基于“天河二号”的水产病原生物信息分析平台构建及其在水产病原分析中的应用

作为生命科学的关键组成,生物信息学已被广泛地应用于基因组学、转录组学和蛋白质组学中。然而,生物信息分析平台的构建需要高性能计算机而非普通的个人电脑,从而极大地限制了生物信息学在水产科学中的应用。本研究基于"天河二号"超级计算机,构建了水产病原生物信息分析平台。该平台由基因组与转录组测序数据分析、蛋白质结构预测和分子动力学模拟3个功能模块组成。为了验证该平台的实用性,以水生动物病原微生物为例进行了生物信息学分析。通过Blast检索、GO和Inter Pro注释,鉴定了约氏黄杆菌(Flavobacterium johnsoniae)M168株的功能基因并对其进行了注释。通过同源模建,构建了草鱼呼肠孤病毒(Grass carp reovirus,GCRV)HZ-08的5个小节段的蛋白结构模型。对嗜水气单胞菌(Aeromonas hydrophila)外膜蛋白A进行了分子动力学模拟,并观察了平衡过程中系统温度、总能量、均方根偏差和环区构象的变化。以上结果均显示本研究成功建立了在"天河二号"超级计算机上运行的水产病原生物信息分析平台。此项研究将为其他学科生物信息分析平台的构建提供思路和线索。     

新医学是解决人类健康问题的真正钥匙——需“精准”理解奥巴马的“精准医学计划”

2015年年初,美国总统奥巴马在国情咨文中提出了一个预算2.15亿美元的“精准医学计划”,希望以此“引领一个医学时代”。新闻一经发布,“精准医学”立刻成为了媒体和百姓嘴边的热词,受此影响国内亦有不少人士纷纷为美国总统的这一计划点“赞”。有人用“医学革命”来形容它,有人用“开创性”来抬高它,还有一个传闻,受奥巴马“精准医学计划”的影响,中国将在15年内投入600亿元人民币启动并发展中国版的“精准医学计划”。对此,有人提出了质疑,美国版精准医学计划是否符合中国国情?是否存在“水土不服”的可能?直接套用美国总统的智慧能否解决具有中国特色的实际问题?争论由此引发一个让人思考的问题,究竟什么才是现代医学的核心?在盲目堆钱的行动前,我们确实有必要从科学和临床应用的角度来探讨和思考一下现代医学的发展方向。 为了能“精准”地看到问题的实质,我将从当下时髦并且相关的词汇谈起,通过梳理,期待找出解决人类健康问题的真正钥匙。     

“地衣”词考

本文考证了中国先秦时期到清末古籍中对“地衣”的解释;其中有共生学意义的“地衣”一词,是在清代李善兰的《植物学》一书中被提出的。     

我国“干细胞及转化研究”重点专项的组织实施及思考

“十三五”期间,我国设立了国家重点研发计划“干细胞及转化研究”重点专项(以下简称“专项”)。通过五年实施,专项取得了显著进展。通过对专项立项和实施情况的回顾,总结管理中的经验和不足,为“十四五”干细胞研究部署提出相关建议,以进一步增强我国干细胞及转化研究的核心竞争力,加快推进干细胞研究成果惠及人民健康。     

“2020年后全球生物多样性框架”的谈判进展以及对我国的建议

“2020年后全球生物多样性框架”是当前《生物多样性公约》谈判的焦点议题, 了解该议题的谈判进展将对我国顺利举办第15次缔约方大会(COP15)产生积极的作用。本文在梳理相关谈判进程的基础上, 分析了各方主要观点, 并就我国应对国际谈判并以东道国身份推进该框架的制定进程提出了建议。各方对制定框架的时间表、程序和一般性原则形成了较为一致的共识, 认为应尽快确定“2020年后全球生物多样性框架”的程序及时间表, 基于“爱知生物多样性目标”的执行经验、科学结论和和广泛的信息来源, 与“可持续发展目标”及其他国际进程衔接, 重视利用情景和模型, 并支持更多利益相关方参与制定过程。同时, 各方认为框架应主要包括土地利用、保护和恢复生物多样性的措施、解决生物多样性丧失的根本原因、主流化、能力建设、资源调动、国家承诺等要素。为应对国际谈判, 建议我国在《公约》谈判会议中适时提出以下观点: 重视实现可持续利用相关的目标; 提升评估指标体系的合理性; 科学制定措施。此外, 建议我国采取以下措施积极推进框架制定进程: 充分利用国际高级别会议, 提升政治重视程度; 积极与主要国际进程协作, 推进该框架深入讨论; 重视调动利益相关方积极性。     

