Improving accuracy of protein contact prediction using balanced network deconvolution

Residue contact map is essential for protein three‐dimensional structure determination. But most of the current contact prediction methods based on residue co‐evolution suffer from high false‐positives as introduced by indirect and transitive contacts (i.e., residues A–B and B–C are in contact, but A–C are not). Built on the work by Feizi et al. (Nat Biotechnol 2013; 31:726–733), which demonstrated a general network model to distinguish direct dependencies by network deconvolution, this study presents a new balanced network deconvolution (BND) algorithm to identify optimized dependency matrix without limit on the eigenvalue range in the applied network systems. The algorithm was used to filter contact predictions of five widely used co‐evolution methods. On the test of proteins from three benchmark datasets of the 9th critical assessment of protein structure prediction (CASP9), CASP10, and PSICOV (precise structural contact prediction using sparse inverse covariance estimation) database experiments, the BND can improve the medium‐ and long‐range contact predictions at the L/5 cutoff by 55.59% and 47.68%, respectively, without additional central processing unit cost. The improvement is statistically significant, with a P‐value < 5.93 × 10^?3 in the Student's t‐test. A further comparison with the ab initio structure predictions in CASPs showed that the usefulness of the current co‐evolution‐based contact prediction to the three‐dimensional structure modeling relies on the number of homologous sequences existing in the sequence databases. BND can be used as a general contact refinement method, which is freely available at: http://www.csbio.sjtu.edu.cn/bioinf/BND/ . Proteins 2015; 83:485–496. © 2014 Wiley Periodicals, Inc.     

Molecular evolution of recombination hotspots and highly recombining pseudoautosomal regions in hominoids

We examined the effects of recombination on the molecular evolution of noncoding regions in pseudoautosomal regions (PARs) and recombination hotspots in hominoids. The PAR-linked regions analyzed had on average longer branch lengths than those of the recombination hotspots. Moreover, contrary to previous observations, we found no correlation between recombination rate and silent site divergence in our data set and little change in the GC content during recent hominoid evolution. This suggests that the current rate of recombination is not a good indicator of the past rates of recombination for these highly recombining regions. Furthermore, human recombination hotspots show increased AT to GC substitutions in the human lineage, while no such pattern is detected for PAR-linked regions. Together, these observations suggest that recombination hotspots in hominoids are transient in the evolutionary time-scale. Interestingly, the 16p13.3 recombination hotspot locus violates a local molecular clock, though the locus appears to be noncoding and should evolve neutrally. We hypothesize that sudden changes in recombination rate have caused the changes in substitution rate at this locus.     

基于文献计量的人地系统耦合研究动态及热点

为深入探究人地系统的研究动态及热点,借助VOSviewer可视化软件,基于Web of Science Core collection (WoSCC)数据库,对1994—2023年国际上人地系统耦合相关文献的逐年发表数量、主要研究力量、关键词共现情况及突现词等进行可视化分析,并运用活力指数(activity index,AI)和吸引力指数(attraction index, AAI)评价不同国家在该领域的研究效率和学术影响力。研究发现：(1)人地耦合研究分为三个阶段：起步阶段(1994—1999年)、波动增长阶段(2000—2008年)、快速发展阶段(2009—2023年),研究数量、尺度及方法都在不断提升。(2)中国在人地耦合领域的研究强度呈现迅猛增加的趋势,但学术影响力及国际合作仍有待加强。(3)城镇化背景下的生态系统保护、修复及管理是当前人地耦合领域的研究重点,未来应尤其注意中、大尺度的多要素、多系统耦合分析方法、框架及模型的研发,同时以要素间、系统间的耦合机制为科学基础,构建以自然保护为根本、社会高质量发展为目标、政策制度为重要手段的自然-经济-社会系统一体化管理模式。此外,应...     

