DNA N6-甲基腺嘌呤(6mA)是一种重要的表观遗传修饰,参与基因调控、DNA复制和修复等生物过程,对疾病研究也具有重要意义,准确识别DNA 6mA位点对理解其功能和机制至关重要。尽管现有的NA 6mA位点预测方法已取得较大成功,但在预测精度和跨...DNA N6-甲基腺嘌呤(6mA)是一种重要的表观遗传修饰,参与基因调控、DNA复制和修复等生物过程,对疾病研究也具有重要意义,准确识别DNA 6mA位点对理解其功能和机制至关重要。尽管现有的NA 6mA位点预测方法已取得较大成功,但在预测精度和跨物种泛化能力上仍有改进空间。本文提出了一种结合双向长短期记忆网络(BiLSTM)和卷积神经网络(CNN)的混合深度学习模型(BiLSTM→CNN)来提高对DNA 6mA位点预测的能力。模型首先采用one-hot、EIIP和DNA二聚体三种编码方式对DNA序列进行编码,然后在不同网络结构、层数和优化器下优化模型。通过在蔷薇科植物、水稻和拟南芥的数据集上的广泛实验表明,BiLSTM→CNN模型在蔷薇科植物中的准确率(ACC)为94.5%,在水稻中为93.8%,在拟南芥中为86.6%。与其他方法相比,BiLSTM→CNN模型在三个植物物种的6mA位点预测中均展现出良好的性能,并具有出色的跨物种泛化能力。DNA N6-methyladenine (6mA) is an important epigenetic modification involved in biological processes such as gene regulation, DNA replication, and repair, making it significant for disease research. Therefore, accurately identifying DNA 6mA sites is crucial for understanding their functions and mechanisms. Despite notable successes with existing methods, there is still room for improvement in prediction accuracy and cross-species generalization. In this study, we propose a hybrid deep learning model (BiLSTM→CNN) that integrates bidirectional long short-term memory networks (BiLSTM) and convolutional neural networks (CNN). Firstly, the model-encoded DNA sequences employ one-hot encoding, EIIP encoding, and DNA dimer encoding. And then optimized under various network architectures, layer configurations and optimizers. We conducted experiments on datasets from Rosaceae, rice and Arabidopsis thaliana, the results indicate that the BiLSTM→CNNmodel achieves an accuracy (ACC) of 94.5% for Rosaceae, 93.8% for rice, and 86.6% for Arabidopsis. Compared to other methods, BiLSTM→CNNdemonstrates excellent performance in predicting 6mA sites across the three plant species, and exhibits cross-species generalization capabilities.展开更多
DNA、RNA的甲基化作为重要的表观遗传标记,在真核生物多个细胞过程中发挥作用。DNA中的N6-甲基腺嘌呤(N6-methyladenine in DNA, 6mA)和RNA中的N6-甲基腺嘌呤(N6-methyladenine in RNA, m6A)均为来自腺嘌呤第6位的甲基化修饰,在合成和...DNA、RNA的甲基化作为重要的表观遗传标记,在真核生物多个细胞过程中发挥作用。DNA中的N6-甲基腺嘌呤(N6-methyladenine in DNA, 6mA)和RNA中的N6-甲基腺嘌呤(N6-methyladenine in RNA, m6A)均为来自腺嘌呤第6位的甲基化修饰,在合成和功能上有相似性也有区别。6mA或m6A的修饰缺陷影响植物胚胎发育、干细胞分化、组织器官发生及应激反应等。meRIPseq等技术的发展为全组甲基化位点鉴定提供了基础,未来将更加注重于功能研究。该文对近年来植物6mA或m6A甲基化位点的全组鉴定、合成、调控及成员功能研究进行回顾和比较,并展望未来的研究方向。展开更多
Technical developments for simple shear deformation experiments at high pressures were made. The newly designed cell assembly can be compressed by deformation-DIA apparatuses with the MA 6-6 system, which consists of ...Technical developments for simple shear deformation experiments at high pressures were made. The newly designed cell assembly can be compressed by deformation-DIA apparatuses with the MA 6-6 system, which consists of six second-stage tungsten carbide anvils （with a truncated edge length of 5 mm） and the anvil guide. Deformation of samples was barely observed during the compression process, showing that the shear strain of the deformed samples can be measured by the rotation of a strain marker. Simple shear deformation experiments on anhydrous and hydrous oli- vine aggregates were conducted under upper mantle conditions （pressures of 5.2-7.6 GPa and temperatures of 1 473-1 573 K）, and sample deformation with a shear strain of 7=0.8-1.2 was successfully achieved at a shear strain rate of 4.0×10^-5-7.5×10^-5 s^-1. The present study extended the pressure range of simple shear deformation experiments in the deformation-DIA apparatus from 3 GPa in an early study to 7.6 GPa at high temperatures.展开更多
