PANoptosis is a revolutionary form of cell death reported to participate in numerous diseases, including CD. In our study, we aimed to uncover the roles of PANoptosis in CD. Differentially expressed PANoptosis-related genes (DE-PRGs) were identified by overlapping PANoptosis-related genes and differentially expressed genes between CD and normal samples in a combined microarray dataset. Three machine learning algorithms were adopted to detect hub DE-PRGs. To stratify the heterogeneity within CD patients, nonnegative matrix factorization clustering was conducted. In terms of immune landscape analysis, the “ssGSEA” method was applied. qRT-PCR was performed to examine the expression levels of the hub DE-PRGs in CD patients and colitis model mice. Ten hub DE-PRGs with satisfactory diagnostic performance were identified and validated: CD44, CIDEC, NDRG1, NUMA1, PEA15, RAG1, S100A8, S100A9, TIMP1 and XBP1. These genes displayed significant associations with certain immune cell types and CD-related genes. We also constructed gene‒microRNA, gene‒transcription factor and drug‒gene interaction networks. CD samples were classified into two PANoptosis patterns according to the expression levels of the hub DE-PRGs. Our results suggest that PANoptosis plays a nonnegligible role in CD by modulating the immune system and interacting with CD-related genes.
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- 2024
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11. Evolution of the SPX gene family and its role in the response mechanism to low phosphorus stress in self-rooted apple stock
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Zenghui Wang, Xiaowen Zhang, Xuemei Yang, Haixia Tang, Lijuan Feng, Yanlei Yin, and Jialin Li
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Self-rooted apple stock ,Expression patterns ,SPX family ,Phosphate starvation ,Regulatory networks ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Phosphorus plays a key role in plant adaptation to adversity and plays a positive role in the yield and quality formation of apples. Genes of the SPX domain-containing family are widely involved in the regulation of phosphorus signalling networks. However, the mechanisms controlling phosphorus deficiency are not completely understood in self-rooted apple stock. Results In this study, 26 members of the apple SPX gene family were identified by genome-wide analysis, and further divided into four subfamilies (SPX, SPX-MFS, SPX-EXS, and SPX-RING) based on their structural features. The chromosome distribution and gene duplications of MdSPXs were also examined. The promoter regions of MdSPXs were enriched for multiple biotic/abiotic stresses, hormone responses and typical P1BS-related elements. Analysis of the expression levels of 26 MdSPXs showed that some members were remarkably induced when subjected to low phosphate (Pi) stress, and in particular MdSPX2, MdSPX3, and MdPHO1.5 exhibited an intense response to low Pi stress. MdSPX2 and MdSPX3 showed significantly divergent expression levels in low Pi sensitive and insensitive apple species. Protein interaction networks were predicted for 26 MdSPX proteins. The interaction of MdPHR1 with MdSPX2, MdSPX3, MdSPX4, and MdSPX6 was demonstrated by yeast two-hybrid assay, suggesting that these proteins might be involved in the Pi-signaling pathway by interacting with MdPHR1. Conclusion This research improved the understanding of the apple SPX gene family and contribute to future biological studies of MdSPX genes in self-rooted apple stock.
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- 2024
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12. Non-Coding Ribonucleic Acids as Diagnostic and Therapeutic Targets in Cardiac Fibrosis.
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Olson, Samuel R., Tang, W. H. Wilson, and Liu, Chia-Feng
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Purpose of Review: Cardiac fibrosis is a crucial juncture following cardiac injury and a precursor for many clinical heart disease manifestations. Epigenetic modulators, particularly non-coding RNAs (ncRNAs), are gaining prominence as diagnostic and therapeutic tools. Recent Findings: miRNAs are short linear RNA molecules involved in post-transcriptional regulation; lncRNAs and circRNAs are RNA sequences greater than 200 nucleotides that also play roles in regulating gene expression through a variety of mechanisms including miRNA sponging, direct interaction with mRNA, providing protein scaffolding, and encoding their own products. NcRNAs have the capacity to regulate one another and form sophisticated regulatory networks. The individual roles and disease relevance of miRNAs, lncRNAs, and circRNAs to cardiac fibrosis have been increasingly well described, though the complexity of their interrelationships, regulatory dynamics, and context-specific roles needs further elucidation. Summary: This review provides an overview of select ncRNAs relevant in cardiac fibrosis as a surrogate for many cardiac disease states with a focus on crosstalk and regulatory networks, variable actions among different disease states, and the clinical implications thereof. Further, the clinical feasibility of diagnostic and therapeutic applications as well as the strategies underway to advance ncRNA theranostics is explored. [ABSTRACT FROM AUTHOR]
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- 2024
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13. A close-up of regulatory networks and signaling pathways of MKK5 in biotic and abiotic stresses.
- Author
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Movahedi, Ali, Hwarari, Delight, Dzinyela, Raphael, Ni, Siyi, and Yang, Liming
- Abstract
AbstractMitogen-activated protein Kinase Kinase 5 (MKK5) is a central hub in the complex phosphorylation chain reaction of the Mitogen-activated protein kinases (MAPK) cascade, regulating plant responses to biotic and abiotic stresses. This review manuscript aims to provide a comprehensive analysis of the regulatory mechanism of the MKK5 involved in stress adaptation. This review will delve into the intricate post-transcriptional and post-translational modifications of the MKK5, discussing how they affect its expression, activity, and subcellular localization in response to stress signals. We also discuss the integration of the MKK5 into complex signaling pathways, orchestrating plant immunity against pathogens and its modulating role in regulating abiotic stresses, such as: drought, cold, heat, and salinity, through the phytohormonal signaling pathways. Furthermore, we highlight potential applications of the MKK5 for engineering stress-resilient crops and provide future perspectives that may pave the way for future studies. This review manuscript aims to provide valuable insights into the mechanisms underlying MKK5 regulation, bridge the gap from numerous previous findings, and offer a firm base in the knowledge of MKK5, its regulating roles, and its involvement in environmental stress regulation. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Evolution of the SPX gene family and its role in the response mechanism to low phosphorus stress in self-rooted apple stock.
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Wang, Zenghui, Zhang, Xiaowen, Yang, Xuemei, Tang, Haixia, Feng, Lijuan, Yin, Yanlei, and Li, Jialin
- Subjects
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GENE families , *PLANT adaptation , *PHOSPHORUS , *CHROMOSOME duplication , *PROMOTERS (Genetics) , *APPLES , *APPLE blue mold - Abstract
Background: Phosphorus plays a key role in plant adaptation to adversity and plays a positive role in the yield and quality formation of apples. Genes of the SPX domain-containing family are widely involved in the regulation of phosphorus signalling networks. However, the mechanisms controlling phosphorus deficiency are not completely understood in self-rooted apple stock. Results: In this study, 26 members of the apple SPX gene family were identified by genome-wide analysis, and further divided into four subfamilies (SPX, SPX-MFS, SPX-EXS, and SPX-RING) based on their structural features. The chromosome distribution and gene duplications of MdSPXs were also examined. The promoter regions of MdSPXs were enriched for multiple biotic/abiotic stresses, hormone responses and typical P1BS-related elements. Analysis of the expression levels of 26 MdSPXs showed that some members were remarkably induced when subjected to low phosphate (Pi) stress, and in particular MdSPX2, MdSPX3, and MdPHO1.5 exhibited an intense response to low Pi stress. MdSPX2 and MdSPX3 showed significantly divergent expression levels in low Pi sensitive and insensitive apple species. Protein interaction networks were predicted for 26 MdSPX proteins. The interaction of MdPHR1 with MdSPX2, MdSPX3, MdSPX4, and MdSPX6 was demonstrated by yeast two-hybrid assay, suggesting that these proteins might be involved in the Pi-signaling pathway by interacting with MdPHR1. Conclusion: This research improved the understanding of the apple SPX gene family and contribute to future biological studies of MdSPX genes in self-rooted apple stock. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
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15. Deciphering the regulatory networks involved in mild and severe salt stress responses in the roots of wild grapevine Vitis vinifera spp. sylvestris.
