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Identification of Potential Genes and Critical Pathways in Postoperative Recurrence of Crohn's Disease by Machine Learning And WGCNA Network Analysis. 机器学习和WGCNA网络分析识别克罗恩病术后复发的潜在基因和关键途径
IF 2.6 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-27 DOI: 10.2174/1389202924666230601122334
Aruna Rajalingam, Kanagaraj Sekar, Anjali Ganjiwale

Background: Crohn's disease (CD) is a chronic idiopathic inflammatory bowel disease affecting the entire gastrointestinal tract from the mouth to the anus. These patients often experience a period of symptomatic relapse and remission. A 20 - 30% symptomatic recurrence rate is reported in the first year after surgery, with a 10% increase each subsequent year. Thus, surgery is done only to relieve symptoms and not for the complete cure of the disease. The determinants and the genetic factors of this disease recurrence are also not well-defined. Therefore, enhanced diagnostic efficiency and prognostic outcome are critical for confronting CD recurrence.

Methods: We analysed ileal mucosa samples collected from neo-terminal ileum six months after surgery (M6=121 samples) from Crohn's disease dataset (GSE186582). The primary aim of this study is to identify the potential genes and critical pathways in post-operative recurrence of Crohn's disease. We combined the differential gene expression analysis with Recursive feature elimination (RFE), a machine learning approach to get five critical genes for the postoperative recurrence of Crohn's disease. The features (genes) selected by different methods were validated using five binary classifiers for recurrence and remission samples: Logistic Regression (LR), Decision tree classifier (DT), Support Vector Machine (SVM), Random Forest classifier (RF), and K-nearest neighbor (KNN) with 10-fold cross-validation. We also performed weighted gene co-expression network analysis (WGCNA) to select specific modules and feature genes associated with Crohn's disease postoperative recurrence, smoking, and biological sex. Combined with other biological interpretations, including Gene Ontology (GO) analysis, pathway enrichment, and protein-protein interaction (PPI) network analysis, our current study sheds light on the in-depth research of CD diagnosis and prognosis in postoperative recurrence.

Results: PLOD2, ZNF165, BOK, CX3CR1, and ARMCX4, are the important genes identified from the machine learning approach. These genes are reported to be involved in the viral protein interaction with cytokine and cytokine receptors, lysine degradation, and apoptosis. They are also linked with various cellular and molecular functions such as Peptidyl-lysine hydroxylation, Central nervous system maturation, G protein-coupled chemoattractant receptor activity, BCL-2 homology (BH) domain binding, Gliogenesis and negative regulation of mitochondrial depolarization. WGCNA identified a gene co-expression module that was primarily involved in mitochondrial translational elongation, mitochondrial translational termination, mitochondrial translation, mitochondrial respiratory chain complex, mRNA splicing via spliceosome pathways, etc.; Both the analysis result emphasizes that the mitochondrial depolarization pathway is linked with CD recurrence leading to oxidative st

克罗恩病(CD)是一种慢性特发性炎症性肠病,影响从口腔到肛门的整个胃肠道。这些患者通常会经历一段时间的症状复发和缓解。据报道,术后第一年症状复发率为20-30%,随后每年增加10%。因此,手术只是为了缓解症状,而不是为了彻底治愈疾病。这种疾病复发的决定因素和遗传因素也没有明确定义。因此,提高诊断效率和预后对于对抗CD复发至关重要。我们分析了克罗恩病数据集(GSE186582)中手术后6个月从新末端回肠收集的回肠粘膜样本(M6=121个样本)。本研究的主要目的是确定克罗恩病术后复发的潜在基因和关键途径。我们将差异基因表达分析与递归特征消除(RFE)相结合,这是一种机器学习方法,可以获得克罗恩病术后复发的五个关键基因。使用五个用于复发和缓解样本的二元分类器对通过不同方法选择的特征(基因)进行验证:逻辑回归(LR)、决策树分类器(DT)、支持向量机(SVM)、随机森林分类器(RF)和K近邻(KNN),并进行10倍交叉验证。我们还进行了加权基因共表达网络分析(WGCNA),以选择与克罗恩病术后复发、吸烟和生物学性别相关的特定模块和特征基因。结合其他生物学解释,包括基因本体论(GO)分析、通路富集和蛋白质-蛋白质相互作用(PPI)网络分析,我们目前的研究为术后复发CD诊断和预后的深入研究提供了线索。PLOD2、ZNF165、BOK、CX3CR1和ARMCX4是通过机器学习方法鉴定的重要基因。据报道,这些基因参与病毒蛋白与细胞因子和细胞因子受体的相互作用、赖氨酸降解和细胞凋亡。它们还与各种细胞和分子功能有关,如肽基赖氨酸羟基化、中枢神经系统成熟、G蛋白偶联化学引诱剂受体活性、BCL-2同源性(BH)结构域结合、胶质形成和线粒体去极化的负调控。WGCNA鉴定出一个基因共表达模块,主要参与线粒体翻译延长、线粒体翻译终止、线粒体翻译、线粒体呼吸链复合体、通过剪接体途径剪接信使核糖核酸等。;这两个分析结果都强调线粒体去极化途径与CD复发有关,导致CD患者的氧化应激促进炎症。这些关键基因是克罗恩病术后复发的新的诊断生物标志物。因此,在迄今为止存在的其他治疗选择中,这些生物标志物将在诊断和预后方面取得成功,旨在获得长期缓解,以防止CD的进一步并发症。