乙型肝炎病毒X蛋白的优势氨基酸序列与热点突变位点的生物信息学分析

乙型肝炎病毒X蛋白(hepatitis B virus X protein,HBx)全长154个氨基酸,与肝癌发生密切相关.为确定HBx的优势氨基酸序列和热点突变位点,在GenBank中下载所有HBx的氨基酸序列13950条,剔除插入突变、缺失突变和起始密码子非甲硫氨酸的序列,最后保留7126条.通过分析这7126条序列,计算出HBx每个位点的氨基酸分布情况,出现频率最高的氨基酸为该位点的优势氨基酸,其他氨基酸为突变氨基酸.154个位点的优势氨基酸组成HBx优势氨基酸序列.突变率>10.0%的热点突变位点有32个.其中第36、42、44、87、88和127位氨基酸有4种(突变率>1.0%)以上突变形式,具有较高的多态性.与肝癌密切相关的K130M/V131I双突变率为34.7%.通过7126条HBx序列与优势序列的同源性比较,随机选出其中50条序列(2条与优势序列同源性<75%,48条同源性为76%~99%),与23条参考序列及优势序列共同构建系统发生树.结果显示,HBx优势氨基酸序列属于基因型C,这与基因型C为全球主要流行型一致.本研究首次系统性分析了GenBank中HBx的优势序列,确定了32个HBx热点突变位点和6个多态性较高的位点,为基于HBx突变的基础和应用研究奠定了基础.     

Understanding on the residue contact network using the log‐normal cluster model and the multilevel wheel diagram

Residue clusters play essential role in stabilizing protein structures in the form of complex networks. We show that the cluster sizes in a native protein follow the log‐normal distribution for a dataset consisting of 424 proteins. To our knowledge, this is the first time of such fitting for the native structures. Based on log‐normal model, the asymptotically increasing mean cluster sizes produce a critical protein chain length of about 200 amino acids, beyond which length most globular proteins have nearly the same mean cluster sizes. This suggests that the larger proteins use a different packing mechanism than the smaller proteins. We confirmed the scale‐free property of the residue contact network for most of the protein structures in the dataset, although the violations were observed for the tightly packed proteins. Residue cluster network wheel (RCNW) is proposed to visualize the relationship between the multiple properties of the residue network such as the cluster size, the residue types and contacts, and the flexibility of the residue. We noticed that the residues with large cluster size have smaller Cα displacement measured using the normal mode analysis. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 904–916, 2010.     

东南亚生物多样性热点地区的形成与演化

东南亚地处热带,生物多样性极为丰富,可分为4个热点地区:印度-缅甸区的中南半岛、巽他区(含马来半岛、婆罗洲、苏门答腊岛)、菲律宾区(菲律宾群岛)、华莱士区(苏拉威西岛、爪哇岛、马鲁古群岛、小巽他群岛等)。中南半岛在泥盆纪便已是欧亚大陆的一部分,在印度板块撞击欧亚大陆之后受挤压而出;巽他区来自于冈瓦纳古陆和澳洲古陆;菲律宾群岛部分来自于劳亚古陆的碎片向南漂移,部分来自于太平洋西南岛弧的向北迁移;华莱士区则是劳亚古陆碎片、太平洋西南岛弧以及澳洲古陆北侧碎片的组合。巽他区地处赤道,常年温湿;菲律宾区、华莱士区、中南半岛则都受到不同程度的季风气候决定的干湿季变动。地质历史和季风气候影响程度的不同,奠定了东南亚4个生物多样性热点地区的雏形。华莱士区保存有大量的早期被子植物原始类群如睡莲目(Nymphaeales)和木兰藤目(Austrobaileyales),是现代被子植物起源地和冰期避难所之一。巽他区(婆罗洲)和中南半岛是亚洲热带植物的现代分布中心和"进化前沿",是整个东南亚地区重要的种源;而华莱士区的爪哇岛和小巽他群岛主要是物种迁入和中转的种库。这样的物种形成历史与迁移格局,塑造了东南亚4个...     

基于系统保护规划方法东北生物多样性热点地区和保护空缺分析

根据东北地区生物多样性特征,利用系统保护规划方法和国际上常用的保护规划软件C- plan,计算了规划单元的不可替代性值,确定了区域生物多样性热点地区,并根据保护区分布现状进行了生物多样性保护空缺分析.结果显示,东北地区不可替代性较高的热点地区有4个,分别是:(1)长白山西北部林区,(2)大兴安岭北段山地区,(3)大兴安岭南部森林与草原过渡区,(4)松嫩平原中部湿地区. 在优先、一般、非优先3个等级中,需要优先保护地区的总面积是19.49×104km2,约占区域总面积的20.91%.同时,根据已建保护区分布情况研究发现,区域内存在3个明显的保护空缺,即长白山西北部林区、大兴安岭北段山地区和大兴安岭南段森林草原过渡区.建议新建和扩建保护区,同时建立生态廊道把相应的保护区关联起来,以实现区域内生物多样性保护目标.     