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Daldoul, Samia, Hanzouli, Faouzia, Boubakri, Hatem, Nick, Peter, Mliki, Ahmed, and Gargouri, Mahmoud
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VITIS vinifera , *GENE regulatory networks , *HEAT shock proteins , *GRAPES , *PLANT adaptation , *SALT , *ABSCISIC acid - Abstract
Transcriptional regulatory networks are pivotal components of plant's response to salt stress. However, plant adaptation strategies varied as a function of stress intensity, which is mainly modulated by climate change. Here, we determined the gene regulatory networks based on transcription factor (TF) TF_gene co-expression, using two transcriptomic data sets generated from the salt-tolerant "Tebaba" roots either treated with 50 mM NaCl (mild stress) or 150 mM NaCl (severe stress). The analysis of these regulatory networks identified specific TFs as key regulatory hubs as evidenced by their multiple interactions with different target genes related to stress response. Indeed, under mild stress, NAC and bHLH TFs were identified as central hubs regulating nitrogen storage process. Moreover, HSF TFs were revealed as a regulatory hub regulating various aspects of cellular metabolism including flavonoid biosynthesis, protein processing, phenylpropanoid metabolism, galactose metabolism, and heat shock proteins. These processes are essentially linked to short-term acclimatization under mild salt stress. This was further consolidated by the protein–protein interaction (PPI) network analysis showing structural and plant growth adjustment. Conversely, under severe salt stress, dramatic metabolic changes were observed leading to novel TF members including MYB family as regulatory hubs controlling isoflavonoid biosynthesis, oxidative stress response, abscisic acid signaling pathway, and proteolysis. The PPI network analysis also revealed deeper stress defense changes aiming to restore plant metabolic homeostasis when facing severe salt stress. Overall, both the gene co-expression and PPI network provided valuable insights on key transcription factor hubs that can be employed as candidates for future genetic crop engineering programs. [ABSTRACT FROM AUTHOR]
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- 2024
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16. LncRNA NDUFA6-DT: A Comprehensive Analysis of a Potential LncRNA Biomarker and Its Regulatory Mechanisms in Gliomas.
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Huang, Ruiting, Kong, Ying, Luo, Zhiqing, and Li, Quhuan
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COMPETITIVE endogenous RNA , *GLIOMAS , *LINCRNA , *GLIOBLASTOMA multiforme , *MACHINE learning , *BIOMARKERS - Abstract
Gliomas are the most prevalent primary malignant tumors affecting the brain, with high recurrence and mortality rates. Accurate diagnoses and effective treatment challenges persist, emphasizing the need for identifying new biomarkers to guide clinical decisions. Long noncoding RNAs (lncRNAs) hold potential as diagnostic and therapeutic biomarkers in cancer. However, only a limited subset of lncRNAs in gliomas have been explored. Therefore, this study aims to identify lncRNA signatures applicable to patients with gliomas across all grades and explore their clinical significance and potential biological mechanisms. Data used in this study were obtained from TCGA, CGGA, and GEO datasets to identify key lncRNA signatures in gliomas through differential and survival analyses and machine learning algorithms. We examined their associations with the clinical characteristics, gene mutations, diagnosis, and prognosis of gliomas. Functional enrichment analysis was employed to elucidate the potential biological mechanisms associated with these significant lncRNA signatures. We explored competing endogenous RNA (ceRNA) regulatory networks. We found that NDUFA6-DT emerged as a significant lncRNA signature in gliomas, with reduced NDUFA6-DT expression associated with a worse prognosis in gliomas. Nomogram analysis incorporating NDUFA6-DT expression levels exhibited excellent prognostic and predictive capabilities. Functional annotation suggested that NDUFA6-DT might influence immunological responses and synaptic transmission, potentially modifying glioma initiation and progression. The associated ceRNA network revealed the possible presence of the NDUFA6-DT-miR-455-3p-YWHAH/YWHAG axis in low-grade glioma (LGG) and glioblastoma multiforme (GBM), regulating the PI3K-AKT signaling pathway and influencing glioma cell survival and apoptosis. We believe that NDUFA6-DT is a novel lncRNA linked to glioma diagnosis and prognosis, potentially becoming a pivotal biomarker for glioma. [ABSTRACT FROM AUTHOR]
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- 2024
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17. MicroRNAs: An important signature molecule to improve health and welfare in livestock: A review
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Khandelwal, V., Sharma, T., Choudhary, P., Gupta, S., Sohal, J. S., Jain, M., and Malik, Y.S.
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- 2024
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18. Integrated transcriptome and miRNA analysis provides insight into the floral buds dormancy in Prunus armeniaca
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Xu, Wanyu, Chen, Chen, Bao, Wenquan, Chen, Yixiao, Chen, Junxing, Zhao, Han, Zhu, Gaopu, Wuyun, Ta-na, and Wang, Lin
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- 2024
- Full Text
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19. Discovering Common Pathogenic Mechanisms of COVID-19 and Parkinson Disease: An Integrated Bioinformatics Analysis.
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Jahanimoghadam, Aria, Abdolahzadeh, Hadis, Rad, Niloofar, and Zahiri, Javad
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Bioinformatics ,COVID-19 ,Parkinson disease ,Regulatory networks ,Signaling pathways ,Transcriptome analysis ,Humans ,Parkinson Disease ,COVID-19 ,Leukocytes ,Mononuclear ,Computational Biology - Abstract
Coronavirus disease 2019 (COVID-19) has emerged since December 2019 and was later characterized as a pandemic by WHO, imposing a major public health threat globally. Our study aimed to identify common signatures from different biological levels to enlighten the current unclear association between COVID-19 and Parkinsons disease (PD) as a number of possible links, and hypotheses were reported in the literature. We have analyzed transcriptome data from peripheral blood mononuclear cells (PBMCs) of both COVID-19 and PD patients, resulting in a total of 81 common differentially expressed genes (DEGs). The functional enrichment analysis of common DEGs are mostly involved in the complement system, type II interferon gamma (IFNG) signaling pathway, oxidative damage, microglia pathogen phagocytosis pathway, and GABAergic synapse. The protein-protein interaction network (PPIN) construction was carried out followed by hub detection, revealing 10 hub genes (MX1, IFI27, C1QC, C1QA, IFI6, NFIX, C1S, XAF1, IFI35, and ELANE). Some of the hub genes were associated with molecular mechanisms such as Lewy bodies-induced inflammation, microglia activation, and cytokine storm. We investigated regulatory elements of hub genes at transcription factor and miRNA levels. The major transcription factors regulating hub genes are SOX2, XAF1, RUNX1, MITF, and SPI1. We propose that these events may have important roles in the onset or progression of PD. To sum up, our analysis describes possible mechanisms linking COVID-19 and PD, elucidating some unknown clues in between.
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- 2022
20. Comparative transcriptome profiling and co-expression network analysis uncover the key genes associated with pear petal defense responses against Monilinia laxa infection.
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Aci, Meriem Miyassa, Tsalgatidou, Polina C., Boutsika, Anastasia, Dalianis, Andreas, Michaliou, Maria, Delis, Costas, Tsitsigiannis, Dimitrios I., Paplomatas, Epaminondas, Malacrinò, Antonino, Schena, Leonardo, and Zambounis, Antonios
- Subjects
TRANSCRIPTOMES ,METABOLISM ,GENES ,SECONDARY metabolism ,BROWN rot ,GENE regulatory networks - Abstract
Pear brown rot and blossom blight caused by Monilinia laxa seriously affect pear production worldwide. Here, we compared the transcriptomic profiles of petals after inoculation with M. laxa using two pear cultivars with different levels of sensitivity to disease (Sissy, a relatively tolerant cultivar, and Kristalli, a highly susceptible cultivar). Physiological indexes were also monitored in the petals of both cultivars at 2 h and 48 h after infection (2 HAI and 48 HAI). RNA-seq data and weighted gene co-expression network analysis (WGCNA) allowed the identification of key genes and pathways involved in immune- and defenserelated responses that were specific for each cultivar in a time-dependent manner. In particular, in the Kristalli cultivar, a significant transcriptome reprogramming occurred early at 2 HAI and was accompanied either by suppression of key differentially expressed genes (DEGs) involved in the modulation of any defense responses or by activation of DEGs acting as sensitivity factors promoting susceptibility. In contrast to the considerably high number of DEGs induced early in the Kristalli cultivar, upregulation of specific DEGs involved in pathogen perception and signal transduction, biosynthesis of secondary and primary metabolism, and other defense-related responses was delayed in the Sissy cultivar, occurring at 48 HAI. The WGCNA highlighted one module that was significantly and highly correlated to the relatively tolerant cultivar. Six hub genes were identified within this module, including three WRKY transcription factor-encoding genes: WRKY 65 (pycom05g27470), WRKY 71 (pycom10g22220), and WRKY28 (pycom17g13130), which may play a crucial role in enhancing the tolerance of pear petals to M. laxa. Our results will provide insights into the interplay of the molecular mechanisms underlying immune responses of petals at the pear–M. laxa pathosystem. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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21. 细菌 sRNA 来源、作用机制及调控网络研究进展.