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引用次数: 0
Taxonomic Status and Phylogenetic Relationship of Family Charadriidae based on Complete Mitogenomes 基于全有丝分裂基因组的蚕科分类地位及系统发育关系
4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-27 DOI: 10.2174/0113892029273517231017051819
Weiya Qian, Yizheng Liu, Keer Miao, Qing Chang, Chaochao Hu
Background: The Charadriiformes provide a good source for researching evolution owing to their diverse distribution, behavior, morphology, and ecology. However, in the Charadrii, family-level relationships remain understudied, and the monophyly of Charadriidae is also a subject of controversy. Method: In the present study, we generated complete mitogenomes for two species, Charadrius leschenaultii and Charadrius mongolus, which were found to be 16,905 bp and 16,844 bp in length, respectively. Among the 13 protein codon genes, we observed variation in the rate of nonsynonymous substitution rates, with the slowest rate found in COI and the fastest rate observed in ATP8. The Ka/Ks ratio for all Charadriidae species was significantly lower than one, which inferred that the protein-coding genes underwent purifying selection. Result: Phylogenetic analysis based on the genes of Cyt b, 12S and ND2 revealed that the genus Pluvialis is the sister group of three families (Haematopodidae, Ibidorhynchidae, Recurvirostridae). However, the phylogenetic analysis based on complete mitogenomes indicated that the genus Pluvialis is within the Charadriidae family. Conclusion: This study highlights the importance of carefully selecting the number of genes used to obtain accurate estimates of the species tree. It also suggests that relying on partial mtDNA genes with fast-evolving rates may lead to misleading results when resolving the Pluvialis sister group. Future research should focus on sequencing more mitogenomes at different taxonomic levels to gain a better understanding of the features and phylogenetic relationships within the Charadriiformes order.
背景:charadriiforma因其分布、行为、形态和生态的多样性,为研究进化提供了良好的资源。然而,在Charadrii中,家庭层面的关系仍然没有得到充分的研究,Charadrii科的单系性也是一个有争议的话题。方法:对leschenaultii Charadrius和mongolus Charadrius进行了完整的有丝分裂基因组测序,发现其长度分别为16,905 bp和16,844 bp。在13个蛋白质密码子基因中,我们观察到非同义取代率的变化,COI的速率最慢,ATP8的速率最快。所有种类的Ka/Ks比值均显著低于1,说明其蛋白编码基因存在纯化选择。结果:基于Cyt b、12S和ND2基因的系统发育分析表明,雨蝇属是血足科、舌足科、反刍病毒科3个科的姐妹群。然而,基于完整有丝分裂基因组的系统发育分析表明,雨蝇属属于雨蝇科。结论:这项研究强调了仔细选择用于获得物种树准确估计的基因数量的重要性。这也表明,依赖于快速进化速率的部分mtDNA基因可能会导致在解决Pluvialis姐妹群时产生误导性的结果。未来的研究应侧重于在不同的分类水平上对更多的有丝分裂基因组进行测序,以更好地了解charadriiforma目的特征和系统发育关系。
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引用次数: 0
Deciphering Target Protein Cascade in Salmonella typhi Biofilm using Genomic Data Mining, and Protein-protein Interaction. 利用基因组数据挖掘和蛋白-蛋白相互作用破译伤寒沙门氏菌生物膜中的靶蛋白级联
IF 2.6 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-27 DOI: 10.2174/1389202924666230815144126
Aditya Upadhyay, Dharm Pal, Awanish Kumar

Background: Salmonella typhi biofilm confers a serious public health issue for lengthy periods and the rise in antibiotic resistance and death rate. Biofilm generation has rendered even the most potent antibiotics ineffective in controlling the illness, and the S. typhi outbreak has turned into a fatal disease typhoid. S. typhi infection has also been connected to other deadly illnesses, such as a gall bladder cancer. The virulence of this disease is due to the interaction of numerous genes and proteins of S. typhi.