中国与“一带一路”参与国家抗击新冠肺炎疫情的国际科技合作现状与展望

2019年底暴发并席卷全球的新型冠状病毒肺炎疫情已经成为需要世界各国共同努力克服的全球重大卫生安全挑战。当前,中国已基本控制国内新冠肺炎疫情,并在疫情相关科学研究及公共卫生产品研发方面取得重大进展,同时加强了与“一带一路”参与国家开展国际科技合作。对中国与“一带一路”参与国家抗击新冠肺炎疫情的基础研究合作、国际科技合作项目等方面进行梳理,可以看到:中国与“一带一路”参与国家形成了领域交叉、节点多样的复杂合作网络,并主要与东南亚、中东欧和西亚各国合作密切;中国与“一带一路”参与国家的科研机构已在防控、流行病学和治疗等领域展开了大量实质研究,合作关系更偏向援助型合作。未来应加强与“一带一路”参与国家的生物技术产业合作与技术转移,发挥“一带一路”区域支点国家的示范效应等方面构建与“一带一路”参与国家更丰富、紧密、务实的科技合作关系。     

“自然对人类的贡献”的实现、发展趋势和启示

生物多样性和生态系统服务政府间科学政策平台(IPBES)的目标是加强科学政策对生物多样性和生态系统服务的影响。为了更好地理解和展示IPBES目标的基本要素及其相互关系, 在千年生态系统评估(MA)的基础上, IPBES融合多种知识体系, 不断完善、创新, 逐步形成了以“自然对人类的贡献” (NCP)为核心的概念框架。本文首先梳理了NCP的发展历程, 论述了NCP与生态系统服务的关系, 指出两者均关注人类福祉, 但与生态系统服务不同的是, NCP涵盖了自然对人类生活的消极影响, 强调社会文化因素、传统知识和土著居民的地位以及人与自然共同作用的重要性。其次, 本文阐述了人与自然共同实现NCP进而影响人类良好生活质量的机制, 并分析了NCP大幅下降的全球趋势, 提出世界各国应不断推动生物多样性保护主流化, 增加国际交流与合作, 致力实现“人与自然和谐共生”的2050年愿景。最后, 本文讨论了NCP在IPBES评估和《生物多样性公约》磋商谈判中的应用前景, 为今后NCP理论研究和实践提供科学支持。     

“教学、实践、科研、临床”四位一体的医学遗传学教学体系建设探索与实践

医学遗传学课程介于基础医学和临床医学之间,是一门应用性很强的学科,在现代医学教育体系中有着重要的地位。教学团队在多年的医学遗传学教学实践中,在建设省级精品课程的过程中,构建了“教学、实践、科研、临床”四位一体的医学遗传学教学体系,主要内容包括“课堂教学、社会实践、科学研究、临床应用”四者之间相互渗透、相互补充、相互促进,以课堂教学为基础,用社会实践补充教学,科学研究提升教学,临床应用促进教学。“四位一体”教学体系为基础课程与临床课程的有机整合探索了一条切实可行的路子。实施几年来,课程建设收到了良好效果,学科团队科研水平、社会声誉、医疗服务能力也有明显提高。     

“整合物种概念”和“分化路上的物种”