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赵子墨, 乔建军, 袁琳, 龙映鹏, 任书江, and 吴昊
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- 2024
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22. Human mtDNA-Encoded Long ncRNAs: Knotty Molecules and Complex Functions.
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Bruni, Francesco
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LINCRNA , *MITOCHONDRIAL DNA , *WHOLE genome sequencing , *MOLECULES , *NON-coding RNA , *CELLULAR pathology - Abstract
Until a few decades ago, most of our knowledge of RNA transcription products was focused on protein-coding sequences, which were later determined to make up the smallest portion of the mammalian genome. Since 2002, we have learnt a great deal about the intriguing world of non-coding RNAs (ncRNAs), mainly due to the rapid development of bioinformatic tools and next-generation sequencing (NGS) platforms. Moreover, interest in non-human ncRNAs and their functions has increased as a result of these technologies and the accessibility of complete genome sequences of species ranging from Archaea to primates. Despite not producing proteins, ncRNAs constitute a vast family of RNA molecules that serve a number of regulatory roles and are essential for cellular physiology and pathology. This review focuses on a subgroup of human ncRNAs, namely mtDNA-encoded long non-coding RNAs (mt-lncRNAs), which are transcribed from the mitochondrial genome and whose disparate localisations and functions are linked as much to mitochondrial metabolism as to cellular physiology and pathology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
23. R‐loops act as regulatory switches modulating transcription of COLD‐responsive genes in rice.
- Author
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He, Zexue, Li, Mengqi, Pan, Xiucai, Peng, Yulian, Shi, Yining, Han, Qi, Shi, Manli, She, Linwei, Borovskii, Gennadii, Chen, Xiaojun, Gu, Xiaofeng, Cheng, Xuejiao, and Zhang, Wenli
- Subjects
- *
GENE expression , *GENES , *RICE breeding , *CROP yields , *CROP losses , *RICE - Abstract
Summary: COLD is a major naturally occurring stress that usually causes complex symptoms and severe yield loss in crops. R‐loops function in various cellular processes, including development and stress responses, in plants. However, how R‐loops function in COLD responses is largely unknown in COLD susceptible crops like rice (Oryza sativa L.).We conducted DRIP‐Seq along with other omics data (RNA‐Seq, DNase‐Seq and ChIP‐Seq) in rice with or without COLD treatment.COLD treatment caused R‐loop reprogramming across the genome. COLD‐biased R‐loops had higher GC content and novel motifs for the binding of distinct transcription factors (TFs). Moreover, R‐loops can directly/indirectly modulate the transcription of a subset of COLD‐responsive genes, which can be mediated by R‐loop overlapping TF‐centered or cis‐regulatory element‐related regulatory networks and lncRNAs, accounting for c. 60% of COLD‐induced expression of differential genes in rice, which is different from the findings in Arabidopsis. We validated two R‐loop loci with contrasting (negative/positive) roles in the regulation of two individual COLD‐responsive gene expression, as potential targets for enhanced COLD resistance.Our study provides detailed evidence showing functions of R‐loop reprogramming during COLD responses and provides some potential R‐loop loci for genetic and epigenetic manipulation toward breeding of rice varieties with enhanced COLD tolerance. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
24. Expression Quantitative Trait Locus of Wood Formation-Related Genes in Salix suchowensis.
- Author
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Chen, Li, Liu, Liyan, Yang, Guo, Li, Xiaoping, Dai, Xiaogang, Xue, Liangjiao, and Yin, Tongming
- Subjects
- *
LOCUS (Genetics) , *GENE expression , *WOOD , *GENETIC engineering , *REGULATOR genes , *WILLOWS - Abstract
Shrub willows are widely planted for landscaping, soil remediation, and biomass production, due to their rapid growth rates. Identification of regulatory genes in wood formation would provide clues for genetic engineering of willows for improved growth traits on marginal lands. Here, we conducted an expression quantitative trait locus (eQTL) analysis, using a full sibling F1 population of Salix suchowensis, to explore the genetic mechanisms underlying wood formation. Based on variants identified from simplified genome sequencing and gene expression data from RNA sequencing, 16,487 eQTL blocks controlling 5505 genes were identified, including 2148 cis-eQTLs and 16,480 trans-eQTLs. eQTL hotspots were identified, based on eQTL frequency in genomic windows, revealing one hotspot controlling genes involved in wood formation regulation. Regulatory networks were further constructed, resulting in the identification of key regulatory genes, including three transcription factors (JAZ1, HAT22, MYB36) and CLV1, BAM1, CYCB2;4, CDKB2;1, associated with the proliferation and differentiation activity of cambium cells. The enrichment of genes in plant hormone pathways indicates their critical roles in the regulation of wood formation. Our analyses provide a significant groundwork for a comprehensive understanding of the regulatory network of wood formation in S. suchowensis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
25. Hsa_circITGA4/ miR-1468/EGFR/ PTEN a Master Regulators Axis in Glioblastoma Development and Progression.
- Author
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Tutunchi, Sara, Bereimipour, Ahmad, and Ghaderian, Sayyed Mohammad Hossein
- Abstract
In the fight against glioblastoma, circular RNA is emerging as a functional molecule. However, how circular RNA (circRNA) is regulated and what role it plays is still a mystery. In this research, different bioinformatics approaches were used to evaluate glioblastoma circRNA sequencing and array data, with the goal of developing a putative molecular sponge mechanism control network. The circRNAs were obtained from the Gene Expression Omnibus datasets. MicroRNA-circRNA interactions were predicted using CircInteractome. The microRNAs' expression and survival trends were screened using the TCGA database. MicroRNA gene targets were predicted using the MiRnet database. Sponge network gene candidates were screened using data from the GEPIA. The roles of the targeted genes were to be explained by analyzing data from Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. To build the network and display the outcomes, we utilized python program, and enrichment online Bioinformatics databases. The circRNAs hsa_circITGA4_002, hsa_circITGA4_001, hsa_circITGA4_003, hsa_circ_0030855, hsa_circ_0030857 were chosen from among GBM patients and control group. Upregulation of hsa-miR-1468, hsa-miR-3683, hsa-miR-1273c, and hsa-miR-4665-3p were associated with a poor prognosis in GBM. MicroRNA targets such as ITGA4, LAMA2, EGFR, PTEN, COL1A4, and NCAM2 were analyzed using expression and survival data. The Apoptosis, cell adhesion molecules, PI3K/AKT and P53 signaling pathways were the most abundant functional categories among gene targets. The circRNA molecular sponge regulatory network includes hsa-miR-1468 and hsa-miR-4665-3p. In this network, hs hsa_circITGA4_002, hsa_circITGA4_001, hsa_circ_0030857, EGFR, PTEN, and ITGA4 may represent GBM therapeutic targets. Their role in GBM needs additional study. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