N6-Methyladenine (6mA)DNA methylation has recently been implicated as a potential new epigenetic marker in eukaryotes,including the dioot modelArabidopsis thaliana.However,the conservation and divergence of 6mA distri...N6-Methyladenine (6mA)DNA methylation has recently been implicated as a potential new epigenetic marker in eukaryotes,including the dioot modelArabidopsis thaliana.However,the conservation and divergence of 6mA distribution patterns and functions in plants remain elusive.Here we report high-quality 6mA methylomes at single-nucleotide resolution in rice based on substantially improved genome sequences of two rice cultivars,Nipponbare (Nip;Japonica)and 93-11 (Indica).Analysis of 6mA genomic distribution and its association with transcription suggest that 6mA distribution and function is rather conserved between rice and Arabidopsis.We found that 6mA levels are positively correlated with the expression of key stressrelated genes,which may be responsible for the difference in stress tolerance between Nip and 93-11. Moreover,we showed that mutations in DDM1 cause defects in plant growth and decreased 6mA level. Our results reveal that 6mA is a conserved DNA modification that is positively associated with gene expression and contributes to key agronomic traits in plants.展开更多
Advances in the detection and mapping of messenger RNA(mRNA)N^6-methyladenosine(m 6A)and 5-methylcytosine(m 5C),and DNA N^6-methyldeoxyadenosine(6mA)redefined our understanding of these modifications as additional tie...Advances in the detection and mapping of messenger RNA(mRNA)N^6-methyladenosine(m 6A)and 5-methylcytosine(m 5C),and DNA N^6-methyldeoxyadenosine(6mA)redefined our understanding of these modifications as additional tiers of epigenetic regulation.In plants,the most prevalent internal mRNA modifications,m^6A and m^5C,play crucial and dynamic roles in many processes,including embryo development,stem cell fate determination,trichome branching,leaf morphogenesis,floral transition,stress responses,fruit ripening,and root development.The newly identified and widespread epigenetic marker 6mA DNA methylation is associated with gene expression,plant development,and stress responses.Here,we review the latest research progress on mRNA and DNA epigenetic modifications,including the detection,dynamics,distribution,functions,regulatory proteins,and evolution,with a focus on m^6A,m^5C,and 6mA.We also provide some perspectives on future research of the newly identified and unknown epigenetic modifications of mRNA and DNA in plants.展开更多
Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequen...Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequences of 14 K.pneumoniae strains covering varying serotypes,multilocus sequence types,clonal groups,viscosity/virulence,and drug resistance.Their methylomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies.We identified 15 methylation motifs[13 N6-methyladenine(6mA)and two 5-methylcytosine(5mC)motifs],among which eight were novel.Their corresponding DNA methyltransferases were also validated.Additionally,we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains,and identified differential distribution patterns of some hemi-/un-methylated GATC motifs,which tend to be located within intergenic regions(IGRs).Specifically,we characterized the in vivo methylation kinetics at single-base resolution on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation.The slow methylation of the GATC motifs in the replication origin(oriC)regions and IGRs implicates the epigenetic regulation of replication initiation and transcription.Our findings illustrate the first comprehensive dynamic methylome map of K.pneumoniae at single-base resolution,and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.展开更多
