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Using Chaos-Game-Representation for Analysing the SARS-CoV-2 Lineages, Newly Emerging Strains and Recombinants 利用混沌博弈表示分析SARS-CoV-2谱系、新出现的毒株和重组体
4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-24 DOI: 10.2174/0113892029264990231013112156
Amarinder Singh Thind, Somdatta Sinha
Background: Viruses have high mutation rates, facilitating rapid evolution and the emergence of new species, subspecies, strains and recombinant forms. Accurate classification of these forms is crucial for understanding viral evolution and developing therapeutic applications. Phylogenetic classification is typically performed by analyzing molecular differences at the genomic and sub-genomic levels. This involves aligning homologous proteins or genes. However, there is growing interest in developing alignment-free methods for whole-genome comparisons that are computationally efficient. Methods: Here we elaborate on the Chaos Game Representation (CGR) method, based on concepts of statistical physics and free of sequence alignment assumptions. We adopt the CGR method for classification of the closely related clades/lineages A and B of the SARS-Corona virus 2019 (SARS-CoV-2), which is one of the fastest evolving viruses. Results: Our study shows that the CGR approach can easily yield the SARS-CoV-2 phylogeny from the available whole genomes of lineage A and lineage B sequences. It also shows an accurate classification of eight different strains and the newly evolved XBB variant from its parental strains. Compared to alignment-based methods (Neighbour-Joining and Maximum Likelihood), the CGR method requires low computational resources, is fast and accurate for long sequences, and, being a K-mer based approach, allows simultaneous comparison of a large number of closely-related sequences of different sizes. Further, we developed an R pipeline CGRphylo, available on GitHub, which integrates the CGR module with various other R packages to create phylogenetic trees and visualize them. Conclusion: Our findings demonstrate the efficacy of the CGR method for accurate classification and tracking of rapidly evolving viruses, offering valuable insights into the evolution and emergence of new SARS-CoV-2 strains and recombinants.
背景:病毒具有高突变率,有利于快速进化和新物种、亚种、毒株和重组形式的出现。这些形式的准确分类对于理解病毒进化和开发治疗应用至关重要。系统发育分类通常通过分析基因组和亚基因组水平上的分子差异来进行。这包括对齐同源蛋白质或基因。然而,越来越多的人对开发计算效率高的全基因组比较的无比对方法感兴趣。方法:本文基于统计物理的概念,不考虑序列对齐的假设,详细阐述了混沌博弈表示(CGR)方法。我们采用CGR方法对进化速度最快的新型冠状病毒(SARS-CoV-2)的A、B两个密切相关分支/谱系进行分类。结果:我们的研究表明,CGR方法可以很容易地从现有的A和B谱系序列全基因组中获得SARS-CoV-2系统发育。它还显示了8种不同菌株的准确分类以及从其亲本菌株新进化的XBB变体。与基于比对的方法(neighbor - joining和Maximum Likelihood)相比,CGR方法需要较少的计算资源,对于长序列具有快速和准确的特点,并且作为一种基于K-mer的方法,可以同时比较大量不同大小的密切相关序列。此外,我们开发了一个R管道CGRphylo,可以在GitHub上获得,它将CGR模块与其他各种R包集成在一起,以创建系统发生树并将其可视化。结论:我们的研究结果证明了CGR方法对快速进化的病毒的准确分类和跟踪的有效性,为新的SARS-CoV-2毒株和重组体的进化和出现提供了有价值的见解。
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引用次数: 0
Deacetylation of Histones and Non-histone Proteins in Inflammatory Diseases and Cancer Therapeutic Potential of Histone Deacetylase Inhibitors 组蛋白去乙酰化和非组蛋白去乙酰化在炎症疾病和癌症中的治疗潜力
4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-24 DOI: 10.2174/0113892029265046231011100327
Ezgi Man, Serap EVRAN
abstract: Epigenetic changes play an important role in the pathophysiology of autoimmune diseases such as allergic asthma, multiple sclerosis, lung diseases, diabetes, cystic fibrosis, atherosclerosis, rheumatoid arthritis, and COVID-19. There are three main classes of epigenetic alterations: post-translational modifications of histone proteins, control by non-coding RNA and DNA methylation. Since histone modifications can directly affect chromatin structure and accessibility, they can regulate gene expression levels. Abnormal expression and activity of histone deacetylases (HDACs) have been reported in immune mediated diseases. Increased acetylated levels of lysine residues have been suggested to be related to the overexpression of inflammatory genes. This review focuses on the effect of HDAC modifications on histone and non–histone proteins in autoimmune diseases. Furthermore, we discuss the potential therapeutic effect of HDAC inhibitors (HDACi) used in these diseases.