26. An engineering perspective on transcription, translation and their regulation.
- Author
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Śmieja, Jarosław
- Subjects
GENETIC transcription ,BIOENGINEERING ,AUTOMATIC control systems ,ENGINEERING ,CELL growth ,ORIGIN of life - Abstract
Information coded in DNA is replicated, modified and transmitted from the origins of protein-based life. Analogies of these processes to information processing, transmission and storage in computer systems is straightforward and can be utilized both in analysis of biological data and in development of biologically based technical systems. Transcription and translation processes are regulated by extremely complex regulatory networks, providing control of cell growth, cell cycle and cellular responses to stress. As such, they constitute engineering control systems exerting their actions at many levels of time scale and spatial organization. This work presents an engineering perspective on DNA-related information processing and biochemical process control in living cells, followed by a review of two-way crosstalk between engineering and biology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
27. The mechanism of ferroptosis and its related diseases
- Author
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Shijian Feng, Dan Tang, Yichang Wang, Xiang Li, Hui Bao, Chengbing Tang, Xiuju Dong, Xinna Li, Qinxue Yang, Yun Yan, Zhijie Yin, Tiantian Shang, Kaixuan Zheng, Xiaofang Huang, Zuheng Wei, Kunjie Wang, and Shiqian Qi
- Subjects
Ferroptosis ,Lipid peroxidation ,Iron metabolism ,Regulatory networks ,Therapeutic strategies ,Diseases ,Medicine - Abstract
Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation of lipid peroxides, provides a novel avenue for delving into the intersection of cellular metabolism, oxidative stress, and disease pathology. We have witnessed a mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological and pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, and traumatic tissue injuries. By unraveling the intricate underpinnings of the molecular machinery, pivotal contributors, intricate signaling conduits, and regulatory networks governing ferroptosis, researchers aim to bridge the gap between the intricacies of this unique mode of cellular death and its multifaceted implications for health and disease. In light of the rapidly advancing landscape of ferroptosis research, we present a comprehensive review aiming at the extensive implications of ferroptosis in the origins and progress of human diseases. This review concludes with a careful analysis of potential treatment approaches carefully designed to either inhibit or promote ferroptosis. Additionally, we have succinctly summarized the potential therapeutic targets and compounds that hold promise in targeting ferroptosis within various diseases. This pivotal facet underscores the burgeoning possibilities for manipulating ferroptosis as a therapeutic strategy. In summary, this review enriched the insights of both investigators and practitioners, while fostering an elevated comprehension of ferroptosis and its latent translational utilities. By revealing the basic processes and investigating treatment possibilities, this review provides a crucial resource for scientists and medical practitioners, aiding in a deep understanding of ferroptosis and its effects in various disease situations.
- Published
- 2023
- Full Text
- View/download PDF
28. Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer
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Zhen Zeng, Minyang Fu, Yuan Hu, Yuquan Wei, Xiawei Wei, and Min Luo
- Subjects
CSCs ,Regulatory networks ,Cancer therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Cancer stem cells (CSCs), initially identified in leukemia in 1994, constitute a distinct subset of tumor cells characterized by surface markers such as CD133, CD44, and ALDH. Their behavior is regulated through a complex interplay of networks, including transcriptional, post-transcriptional, epigenetic, tumor microenvironment (TME), and epithelial-mesenchymal transition (EMT) factors. Numerous signaling pathways were found to be involved in the regulatory network of CSCs. The maintenance of CSC characteristics plays a pivotal role in driving CSC-associated tumor metastasis and conferring resistance to therapy. Consequently, CSCs have emerged as promising targets in cancer treatment. To date, researchers have developed several anticancer agents tailored to specifically target CSCs, with some of these treatment strategies currently undergoing preclinical or clinical trials. In this review, we outline the origin and biological characteristics of CSCs, explore the regulatory networks governing CSCs, discuss the signaling pathways implicated in these networks, and investigate the influential factors contributing to therapy resistance in CSCs. Finally, we offer insights into preclinical and clinical agents designed to eliminate CSCs.
- Published
- 2023
- Full Text
- View/download PDF
29. Integrative single-nucleus multi-omics analysis prioritizes candidate cis and trans regulatory networks and their target genes in Alzheimer’s disease brains
- Author
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Julia Gamache, Daniel Gingerich, E. Keats Shwab, Julio Barrera, Melanie E. Garrett, Cordelia Hume, Gregory E. Crawford, Allison E. Ashley-Koch, and Ornit Chiba-Falek
- Subjects
Late onset Alzheimer’s disease ,Single-nucleus (sn)RNA-seq ,snATAC-seq ,Regulatory networks ,Chromatin accessibility ,Transcriptomics ,Biotechnology ,TP248.13-248.65 ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
Abstract Background The genetic underpinnings of late-onset Alzheimer’s disease (LOAD) are yet to be fully elucidated. Although numerous LOAD-associated loci have been discovered, the causal variants and their target genes remain largely unknown. Since the brain is composed of heterogenous cell subtypes, it is imperative to study the brain on a cell subtype specific level to explore the biological processes underlying LOAD. Methods Here, we present the largest parallel single-nucleus (sn) multi-omics study to simultaneously profile gene expression (snRNA-seq) and chromatin accessibility (snATAC-seq) to date, using nuclei from 12 normal and 12 LOAD brains. We identified cell subtype clusters based on gene expression and chromatin accessibility profiles and characterized cell subtype-specific LOAD-associated differentially expressed genes (DEGs), differentially accessible peaks (DAPs) and cis co-accessibility networks (CCANs). Results Integrative analysis defined disease-relevant CCANs in multiple cell subtypes and discovered LOAD-associated cell subtype-specific candidate cis regulatory elements (cCREs), their candidate target genes, and trans-interacting transcription factors (TFs), some of which, including ELK1, JUN, and SMAD4 in excitatory neurons, were also LOAD-DEGs. Finally, we focused on a subset of cell subtype-specific CCANs that overlap known LOAD-GWAS regions and catalogued putative functional SNPs changing the affinities of TF motifs within LOAD-cCREs linked to LOAD-DEGs, including APOE and MYO1E in a specific subtype of microglia and BIN1 in a subpopulation of oligodendrocytes. Conclusions To our knowledge, this study represents the most comprehensive systematic interrogation to date of regulatory networks and the impact of genetic variants on gene dysregulation in LOAD at a cell subtype resolution. Our findings reveal crosstalk between epigenetic, genomic, and transcriptomic determinants of LOAD pathogenesis and define catalogues of candidate genes, cCREs, and variants involved in LOAD genetic etiology and the cell subtypes in which they act to exert their pathogenic effects. Overall, these results suggest that cell subtype-specific cis–trans interactions between regulatory elements and TFs, and the genes dysregulated by these networks contribute to the development of LOAD.
- Published
- 2023
- Full Text
- View/download PDF
30. Evolution and regulation of virulence and antimicrobial resistance in Pseudomonas aeruginosa
- Author
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Figueroa Chávez, Wendy and Welch, Martin
- Subjects
Antimicrobial resistance ,Virulence ,Pathogenesis ,Regulatory networks ,Pseudomonas aeruginosa - Abstract
Pseudomonas aeruginosa is a bacterium responsible for various life-threatening infections. There are several factors that make P. aeruginosa a successful pathogen, including its metabolic versatility, its propensity to acquire antimicrobial resistance (AMR) and the ability to produce numerous virulence factors. However, the expression of virulence factors is costly for the cell and, therefore, tightly regulated via quorum sensing (QS). P. aeruginosa has three main interconnected QS systems (las, rhl and pqs), which are in turn modulated by the Stringent Response (SR). This system allows bacteria to sense and respond to nutrient limitations and related stresses by modulating cellular transcription patterns. Notably, it has always been assumed that the stringent response is essential for the activation of QS systems, and therefore, for the expression of virulence factors in P. aeruginosa. Furthermore, the structure of the regulatory network linking QS and the SR remains unknown. Here, I studied the regulation of virulence factors in P. aeruginosa by characterising the mechanism by which avirulent strains become virulent via compensatory mutations. I constructed and characterised an extensive collection of mutants in a mutant that is defective in the SR (due to deletion of the relA and spoT genes) and discovered that QS-dependent virulence factor production can be restored independently of the SR. Whole-genome sequencing of these "bypassing mutants" revealed mutations in several genes, including mexT. Through genome editing, I confirmed that mutations in mexT are responsible for the increased virulence and, surprisingly, resistance to aminoglycoside antibiotics and the "last-resort" antibiotic, colistin. RNA-seq of the mexT mutants revealed that many virulence and AMR-related genes were upregulated, including the H2-T6SS and the mexGHI-opmD efflux pump. Genomics analysis of mutations in mexT in P. aeruginosa genomes showed that those are prevalent amongst clinical and environmental isolates and not restricted to a particular region of the gene. My findings describe a novel mechanism by which P. aeruginosa can restore virulence in an SRindependent manner and show that mexT can be a mutational hotspot for the emergence of antimicrobial resistance.
- Published
- 2022
- Full Text
- View/download PDF
31. Regulatory mechanisms of the LBD40 transcription factor in Arabidopsis thaliana somatic embryogenesis.
- Author
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Joshi, Sanjay, Hill, Kristine, Chakrabarti, Manohar, and Perry, Sharyn E.