N^(6)-methyladenine(N^(6)-mA,m^(6)dA,or 6mA),a prevalent DNA modification in prokaryotes,has recently been identified in higher eukaryotes,including mammals.Although 6mA has been well-studied in prokaryotes,the functi...N^(6)-methyladenine(N^(6)-mA,m^(6)dA,or 6mA),a prevalent DNA modification in prokaryotes,has recently been identified in higher eukaryotes,including mammals.Although 6mA has been well-studied in prokaryotes,the function and regulatory mechanism of 6mA in eukaryotes are still poorly understood.Recent studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes,from transposable-element suppression to environmental stress response.Here,we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes,predominantly mammals.展开更多
文摘DNA N6-甲基腺嘌呤(6mA)是一种重要的表观遗传修饰,参与基因调控、DNA复制和修复等生物过程,对疾病研究也具有重要意义,准确识别DNA 6mA位点对理解其功能和机制至关重要。尽管现有的NA 6mA位点预测方法已取得较大成功,但在预测精度和跨物种泛化能力上仍有改进空间。本文提出了一种结合双向长短期记忆网络(BiLSTM)和卷积神经网络(CNN)的混合深度学习模型(BiLSTM→CNN)来提高对DNA 6mA位点预测的能力。模型首先采用one-hot、EIIP和DNA二聚体三种编码方式对DNA序列进行编码,然后在不同网络结构、层数和优化器下优化模型。通过在蔷薇科植物、水稻和拟南芥的数据集上的广泛实验表明,BiLSTM→CNN模型在蔷薇科植物中的准确率(ACC)为94.5%,在水稻中为93.8%,在拟南芥中为86.6%。与其他方法相比,BiLSTM→CNN模型在三个植物物种的6mA位点预测中均展现出良好的性能,并具有出色的跨物种泛化能力。DNA N6-methyladenine (6mA) is an important epigenetic modification involved in biological processes such as gene regulation, DNA replication, and repair, making it significant for disease research. Therefore, accurately identifying DNA 6mA sites is crucial for understanding their functions and mechanisms. Despite notable successes with existing methods, there is still room for improvement in prediction accuracy and cross-species generalization. In this study, we propose a hybrid deep learning model (BiLSTM→CNN) that integrates bidirectional long short-term memory networks (BiLSTM) and convolutional neural networks (CNN). Firstly, the model-encoded DNA sequences employ one-hot encoding, EIIP encoding, and DNA dimer encoding. And then optimized under various network architectures, layer configurations and optimizers. We conducted experiments on datasets from Rosaceae, rice and Arabidopsis thaliana, the results indicate that the BiLSTM→CNNmodel achieves an accuracy (ACC) of 94.5% for Rosaceae, 93.8% for rice, and 86.6% for Arabidopsis. Compared to other methods, BiLSTM→CNNdemonstrates excellent performance in predicting 6mA sites across the three plant species, and exhibits cross-species generalization capabilities.
文摘DNA、RNA的甲基化作为重要的表观遗传标记,在真核生物多个细胞过程中发挥作用。DNA中的N6-甲基腺嘌呤(N6-methyladenine in DNA, 6mA)和RNA中的N6-甲基腺嘌呤(N6-methyladenine in RNA, m6A)均为来自腺嘌呤第6位的甲基化修饰,在合成和功能上有相似性也有区别。6mA或m6A的修饰缺陷影响植物胚胎发育、干细胞分化、组织器官发生及应激反应等。meRIPseq等技术的发展为全组甲基化位点鉴定提供了基础,未来将更加注重于功能研究。该文对近年来植物6mA或m6A甲基化位点的全组鉴定、合成、调控及成员功能研究进行回顾和比较,并展望未来的研究方向。
基金supported by the Global COE Program of Ehime University "Deep Earth Mineralogy"
文摘Technical developments for simple shear deformation experiments at high pressures were made. The newly designed cell assembly can be compressed by deformation-DIA apparatuses with the MA 6-6 system, which consists of six second-stage tungsten carbide anvils （with a truncated edge length of 5 mm） and the anvil guide. Deformation of samples was barely observed during the compression process, showing that the shear strain of the deformed samples can be measured by the rotation of a strain marker. Simple shear deformation experiments on anhydrous and hydrous oli- vine aggregates were conducted under upper mantle conditions （pressures of 5.2-7.6 GPa and temperatures of 1 473-1 573 K）, and sample deformation with a shear strain of 7=0.8-1.2 was successfully achieved at a shear strain rate of 4.0×10^-5-7.5×10^-5 s^-1. The present study extended the pressure range of simple shear deformation experiments in the deformation-DIA apparatus from 3 GPa in an early study to 7.6 GPa at high temperatures.
