基于极端途径的生化网络模块化分析

近年来,对于复杂生化网络系统进行模块化分析引起了科研人员的极大关注。一般认为,模块化分析有助于理解这些网络的结构与功能关系。但是,当前的模块化分析方法大多将生化网络考虑为普通的复杂网络,所得模块的生物学意义较低。介绍了化学计量矩阵及极端途径分析等基本概念,对苏云金杆菌的丁醇代谢系统进行建模分析,研究结果表明：极端途径分析可用于识别网络中的功能模块,具备较好的生物学意义。     

产甲烷常温菌和嗜热菌代谢网络特征的比较研究

以产甲烷的常温古细菌Methanosarcina aeefivorans(MAC)和嗜热古细菌Methanopyrus kandleri(MKA)的代谢网络为研究对象,分析了网络的拓扑结构与功能之间的关联性。本文利用Networkx计算了代谢网络的度、度的中心性、紧密度中心性以及介数中心性等参数值,通过比较分析发现常温古细菌MAC和嗜热古细菌MKA存在氨基酸代谢以及碳水化合物代谢保守途径,且都具有明显更高的度。结果同时表明子途径00010(糖酵解/糖异生)、00020(柠檬酸循环)、00250(丙氨酸、天冬氨酸和谷氨酸代谢)是常温古细菌MAC与嗜热古细菌MKA2个生物体的重要途径。     

基于嗜盐菌合成生物学的下一代工业生物技术

嗜盐微生物是在高盐、高pH环境中具备正常生长能力的极端微生物,是珍贵的科研素材和生产资源.相关研究通过对嗜盐菌合成生物学的改造和"下一代工业生物技术"的探索,实现了嗜盐工程菌在生物反应器中利用海水进行不灭菌连续发酵并产生类型多样、性能各异的聚羟基脂肪酸酯,且与其他高附加值化学品实现了联产.基于嗜盐菌的下一代工业生物技术...     

极端路径分析及在色氨酸合成代谢网络中的应用

代谢途径分析在鉴别和量化生化反应网络中的大量代谢物变得越来越重要,其中极端路径分析是用来分析复杂代谢网络结构和功能的方法.本文主要论述了当今最常用的代谢途径分析方法,描述了极端路径算法的具体方法,并将这种方法用于色氨酸合成代谢网络中,分析其代谢网络的结构和功能,并与传统的路径比较.     

氨基酸嗜盐不对称指数与其理化性质的相关性

了解嗜盐蛋白氨基酸使用的偏好及该偏好与其理化性质之间的联系对探索嗜盐蛋白构效关系具有重要意义。本文选取极端嗜盐细菌Salinibacter ruber和非嗜盐菌Pelodictyon luteolum中362对同源蛋白,统计了52102个氨基酸突变位点,以此计算氨基酸的嗜盐不对称指数(HAI),并与243个理化性质进行相关性分析。结果表明:天冬氨酸的嗜盐性能最强,而异亮氨酸和赖氨酸最弱;243个理化性质中有16个同HAI存在显著相关性,其中5个呈正相关;氨基酸的亲疏水性及β折叠的倾向性是影响HAI值的两种最重要的理化性质。本文提出的氨基酸嗜盐不对称指数为了解嗜盐蛋白稳定性机制提供了新视角。     

基于复杂网络理论的产甲烷常温菌和嗜热菌的代谢网络的拓扑与模块化的研究

近几年,复杂网络的研究正成为广泛关注的热点,代谢网络是复杂网络的一个例子。本文以产甲烷的常温古细菌Methanosarcina acetivorans(M.acetivorans)和嗜热古细菌Methanopyrus kandleri(M.kandleri)的代谢网络为对象,从拓扑参数以及模块化两方面进行比较研究。结果表明:M.acetivorans与M.kandleri的代谢网络均具有较高的模块化结构。同时发现它们模块化后的代谢网络中的Hub模块均属于氨基酸代谢和碳水化合物代谢,表明这些网络模块均具有一定的功能意义。最后将Hub模块与最紧密的k-核心网络相比较,发现它们节点完全相同,此结果表明代谢网络的最紧密k-核心网络部分也是不同网络比较的重要因素。     

Petri网在代谢网络模块化分析中的应用

代谢网络的模块化分析有助于理解网络的结构和功能。然而,当前众多的模块化分析方法大多将代谢网络考虑为普通的复杂网络,所得模块的生物学意义较低。对枯草芽孢杆菌的核黄素代谢进行Petri网建模分析,研究结果表明：Petri网的T不变量可用于识别代谢网络中的功能模块,具备较好的生物学意义。     

基于PCA-SVM混合算法的嗜热菌和常温菌网络特征的研究

通过比较嗜热菌和常温菌代谢网络的特征参数,可以从系统角度确定微生物嗜热性的主要因素。本文首先利用主成分分析法对22个网络特征进行相关性分析,根据特征值、载荷值的大小最终选择了11个主要网络特征;用选出的这11个网络特征组成特征向量,利用支持向量机构建分类器,对嗜热菌和常温菌进行分类,其全局平均预测率为82.93%,对常温菌和嗜热菌的平均预测率分别为87.86%和72.40%。结果表明利用主成分分析法选择的网络特征可以很好的表征嗜热菌和常温菌的耐热性,因此簇大小分布的平均信息等11个网络特征是影响微生物耐热性的关键的代谢网络特征因素。     