- Subjects
IMMUNOPRECIPITATION ,TRANSCRIPTION factors ,SOMATIC embryogenesis ,NUCLEOTIDE sequencing ,AGRICULTURE ,GENE expression ,SEED development ,ARABIDOPSIS thaliana - Abstract
Somatic embryogenesis (SE) is a process by which an embryo is derived from somatic tissue. Transcription factors (TFs) have been identified that control this process. One such TF that promotes SE is AGAMOUS‐like 15 (AGL15). Prior work has shown that AGL15 can both induce and repress gene expression. One way this type of dual function TF works is via protein interactions, so a yeast 2‐hybrid (Y2H) screen was undertaken. One intriguing protein with which AGL15 interacted in Y2H was LBD40. LBD40 encodes a LATERAL ORGAN BOUNDARIES (LOB)‐domain TF that is unique to plants and is primarily expressed during seed development. Here, we confirm the AGL15‐LBD40 interaction by quantitative assays and in planta co‐immunoprecipation. We also document a role for LBD40, and the closely related protein LBD41, in supporting SE. To determine downstream genes potentially controlled by LBD40, chromatin immunoprecipitation followed by high throughput sequencing (ChIP‐seq) was used. More than 400 binding regions for LBD40 were consistently found genome‐wide. To determine genes responsive to LBD40/41 accumulation, RNA‐seq analysis of transcriptomes of wild‐type control and loss‐of‐function lbd40/lbd41 was performed. Combining these datasets provides insight into genes directly and indirectly controlled by these LOB domain TFs. The gene ontology (GO) enrichment analysis of these regulated genes showed an overrepresentation of biological processes that are associated with SE, further indicating the importance of LBD40 in SE. This work provides insight into SE, a poorly understood, but essential process to generate transgenic plants to meet agricultural demands or test gene function. This manuscript reports on experiments to understand the role that LDB40, a TF, plays in support of SE by investigating genes directly and indirectly controlled by LBD40 and examining physical and genetic interactions with other TFs active in SE. We uncover targets of LBD40 and an interacting TF of the MADS family and investigate targets involvement in SE. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
32. Every road leads to Rome: diverse biosynthetic regulation of plant cell wall-degrading enzymes in filamentous fungi <italic>Penicillium oxalicum</italic> and <italic>Trichoderma reesei</italic>.
- Author
-
Zhao, Shuai, Zhang, Ting, Hasunuma, Tomohisa, Kondo, Akihiko, Zhao, Xin-Qing, and Feng, Jia-Xun
- Abstract
Abstract Cellulases and xylanases are plant cell wall-degrading enzymes (CWDEs) that are critical to sustainable bioproduction based on renewable lignocellulosic biomass to reduce carbon dioxide emission. Currently, these enzymes are mainly produced from filamentous fungi, especially
Trichoderma reesei andPenicillium oxalicum . However, an in-depth comparison of these two producers has not been performed. Although bothP. oxalicum andT. reesei harbor CWDE systems, they exhibit distinct features regulating the production of these enzymes, mainly through different transcriptional regulatory networks. This review presents the strikingly different modes of genome-wide regulation of cellulase and xylanase biosynthesis inP. oxalicum andT. reesei , including sugar transporters, signal transduction cascades, transcription factors, chromatin remodeling, and three-dimensional organization of chromosomes. In addition, different molecular breeding approaches employed, based on the understanding of the regulatory networks, are summarized. This review highlights the existence of very different regulatory modes leading to the efficient regulation of CWDE production in filamentous fungi, akin to the adage that “every road leads to Rome.” An understanding of this divergence may help further improvements in fungal enzyme production through the metabolic engineering and synthetic biology of certain fungal species. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
33. Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.
- Author
-
Zeng, Zhen, Fu, Minyang, Hu, Yuan, Wei, Yuquan, Wei, Xiawei, and Luo, Min
- Subjects
- *
CANCER stem cells , *CELLULAR signal transduction , *CANCER treatment , *EPITHELIAL-mesenchymal transition , *METASTASIS - Abstract
Cancer stem cells (CSCs), initially identified in leukemia in 1994, constitute a distinct subset of tumor cells characterized by surface markers such as CD133, CD44, and ALDH. Their behavior is regulated through a complex interplay of networks, including transcriptional, post-transcriptional, epigenetic, tumor microenvironment (TME), and epithelial-mesenchymal transition (EMT) factors. Numerous signaling pathways were found to be involved in the regulatory network of CSCs. The maintenance of CSC characteristics plays a pivotal role in driving CSC-associated tumor metastasis and conferring resistance to therapy. Consequently, CSCs have emerged as promising targets in cancer treatment. To date, researchers have developed several anticancer agents tailored to specifically target CSCs, with some of these treatment strategies currently undergoing preclinical or clinical trials. In this review, we outline the origin and biological characteristics of CSCs, explore the regulatory networks governing CSCs, discuss the signaling pathways implicated in these networks, and investigate the influential factors contributing to therapy resistance in CSCs. Finally, we offer insights into preclinical and clinical agents designed to eliminate CSCs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
34. The mechanism of ferroptosis and its related diseases.
- Author
-
Feng, Shijian, Tang, Dan, Wang, Yichang, Li, Xiang, Bao, Hui, Tang, Chengbing, Dong, Xiuju, Li, Xinna, Yang, Qinxue, Yan, Yun, Yin, Zhijie, Shang, Tiantian, Zheng, Kaixuan, Huang, Xiaofang, Wei, Zuheng, Wang, Kunjie, and Qi, Shiqian
- Subjects
PATHOLOGY ,MEDICAL scientists ,RESEARCH personnel ,SOFT tissue injuries ,HUMAN origins ,BLEPHAROPTOSIS - Abstract
Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation of lipid peroxides, provides a novel avenue for delving into the intersection of cellular metabolism, oxidative stress, and disease pathology. We have witnessed a mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological and pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, and traumatic tissue injuries. By unraveling the intricate underpinnings of the molecular machinery, pivotal contributors, intricate signaling conduits, and regulatory networks governing ferroptosis, researchers aim to bridge the gap between the intricacies of this unique mode of cellular death and its multifaceted implications for health and disease. In light of the rapidly advancing landscape of ferroptosis research, we present a comprehensive review aiming at the extensive implications of ferroptosis in the origins and progress of human diseases. This review concludes with a careful analysis of potential treatment approaches carefully designed to either inhibit or promote ferroptosis. Additionally, we have succinctly summarized the potential therapeutic targets and compounds that hold promise in targeting ferroptosis within various diseases. This pivotal facet underscores the burgeoning possibilities for manipulating ferroptosis as a therapeutic strategy. In summary, this review enriched the insights of both investigators and practitioners, while fostering an elevated comprehension of ferroptosis and its latent translational utilities. By revealing the basic processes and investigating treatment possibilities, this review provides a crucial resource for scientists and medical practitioners, aiding in a deep understanding of ferroptosis and its effects in various disease situations. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
35. Exploring the identity of individual plant cells in space and time.
- Author
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Oliva, Marina and Lister, Ryan
- Subjects
- *
PLANT spacing , *BOTANY , *BIOLOGICAL systems , *PLANT physiology , *PLANT development , *COMPREHENSION in children - Abstract
Summary: In recent years, single‐cell genomics, coupled to imaging techniques, have become the state‐of‐the‐art approach for characterising biological systems. In plant sciences, a variety of tissues and species have been profiled, providing an enormous quantity of data on cell identity at an unprecedented resolution, but what biological insights can be gained from such data sets? Using recently published studies in plant sciences, we will highlight how single‐cell technologies have enabled a better comprehension of tissue organisation, cell fate dynamics in development or in response to various stimuli, as well as identifying key transcriptional regulators of cell identity. We discuss the limitations and technical hurdles to overcome, as well as future directions, and the promising use of single‐cell omics to understand, predict, and manipulate plant development and physiology. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
36. Functional Characterization of AP2/ERF Transcription Factors during Flower Development and Anthocyanin Biosynthesis Related Candidate Genes in Lycoris.