Objective: The study aimed to identify a cascade of target proteins in S. typhi biofilm condition with the help of genomic data mining and protein-protein interaction analysis.

Methods: The goal of this study was to notice some important pharmacological targets in S. typhi. using genomic data mining, and protein-protein interaction approaches were used so that new drugs could be developed to combat the disease.

Results: In this study, we identified 15 potential target proteins that are critical for S. typhi biofilm growth and maturation. Three proteins, CsgD, AdrA, and BcsA, were deciphered with their significant role in the synthesis of cellulose, a critical component of biofilm's extracellular matrix. The CsgD protein was also shown to have high interconnectedness and strong interactions with other important target proteins of S. typhi. As a result, it has been concluded that CsgD is involved in a range of activities, including cellulose synthesis, bacterial pathogenicity, quorum sensing, and bacterial virulence.

Conclusion: All identified targets in this study possess hydrophobic properties, and their cellular localization offered proof of a potent therapeutic target. Overall results of this study, drug target shortage in S. typhi is also spotlighted, and we believe that obtained result could be useful for the design and development of some potent anti-salmonella agents for typhoid fever in the future.

伤寒沙门氏菌生物膜在很长一段时间内造成严重的公共卫生问题,并导致抗生素耐药性和死亡率上升。生物膜的产生使得即使是最有效的抗生素也无法控制这种疾病,伤寒沙门氏菌的爆发已经变成了一种致命的疾病伤寒。伤寒沙门氏菌感染也与其他致命疾病有关,比如胆囊癌。这种疾病的毒力是由于伤寒沙门氏菌的许多基因和蛋白质的相互作用。本研究旨在利用基因组数据挖掘和蛋白-蛋白相互作用分析方法,鉴定Typhi S. Typhi生物膜条件下的一系列靶蛋白。利用基因组数据挖掘和蛋白质-蛋白质相互作用的方法,可以开发新的药物来对抗这种疾病。在这项研究中,我们确定了15种潜在的靶蛋白,这些蛋白对伤寒沙门氏菌生物膜的生长和成熟至关重要。三种蛋白,CsgD, AdrA和BcsA,在生物膜细胞外基质的关键成分纤维素的合成中起着重要作用。CsgD蛋白还与伤寒沙门氏菌的其他重要靶蛋白具有高度的互联性和强相互作用。因此,已经得出结论,CsgD参与了一系列活动,包括纤维素合成,细菌致病性,群体感应和细菌毒力。本研究中所有确定的靶点都具有疏水特性,它们的细胞定位为有效的治疗靶点提供了证据。本研究的总体结果也突出了伤寒沙门氏菌的药物靶点短缺问题,我们相信所获得的结果可以为未来一些有效的抗伤寒沙门氏菌药物的设计和开发提供参考。
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引用次数: 0
Application of Feature Definition and Quantification in Biological Sequence Analysis. 特征定义与量化在生物序列分析中的应用
IF 2.6 4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-27 DOI: 10.2174/1389202924666230816150732
Weiyang Chen, Weiwei Li

Biological sequence analysis is the most fundamental work in bioinformatics. Many research methods have been developed in the development of biological sequence analysis. These methods include sequence alignment-based methods and alignment-free methods. In addition, there are also some sequence analysis methods based on the feature definition and quantification of the sequence itself. This editorial introduces the methods of biological sequence analysis and explores the significance of defining features and quantitative research of biological sequences.