可持续生计研究热点与前沿的可视化分析

可持续生计目前已成为全球环境变化研究的热点领域,正日益发展为可持续性科学的重要研究范式之一。论文以Web of science核心库为数据源,应用可视化分析软件CiteS paceⅢ,采取关键词共现分析、文献共被引分析、突现词分析等方法对国际可持续生计研究现状进行系统分析。研究发现,可持续生计研究文献数量呈逐年上升趋势,主要分布在生态、环境、资源及管理相关学科;瓦赫宁恩大学、中国科学院、昆士兰大学、哥伦比亚大学、博茨瓦纳大学等研究机构表现出较强的研究实力;研究人员及机构的成规模的合作网络已经形成。Scoones I、Chambers R、Conway G、Ellis F和Ostrom E等学者及其代表作品对可持续生计理论知识基础的构建及相关研究的推进奠定了坚实的基础。生计与生态环境的相互关系一直是研究重点,交叉学科的综合集成研究将成为可持续生计研究的新热点。     

果树中糖类代谢和调控研究

糖是生物体内主要的碳源,是光合作用的主要产物,可为生物体提供能量,在植物的生长发育过程中起重要作用。本文综述了近年来关于糖类与果树生长发育及品质形成方面的相关研究进展,重点介绍了糖类运输、积累与基因表达、糖信号传导和糖类调控网络等方面的研究进展,并对今后利用分子生物学手段进行果实品质改良等方面的研究方向进行了展望。     

Effect of using suboptimal alignments in template-based protein structure prediction

Computational protein structure prediction remains a challenging task in protein bioinformatics. In the recent years, the importance of template-based structure prediction is increasing because of the growing number of protein structures solved by the structural genomics projects. To capitalize the significant efforts and investments paid on the structural genomics projects, it is urgent to establish effective ways to use the solved structures as templates by developing methods for exploiting remotely related proteins that cannot be simply identified by homology. In this work, we examine the effect of using suboptimal alignments in template-based protein structure prediction. We showed that suboptimal alignments are often more accurate than the optimal one, and such accurate suboptimal alignments can occur even at a very low rank of the alignment score. Suboptimal alignments contain a significant number of correct amino acid residue contacts. Moreover, suboptimal alignments can improve template-based models when used as input to Modeller. Finally, we use suboptimal alignments for handling a contact potential in a probabilistic way in a threading program, SUPRB. The probabilistic contacts strategy outperforms the partly thawed approach, which only uses the optimal alignment in defining residue contacts, and also the re-ranking strategy, which uses the contact potential in re-ranking alignments. The comparison with existing methods in the template-recognition test shows that SUPRB is very competitive and outperforms existing methods.     

Extending the Namibian protected area network to safeguard hotspots of endemism and diversity

Namibia's state protected area network (PAN) covers 13.8% of the country's land area, but is seriously inadequate as a basis for effective biodiversity conservation. The early parks system was not designed with biological diversity in mind, and reflects instead a history of ideological, economic and veterinary considerations. Currently, parks in the Namib Desert biome make up 69% of the PAN, while savanna and woodland biomes are somewhat underrepresented (7.5 and 8.4% of their respective land areas), and the Karoo biome is badly underrepresented (1.6%). Four of 14 desert vegetation types are comprehensively protected, with 67 to 94% representation in the PAN, yet six savanna types have 0 to 2% representation by area. Mountain Savanna, a vegetation type unique to Namibia, is wholly unprotected. The status of two marine reserves, which in theory protect only 0.01% of Namibia's marine environment, needs clarification and augmentation with new reserves. Nearly 85% of Namibia's land is zoned for agriculture, so effective biodiversity protection means working outside the PAN to improve the sustainability and diversity of farming practices. Wildlife conservancies on commercial and communal farmlands show excellent potential to mitigate the ecological skew in the state PAN, with the ecological management of large areas being decentralized to rural communities in habitats otherwise neglected for conservation. Two important endemism zones, the Kaoko escarpment and coastal plain and the Sperrgebiet succulent steppe, plus the species-rich Caprivi area, offer three valuable opportunities for regional consolidation of protected areas into transboundary 'peace parks' or biosphere reserves.     