表观遗传变化在变应性哮喘、多发性硬化、肺部疾病、糖尿病、囊性纤维化、动脉粥样硬化、类风湿性关节炎和COVID-19等自身免疫性疾病的病理生理中发挥重要作用。表观遗传改变主要有三类:组蛋白翻译后修饰、非编码RNA控制和DNA甲基化。由于组蛋白修饰可以直接影响染色质结构和可及性,因此它们可以调节基因表达水平。组蛋白去乙酰化酶(hdac)的异常表达和活性在免疫介导的疾病中有报道。赖氨酸残基乙酰化水平的增加被认为与炎症基因的过度表达有关。本文综述了HDAC修饰对自身免疫性疾病中组蛋白和非组蛋白的影响。此外,我们还讨论了HDAC抑制剂(HDACi)在这些疾病中的潜在治疗效果。
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引用次数: 0
DLC-ac4C: A Prediction Model for N4-acetylcytidine Sites in Human mRNA Based on DenseNet and Bidirectional LSTM Methods DLC-ac4C:基于DenseNet和双向LSTM方法的人mRNA n4 -乙酰胞苷位点预测模型
4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-19 DOI: 10.2174/0113892029270191231013111911
Jianhua Jia, Xiaojing Cao, Zhangying Wei
Introduction: N4 acetylcytidine (ac4C) is a highly conserved nucleoside modification that is essential for the regulation of immune functions in organisms. Currently, the identification of ac4C is primarily achieved using biological methods, which can be time-consuming and laborintensive. In contrast, accurate identification of ac4C by computational methods has become a more effective method for classification and prediction Aim: To the best of our knowledge, although there are several computational methods for ac4C locus prediction, the performance of the models they constructed is poor, and the network structure they used is relatively simple and suffers from the disadvantage of network degradation. This study aims to improve these limitations by proposing a predictive model based on integrated deep learning to better help identify ac4C sites. Methods: In this study, we propose a new integrated deep learning prediction framework, DLCac4C. First, we encode RNA sequences based on three feature encoding schemes, namely C2 encoding, nucleotide chemical property (NCP) encoding, and nucleotide density (ND) encoding. Second, one-dimensional convolutional layers and densely connected convolutional networks (DenseNet) are used to learn local features, and bi-directional long short-term memory networks (Bi-LSTM) are used to learn global features. Third, a channel attention mechanism is introduced to determine the importance of sequence characteristics. Finally, a homomorphic integration strategy is used to limit the generalization error of the model, which further improves the performance of the model. Results: The DLC-ac4C model performed well in terms of sensitivity (Sn), specificity (Sp), accuracy (Acc), Mathews correlation coefficient (MCC), and area under the curve (AUC) for the independent test data with 86.23%, 79.71%, 82.97%, 66.08%, and 90.42%, respectively, which was significantly better than the prediction accuracy of the existing methods. Conclusion: Our model not only combines DenseNet and Bi-LSTM, but also uses the channel attention mechanism to better capture hidden information features from a sequence perspective, and can identify ac4C sites more effectively.