基于PCA-SVM混合算法的嗜热菌和常温菌网络特征的研究

通过比较嗜热菌和常温菌代谢网络的特征参数,可以从系统角度确定微生物嗜热性的主要因素。本文首先利用主成分分析法对22个网络特征进行相关性分析,根据特征值、载荷值的大小最终选择了11个主要网络特征:用选出的这11个网络特征组成特征向量,利用支持向量机构建分类器,对嗜热菌和常温菌进行分类,其全局平均预测率为82.93%,对常温菌和嗜热菌的平均预测率分别为87.86%和72.40%。结果表明利用主成分分析法选择的网络特征可以很好的表征嗜热菌和常温菌的耐热性,因此簇大小分布的平均信息等11个网络特征是影响微生物耐热性的关键的代谢网络特征因素。     

代谢途径分析研究进展及其应用

由于缺乏详尽的热力学参数,基于网络拓扑的代谢途径分析是现阶段最重要的途径分析方法。首先简单地介绍了基于网络的途径分析方法发展简史,随后着重说明了基于凸分析的两种代谢途径分析方法：基元模式和极端途径及它们之间的异同,并详细阐述了这两种方法的具体应用。最后,使用极端途径分析了苏云金杆菌的PHB代谢。结果表明,除了传统的途径,还存在一些新颖的途径可用于PHB合成。     

系统发育与古细菌Val-tRNA合成酶耐热性的关系

嗜热古细菌和常温古细菌的氨基酰-tRNA合成酶在生物合成蛋白质中都起着至关重要的作用,它们的功能相似而耐热性相差很大。为了阐明氨基酰-tRNA合成酶的耐热机制,本文从进化角度研究了具有全基因组的8种超高温古细菌、3种高温古细菌和2种常温古细菌的Val-tRNA合成酶耐热性的差异。从构建的进化树可知,不同的微生物依据其耐热性而严格的分开;进化关系较近的4种微生物,都是产甲烷的古细菌;序列比对结果表明,耐热Val-tRNA合成酶中的带电荷氨基酸随着进化,突变为疏水性氨基酸,表明常温Val-tRNA合成酶中缺乏像耐热Val-tRNA合成酶中形成盐桥的氨基酸。这表明盐桥是氨基酰-tRNA合成酶耐热的主要因素。     

Identification of minimal metabolic pathway models consistent with phenotypic data

In metabolic systems, the cellular network of metabolic reactions together with constraints of (ir)reversibility of enzymes determines the space of all possible steady-state phenotypes. Analysis of large metabolic models, however, is not feasible in real-time and identification of a smaller model without loss of accuracy is desirable for model-based bioprocess optimization and control. To this end, we propose two search algorithms for systematic identification of a subset of pathways that match the observed cellular phenotype relevant for a particular process condition. Central carbon metabolism of Escherichia coli was used as a case-study together with three phenotypic datasets obtained from the literature. The first search method is based on ranking pathways and the second is a controlled random search (CRS) algorithm. Since we wish to obtain a biologically realistic subset of pathways, the objective function to be minimized is a trade-off between the error and investment costs. We found that the CRS outperforms the ranking algorithm, as it is less likely to fall into local minima. In addition, we compared two pathway analysis methods (elementary modes versus generating vectors) in terms of modelling accuracy and computational intensity. We conclude that generating vectors have preference over elementary modes to describe a particular phenotype. Overall, the original model containing 433 generating vectors or 2706 elementary modes could be reduced to a system of one to three pathways giving a good correlation with the measured datasets. We consider this work as a first step towards the use of detailed metabolic models to improve real-time optimization, monitoring, and control of biological processes.     

Pathway Preserving Representation of Metabolic Networks

Improvements in biological data acquisition and genomes sequencing now allow to reconstruct entire metabolic networks of many living organisms. The size and complexity of these networks prohibit manual drawing and thereby urge the need of dedicated visualization techniques. An efficient representation of such a network should preserve the topological information of metabolic pathways while respecting biological drawing conventions. These constraints complicate the automatic generation of such visualization as it raises graph drawing issues. In this paper we propose a method to lay out the entire metabolic network while preserving the pathway information as much as possible. That method is flexible as it enables the user to define whether or not node duplication should be performed, to preserve or not the network topology. Our technique combines partitioning, node placement and edge bundling to provide a pseudo‐orthogonal visualization of the metabolic network. To ease pathway information retrieval, we also provide complementary interaction tools that emphasize relevant pathways in the entire metabolic context.     