生物序列分析是生物信息学中最基础的工作。在生物序列分析的发展过程中,已经发展了许多研究方法。这些方法包括基于序列比对的方法和无比对的方法。此外,还有一些基于序列本身的特征定义和量化的序列分析方法。这篇社论介绍了生物序列分析的方法,并探讨了生物序列特征定义和定量研究的意义。
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引用次数: 0
High Prevalence of a c.5979dupA Variant in the Dysferlin Gene (DYSF) in Individuals from a Semiarid Region of Brazil 一种c.5979dupA异常铁蛋白基因(DYSF)变异在巴西半干旱地区个体中的高流行率
4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-25 DOI: 10.2174/0113892029257856231013115036
Isabella A. Motta, Maria Lucrécia A. Gouveia, Ana Paula M. Braga, Rafael S. Andrade, Mayra F.F. Montenegro, Sandra N. Gurgel, Keila M.F. Albuquerque, Priscilla A.N.G. Souto, Flávia P.B.F. Cardoso, Joseane S. Araujo, Mirella C.L. Pinheiro, Carlos E.P. da Silva, Pamella A.S. Gurgel, David Feder, Matheus M. Perez, Glaucia Luciano da Veiga, Beatriz C.A. Alves, Fernando L.A. Fonseca, Alzira A.S. Carvalho
Background: Dysferlinopathies represent a group of limb girdle or distal muscular dystrophies with an autosomal-recessive inheritance pattern resulting from the presence of pathogenic variants in the dysferlin gene (DYSF). Objective: In this work, we describe a population from a small city in Brazil carrying the c.5979dupA pathogenic variant of DYSF responsible for limb girdle muscular dystrophy type 2R and distal muscular dystrophy. Methods: Genotyping analyses were performed by qPCR using customized probe complementary to the region with the duplication under analysis in the DYSF. Results: A total of 104 individuals were examined. c.5979dupA was identified in 48 (46.15%) individuals. Twenty-three (22%) were homozygotes, among whom 13 (56.5%) were female. A total of 91.3% (21) of homozygous individuals had a positive family history, and seven (30.4%) reported consanguineous marriages. Twenty-five (24%) individuals were heterozygous (25.8±16 years) for the same variant, among whom 15 (60%) were female. The mean CK level was 697 IU for homozygotes, 140.5 IU for heterozygotes and 176 IU for wild-type homo-zygotes. The weakness distribution pattern showed 17.3% of individuals with a proximal pattern, 13% with a distal pattern and 69.6% with a mixed pattern. Fatigue was present in 15 homozygotes and one heterozygote. Conclusion: The high prevalence of this variant in individuals from this small community can be explained by a possible founder effect associated with historical, geographical and cultural aspects.
背景:异常铁蛋白病是一组肢体带或远端肌肉营养不良症,具有常染色体隐性遗传模式,由异常铁蛋白基因(DYSF)的致病变异引起。目的:在这项工作中,我们描述了来自巴西一个小城市的人群携带的c.5979dupA致病变异的DYSF负责肢带肌营养不良2R型和远端肌营养不良。方法:采用定制探针与DYSF中待分析重复区域互补的qPCR方法进行基因分型分析。结果:共检查104例。检出c.5979dupA 48例(46.15%)。纯合子23只(22%),其中雌性13只(56.5%)。共有91.3%(21人)的纯合个体有阳性家族史,7人(30.4%)报告有近亲婚姻。同一变异的杂合个体25例(24%)(25.8±16岁),其中女性15例(60%)。纯合子CK均值为697 IU,杂合子CK均值为140.5 IU,野生型纯合子CK均值为176 IU。其中,17.3%为近端型,13%为远端型,69.6%为混合型。15个纯合子和1个杂合子存在疲劳。结论:该变异在该小社区个体中的高流行率可能与历史、地理和文化方面相关的创始人效应有关。
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引用次数: 0
Pan-Cancer Analysis Identifies AIMP2 as a Potential Biomarker for Breast Cancer 泛癌症分析确定AIMP2为乳腺癌的潜在生物标志物
4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-25 DOI: 10.2174/0113892029255941231014142050
Jie Qiu, Tao Zhou, Danhong Wang, Weimin Hong, Da Qian, Xiaozhen Liu, Xuli Meng
Introduction:: Aminoacyl tRNA synthetase complex interacting with multifunctional protein 2 (AIMP2) is a significant regulator of cell proliferation and apoptosis. Despite its abnormal expression in various tumor types, the specific functions and effects of AIMP2 on tumor immune cell infiltration, proliferation, and migration remain unclear. background: AIMP2, Aminoacyl TRNA Synthetase Complex Interacting Multifunctional Protein 2, also known as JTV1, a multifunctional protein that forms a macromolecular complex with human aminoacyl tRNA synthetase, which consists of three non-enzymatic proteins, including p43, p38 and p18 proteins, of which p38 protein is AIMP2[1]. AIMP2 is necessary for the assembly and stability of aminoacyl tRNA synthetase complex[2]. Besides being important for efficient protein synthesis, additional physiological roles for AIMP2 have been discovered[3, 4]. For example, following DNA damage, AIMP2 is liberated from the ARS complex, phosphorylated in a