简介:N4乙酰胞苷(ac4C)是一种高度保守的核苷修饰,对生物体免疫功能的调节至关重要。目前,ac4C的鉴定主要是通过生物学方法来实现的,这可能是耗时和费力的。目的:据我们所知,虽然ac4C基因座预测的计算方法有几种,但它们构建的模型性能较差,使用的网络结构相对简单,存在网络退化的缺点。本研究旨在通过提出基于集成深度学习的预测模型来改善这些局限性,以更好地帮助识别ac4C位点。方法:在本研究中,我们提出了一个新的集成深度学习预测框架DLCac4C。首先,基于C2编码、核苷酸化学性质(NCP)编码和核苷酸密度(ND)编码三种特征编码方案对RNA序列进行编码。其次,使用一维卷积层和密集连接卷积网络(DenseNet)学习局部特征,使用双向长短期记忆网络(Bi-LSTM)学习全局特征。第三,引入通道注意机制来确定序列特征的重要性。最后,采用同态积分策略限制了模型的泛化误差,进一步提高了模型的性能。结果:DLC-ac4C模型对独立检测数据的敏感性(Sn)、特异性(Sp)、准确度(Acc)、Mathews相关系数(MCC)和曲线下面积(AUC)分别为86.23%、79.71%、82.97%、66.08%和90.42%,均有较好的预测效果,显著优于现有方法的预测精度。结论:我们的模型不仅结合了DenseNet和Bi-LSTM,而且利用通道注意机制从序列角度更好地捕捉隐藏信息特征,能够更有效地识别ac4C位点。
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引用次数: 0
Decoding the Link between Periodontitis and Neuroinflammation: The Journey of Bacterial Extracellular Vesicles 破解牙周炎和神经炎症之间的联系:细菌细胞外囊泡的旅程
4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-10-15 DOI: 10.2174/0113892029258657231010065320
Heon-Jin Lee, Youngkyun Lee, Su-Hyung Hong, Jin-Woo Park
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引用次数: 0
The Era of Plant Breeding: Conventional Breeding to Genomics-assisted Breeding for Crop Improvement. 植物育种的时代:传统育种到基因组学辅助育种的作物改良
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-06-23 DOI: 10.2174/1389202924666230517115912
Thumadath Palayullaparambil Ajeesh Krishna, Duraipandiyan Veeramuthu, Theivanayagam Maharajan, Mariapackiam Soosaimanickam

Plant breeding has made a significant contribution to increasing agricultural production. Conventional breeding based on phenotypic selection is not effective for crop improvement. Because phenotype is considerably influenced by environmental factors, which will affect the selection of breeding materials for crop improvement. The past two decades have seen tremendous progress in plant breeding research. Especially the availability of high-throughput molecular markers followed by genomic-assisted approaches significantly contributed to advancing plant breeding. Integration of speed breeding with genomic and phenomic facilities allowed rapid quantitative trait loci (QTL)/gene identifications and ultimately accelerated crop improvement programs. The advances in sequencing technology helps to understand the genome organization of many crops and helped with genomic selection in crop breeding. Plant breeding has gradually changed from phenotype-to-genotype-based to genotype-to-phenotype-based selection. High-throughput phenomic platforms have played a significant role in the modern breeding program and are considered an essential part of precision breeding. In this review, we discuss the rapid advance in plant breeding technology for efficient crop improvements and provide details on various approaches/platforms that are helpful for crop improvement. This review will help researchers understand the recent developments in crop breeding and improvements.

植物育种对提高农业产量作出了重大贡献。基于表型选择的常规育种对作物改良无效。因为表型在很大程度上受到环境因素的影响,环境因素会影响作物改良育种材料的选择。在过去的二十年里,植物育种研究取得了巨大进展。特别是高通量分子标记的可用性,以及基因组辅助方法,对推进植物育种做出了重大贡献。将快速育种与基因组和表型设施相结合,可以快速鉴定数量性状基因座(QTL)/基因,并最终加快作物改良计划。测序技术的进步有助于了解许多作物的基因组组织,并有助于作物育种中的基因组选择。植物育种逐渐从表型到基因型,从基因型到表型选择。高通量表型平台在现代育种计划中发挥了重要作用,被认为是精确育种的重要组成部分。在这篇综述中,我们讨论了高效作物改良的植物育种技术的快速发展,并提供了有助于作物改良的各种方法/平台的详细信息。这篇综述将帮助研究人员了解作物育种和改良的最新进展。
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引用次数: 0
Insights into Metabolic Engineering of Bioactive Molecules in Tetrastigma Hemsleyanum Diels & Gilg: A Traditional Medicinal Herb 赤柱藻生物活性分子代谢工程研究进展吉尔:一种传统的草药
4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-01 DOI: 10.2174/0113892029251472230921053135
Ajeesh Krishna TP, Maharajan Theivanayagam, Adarsh Krishna, Antony Ceasar Stanislaus
Abstract: Plants are a vital source of bioactive molecules for various drug development processes. Tetrastigma hemsleyanum is one of the endangered medicinal plant species well known to the world due to its wide range of therapeutic effects. Many bioactive molecules have been identified from this plant, including many classes of secondary metabolites such as flavonoids, phenols, terpenoids, steroids, alkaloids, etc. Due to its slow growth, it usually takes 3-5 years to meet commercial medicinal materials for this plant. Also, T. hemsleyanum contains low amounts of specific bioactive compounds, which are challenging to isolate easily. Currently, scientists are attempting to increase bioactive molecules' production from medicinal plants in different ways or to synthesize them chemically. The genomic tools helped to understand medicinal plants' genome organization and led to manipulating genes responsible for various biosynthesis pathways. Metabolic engineering has made it possible to enhance the production of secondary metabolites by introducing manipulated biosynthetic pathways to attain high levels of desirable bioactive molecules. Metabolic engineering is a promising approach for improving the production of secondary metabolites over a short time period. In this review, we have highlighted the scope of various biotechnological approaches for metabolic engineering to enhance the production of secondary metabolites for pharmaceutical applications in T. hemsleyanum. Also, we summarized the progress made in metabolic engineering for bioactive molecule enhancement in T. hemsleyanum. It may lead to reducing the destruction of the natural habitat of T. hemsleyanum and conserving them through the cost-effective production of bioactive molecules in the future.