- Author
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Wang, Zhong, Song, Guowei, Zhang, Fengjiao, Shu, Xiaochun, and Wang, Ning
- Subjects
- *
FLOWER development , *FRUIT development , *TRANSCRIPTION factors , *BIOSYNTHESIS , *ANTHOCYANINS , *TANDEM mass spectrometry - Abstract
The APETALA2/ethylene-responsive transcription factor (AP2/ERF) family has been extensively investigated because of its significant involvement in plant development, growth, fruit ripening, metabolism, and plant stress responses. To date, there has been little investigation into how the AP2/ERF genes influence flower formation and anthocyanin biosynthesis in Lycoris. Herein, 80 putative LrAP2/ERF transcription factors (TFs) with complete open reading frames (ORFs) were retrieved from the Lycoris transcriptome sequence data, which could be divided into five subfamilies dependent on their complete protein sequences. Furthermore, our findings demonstrated that genes belonging to the same subfamily had structural similarities and conserved motifs. LrAP2/ERF genes were analyzed for playing an important role in plant growth, water deprivation, and flower formation by means of gene ontology (GO) enrichment analysis. The expression pattern of the LrAP2/ERF genes differed across tissues and might be important for Lycoris growth and flower development. In response to methyl jasmonate (MeJA) exposure and drought stress, the expression of each LrAP2/ERF gene varied across tissues and time. Moreover, a total of 20 anthocyanin components were characterized using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) analysis, and pelargonidin-3-O-glucoside-5-O-arabinoside was identified as the major anthocyanin aglycone responsible for the coloration of the red petals in Lycoris. In addition, we mapped the relationships between genes and metabolites and found that LrAP2/ERF16 is strongly linked to pelargonidin accumulation in Lycoris petals. These findings provide the basic conceptual groundwork for future research into the molecular underpinnings and regulation mechanisms of AP2/ERF TFs in anthocyanin accumulation and Lycoris floral development. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
37. Phenotype Control techniques for Boolean gene regulatory networks.
- Author
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Plaugher, Daniel and Murrugarra, David
- Abstract
Modeling cell signal transduction pathways via Boolean networks (BNs) has become an established method for analyzing intracellular communications over the last few decades. What’s more, BNs provide a course-grained approach, not only to understanding molecular communications, but also for targeting pathway components that alter the long-term outcomes of the system. This has come to be known as phenotype control theory. In this review we study the interplay of various approaches for controlling gene regulatory networks such as: algebraic methods, control kernel, feedback vertex set, and stable motifs. The study will also include comparative discussion between the methods, using an established cancer model of T-Cell Large Granular Lymphocyte Leukemia. Further, we explore possible options for making the control search more efficient using reduction and modularity. Finally, we will include challenges presented such as the complexity and the availability of software for implementing each of these control techniques. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
38. Integrative single-nucleus multi-omics analysis prioritizes candidate cis and trans regulatory networks and their target genes in Alzheimer's disease brains.
- Author
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Gamache, Julia, Gingerich, Daniel, Shwab, E. Keats, Barrera, Julio, Garrett, Melanie E., Hume, Cordelia, Crawford, Gregory E., Ashley-Koch, Allison E., and Chiba-Falek, Ornit
- Subjects
- *
ALZHEIMER'S disease , *GENETIC load , *GENE expression , *MULTIOMICS , *GENETIC variation , *GENE regulatory networks - Abstract
Background: The genetic underpinnings of late-onset Alzheimer's disease (LOAD) are yet to be fully elucidated. Although numerous LOAD-associated loci have been discovered, the causal variants and their target genes remain largely unknown. Since the brain is composed of heterogenous cell subtypes, it is imperative to study the brain on a cell subtype specific level to explore the biological processes underlying LOAD. Methods: Here, we present the largest parallel single-nucleus (sn) multi-omics study to simultaneously profile gene expression (snRNA-seq) and chromatin accessibility (snATAC-seq) to date, using nuclei from 12 normal and 12 LOAD brains. We identified cell subtype clusters based on gene expression and chromatin accessibility profiles and characterized cell subtype-specific LOAD-associated differentially expressed genes (DEGs), differentially accessible peaks (DAPs) and cis co-accessibility networks (CCANs). Results: Integrative analysis defined disease-relevant CCANs in multiple cell subtypes and discovered LOAD-associated cell subtype-specific candidate cis regulatory elements (cCREs), their candidate target genes, and trans-interacting transcription factors (TFs), some of which, including ELK1, JUN, and SMAD4 in excitatory neurons, were also LOAD-DEGs. Finally, we focused on a subset of cell subtype-specific CCANs that overlap known LOAD-GWAS regions and catalogued putative functional SNPs changing the affinities of TF motifs within LOAD-cCREs linked to LOAD-DEGs, including APOE and MYO1E in a specific subtype of microglia and BIN1 in a subpopulation of oligodendrocytes. Conclusions: To our knowledge, this study represents the most comprehensive systematic interrogation to date of regulatory networks and the impact of genetic variants on gene dysregulation in LOAD at a cell subtype resolution. Our findings reveal crosstalk between epigenetic, genomic, and transcriptomic determinants of LOAD pathogenesis and define catalogues of candidate genes, cCREs, and variants involved in LOAD genetic etiology and the cell subtypes in which they act to exert their pathogenic effects. Overall, these results suggest that cell subtype-specific cis–trans interactions between regulatory elements and TFs, and the genes dysregulated by these networks contribute to the development of LOAD. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
39. Comparative transcriptome profiling and co-expression network analysis uncover the key genes associated with pear petal defense responses against Monilinia laxa infection
- Author
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Meriem Miyassa Aci, Polina C. Tsalgatidou, Anastasia Boutsika, Andreas Dalianis, Maria Michaliou, Costas Delis, Dimitrios I. Tsitsigiannis, Epaminondas Paplomatas, Antonino Malacrinò, Leonardo Schena, and Antonios Zambounis
- Subjects
pear flower ,RNA-seq ,WGCNA ,regulatory networks ,immune response ,pathogens ,Plant culture ,SB1-1110 - Abstract
Pear brown rot and blossom blight caused by Monilinia laxa seriously affect pear production worldwide. Here, we compared the transcriptomic profiles of petals after inoculation with M. laxa using two pear cultivars with different levels of sensitivity to disease (Sissy, a relatively tolerant cultivar, and Kristalli, a highly susceptible cultivar). Physiological indexes were also monitored in the petals of both cultivars at 2 h and 48 h after infection (2 HAI and 48 HAI). RNA-seq data and weighted gene co-expression network analysis (WGCNA) allowed the identification of key genes and pathways involved in immune- and defense-related responses that were specific for each cultivar in a time-dependent manner. In particular, in the Kristalli cultivar, a significant transcriptome reprogramming occurred early at 2 HAI and was accompanied either by suppression of key differentially expressed genes (DEGs) involved in the modulation of any defense responses or by activation of DEGs acting as sensitivity factors promoting susceptibility. In contrast to the considerably high number of DEGs induced early in the Kristalli cultivar, upregulation of specific DEGs involved in pathogen perception and signal transduction, biosynthesis of secondary and primary metabolism, and other defense-related responses was delayed in the Sissy cultivar, occurring at 48 HAI. The WGCNA highlighted one module that was significantly and highly correlated to the relatively tolerant cultivar. Six hub genes were identified within this module, including three WRKY transcription factor-encoding genes: WRKY 65 (pycom05g27470), WRKY 71 (pycom10g22220), and WRKY28 (pycom17g13130), which may play a crucial role in enhancing the tolerance of pear petals to M. laxa. Our results will provide insights into the interplay of the molecular mechanisms underlying immune responses of petals at the pear–M. laxa pathosystem.