Ecological research in Australia: Identifying links versus gaps between hotspots of ecological research and biodiversity

Increasing anthropogenic impacts on biodiversity has been a cause for concern in Australia in recent years. Areas that hold high levels of endemic species and also face exceptional threats of destruction have been described as biodiversity hotspots. Ecological research focused on biodiversity hotspots will provide a better understanding of the flora and fauna of these regions and thus inform conservation strategies. Consequently, it is important to understand where biodiversity hotspots are located and how well they have been researched in the past. However, the choice of ecological research sites may be influenced by a variety of factors such as proximity to research institutions. This study utilized a geographic information system to investigate the spatial distribution of ecological research field sites in Australia and its territorial waters, the hotspots of the field sites around research institutions and the proximity of ecological research field sites from the main campus of the research institutions. Furthermore, these hotspots of ecological research were linked to biodiversity hotspots to identify the regions that were commonly depicted in the ecological literature and to identify others that may need more attention. We demonstrated that hotspots of ecological research were concentrated around research institutions, with a large number of field sites being located between 0 km and 500 km from the nearest institution, especially along the eastern coast. This study highlighted areas that have been the focus of much ecological research as well as areas that need more attention from ecologists to add new knowledge to Australian ecological science.     

药物靶标蛋白在蛋白网络中的分布

药物靶标发现是目前生物学研究领域的热点和难点问题。从已有药物靶标中寻找规律可以为新靶标的发现总结规律,提供依据。随着功能基因组学的发展,这种组学数据的积累为这一问题的研究提供了契机。本文研究了已有靶标在蛋白网络中的分布,并分析了它们的蛋白功能域组成情况。结果显示靶标基因倾向位于网络的核心区域,并且集中在一些特定蛋白家族中。这些规律的总结将对药物研发过程中药物靶点的选择提供一定的帮助。     

应用CiteSpace对生态学科meta分析的文献计量学和可视化分析

Meta分析是针对一系列独立研究结果进行定量综合分析的方法。从20世纪90年代初开始被应用于生态学的研究中,已经对这一学科的数据汇总方式产生重大影响。为了探究meta分析方法在生态学领域的研究现状及热点,以Web of Science论文核心合集为检索数据库,通过输入关键词检索了1992至2018年之间的论文,并利用Web of Science自带的文献分析工具和Histcite对检索的文献信息进行统计分析,分析了不同年份、国家、期刊、学科基础知识论文的发表和被引情况,用CiteSpace软件对其进行热点分析并绘制了知识图谱。研究发现,我国生态学研究在meta分析方法的改进和利用方面与美国、英国等国家相比尚有差距;使用meta分析方法开展研究越来越多,但研究方向上出现了一些转变,越来越多的研究关注全球变化背景下植物光合作用、物种入侵的机理以及模拟氮循环过程对物候和植被生产力的影响及价值评估的研究,并成为本领域的研究前沿。     

洞庭湖水系(湖南地区)主要防护型经济树种草种生态类型区选择研究

为了减少或避免在农林业生产中因土壤、气候不适宜造成的冻害或其它自然灾害造成的不必要的损失,最大限度地利用洞庭湖水系(湖南地区)区域内的气候资源、水热资源以及土壤资源,本文依据洞庭湖水系(湖南地区)区域内89个样本县(市)气象台(站)30年的气候资料及其地貌、土壤等生态环境特性值,采用主分量(PCA)分析的方法,并结合定性分桥,对洞庭湖水系(湖南地区)进行了生态类型区划分的研究,其结果将该区域划分成5个生态类型区,并结合26个主要经济树种草种分布的气候、水热条件、地貌和土壤等生态环境的差异性,对26个树种草种进行了最适宜、适宜、较适宜栽培的生态类型区的选择研究,相应地对各生态类型区进行了主栽树种和辅栽树种的分析。     