摘要:植物是各种药物开发过程中生物活性分子的重要来源。赤藓(Tetrastigma hemsleyanum)是一种因其广泛的治疗作用而为世界所熟知的濒危药用植物。从该植物中已鉴定出许多生物活性分子,包括黄酮类、酚类、萜类、类固醇、生物碱等多种次生代谢产物。由于其生长缓慢,通常需要3-5年才能达到商业药用材料的要求。此外,T. hemsleyanum含有少量的特定生物活性化合物,很难轻易分离。目前,科学家们正试图用不同的方法从药用植物中增加生物活性分子的产量,或者用化学方法合成它们。基因组工具有助于了解药用植物的基因组组织,并导致操纵负责各种生物合成途径的基因。代谢工程使得通过引入操纵的生物合成途径来获得高水平的理想生物活性分子来提高次生代谢物的生产成为可能。代谢工程是一种很有前途的方法,可以在短时间内提高次生代谢物的产量。在这篇综述中,我们重点介绍了各种生物技术方法的代谢工程范围,以提高T. hemsleyanum的次生代谢产物的生产用于制药应用。最后,综述了利用代谢工程技术增强赤霉病菌生物活性分子的研究进展。这可能会导致未来通过经济有效的生产生物活性分子来减少对T. hemsleyanum自然栖息地的破坏并保护它们。
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引用次数: 0
Circular RNA Translation in Cardiovascular Diseases 心血管疾病中的环状RNA翻译
4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-01 DOI: 10.2174/1389202924666230911121358
Lijun Wang, Xinxin Cui, Fei Jiang, Yuxue Hu, Wensi Wan, Guoping Li, Yanjuan Lin, Junjie Xiao
Abstract: Circular RNAs (circRNAs) are a class of endogenous functional RNA generated by backsplicing. Recently, circRNAs have been found to have certain coding potential. Proteins/peptides translated from circRNAs play essential roles in various diseases. Here, we briefly summarize the basic knowledge and technologies that are usually applied to study circRNA translation. Then, we focus on the research progress of circRNA translation in cardiovascular diseases and discuss the perspective and future direction of translatable circRNA study in cardiovascular diseases.
摘要:环状RNA (Circular RNA, circRNAs)是一类通过反剪接产生的内源性功能性RNA。最近,人们发现环状rna具有一定的编码潜能。由环状rna翻译的蛋白质/肽在多种疾病中发挥重要作用。在这里,我们简要总结了circRNA翻译研究中常用的基本知识和技术。然后,我们重点关注circRNA翻译在心血管疾病中的研究进展,并讨论可翻译circRNA在心血管疾病中的研究前景和未来方向。
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引用次数: 0
Mitochondrial Lipid Metabolism Genes as Diagnostic and Prognostic Indicators in Hepatocellular Carcinoma 线粒体脂质代谢基因作为肝细胞癌的诊断和预后指标
4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-03-01 DOI: 10.2174/1389202924666230914110649
Xuejing Li, Ying Tan, Bihan Liu, Houtian Guo, Yongjian Zhou, Jianhui Yuan, Feng Wang
Background: Due to the heterogeneity of Hepatocellular carcinoma (HCC), there is an urgent need for reliable diagnosis and prognosis. Mitochondria-mediated abnormal lipid metabolism affects the occurrence and progression of HCC. Objective: This study aims to investigate the potential of mitochondrial lipid metabolism (MTLM) genes as diagnostic and independent prognostic biomarkers for HCC. Methods: MTLM genes were screened from the Gene Expression Omnibus (GEO) and Gene Set Enrichment Analysis (GSEA) databases, followed by an evaluation of their diagnostic values in both The Cancer Genome Atlas Program (TCGA) and the Affiliated Cancer Hospital of Guangxi Medical University (GXMU) cohort. The TCGA dataset was utilized to construct a gene signature and investigate the prognostic significance, immune infiltration, and copy number alterations. The validity of the prognostic signature was confirmed through GEO, International Cancer Genome Consortium (ICGC), and GXMU cohorts. Results: The diagnostic receiver operating characteristic (ROC) curve revealed that eight MTLM genes have excellent diagnostic of HCC. A prognostic signature comprising 5 MTLM genes with robust predictive value was constructed using the lasso regression algorithm based on TCGA data. The results of the Stepwise regression model showed that the combination of signature and routine clinical parameters had a higher area under the curve (AUC) compared to a single risk score. Further, a nomogram was constructed to predict the survival probability of HCC, and the calibration curves demonstrated a perfect predictive ability. Finally, the risk score also unveiled the different immune and mutation statuses between the two different risk groups. Conclusion: MTLT-related genes may serve as diagnostic and prognostic biomarkers for HCC as well as novel therapeutic targets, which may be beneficial for facilitating further understanding the molecular pathogenesis and providing potential therapeutic strategies for HCC.