The effect of appraisers in estimating metabolic rate with the Edholm scale

A study was made of the appraisers' effect on the estimation of metabolic rate with the Edholm scale and a table of the ISO 7243 heat stress standard. The appraisers, five experienced and five inexperienced persons, estimated the metabolic rate of three different work tasks from videotapes. Analysis of variance indicated significant ( [Formula: see text] ) differences in the appraisers' recordings of the activities. The appraisers were grouped according to the similarity of the estimated values they gave. The groups thus contained both experienced and inexperienced appraisers, and it was not possible to classify the appraisers into experienced and inexperienced groups according to their earlier experience. The metabolic rates according to the Edholm scale were higher than according to the ISO 7243 table. The differences in metabolic rates given by the individual observers varied from 38 to 118 W/m(2). The variations in the estimation of metabolic rates were greater when the Edholm scale was used. This variation caused considerable variation also in the predicted mean vote, PMV index. It is recommended that the appraisers be selected carefully, because it is not possible to know whether a randomly selected appraiser is an 'average' or an 'extreme' appraiser without a test. Before conducting extensive field surveys where several appraisers estimate the metabolic rates, it would be useful to arrange training in order to calibrate the levels of the Edholm scale as well as ISO method among the appraisers because training clearly unified the estimation.     

The application of metabolic resistance theory to the selection of preferred target enzymes for therapeutic drugs

A number of drugs act by inhibition of a specific target enzyme, thereby interfering with the synthesis of a key metabolite. When a specific enzyme inhibitor is applied to a functioning metabolic pathway, the substrate will accumulate and the inhibition will be counteracted, a phenomenon known as metabolic resistance. The work described in this report delineates the circumstances which accentuate, and those which suppress, metabolic resistance. By computer simulation it is shown that the effect of an inhibitor is less pronounced when the target enzyme is remote from the reaction which produces the key metabolite, separated from it by a large pool of intermediates, or separated by an enzyme which is nearly saturated with its substrate. Further, it is shown that noncompetitive, uncompetitive, or irreversible inhibitors are more effective than competitive inhibitors. Finally, enzymes immediately following a branch point and those which form part of a cycle are the least likely to exhibit metabolic resistance. These considerations are encapsulated in six rules for the selection of preferred enzyme targets for drug action.     

Pathway Hunter Tool在代谢途径分析中的应用

随着重建的基因组规模代谢网络越来越多,自动化的生物化学途径分析方法显得越来越重要,已经有多种基于此的途径分析工具开发出来了。其中,Pathway Hunter Tool(PHT)是主要用于分析代谢网络的最短路径、代谢物和酶负载点和瓶颈.以及计算相关统计学数据(如平均路径长度、平均节点连接度等)的工具。本文首先简介PHT,随后用它分析E.coli K-12 MG1655代谢网络中a-D-葡萄糖和丙酮酸之间的最短路径及其代谢网络的瓶颈,最后计算4种典型生物的平均路径长度、平均节点连接度以及它们代谢网络中节点连接度最高的10种代谢物。结果表明它的分析与计算快速、准确,加之其用户界面友好、便于操作,因此可以作为代谢途径分析的强有力工具。     

Parallelization of Nullspace Algorithm for the computation of metabolic pathways

Elementary mode analysis is a useful metabolic pathway analysis tool in understanding and analyzing cellular metabolism, since elementary modes can represent metabolic pathways with unique and minimal sets of enzyme-catalyzed reactions of a metabolic network under steady state conditions. However, computation of the elementary modes of a genome- scale metabolic network with 100-1000 reactions is very expensive and sometimes not feasible with the commonly used serial Nullspace Algorithm. In this work, we develop a distributed memory parallelization of the Nullspace Algorithm to handle efficiently the computation of the elementary modes of a large metabolic network. We give an implementation in C++ language with the support of MPI library functions for the parallel communication. Our proposed algorithm is accompanied with an analysis of the complexity and identification of major bottlenecks during computation of all possible pathways of a large metabolic network. The algorithm includes methods to achieve load balancing among the compute-nodes and specific communication patterns to reduce the communication overhead and improve efficiency.     

人体局部代谢率监测系统设计

在实现将温度、湿度及辐射传感器集成于独立检测探头基础上,设计了一种人体局部代谢率监测系统。系统通过采集人体指端生理参数,根据人体能量代谢守恒法,建立数学模型并计算静息代谢率。经过实验验证:该系统可以实现代谢率的方便测量,测试结果能够反映人体正常的代谢情况。由于系统设计简便、成本低,可被广泛用于人体的能量代谢率检测。     

Petri nets for modelling metabolic pathways: a survey

In the last 15 years, several research efforts have been directed towards the representation and the analysis of metabolic pathways by using Petri nets. The goal of this paper is twofold. First, we discuss how the knowledge about metabolic pathways can be represented with Petri nets. We point out the main problems that arise in the construction of a Petri net model of a metabolic pathway and we outline some solutions proposed in the literature. Second, we present a comprehensive review of recent research on this topic, in order to assess the maturity of the field and the availability of a methodology for modelling a metabolic pathway by a corresponding Petri net.