JNK2-dependent pathway and translocated into the nucleus where it has been suggested to bind and sequester p53 from Mdm2-dependent ubiquitination[5]. AIMP2 has also been shown to be a substrate of E3 ligase Parkin[6]. Accumulation of AIMP2 as a result of Parkin mutation has been speculated to contribute to the characteristic dopaminergic cell death observed in Parkinson patients[7]. In addition, AIMP2 augments tumor necrosis factor-α-induced apoptotic signaling and exerts antiproliferative activities in TGF-β and Wnt pathways via distinct working mechanisms [8-10]. Therefore, we wonder that AIMP2 may play a crucial role in the occurrence and development of cancer. However, there are relatively few reseaches on AIMP2 in oncology. Current studies confirmed that AIMP2 may function as a multifunctional tumor suppressor[9, 11]. In this study, we analyzed the expression of AIMP2 and its relationship with the prognosis, Tumor Mutation Burden (TMB) and Microsatellite Instability (MSI) in 33 cancer types. In addition, we examined the correlation between AIMP2 and the immune microenvironment, immune-related antigens, and immune checkpoint genes. The results showed that AIMP2 was higher expressed in tumor tissue compared with normal tissue. Moreover, AIMP2 was associated with several tumor stages. Survival analysis showed that AIMP2 expression was strongly associated with OS in some cancer patients, where the high expression of AIMP2 was associated with a worse prognosis in five types of cancer. Then, we confirmed that the expression level of AIMP2 was associated with tumor immune infiltration and tumor microenvironment, especially in BRCA. Finally, si-RNA mediated knockdown of AIMP2 suppressed the proliferation and migration of BC cells in vitro. In conclusion, AIMP2 was found to be differentially expressed in the pan-cancer analysis and might play an important role in tumor immunity, which is expected to be a potential tumor prognostic marker, especially in BRCA. Method:: To assess AIMP
氨基酰基tRNA合成酶复合体与多功能蛋白2 (AIMP2)相互作用,是细胞增殖和凋亡的重要调节因子。尽管AIMP2在多种肿瘤类型中表达异常,但其对肿瘤免疫细胞浸润、增殖和迁移的具体功能和作用尚不清楚。背景:AIMP2, Aminoacyl TRNA Synthetase Complex Interacting Multifunctional Protein 2,又称JTV1,是一种与人氨酰基TRNA合成酶形成大分子复合物的多功能蛋白,由p43、p38和p18三种非酶蛋白组成,其中p38蛋白为AIMP2[1]。AIMP2是氨基酸基tRNA合成酶复合物的组装和稳定所必需的[2]。除了对高效蛋白质合成很重要外,还发现了AIMP2的其他生理作用[3,4]。例如,在DNA损伤后,AIMP2从ARS复合体中解放出来,在依赖jnk2的途径中磷酸化,并易位到细胞核中,在那里它被认为与依赖mdm2的泛素化p53结合并隔离[5]。AIMP2也被证明是E3连接酶Parkin的底物[6]。据推测,帕金突变导致AIMP2的积累可能导致帕金森患者出现特征性的多巴胺能细胞死亡[7]。此外,AIMP2增强肿瘤坏死因子-α-诱导的凋亡信号,并通过不同的工作机制在TGF-β和Wnt通路中发挥抗增殖活性[8-10]。因此,我们猜想AIMP2可能在癌症的发生发展中起着至关重要的作用。然而,关于AIMP2在肿瘤学中的研究相对较少。目前的研究证实AIMP2可能是一种多功能的肿瘤抑制因子[9,11]。在本研究中,我们分析了AIMP2在33种肿瘤类型中的表达及其与预后、肿瘤突变负荷(Tumor Mutation Burden, TMB)和微卫星不稳定性(Microsatellite Instability, MSI)的关系。此外,我们还研究了AIMP2与免疫微环境、免疫相关抗原和免疫检查点基因之间的相关性。结果表明,AIMP2在肿瘤组织中的表达高于正常组织。此外,AIMP2与多个肿瘤分期相关。生存分析显示,AIMP2的表达与部分癌症患者的OS密切相关,其中AIMP2的高表达与5种癌症的预后较差相关。然后,我们证实了AIMP2的表达水平与肿瘤免疫浸润和肿瘤微环境有关,尤其是在BRCA中。最后,si-RNA介导的AIMP2的下调抑制了体外BC细胞的增殖和迁移。综上所述,在泛癌分析中发现AIMP2存在差异表达,可能在肿瘤免疫中发挥重要作用,有望成为潜在的肿瘤预后标志物,尤其是在BRCA中。方法:为了评估AIMP2在肿瘤免疫中的作用,我们使用癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)和癌症细胞系百科全书(CCLE)数据集进行了泛癌症多数据库分析,检查表达水平、预后、肿瘤进展和免疫微环境。此外,我们使用细胞计数试剂盒8 (CCK-8)试验、transwell试验和western blot分析研究了AIMP2对乳腺癌(BRCA)增殖和迁移的影响。目的:在泛肿瘤数据库中评价AIMP2在肿瘤免疫中的作用。结果:与正常组织相比,AIMP2在24种肿瘤组织中过表达,并与4种肿瘤分期相关。生存分析表明,AIMP2表达与某些癌症患者的总生存期(OS)密切相关,在5种癌症类型中,AIMP2高表达与预后较差相关。结论:sirna介导的AIMP2敲低最终抑制了BRCA细胞的体外增殖和迁移。总之,我们的泛癌症分析表明,AIMP2可能在肿瘤免疫中发挥关键作用,并可能作为潜在的预后标志物,特别是在BRCA中。结论:在泛癌分析中发现AIMP2存在差异表达,可能在肿瘤免疫中发挥重要作用,有望成为潜在的肿瘤预后标志物,尤其是在BRCA中。其他:-
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引用次数: 0
Unraveling the Concealed Transcriptomic Landscape of PTEN in Human Malignancies 揭示PTEN在人类恶性肿瘤中隐藏的转录组学景观
4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-25 DOI: 10.2174/0113892029265367231013113304
Michaela A. Boti, Panagiotis G. Adamopoulos, Dido Vassilacopoulou, Andreas Scorilas