已有的各个物种概念对物种的认识类似盲人摸象, 只包含了物种的某一个方面; 而一个分化后期的成熟物种应涵盖了所有的物种概念。但是, 尚未到达分化后期的物种往往又已开始新一轮的物种分化; 自然中存在的多数“物种”处于分化路上。这种循环往复连续分化产生的物种, 存在种间生殖隔离不彻底、基因流频繁发生、网状进化突出等现象。此外, 对于不同的物种对, 最早开始分化的基因以及不同物种概念所要求的条件的分化顺序不是统一的, 而是随机的。定义一个适合所有“分化路上的物种”概念存在较大困难。但是, 应采用尽可能多的物种概念来界定分化路上的物种、发表新种和进行分类处理; 也应承认种间可能广泛存在不完全的生殖隔离和有限的基因流, 即有不属于两个物种群体的杂交或回交个体的存在。这样划分的物种比只依据一个物种概念认定的物种具有更高的客观性和科学性。     

用青春追逐心中的科研梦想——记第19届“中国青年五四奖章”获得者于黎博士

2015年5月在“五四青年节”来临之际,共青团中央、全国青联联合授予了25 名同志“第19届中国青年五四奖章”的荣誉称号。在这25名获奖者中,我刊编委来自云南大学的于黎研究员作为唯一的女性科学家代表令人瞩目。作为中国优秀青年最高荣誉的获得者,于黎博士无疑成为科研界青年学子学习的又一个榜样。她是如何走上科研的道路,又是如何追逐自己的科研梦想的?带着这些问题,我们一起走进她的世界。     

BDCGrid:基于Globus的生物信息高性能计算网格系统

随着分子生物信息数据量高速增长,生物信息学面临着大规模、高通量、密集型计算的巨大挑战。为有效利用计算机资源,缩短高通量生物信息计算程序执行时间,我们基于Globus Toolkit网格中间件,实现了一个支持高通量生物数据计算的网格系统(Biological Data Computing Grid,简称BDCGrid)。BDCGrid计算网格系统模型可以有效整合中小型生物信息学实验室计算机资源,大大缩短高通量生物信息计算程序执行时间,为相关研究人员利用现有计算机资源处理大规模、高通量生物信息计算任务提供一种新的途径。     

环境微生物宏基因组学研究中的生物信息学方法

高通量测序技术的发展促进了组学技术在环境微生物研究中的广泛应用,而宏基因组学是目前最为关键和成熟的组学方法。生物信息学在微生物宏基因组学研究中具有至关重要的作用。它贯穿于宏基因组学的数据收集和存储、数据处理和分析等各个阶段,既是宏基因组学推广的最大瓶颈,也是目前宏基因组学研究发展的关键所在。本文主要介绍和归纳了目前在高通量宏基因组测序中常用的生物信息学分析平台及其重要的信息分析工具。未来几年之内,测序成本的下降和测序深度的增加将进一步增大宏基因组学研究在数据存储、数据处理和数据挖掘层面的难度,因此相应生物信息学技术与方法的研究和发展也势在必行。近期内我们应该首先加强基础性分析和存储平台的建设以方便普通环境微生物研究者使用,同时针对目前生物信息分析的瓶颈步骤和关键任务重点突破,逐步发展。     

BioManager: the use of a bioinformatics web application as a teaching tool in undergraduate bioinformatics training

The completion of the human genome project, and other genome sequencing projects, has spearheaded the emergence of the field of bioinformatics. Using computer programs to analyse DNA and protein information has become an important area of life science research and development. While it is not necessary for most life science researchers to develop specialist bioinformatic skills (including software development), basic skills in the application of common bioinformatics software and the effective interpretation of results are increasingly required by all life science researchers. Training in bioinformatics is increasingly occurring within the university system as part of existing undergraduate science and specialist degrees. One difficulty in bioinformatics education is the sheer number of software programs required in order to provide a thorough grounding in the subject to the student. Teaching requires either a well-maintained internal server with all the required software, properly interfacing with student terminals, and with sufficient capacity to handle multiple simultaneous requests, or it requires the individual installation and maintenance of every piece of software on each computer. In both cases, there are difficult issues regarding site maintenance and accessibility. In this article, we discuss the use of BioManager, a web-based bioinformatics application integrating a variety of common bioinformatics tools, for teaching, including its role as the main bioinformatics training tool in some Australian and international universities. We discuss some of the issues with using a bioinformatics resource primarily created for research in an undergraduate teaching environment.     