- Published
- 2024
- Full Text
- View/download PDF
40. Editorial: The role of regulatory networks in virulence and antimicrobial resistance of microbial pathogens
- Author
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Abdelaziz Elgaml, Rami Elshazli, and Shin-ichi Miyoshi
- Subjects
antimicrobial resistance ,global regulators ,microbial pathogens ,regulatory networks ,virulence factors ,Microbiology ,QR1-502 - Published
- 2024
- Full Text
- View/download PDF
41. Harissa: Stochastic Simulation and Inference of Gene Regulatory Networks Based on Transcriptional Bursting
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Herbach, Ulysse, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Pang, Jun, editor, and Niehren, Joachim, editor
- Published
- 2023
- Full Text
- View/download PDF
42. Non-coding RNAs identification and regulatory networks in pathogen-host interaction in the microsporidia congenital infection
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Zigang Shen, Qiong Yang, Lie Luo, Tangxin Li, Zhuojun Ke, Tian Li, Jie Chen, Xianzhi Meng, Heng Xiang, Chunfeng Li, Zeyang Zhou, Ping Chen, and Guoqing Pan
- Subjects
Congenital infection ,Microsporidia ,Nosema bombycis ,Non-coding RNAs ,Regulatory networks ,Host–pathogen interaction ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background The interaction networks between coding and non-coding RNAs (ncRNAs) including long non-coding RNA (lncRNA), covalently closed circular RNA (circRNA) and miRNA are significant to elucidate molecular processes of biological activities and interactions between host and pathogen. Congenital infection caused by vertical transmission of microsporidia N. bombycis can result in severe economic losses in the silkworm-feeding industry. However, little is known about ncRNAs that take place in the microsporidia congenital infection. Here we conducted whole-transcriptome RNA-Seq analyses to identify ncRNAs and regulatory networks for both N. bombycis and host including silkworm embryos and larvae during the microsporidia congenital infection. Results A total of 4,171 mRNAs, 403 lncRNA, 62 circRNAs, and 284 miRNAs encoded by N. bombycis were identified, among which some differentially expressed genes formed cross-talk and are involved in N. bombycis proliferation and infection. For instance, a lncRNA/circRNA competing endogenous RNA (ceRNA) network including 18 lncRNAs, one circRNA, and 20 miRNAs was constructed to describe 14 key parasites genes regulation, such as polar tube protein 3 (PTP3), ricin-B-lectin, spore wall protein 4 (SWP4), and heat shock protein 90 (HSP90). Regarding host silkworm upon N. bombycis congenital infection, a total of 14,889 mRNAs, 3,038 lncRNAs, 19,039 circRNAs, and 3,413 miRNAs were predicted based on silkworm genome with many differentially expressed coding and non-coding genes during distinct developmental stages. Different species of RNAs form interacting network to modulate silkworm biological processes, such as growth, metamorphosis and immune responses. Furthermore, a lncRNA/circRNA ceRNA network consisting of 140 lncRNAs, five circRNA, and seven miRNAs are constructed hypothetically to describe eight key host genes regulation, such as Toll-6, Serpin-6, inducible nitric oxide synthase (iNOS) and Caspase-8. Notably, cross-species analyses indicate that parasite and host miRNAs play a vital role in pathogen-host interaction in the microsporidia congenital infection. Conclusion This is the first comprehensive pan-transcriptome study inclusive of both N. bombycis and its host silkworm with a specific focus on the microsporidia congenital infection, and show that ncRNA-mediated regulation plays a vital role in the microsporidia congenital infection, which provides a new insight into understanding the basic biology of microsporidia and pathogen-host interaction.
- Published
- 2023
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43. The anti-cancerous mechanism of licochalcone A on human hepatoma cell HepG2 based on the miRNA omics
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Jun Wang, Xiuxiu Zhang, Zhijing Ni, Elnur Elam, Kiran Thakur, Kexin Li, Chuyan Wang, Jianguo Zhang, and Zhaojun Wei
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Licochalcone A ,HepG2 cells ,Dysregulated miRNAs ,Transcription factors ,Targets ,Regulatory networks ,Nutrition. Foods and food supply ,TX341-641 - Abstract
To explore the function of licochalcone A as an anticancer phytochemical on HepG2 cells and investigate its potential mechanisms, we analyzed the microRNAs (miRNAs) expression profile of HepG2 cells in response to licochalcone A (70 μmol/L) in vitro. 102 dysregulated miRNAs were detected, and SP1 was expected as the transcription factor that regulates the functions of most screened miRNAs. A sum of 431 targets, the overlap of predicted mRNAs from TargetScan, miRDB, and miRtarbase were detected as the targets for these dysregulated miRNAs. FoxO signaling pathway was the hub pathway for the targets. A protein-protein interaction network was structured on the STRING platform to discover the hub genes. Among them, PIK3R1, CDC42, ESR1, SMAD4, SUMO1, KRAS, AGO1, etc. were screened out. Afterwards, the miRNA-target networks were established to screen key dysregulated miRNAs. Two key miRNAs (hsa-miR-133b and hsa-miR-145-5p) were filtered. Finally, the miRNA-target-transcription factor networks were constructed for these key miRNAs. The networks for these key miRNAs included three and two transcription factors, respectively. These identified miRNAs, transcription factors, targets, and regulatory networks may offer hints to understand the molecular mechanism of licochalcone A as a natural anticarcinogen.
- Published
- 2023
- Full Text
- View/download PDF
44. Editorial: The role of regulatory networks in virulence and antimicrobial resistance of microbial pathogens.
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Elgaml, Abdelaziz, Elshazli, Rami, and Shin-ichi Miyoshi
- Subjects
DRUG resistance in microorganisms ,PATHOGENIC microorganisms ,BIOLOGICAL evolution - Abstract
This document is an editorial titled "The role of regulatory networks in virulence and antimicrobial resistance of microbial pathogens." It discusses the issue of antimicrobial resistance (AMR) and the need for research in various areas related to AMR, such as identifying resistance mechanisms, developing new therapeutic approaches, and improving epidemiological investigation and diagnostics. The editorial highlights several articles within the research topic that cover topics such as mechanisms of resistance in specific pathogens, the role of efflux pumps, and the impact of regulatory networks on virulence and drug resistance. The overall goal of the research topic is to advance our understanding of microbial drug resistance and regulatory networks in order to develop more effective intervention strategies. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
45. LncRNA NDUFA6-DT: A Comprehensive Analysis of a Potential LncRNA Biomarker and Its Regulatory Mechanisms in Gliomas
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Ruiting Huang, Ying Kong, Zhiqing Luo, and Quhuan Li
- Subjects
glioma ,NDUFA6-DT ,lncRNA ,biomarker ,prognostic factor ,regulatory networks ,Genetics ,QH426-470 - Abstract
Gliomas are the most prevalent primary malignant tumors affecting the brain, with high recurrence and mortality rates. Accurate diagnoses and effective treatment challenges persist, emphasizing the need for identifying new biomarkers to guide clinical decisions. Long noncoding RNAs (lncRNAs) hold potential as diagnostic and therapeutic biomarkers in cancer. However, only a limited subset of lncRNAs in gliomas have been explored. Therefore, this study aims to identify lncRNA signatures applicable to patients with gliomas across all grades and explore their clinical significance and potential biological mechanisms. Data used in this study were obtained from TCGA, CGGA, and GEO datasets to identify key lncRNA signatures in gliomas through differential and survival analyses and machine learning algorithms. We examined their associations with the clinical characteristics, gene mutations, diagnosis, and prognosis of gliomas. Functional enrichment analysis was employed to elucidate the potential biological mechanisms associated with these significant lncRNA signatures. We explored competing endogenous RNA (ceRNA) regulatory networks. We found that NDUFA6-DT emerged as a significant lncRNA signature in gliomas, with reduced NDUFA6-DT expression associated with a worse prognosis in gliomas. Nomogram analysis incorporating NDUFA6-DT expression levels exhibited excellent prognostic and predictive capabilities. Functional annotation suggested that NDUFA6-DT might influence immunological responses and synaptic transmission, potentially modifying glioma initiation and progression. The associated ceRNA network revealed the possible presence of the NDUFA6-DT-miR-455-3p-YWHAH/YWHAG axis in low-grade glioma (LGG) and glioblastoma multiforme (GBM), regulating the PI3K-AKT signaling pathway and influencing glioma cell survival and apoptosis. We believe that NDUFA6-DT is a novel lncRNA linked to glioma diagnosis and prognosis, potentially becoming a pivotal biomarker for glioma.