Background: Phosphatase and tensin homolog, widely known as PTEN, is a major negative regulator of the PI3K/AKT/mTOR signaling pathway, involved in the regulation of a variety of important cellular processes, including cell proliferation, growth, survival, and metabolism. Since most of the molecules involved in this biological pathway have been described as key regulators in cancer, the study of the corresponding genes at several levels is crucial. Objective: Although previous studies have elucidated the physiological role of PTEN under normal conditions and its involvement in carcinogenesis and cancer progression, the transcriptional profile of PTEN has been poorly investigated. Methods: In this study, instead of conducting the “gold-standard” direct RNA sequencing that fails to detect less abundant novel mRNAs due to the decreased sequencing depth, we designed and implemented a multiplexed PTEN-targeted sequencing approach that combined both short- and longread sequencing. Results: Our study has highlighted a broad spectrum of previously unknown PTEN mRNA transcripts and assessed their expression patterns in a wide range of human cancer and non-cancer cell lines, shedding light on the involvement of PTEN in cell cycle dysregulation and thus tumor development. Conclusion: The identification of the described novel PTEN splice variants could have significant implications for understanding PTEN regulation and function, and provide new insights into PTEN biology, opening new avenues for monitoring PTEN-related diseases, including cancer.
背景:磷酸酶和紧张素同源物,被广泛称为PTEN,是PI3K/AKT/mTOR信号通路的主要负调控因子,参与调节多种重要的细胞过程,包括细胞增殖、生长、存活和代谢。由于参与这一生物途径的大多数分子已被描述为癌症的关键调节因子,因此在几个水平上对相应基因的研究至关重要。目的:虽然以往的研究已经阐明了PTEN在正常情况下的生理作用及其在癌变和癌症进展中的作用,但对PTEN的转录谱的研究却很少。方法:在本研究中,我们设计并实现了一种结合短链和长链测序的多路pten靶向测序方法,而不是进行“金标准”的直接RNA测序,因为测序深度降低而无法检测到较少的新mrna。结果:我们的研究强调了以前未知的PTEN mRNA转录物的广谱,并评估了它们在广泛的人类癌症和非癌症细胞系中的表达模式,揭示了PTEN在细胞周期失调和肿瘤发展中的作用。结论:发现新的PTEN剪接变异可能对理解PTEN的调控和功能具有重要意义,并为PTEN生物学提供新的见解,为监测包括癌症在内的PTEN相关疾病开辟新的途径。
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引用次数: 0
Complete Chloroplast Genomes of Pterodon emarginatus Vogel and Pterodon pubescens Benth: Comparative and Phylogenetic Analyses 狭边翼龙与短毛翼龙叶绿体全基因组的比较与系统发育分析
4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-25 DOI: 10.2174/0113892029244147231016050434
Juliana Borges Pereira Brito, Adriana Maria Antunes, Ramilla dos Santos Braga Ferreira, Mariana Pires de Campos Telles, Cíntia Pelegrineti Targueta de Azevedo Brito, Thannya Nascimento Soares
Background: The species Pterodon emarginatus and P. pubescens, popularly known as white sucupira or faveira, are native to the Cerrado biome and have the potential for medicinal use and reforestation. They are sister species with evolutionary proximity. Objective: The species Pterodon emarginatus and P. pubescens, popularly known as white sucupira or faveira, are native to the Cerrado biome and have the potential for medicinal use and reforestation. They are sister species with evolutionary proximity. Methods: The chloroplast genomes of P. emarginatus and P. pubescens were sequenced on the Illumina MiSeq platform. The genomes were assembled based on the de novo strategy. We performed the annotation of the genes and the repetitive regions of the genomes. The nucleotide diversity and phylogenetic relationships were analyzed using the gene sequences of these species and others of the Leguminosae family, whose genomes are available in databases. Results: The complete chloroplast genome of P. emarginatus is 159,877 bp, and that of P. pubescens is 159,873 bp. The genomes of both species have circular and quadripartite structures. A total of 127 genes were predicted in both species, including 110 single-copy genes and 17 duplicated genes in the inverted regions. 141 microsatellite regions were identified in P. emarginatus and 140 in P. pubescens. The nucleotide diversity estimates of the gene regions in twenty-one species of the Leguminosae family were 0.062 in LSC, 0.086 in SSC, and 0.036 in IR. The phylogenetic analysis demonstrated the proximity between the genera Pterodon and Dipteryx, both from the clade Dipterygeae. Ten pairs of primers with potential for the development of molecular markers were designed. Conclusion: The genetic information obtained on the chloroplast genomes of P. emarginatus and P. pubescens presented here reinforces the similarity and evolutionary proximity between these species, with a similarity percentage of 99.8%.