Advances in biomolecular simulations: methodology and recent applications

Molecular dynamics simulations are widely used today to tackle problems in biochemistry and molecular biology. In the 25 years since the first simulation of a protein computers have become faster by many orders of magnitude, algorithms and force fields have been improved, and simulations can now be applied to very large systems, such as protein-nucleic acid complexes and multimeric proteins in aqueous solution. In this review we give a general background about molecular dynamics simulations, and then focus on some recent technical advances, with applications to biologically relevant problems.     

Using molecular dynamics simulations on crambin to evaluate the suitability of different continuum dielectric and hydrogen atom models for protein simulations

Molecular dynamics simulations of enzymes with enough explicit waters of solvation to realistically account for solute-solvent interactions can burden the computational resources required to perform the simulation by more than two orders of magnitude. Since enzyme simulations even with an implicit solvation model can be imposing for a supercomputer, it is important to assess the suitability of different continuum dielectric models for protein simulations. A series of 100-picosecond molecular dynamics simulations were performed on the X-ray crystal structure of the protein crambin to examine how well computed structures, obtained using seven continuum dielectric and two hydrogen atom models, agreed with the X-ray structure. The best level of agreement between computed and experimental structures was obtained using a constant dielectric of 2 and the all-hydrogen model. Continuum dielectric models of 1, 1r, and 2r also led to computed structures in reasonably good agreement with the X-ray structure. In all cases, the all-hydrogen model gave better agreement than the united atom model, although, in one case, the difference was not significant. Dielectric models of 4, 80, and 4r with either hydrogen model yielded significantly poorer fits. It is especially noteworthy that the observed trends did not semiquantitatively converge until about 50 picoseconds into the simulations, suggesting that validation studies for protein calculations based on energy minimizations or short simulations should be viewed with caution.     

嗜吞噬无形体Msp2蛋白与宿主互作靶蛋白筛选及生物信息分析

目的:筛选与嗜吞噬无形体Msp2蛋白互作的THP-1细胞靶蛋白,有助于理解病原体侵袭宿主的分子机理。方法:PCR获得无形体msp2基因克隆到pGBKT7载体上构建诱饵质粒并转化酵母菌株Y2HGold,营养缺陷培养基及蓝白斑实验验证诱饵质粒是否有自激活、毒性;抽提THP-1总RNA,经反转录、Long-distance PCR、同源重组等构建到pGADT7-Rec载体上并转化酵母菌株Y187,鉴定cDNA文库质量;酵母双杂交筛选与无形体Msp2互作的宿主细胞靶蛋白,生物信息学分析蛋白互作可能导致的信号通路变化。结果:成功构建诱饵质粒;cDNA文库容量达4×106克隆,插入片段大小100-3000 bp,且无污染;酵母双杂交获得宿主靶蛋白7个,分别是NADH脱氢酶(泛醌)1α亚体13(NDUFA13)、锌指蛋白36, C3H样2(ZFP36L2)、核糖体蛋白11(RPL11)、前胸腺素α(PTMA)、C19orf10、组织蛋白酶G(CTSG)、核糖体蛋白S25(RPS25);生物信息学分析,互作的宿主靶蛋白主要参与细胞增殖、细胞凋亡、溶酶体成熟及其它一些信号通路等生物学过程。结论:应用酵母双杂交系统初步筛选出与嗜吞噬细胞无形体表面蛋白Msp2互作的宿主细胞靶蛋白,并利用生物信息学初步分析了其参与的生物学过程,为进一步研究病原菌胞内生存分子机制奠定了基础。     

