黏着斑激酶生物信息学分析

从生物信息学的角度对黏着斑激酶进行分析,为进一步研究其高级结构及探寻黏着斑激酶的潜在功能提供理论数据.用生物信息学方法对已在GenBank上注册的人、牛、鸡、非洲蟾蜍、斑马鱼等动物黏着斑激酶基因的核苷酸序列以及推导的氨基酸序列、组成成分、氨基酸翻译后修饰、信号肽、跨膜拓朴结构域、疏水性/亲水性、蛋白质二级结构以及三级结构等进行分析预测和推断.结果表明:这些动物的黏着斑激酶属于非跨膜的亲水性蛋白,α-螺旋和不规则卷曲是其蛋白质二级结构的主要结构元件,β-转角和延伸链散布在整个蛋白质中,包含三个结构域,即N末端FERM同源结构域,中部的激酶结构域和C末端富含脯氨酸的位点和FAT结构域.     

代谢组学中机器学习研究进展

以往代谢组学的综述都着眼于对其应用情况进行总结,而对机器学习方法的对比研究不多。为此,在分析讨论目前机器学习方法在代谢组学研究方面最新进展的基础上,对各种机器学习方法及在代谢组学研究上的应用效果进行了总结,给出了代谢组学研究所使用的数据源,比较了各方法的应用效果及其利弊,指出目前代谢组研究中存在的主要问题及可能的改进方案。列举了相关方法在疾病诊断、药物开发等方面的最新应用,展望了代谢组学的研究前景,以期为改进代谢组学研究中机器学习算法的研究工作提供启示和帮助。     

基于动态算法的序列分析

为了获得2009年新型甲型H1N1流感病毒与2008流感病毒的基因序列及氨基酸序列的一致性,以便对一个基因家族的生物学特征有一个简明扼要的了解,针对目前流行的新型甲型H1N1流感病毒的基因序列及其所编码的氨基酸序列,采用动态规划算法对其一级序列进行序列相似度分析,获得了2009年新型甲型H1N1流感病毒的NA和M基因片段以及2008年猪源性甲型H1N1流感病毒的相应基因片段同源性高、在有些位点发生了基因突变增添和突变缺失等重要基因信息。为此次新型甲型H1N1流感病毒的研究提供了依据。     

针对H1N1病毒的多特征siRNA设计

针对甲型流感病毒H1N1基因,从RNAi的角度出发,采用多特征融合的方法,进行siRNA预测。对2009年的46株病毒序列的PA片段进行分析,从经过序列分析所获得的众多靶序列中,采用结构分析手段对靶序列进行筛选,获得较易干扰的靶序列及设计出相应的siRNA。2009年爆发的H1N1病毒,序列保守性高,靶序列一致性高,结构保守性高。该方法可以有效选择可能的靶序列,并在此基础上进一步筛选,以获得少量较易干扰的靶序列,该方法为复杂序列siRNA的设计提供了新思路,对siRNA的优化设计有指导意义,有助于利用RNAi进行H1N1治疗的后续研究。     

Brief review:frontiers in the computational studies of gene regulations

Computational methods have greatly expanded our understanding of complex gene regulations in a systematic view. The rapid progress in molecular biology and highthroughput bio-techniques is providing new opportunities and challenges for the computational analysis of gene regulations.     

Transcriptional Profiling of Cardiac Cells Links Age-Dependent Changes in Acetyl-CoA Signaling to Chromatin Modifications

Metabolism has emerged as a regulator of core stem cell properties such as proliferation, survival, self-renewal, and multilineage potential. Metabolites serve as secondary messengers, fine-tuning signaling pathways in response to microenvironment alterations. Studies show a role for central metabolite acetyl-CoA in the regulation of chromatin state through changes in histone acetylation. Nevertheless, metabolic regulators of chromatin remodeling in cardiac cells in response to increasing biological age remains unknown. Previously, we identified novel cardiac-derived stem-like cells (CTSCs) that exhibit increased functional properties in the neonatal heart (nCTSC). These cells are linked to a unique metabolism which is altered with CTSC aging (aCTSC). Here, we present an in-depth, RNA-sequencing-based (RNA-Seq) bioinformatic with cluster analysis that details a distinct epigenome present in nCTSCs but not in aCTSCs. Gene Ontology (GO) and pathway enrichment reveal biological processes, including metabolism, gene regulation enriched in nCTSCs, and STRING analysis that identifies a network of genes related to acetyl-CoA that can potentially influence chromatin remodeling. Additional validation by Western blot and qRT-PCR shows increased acetyl-CoA signaling and histone acetylation in nCTSCs compared to aCTSCs. In conclusion, our data reveal that the link between metabolism and histone acetylation in cardiac cells is altered with the aging of the cardiac tissue.     

