肠道噬菌体组生物信息学分析方法的研究进展

噬菌体是感染细菌的病毒,广泛存在于各类环境中。由于传统实验研究的局限性及噬菌体基因的特异性,导致对肠道噬菌体的研究很少。随着宏基因组测序技术的发展和各种生物信息分析软件的开发,可以通过噬菌体组学,加深对肠道噬菌体的认识。噬菌体组分析流程主要包括原始数据质量控制和预处理,病毒基因组序列的拼接组装,类病毒颗粒的筛选和系统分类注释以及进化分析和预测相应宿主细菌。本文对噬菌体组分析流程和其中所需要的常用生物信息分析工具和数据库进行详细的介绍,可以为肠道噬菌体研究以及相关的研究人员提供参考。     

中国植物标本馆数字化发展的缩影——江苏省中国科学院植物研究所标本馆(NAS)

江苏省中国科学院植物研究所标本馆(NAS)是中国最早的植物标本馆之一,也是国内最早开展植物标本数字化的标本馆,其标本数字化发展经历了4个阶段: 20世纪80年代后期尝试的标本文字信息数字化的起步阶段; 20世纪90年代末的标本图像数字化和文字信息数字化规范阶段; 2004年以后的标本批量数字化与信息网络共享快速发展阶段; 2018年后的标本数字化信息维护与优化阶段。这一过程集中代表和反映了中国植物标本数字化的发展历程。此外,近年来开始了发掘和利用江苏植物标本的数字化信息工作,包括建设江苏省级数字植物标本馆、开发江苏省维管植物标本时空分布可视化系统、开展标本采集-入库过程数字化等。今后,将不断深化标本数字化的工作,以期形成有NAS特色的数字化植物标本馆。     

MolMod – an open access database of force fields for molecular simulations of fluids

The MolMod database is presented, which is openly accessible at http://molmod.boltzmann-zuse.de and contains intermolecular force fields for over 150 pure fluids at present. It was developed and is maintained by the Boltzmann-Zuse Society for Computational Molecular Engineering (BZS). The set of molecular models in the MolMod database provides a coherent framework for molecular simulations of fluids. The molecular models in the MolMod database consist of Lennard-Jones interaction sites, point charges, and point dipoles and quadrupoles, which can be equivalently represented by multiple point charges. The force fields can be exported as input files for the simulation programmes ms2 and ls1 mardyn, GROMACS, and LAMMPS. To characterise the semantics associated with the numerical database content, a force field nomenclature is introduced that can also be used in other contexts in materials modelling at the atomistic and mesoscopic levels. The models of the pure substances that are included in the database were generally optimised such as to yield good representations of experimental data of the vapour–liquid equilibrium with a focus on the vapour pressure and the saturated liquid density. In many cases, the models also yield good predictions of caloric, transport, and interfacial properties of the pure fluids. For all models, references to the original works in which they were developed are provided. The models can be used straightforwardly for predictions of properties of fluid mixtures using established combination rules. Input errors are a major source of errors in simulations. The MolMod database contributes to reducing such errors.     

基于PDB数据库的三个RNA二级结构预测软件评估

随着21世纪分子生物学研究的蓬勃发展,RNA二级结构预测成为其中一项重要内容。由于RNA二级结构预测的准确性最为关键,因此寻找高精度且易操作的二级结构预测工具显得非常重要。本文选取三种简单且易操作的二级结构预测软件,先基于PDB数据库收录的318个RNA发夹序列进行二级结构预测,进而通过比较预测结果与实验测定结果进行软件预测性能评估。比较结果显示,RNAstructure为三个软件中性能最优的RNA二级结构预测软件。     

生物信息学数据库研究文献引文与热点分析

以Web of Science为数据源,简要概括生物信息学数据库研究的发展趋势。利用Cite Space可视化工具展现生物信息学数据库研究的知识基础和研究热点图谱,为开展生物信息学数据库领域相关的理论研究和实践活动提供借鉴,以便推动生物信息学数据库研究的发展。研究表明：1990年Altschul SF发表的＂局部比对搜索工具——BLAST＂是生物信息学数据库研究的重要知识来源文献;热点主题集中在序列库、基因组数据库、分类数据库、蛋白质数据库、数据库更新、集成系统等。     

基于设计模板的BRD-like折叠类型综合分类方法

蛋白质折叠规律研究是生命科学重大前沿课题,折叠类型分类是蛋白质折叠研究的基础。构建BRD-like折叠类型模板数据库,建立了基于多模板的综合分类方法,并用于该折叠类型的分类。对实验集的12 117个样本进行检验,结果的敏感性、特异性分别为0.923和0.997,MCC值为0.72;对独立检验集2 260个样本的检验,结果发现:敏感性、特异性分别为0.941和0.998,MCC值为0.86.结果表明:基于多模板的综合分类方法可用于蛋白质折叠类型分类。     