海洋创伤弧菌反式翻译系统关键因子SmpB基因的克隆及原核表达

创伤弧菌(Vibrio vulnificus)是一种重要的"人鱼共患病"病原菌。通过克隆创伤弧菌反式翻译系统核心因子小蛋白B(Small molecular protein B,SmpB)基因,构建携带目的基因的原核表达质粒,为后续研究SmpB蛋白的互作网络、SmpB蛋白与创伤弧菌致病性之间的关系并以此开发新型的抑菌靶标奠定基础。使用LiCl沉淀法提取创伤弧菌基因组DNA,以它为模板,PCR扩增目的基因,并构建到pET-28a原核表达载体上测序鉴定后对SmpB序列进行生物信息学分析,将正确的重组质粒转化E.coli BL21(DE3),IPTG诱导表达,SDS-PAGE凝胶电泳鉴定。结果表明使用LiCl沉淀法成功提取到高质量创伤弧菌基因组DNA,以其为模板,扩增到smpB基因,并成功构建pET-28a原核表达重组质粒,测序鉴定正确;smpB基因全长为486 bp,编码161个氨基酸,分子量为18.41 kD,理论等电点为10.28,不稳定系数为35.02,总平均亲水性为-0.635,SmpB蛋白整体表现为稳定亲水性蛋白。生物信息学分析显示其高级结构核心部分为5个β折叠组成的桶状结构,外围由3个α螺旋组成,SmpB C-端亦为α螺旋。诱导表达的重组融合蛋白相对分子质量大小在25.0 kD附近,显示在E.coli中成功表达了SmpB蛋白。     

Bacterial colonization and extinction on marine aggregates: stochastic model of species presence and abundance

Organic aggregates provide a favorable habitat for aquatic microbes, are efficiently filtered by shellfish, and may play a major role in the dynamics of aquatic pathogens. Quantifying this role requires understanding how pathogen abundance in the water and aggregate size interact to determine the presence and abundance of pathogen cells on individual aggregates. We build upon current understanding of the dynamics of bacteria and bacterial grazers on aggregates to develop a model for the dynamics of a bacterial pathogen species. The model accounts for the importance of stochasticity and the balance between colonization and extinction. Simulation results suggest that while colonization increases linearly with background density and aggregate size, extinction rates are expected to be nonlinear on small aggregates in a low background density of the pathogen. Under these conditions, we predict lower probabilities of pathogen presence and reduced abundance on aggregates compared with predictions based solely on colonization. These results suggest that the importance of aggregates to the dynamics of aquatic bacterial pathogens may be dependent on the interaction between aggregate size and background pathogen density, and that these interactions are strongly influenced by ecological interactions and pathogen traits. The model provides testable predictions and can be a useful tool for exploring how species‐specific differences in pathogen traits may alter the effect of aggregates on disease transmission.     

Using Molecular Dynamics Simulations on Crambin to Evaluate the Suitability of Different Continuum Dielectric and Hydrogen Atom Models for Protein Simulations

Abstract

Molecular dynamics simulations of enzymes with enough explicit waters of solvation to realistically account for solute-solvent interactions can burden the computational resources required to perform the simulation by more than two orders of magnitude. Since enzyme simulations even with an implicit solvation model can be imposing for a supercomputer, it is important to assess the suitability of different continuum dielectric models for protein simulations. A series of 100-picosecond molecular dynamics simulations were performed on the X-ray crystal structure of the protein crambin to examine how well computed structures, obtained using seven continuum dielectric and two hydrogen atom models, agreed with the X-ray structure. The best level of agreement between computed and experimental structures was obtained using a constant dielectric of 2 and the all-hydrogen model. Continuum dielectric models of 1,1^*r, and 2^*r also led to computed structures in reasonably good agreement with the X-ray structure. In all cases, the all-hydrogen model gave better agreement than the united atom model, although, in one case, the difference was not significant. Dielectric models of 4, 80, and 4^*r with either hydrogen model yielded significantly poorer fits. It is especially noteworthy that the observed trends did not semiquantitatively converge until about 50 picoseconds into the simulations, suggesting that validation studies for protein calculations based on energy minimizations or short simulations should be viewed with caution.