酸土脂环酸芽孢杆菌Fe-SOD基因克隆及生物信息学分析

酸土脂环酸芽孢杆菌具有嗜酸耐热的独特生理特性,从该属细菌中分离到的多种酶类都具有耐酸热稳定性,是筛选耐酸耐热酶的重要菌种资源。超氧化物歧化酶(SOD)由于具有重要的生理功能而广泛用于食品、药品及化妆品等行业。为了深入探讨酸土脂环酸芽孢杆菌SOD的分子生物学特性,本研究利用同源克隆、交错式热不对称PCR技术和生物信息学方法进行Fe-SOD基因克隆、测序及序列分析。结果表明,Fe-SOD基因(GenBank序列号:JN614998)ORF全长为606bp,编码202个氨基酸,其推测氨基酸序列与来源于酸热脂环酸芽孢杆菌DSM446的Fe-SOD(ACV58017.1)序列相似性最高,为78%。整个蛋白序列含有Fe/MnSODs家族的5个模体,SOD活性中心含有金属离子结合配基His27、His82、Asp164和His168,具有Fe/MnSODs家族典型的蛋白结构特征。酸土脂环酸芽孢杆菌Fe-SOD基因的克隆和生物信息学分析为进一步构建原核表达载体、获得生产耐酸热Fe-SOD的基因工程菌株奠定基础。     

Metabolic engineering--integrating methodologies of molecular breeding and bioprocess systems engineering

Metabolic engineering is an integrating methodology of analysis and synthesis for the improvement of flux distribution of metabolic pathways in complicated bioprocesses, which are highly multi-hierarchical systems to extend from macroscopic to microscopic levels. Recent progress in metabolic engineering methodologies to improve metabolic pathways in microorganisms was reviewed with many studies in this paper. Metabolic flux distribution was analyzed under different environmental conditions, using a metabolic reaction model. The physiological states of microorganisms were understood by interpreting metabolic flux analysis (MFA). This analysis was also used for development of process operation and control strategy. Cell capability to form a targeted product was analyzed with a metabolic reaction model and linear programming (LP). The use of a 13C-enriched carbon source and nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GCMS) analyses of intracellular and extracellular metabolites enabled determination of a metabolic flux distribution more accurately than the flux distribution determined only by the metabolic reaction model, which involves not only metabolite balances but also energy and redox balances. The comparison of metabolic flux distributions between before and after genetic modification of cells yielded information on the mechanism of regulation of metabolic flux in microorganisms. Finally, integration of bioinformatics and metabolic engineering is discussed, and cyclic modification of the complex bionetwork and process development were emphasized.     

腰果过敏蛋白Ana o 2与Ana o 3结构分析及致敏性预测

为了解腰果主要过敏蛋白的分子结构及过敏性特征,通过有机溶剂脱脂、盐析、透析、葡聚糖凝胶Sephadex G-150分离纯化得到腰果主要过敏蛋白,采用紫外分光光度计、BCA定量试剂盒、十二烷基硫酸钠聚丙烯酰胺凝胶电泳（SDS-PAGE）、蛋白质免疫印迹(Western-Blotting)等手段检测腰果过敏蛋白及评价其免疫原性;应用NCBI数据库与蛋白质谱测序分析获得腰果过敏蛋白氨基酸序列、DNA序列,结合生物信息软件DNAstar与圆二色谱（CD）谱图预测腰果过敏蛋白结构。结果表明:Ana o 2与Ana o 3为腰果主要过敏蛋白,分子量分别为33和17 kD左右,根据圆二色谱检测结果与DNAstar中的Protean程序预测分析可知,Ana o 2中α-螺旋、β-折叠区段和转角区域均存在,是致敏性较强的一种亲水性蛋白,β-转角和无规则卷曲在Ana o 2氨基酸序列中出现率总和为54%,所在区域为优势抗原表位区。Ana o 3仅有少量的 β-折叠区段和转角区域,出现率总和为12%,Ana o 3的二级结构主要为 α-螺旋结构和无规则卷曲结构,不适宜作为抗原的表位,形成过敏性表位相对较弱。本研究结果为进一步明确天然腰果主要过敏原结构并对探索腰果致敏机理提供参考。