南京市老城区行道树的组成及结构分析

对南京市老城区125条主要路段行道树的种类组成及结构特征进行了分析。结果表明,研究区内的行道树共有乔木27种、灌木24种,其中悬铃木〔Platanus acerifolia(Ait.)Willd.〕、香樟〔Cinnamomum camphora(L.)Presl〕、国槐(Sophora japonica L.)、水杉(Metasequoia glyptostroboides Hu et Cheng)、女贞(Ligustrum lucidum Ait.)、雪松〔Cedrus deodara(Roxb.)G.Don〕和枫杨(Pterocarya stenoptera C.DC.)是南京市老城区行道树群落的优势种,决定了道路绿化景观的外貌;在7种优势树种中,悬铃木的年龄结构属稳定型,香樟、国槐和女贞处于增长阶段,水杉、雪松和枫杨则趋于老龄化。在行道树配植的4种垂直结构类型中,乔木单层结构最多,占52.8%;乔灌两层和乔灌草三层结构所占比例相近(21.6%和22.4%);乔草两层结构最少(3.2%)。本研究结果对南京市行道树的合理配置具有重要的参考价值。     

Validation of protein structure models using network similarity score

Accurate structural validation of proteins is of extreme importance in studies like protein structure prediction, analysis of molecular dynamic simulation trajectories and finding subtle changes in very similar structures. The benchmarks for today's structure validation are scoring methods like global distance test‐total structure (GDT‐TS), TM‐score and root mean square deviations (RMSD). However, there is a lack of methods that look at both the protein backbone and side‐chain structures at the global connectivity level and provide information about the differences in connectivity. To address this gap, a graph spectral based method (NSS—network similarity score) which has been recently developed to rigorously compare networks in diverse fields, is adopted to compare protein structures both at the backbone and at the side‐chain noncovalent connectivity levels. In this study, we validate the performance of NSS by investigating protein structures from X‐ray structures, modeling (including CASP models), and molecular dynamics simulations. Further, we systematically identify the local and the global regions of the structures contributing to the difference in NSS, through the components of the score, a feature unique to this spectral based scoring scheme. It is demonstrated that the method can quantify subtle differences in connectivity compared to a reference protein structure and can form a robust basis for protein structure comparison. Additionally, we have also introduced a network‐based method to analyze fluctuations in side chain interactions (edge‐weights) in an ensemble of structures, which can be an useful tool for the analysis of MD trajectories.     

Simplicial edge representation of protein structures and alpha contact potential with confidence measure

Protein representation and potential function are two important ingredients for studying protein folding, equilibrium thermodynamics, and sequence design. We introduce a novel geometric representation of protein contact interactions using the edge simplices from the alpha shape of the protein structure. This representation can eliminate implausible neighbors that are not in physical contact, and can avoid spurious contact between two residues when a third residue is between them. We developed statistical alpha contact potential using an odds-ratio model. A studentized bootstrap method was then introduced to assess the 95% confidence intervals for each of the 210 propensity parameters. We found, with confidence, that there is significant long-range propensity (>30 residues apart) for hydrophobic interactions. We tested alpha contact potential for native structure discrimination using several sets of decoy structures, and found that it often performs comparably with atom-based potentials requiring many more parameters. We also show that accurate geometric representation is important, and that alpha contact potential has better performance than potential defined by cutoff distance between geometric centers of side chains. Hierarchical clustering of alpha contact potentials reveals natural grouping of residues. To explore the relationship between shape and physicochemical representations, we tested the minimum alphabet size necessary for native structure discrimination. We found that there is no significant difference in performance of discrimination when alphabet size varies from 7 to 20, if geometry is represented accurately by alpha simplicial edges. This result suggests that the geometry of packing plays an important role, but the specific residue types are often interchangeable.     

Landscape of ecological research in Australia: A bibliometric analysis of trends in research output and hotspots of research from 1991 to 2010

The spatial distribution and density of scientists can have important implications for key aspects of scientific processes, such as innovation, networking, rates of knowledge exchange and success in large competitive grants. In this paper, we examine the research output of different research organizations and universities in Australia, with the aim of identifying hotspots of ecological research and how these hotspots have changed over the last 20 years. We used publications from 10 reputable peer‐reviewed international journals as a measure of research output. We identified a number of ecology hotspot clusters. Some clusters have developed significantly over the last 20 years, while others have declined in output over time. The University of Sydney, University of Queensland, James Cook University and Melbourne University had the largest output levels among universities. Results also showed large increases in output over the last 5‐year period (2006–2010), possibly because of the impending introduction of the Excellence in Research for Australia.