背景:该物种翼虎(terodon emarginatus)和P. pubescens,俗称白色sucupira或faveira,原产于塞拉多生物群系,具有药用和重新造林的潜力。它们是进化上接近的姐妹物种。目的:该物种翼虎(terodon emarginatus)和P. pubescens,俗称白色sucupira或faveira,原产于塞拉多生物群落,具有药用和重新造林的潜力。它们是进化上接近的姐妹物种。方法:在Illumina MiSeq平台上对麻豆和毛毛豆的叶绿体基因组进行测序。基因组是基于de novo策略组装的。我们对基因和基因组的重复区域进行了注释。利用这些物种和其他豆科植物的基因序列分析了它们的核苷酸多样性和系统发育关系。结果:油松和短毛松叶绿体全基因组分别为159,877 bp和159,873 bp。这两个物种的基因组都具有环状和四分体结构。两个物种共预测127个基因,其中110个为单拷贝基因,17个为倒置区重复基因。微卫星区分别为微卫星区141个、微卫星区140个。21种豆科植物LSC、SSC和IR基因区核苷酸多样性分别为0.062、0.086和0.036。系统发育分析表明,翼龙属与双翅鸟属相近,均属于双翅目分支。设计了10对具有开发分子标记潜力的引物。结论:本文所获得的麻豆和毛毛豆叶绿体基因组遗传信息强化了这两个物种之间的相似性和进化接近性,相似率为99.8%。
{"title":"Complete Chloroplast Genomes of Pterodon emarginatus Vogel and Pterodon pubescens Benth: Comparative and Phylogenetic Analyses","authors":"Juliana Borges Pereira Brito, Adriana Maria Antunes, Ramilla dos Santos Braga Ferreira, Mariana Pires de Campos Telles, Cíntia Pelegrineti Targueta de Azevedo Brito, Thannya Nascimento Soares","doi":"10.2174/0113892029244147231016050434","DOIUrl":"https://doi.org/10.2174/0113892029244147231016050434","url":null,"abstract":"Background: The species Pterodon emarginatus and P. pubescens, popularly known as white sucupira or faveira, are native to the Cerrado biome and have the potential for medicinal use and reforestation. They are sister species with evolutionary proximity. Objective: The species Pterodon emarginatus and P. pubescens, popularly known as white sucupira or faveira, are native to the Cerrado biome and have the potential for medicinal use and reforestation. They are sister species with evolutionary proximity. Methods: The chloroplast genomes of P. emarginatus and P. pubescens were sequenced on the Illumina MiSeq platform. The genomes were assembled based on the de novo strategy. We performed the annotation of the genes and the repetitive regions of the genomes. The nucleotide diversity and phylogenetic relationships were analyzed using the gene sequences of these species and others of the Leguminosae family, whose genomes are available in databases. Results: The complete chloroplast genome of P. emarginatus is 159,877 bp, and that of P. pubescens is 159,873 bp. The genomes of both species have circular and quadripartite structures. A total of 127 genes were predicted in both species, including 110 single-copy genes and 17 duplicated genes in the inverted regions. 141 microsatellite regions were identified in P. emarginatus and 140 in P. pubescens. The nucleotide diversity estimates of the gene regions in twenty-one species of the Leguminosae family were 0.062 in LSC, 0.086 in SSC, and 0.036 in IR. The phylogenetic analysis demonstrated the proximity between the genera Pterodon and Dipteryx, both from the clade Dipterygeae. Ten pairs of primers with potential for the development of molecular markers were designed. Conclusion: The genetic information obtained on the chloroplast genomes of P. emarginatus and P. pubescens presented here reinforces the similarity and evolutionary proximity between these species, with a similarity percentage of 99.8%.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135218842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genome Sequencing and Organization of Three Geographically Different Isolates of Nucleopolyhedrovirus from the Gypsy Moth Reveal Significant Genomic Differences 舞毒蛾核多角体病毒三个地理上不同分离株的基因组测序和组织揭示了显著的基因组差异
4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-10-25 DOI: 10.2174/0113892029249830231014163829