- Published
- 2024
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46. Regulatory mechanisms of the LBD40 transcription factor in Arabidopsis thaliana somatic embryogenesis
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Sanjay Joshi, Kristine Hill, Manohar Chakrabarti, and Sharyn E. Perry
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embryogenesis ,gene regulation ,regeneration ,regulatory networks ,transcription factor ,Botany ,QK1-989 - Abstract
Abstract Somatic embryogenesis (SE) is a process by which an embryo is derived from somatic tissue. Transcription factors (TFs) have been identified that control this process. One such TF that promotes SE is AGAMOUS‐like 15 (AGL15). Prior work has shown that AGL15 can both induce and repress gene expression. One way this type of dual function TF works is via protein interactions, so a yeast 2‐hybrid (Y2H) screen was undertaken. One intriguing protein with which AGL15 interacted in Y2H was LBD40. LBD40 encodes a LATERAL ORGAN BOUNDARIES (LOB)‐domain TF that is unique to plants and is primarily expressed during seed development. Here, we confirm the AGL15‐LBD40 interaction by quantitative assays and in planta co‐immunoprecipation. We also document a role for LBD40, and the closely related protein LBD41, in supporting SE. To determine downstream genes potentially controlled by LBD40, chromatin immunoprecipitation followed by high throughput sequencing (ChIP‐seq) was used. More than 400 binding regions for LBD40 were consistently found genome‐wide. To determine genes responsive to LBD40/41 accumulation, RNA‐seq analysis of transcriptomes of wild‐type control and loss‐of‐function lbd40/lbd41 was performed. Combining these datasets provides insight into genes directly and indirectly controlled by these LOB domain TFs. The gene ontology (GO) enrichment analysis of these regulated genes showed an overrepresentation of biological processes that are associated with SE, further indicating the importance of LBD40 in SE. This work provides insight into SE, a poorly understood, but essential process to generate transgenic plants to meet agricultural demands or test gene function. This manuscript reports on experiments to understand the role that LDB40, a TF, plays in support of SE by investigating genes directly and indirectly controlled by LBD40 and examining physical and genetic interactions with other TFs active in SE. We uncover targets of LBD40 and an interacting TF of the MADS family and investigate targets involvement in SE.
- Published
- 2023
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- View/download PDF
47. A machine learning and directed network optimization approach to uncover TP53 regulatory patterns
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Charalampos P. Triantafyllidis, Alessandro Barberis, Fiona Hartley, Ana Miar Cuervo, Enio Gjerga, Philip Charlton, Linda van Bijsterveldt, Julio Saez Rodriguez, and Francesca M. Buffa
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Regulatory networks ,directed networks ,causal inference ,mutations ,cancer systems biology ,machine learning ,Science - Abstract
Summary: TP53, the Guardian of the Genome, is the most frequently mutated gene in human cancers and the functional characterization of its regulation is fundamental. To address this we employ two strategies: machine learning to predict the mutation status of TP53 from transcriptomic data, and directed regulatory networks to reconstruct the effect of mutations on the transcipt levels of TP53 targets. Using data from established databases (Cancer Cell Line Encyclopedia, The Cancer Genome Atlas), machine learning could predict the mutation status, but not resolve different mutations. On the contrary, directed network optimization allowed to infer the TP53 regulatory profile across: (1) mutations, (2) irradiation in lung cancer, and (3) hypoxia in breast cancer, and we could observe differential regulatory profiles dictated by (1) mutation type, (2) deleterious consequences of the mutation, (3) known hotspots, (4) protein changes, (5) stress condition (irradiation/hypoxia). This is an important first step toward using regulatory networks for the characterization of the functional consequences of mutations, and could be extended to other perturbations, with implications for drug design and precision medicine.
- Published
- 2023
- Full Text
- View/download PDF
48. Subtype-specific network organization of molecular complexes in breast cancer.
- Author
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Kumar, Swapnil, Ramaswamy, Ramakrishna, Vindal, Vaibhav, and Srivastava, Alok
- Abstract
Breast cancer, a leading cause of death in women, is a complex heterogeneous disease comprising multiple molecular subtypes with different treatment responses and hence clinical outcomes. The present study aims to gain a deeper insight into the disease complexities at the level of molecular subtypes. For this, first, three subtype networks of breast cancer, viz., ER−/HER2−, ER+/HER2−, and HER2+, were constructed utilizing mRNA expression profiles of tumor tissues. Subsequently, these networks were used to construct three exclusively subtype-specific networks. Further, the mRNA expression profiles of all three subtypes were analyzed using differential correlations based on z-statistics of the F-test. Finally, functional enrichment analysis was carried out to elucidate functions and processes of important genes involved in subtype networks. From this analysis, it was observed that these subtype networks share a commonality among them in terms of preserved patterns. However, these networks possess specific patterns that result in exclusively subtype-specific networks having unique sets of wiring among the genes. Additionally, the significantly differentially correlated gene pairs between two subtypes demonstrate subtype-specific expressional patterns which make them different at the molecular level. Furthermore, the network analysis also revealed ER−/HER2−-specific genes, viz., LUM, RARB, and ERCC6. Thus, the present analysis provides new insights for further research on breast cancer subtypes and hence the development of the most effective diagnosis and treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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49. The regulation of expression and splicing of transcription factors are related to the muscle damage caused by radiation in tree shrews.
- Author
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Liu, Heng, Ke, Shenghui, Xie, Mao, Niu, Zhijie, Liu, Huayu, Li, Jingyu, Tang, Anzhou, Xia, Wei, and He, Guangyao
- Subjects
- *
GENE expression , *ALTERNATIVE RNA splicing , *TRANSCRIPTION factors , *SHREWS , *RADIATION damage , *RNA splicing , *GENE regulatory networks - Abstract
Radiotherapy-induced muscle injury (RIMI) is a major complication of radiotherapy for nasopharyngeal carcinoma. Transcription factor (TF) expression and alternative splicing are crucial events in transcriptional and posttranscriptional regulation, respectively, and are known to be involved in key signaling pathways contributing to a variety of human disorders, including radiation injury. To investigate the TFs and alternative splicing events involved in RIMI, we constructed a tree shrew model as described previously in which the RIMI group received 20 Gy of irradiation on the tensor veli palatini (TVP) muscles. The irradiated muscles were evaluated by RNA sequencing (RNA-seq) 6 months later, and the results compared with those for normal TVP muscles. The alt5p and alt3p events were the two main types of differentially regulated alternative splicing events (RASEs) identified via the Splice sites Usage Variation Analysis (SUVA) software, and these RASEs were highly conserved in RIMI. According to functional enrichment analysis, the differentially RASEs were primarily enriched in pathways related to transcriptional regulation. Furthermore, we identified 16 alternative splicing TFs (ASTFs) in ASTF–differentially expressed gene (DEG) networks based on co-expression analysis, and the regulatory networks were chiefly enriched in pathways linked to cell proliferation and differentiation. This study revealed that RASEs and ASTF–DEG networks may both play important regulatory roles in gene expression network alteration in RIMI. Future studies on the targeting mechanisms and early interventions directed at RASEs and ASTF–DEG networks may aid in the treatment of RIMI. • Radiotherapy-induced muscle injury(RIMI) is a major complication of radiotherapy for nasopharyngeal carcinoma. • Tree shrew model simulating radiotherapy for NPC is useful for research into RIMI. • RASEs and ASTF–DEG networks may both play important regulatory roles in gene expression network alteration in RIMI. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
50. Core conserved transcriptional regulatory networks define the invasive trophoblast cell lineage.
- Author
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Vu, Ha T. H., Scott, Regan L., Iqbal, Khursheed, Soares, Michael J., and Tuteja, Geetu
- Subjects
- *
TROPHOBLAST , *GENE regulatory networks , *GENETIC regulation , *CELL populations , *SMOOTH muscle , *MUSCLE cells - Abstract
The invasive trophoblast cell lineages in rat and human share crucial responsibilities in establishing the uterine-placental interface of the hemochorial placenta. These observations have led to the rat becoming an especially useful animal model for studying hemochorial placentation. However, our understanding of similarities or differences between regulatory mechanisms governing rat and human invasive trophoblast cell populations is limited. In this study, we generated single-nucleus ATAC-seq data from gestation day 15.5 and 19.5 rat uterine-placental interface tissues, and integrated the data with singlecell RNA-seq data generated at the same stages. We determined the chromatin accessibility profiles of invasive trophoblast, natural killer, macrophage, endothelial and smooth muscle cells, and compared invasive trophoblast chromatin accessibility with extravillous trophoblast cell accessibility. In comparing chromatin accessibility profiles between species, we found similarities in patterns of gene regulation and groups of motifs enriched in accessible regions. Finally, we identified a conserved gene regulatory network in invasive trophoblast cells. Our data, findings and analysis will facilitate future studies investigating regulatory mechanisms essential for the invasive trophoblast cell lineage. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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