SCOP数据库蛋白质折叠类型的自动分类分析

蛋白质折叠规律研究是生命科学领域重要的前沿课题之一,蛋白质折叠类型分类是折叠规律研究的基础。本研究以SCOP数据库的蛋白质折叠类型分类为基础、以Astral SCOPe 2.05数据库中相似性小于40%的α、β、α+β及α/β类所属的折叠类型为研究对象,完成了989种蛋白质折叠类型的模板构建并形成模板数据库;基于折叠类型设计模板建立了蛋白质折叠类型分类方法,实现了SCOP数据库蛋白质折叠类型的自动化分类。家族模板自洽性检验与独立性检验所得的敏感性、特异性以及MCC的平均值分别为:95.00%、99.99%、0.94与90.00%、99.97%、0.92,折叠类型模板自洽性检验与独立性检验所得的敏感性、特异性以及MCC的平均值分别为:93.71%、99.97%、0.91与86.00%、99.93%、0.87。结果表明:模板设计合理,可有效用于对已知结构的蛋白质进行分类。     

Molecular docking analysis of Clostridium perfringens beta toxin model with potential inhibitors from the ZINC database

Beta toxin from Clostridium perfringens after being secreted in gut is capable of causing necrotic enteritis in humans and several other animal species and does not respond to routinely used antibiotics. Therefore, there is a need to design an effective inhibitor for the Clostridium perfringens beta toxin (CPB) using cutting edge drug discovery technologies. Hence, potential CPB inhibitors were identified using computer aided screening of compounds from the ZINC database. Further, we document the molecular docking analysis of Clostridium perfringens beta toxin model (that revealed 4 binding pockets, A-D) with the identified potential inhibitors. We show that ZINC291192 [N-[(1-methylindol-3-yl) methyl eneamino]-7,10-dioxabicyclo[4.4.0]deca-2,4,11-triene-8- carboxamide] has optimal binding features with calculated binding energy of -10.38 kcal/mol and inhibition constant of 24.76 nM for further consideration.     

The mRNA–miRNA–lncRNA Regulatory Network and Factors Associated with Prognosis Prediction of Hepatocellular Carcinoma

The aim of this study was to identify novel prognostic mRNA and microRNA (miRNA) biomarkers for hepatocellular carcinoma (HCC) using methods in systems biology. Differentially expressed mRNAs, miRNAs, and long non-coding RNAs (lncRNAs) were compared between HCC tumor tissues and normal liver tissues in The Cancer Genome Atlas (TCGA) database. Subsequently, a prognosis-associated mRNA co-expression network, an mRNA–miRNA regulatory network, and an mRNA–miRNA–lncRNA regulatory network were constructed to identify prognostic biomarkers for HCC through Cox survival analysis. Seven prognosis-associated mRNA co-expression modules were obtained by analyzing these differentially expressed mRNAs. An expression module including 120 mRNAs was significantly correlated with HCC patient survival. Combined with patient survival data, several mRNAs and miRNAs, including CHST4, SLC22A8, STC2, hsa-miR-326, and hsa-miR-21 were identified from the network to predict HCC patient prognosis. Clinical significance was investigated using tissue microarray analysis of samples from 258 patients with HCC. Functional annotation of hsa-miR-326 and hsa-miR-21-5p indicated specific associations with several cancer-related pathways. The present study provides a bioinformatics method for biomarker screening, leading to the identification of an integrated mRNA–miRNA–lncRNA regulatory network and their co-expression patterns in relation to predicting HCC patient survival.     

Metabolic Enzyme Alterations and Astrocyte Dysfunction in a Murine Model of Alexander Disease With Severe Reactive Gliosis

Alexander disease (AxD) is a rare and fatal neurodegenerative disorder caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). In this report, a mouse model of AxD (GFAP^Tg;Gfap^+/R236H) was analyzed that contains a heterozygous R236H point mutation in murine Gfap as well as a transgene with a GFAP promoter to overexpress human GFAP. Using label-free quantitative proteomic comparisons of brain tissue from GFAP^Tg;Gfap^+/R236H versus wild-type mice confirmed upregulation of the glutathione metabolism pathway and indicated proteins were elevated in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which had not been reported previously in AxD. Relative protein-level differences were confirmed by a targeted proteomics assay, including proteins related to astrocytes and oligodendrocytes. Of particular interest was the decreased level of the oligodendrocyte protein, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (Ugt8), since Ugt8-deficient mice exhibit a phenotype similar to GFAP^Tg;Gfap^+/R236H mice (e.g., tremors, ataxia, hind-limb paralysis). In addition, decreased levels of myelin-associated proteins were found in the GFAP^Tg;Gfap^+/R236H mice, consistent with the role of Ugt8 in myelin synthesis. Fabp7 upregulation in GFAP^Tg;Gfap^+/R236H mice was also selected for further investigation due to its uncharacterized association to AxD, critical function in astrocyte proliferation, and functional ability to inhibit the anti-inflammatory PPAR signaling pathway in models of amyotrophic lateral sclerosis (ALS). Within Gfap⁺ astrocytes, Fabp7 was markedly increased in the hippocampus, a brain region subjected to extensive pathology and chronic reactive gliosis in GFAP^Tg;Gfap^+/R236H mice. Last, to determine whether the findings in GFAP^Tg;Gfap^+/R236H mice are present in the human condition, AxD patient and control samples were analyzed by Western blot, which indicated that Type I AxD patients have a significant fourfold upregulation of FABP7. However, immunohistochemistry analysis showed that UGT8 accumulates in AxD patient subpial brain regions where abundant amounts of Rosenthal fibers are located, which was not observed in the GFAP^Tg;Gfap^+/R236H mice.