基金The Ministry of Science and Technology of the People's Republic of China (2016YFD0101001)to X.G.,National Natural Science Foundation of China (31871606,31671670)to X.G.,Recruitment program of Global Youth Expert of China to X.G.,and Fundamental Research funds for Central Non-profit Scientific Institution (1610392017001)to X.G.
文摘N6-Methyladenine (6mA)DNA methylation has recently been implicated as a potential new epigenetic marker in eukaryotes,including the dioot modelArabidopsis thaliana.However,the conservation and divergence of 6mA distribution patterns and functions in plants remain elusive.Here we report high-quality 6mA methylomes at single-nucleotide resolution in rice based on substantially improved genome sequences of two rice cultivars,Nipponbare (Nip;Japonica)and 93-11 (Indica).Analysis of 6mA genomic distribution and its association with transcription suggest that 6mA distribution and function is rather conserved between rice and Arabidopsis.We found that 6mA levels are positively correlated with the expression of key stressrelated genes,which may be responsible for the difference in stress tolerance between Nip and 93-11. Moreover,we showed that mutations in DDM1 cause defects in plant growth and decreased 6mA level. Our results reveal that 6mA is a conserved DNA modification that is positively associated with gene expression and contributes to key agronomic traits in plants.
基金This work was supported by funding from the National Transgenic Major Program of China(2019ZX08010-002)to X.G.the National Natural Sci ence Foundation of China(31871606,31671670)toX.G.,and the Recruit ment Program of Global Youth Expert of China to X.G.
文摘Advances in the detection and mapping of messenger RNA(mRNA)N^6-methyladenosine(m 6A)and 5-methylcytosine(m 5C),and DNA N^6-methyldeoxyadenosine(6mA)redefined our understanding of these modifications as additional tiers of epigenetic regulation.In plants,the most prevalent internal mRNA modifications,m^6A and m^5C,play crucial and dynamic roles in many processes,including embryo development,stem cell fate determination,trichome branching,leaf morphogenesis,floral transition,stress responses,fruit ripening,and root development.The newly identified and widespread epigenetic marker 6mA DNA methylation is associated with gene expression,plant development,and stress responses.Here,we review the latest research progress on mRNA and DNA epigenetic modifications,including the detection,dynamics,distribution,functions,regulatory proteins,and evolution,with a focus on m^6A,m^5C,and 6mA.We also provide some perspectives on future research of the newly identified and unknown epigenetic modifications of mRNA and DNA in plants.
基金supported by the National Key Program for Infectious Disease of China(Grant No.2018ZX10302301-004-003)the National Natural Science Foundation of China(Grant Nos.31770870 and 31801093).
文摘Klebsiella pneumoniae(K.pneumoniae)is an important pathogen that can cause severe hospital-and community-acquired infections.To systematically investigate its methylation features,we determined the whole-genome sequences of 14 K.pneumoniae strains covering varying serotypes,multilocus sequence types,clonal groups,viscosity/virulence,and drug resistance.Their methylomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies.We identified 15 methylation motifs[13 N6-methyladenine(6mA)and two 5-methylcytosine(5mC)motifs],among which eight were novel.Their corresponding DNA methyltransferases were also validated.Additionally,we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains,and identified differential distribution patterns of some hemi-/un-methylated GATC motifs,which tend to be located within intergenic regions(IGRs).Specifically,we characterized the in vivo methylation kinetics at single-base resolution on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation.The slow methylation of the GATC motifs in the replication origin(oriC)regions and IGRs implicates the epigenetic regulation of replication initiation and transcription.Our findings illustrate the first comprehensive dynamic methylome map of K.pneumoniae at single-base resolution,and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.
基金This work is supported by grants from CPRIT(RR180072)Rivkin Center Scientific Scholar Award.
文摘N^(6)-methyladenine(N^(6)-mA,m^(6)dA,or 6mA),a prevalent DNA modification in prokaryotes,has recently been identified in higher eukaryotes,including mammals.Although 6mA has been well-studied in prokaryotes,the function and regulatory mechanism of 6mA in eukaryotes are still poorly understood.Recent studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes,from transposable-element suppression to environmental stress response.Here,we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes,predominantly mammals.