Donus Gencer, Cihan Inan, Zeynep Bayramoglu, Remziye Nalcacioglu, Feifei Yin, Zheng Zhu, Jun Wang, Zhihong Hu, Lillian Pavlik, Basil Arif, Zihni Demirbag, Ismail Demir
Background: The gypsy moth (Lymantria dispar L., Lepidoptera: Erebidae) is a worldwide pest of trees and forests. Lymantria dispar nucleopolyhedrovirus (LdMNPV) belongs to the Baculoviridae family and is an insect virus specific to gypsy moth larvae. In this study, we describe the complete genome sequences of three geographically diverse isolates, H2 (China), J2 (Japan), and T3 (Turkey), of Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV). Method: The genomes of isolates H2, J2, and T3 were subjected to shotgun pyrosequencing using Roche 454 FLX and assembled using Roche GS De Novo Assembler. Comparative analysis of all isolates was performed using bioinformatics methods. Results: The genomes of LdMNPV-H2, J2, and T3 were 164,746, 162,249, and 162,614 bp in size, had GC content of 57.25%, 57.30%, and 57.46%, and contained 162, 165, and 164 putative open reading frames (ORFs ≥ 150 nt), respectively. Comparison between the reference genome LdMNPV-5/6 (AF081810) and the genomes of LdMNPV-H2, J2, and T3 revealed differences in gene content. Compared with LdMNPV-5/6, ORF5, 6, 8, 10, 31, and 67 were absent in LdMNPVH2, ORF5, 13, and 66 were absent in LdMNPV-J2, and ORF10, 13, 31, and 67 were absent in LdMNPV-T3. In addition, the gene encoding the mucin-like protein (ORF4) was split into two parts in isolates H2 and T3 and designated ORF4a and ORF4b. Phylogenetic analysis grouped isolates H2 and J2 in a different cluster than isolate T3, which is more closely related to the Turkish and Polish isolates. In addition, H2 was found to be closely related to a South Korean LdMNPV isolate. Conclusion: This study provided a more detailed overview of the relationships between different geographic LdMNPV isolates. The results showed remarkable differences between groups at the genome level.
背景:舞毒蛾(Lymantria dispar L.,鳞翅目:舞毒蛾科)是一种世界性的树木和森林害虫。异毒蛾核多角体病毒(Lymantria dispar nuclear polyhedrovirus, LdMNPV)属于杆状病毒科,是舞毒蛾幼虫特有的一种昆虫病毒。在这项研究中,我们描述了三个地理上不同的Lymantria dispar multiple nuclear polyhedrovirus (LdMNPV)分离株H2(中国)、J2(日本)和T3(土耳其)的全基因组序列。方法:分离株H2、J2和T3基因组采用Roche 454 FLX进行鸟枪法pyrosequencing,并用Roche GS De Novo Assembler进行组装。采用生物信息学方法对所有分离株进行比较分析。结果:LdMNPV-H2、J2和T3基因组大小分别为164,746、162,249和162,614 bp, GC含量分别为57.25%、57.30%和57.46%,包含162、165和164个推定开放阅读框(orf≥150 nt)。将参考基因组LdMNPV-5/6 (AF081810)与LdMNPV-H2、J2和T3基因组进行比较,发现基因含量存在差异。与LdMNPV-5/6相比,LdMNPVH2中缺失ORF5、6、8、10、31和67,LdMNPV-J2中缺失ORF5、13和66,LdMNPV-T3中缺失ORF10、13、31和67。另外,在分离株H2和T3中,编码黏蛋白样蛋白(mucin-like protein, ORF4)的基因被分成两部分,分别命名为ORF4a和ORF4b。分离株H2和J2与分离株T3在不同的聚类中,其与土耳其和波兰分离株的亲缘关系更近。此外,H2被发现与韩国的LdMNPV分离株密切相关。结论:本研究对不同地理LdMNPV分离株之间的关系提供了更详细的概述。结果显示,在基因组水平上,两组之间存在显著差异。
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引用次数: 0
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 Q2 Biochemistry, Genetics and 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。
{"title":"Using Chaos-Game-Representation for Analysing the SARS-CoV-2 Lineages, Newly Emerging Strains and Recombinants","authors":"Amarinder Singh Thind, Somdatta Sinha","doi":"10.2174/0113892029264990231013112156","DOIUrl":"https://doi.org/10.2174/0113892029264990231013112156","url":null,"abstract":"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.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135315919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Current Genomics
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