背景:由于肝细胞癌(HCC)的异质性,迫切需要可靠的诊断和预后。线粒体介导的脂质代谢异常影响HCC的发生和发展。目的:本研究旨在探讨线粒体脂质代谢(MTLM)基因作为HCC诊断和独立预后生物标志物的潜力。方法:从基因表达综合(GEO)和基因集富集分析(GSEA)数据库中筛选MTLM基因,并在肿瘤基因组图谱计划(TCGA)和广西医科大学附属肿瘤医院(GXMU)队列中评估其诊断价值。利用TCGA数据集构建基因标记,并研究预后意义、免疫浸润和拷贝数改变。通过GEO、国际癌症基因组联盟(ICGC)和GXMU队列证实了预后特征的有效性。结果:诊断性受试者工作特征(ROC)曲线显示8个MTLM基因对HCC具有良好的诊断价值。基于TCGA数据,采用lasso回归算法构建了具有鲁棒预测值的5个MTLM基因的预后特征。逐步回归模型结果显示,与单一风险评分相比,特征与常规临床参数的组合具有更高的曲线下面积(AUC)。进一步构建了预测HCC生存概率的nomogram,校正曲线具有较好的预测能力。最后,风险评分还揭示了两个不同风险组之间不同的免疫和突变状态。结论:mtlt相关基因可作为HCC诊断和预后的生物标志物和新的治疗靶点,有助于进一步了解HCC的分子发病机制和提供潜在的治疗策略。
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引用次数: 0
ACKNOWLEDGEMENTS TO REVIEWERS. 向评审员致谢。
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-02-14 DOI: 10.2174/138920292306230209163617
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引用次数: 0
Chromosome-level genome assembly and sex-specific differential transcriptome of the white-backed planthopper, Sogatella furcifera 白背飞虱的染色体水平基因组组装和性别特异性差异转录组
IF 2.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-01-02 DOI: 10.2174/1389202924666230102092822
C. Zhang, Yu-Xuan Ye, Dan-Ting Li, Si-Yu Zhang, Z. Shen
Anti-Inflammatory & Anti-Allergy Agents in Medicinal ChemistryIn this study, we report a de novo assembly of the chromosome-level WBPH genome with characterized sex chromosomes using third-generation sequencing technologies, Hi-C data and full-length transcripts, and provide a dense landscape of sex-specific transcriptome.We generated a high-quality chromosome-level assembly with a contig N50 of 2.20 Mb and a scaffold N50 of 45.25 Mb. Fourteen autosomes and one X chromosomes were identified. More than 99.5% of the assembled bases located on the 15 chromosomes. 95.9% of the BUSCO complete genes were detected in the final assembly and 16,880 genes were annotated.The integrated genome, definite sex chromosomes, comprehensive transcriptome profiles, high efficiency of RNA interference and short life cycle substantially made WBPH an efficient research object for functional genomics.
药物化学中的抗炎和变态反应剂在这项研究中,我们报告了使用第三代测序技术、Hi-C数据和全长转录本对染色体水平的WBPH基因组与特征性染色体的从头组装,并提供了性别特异性转录组的密密景观。我们产生了具有2.20Mb的重叠群N50和45.25Mb的支架N50的高质量染色体水平组装。鉴定出14条常染色体和1条X染色体。99.5%以上的组装碱基位于15条染色体上。在最终组装中检测到95.9%的BUSCO完整基因,并注释了16880个基因。基因组完整、性染色体明确、转录组图谱全面、RNA干扰效率高、生命周期短,使WBPH成为功能基因组学的有效研究对象。
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引用次数: 0
期刊
Current Genomics
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