首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Attribution of biological robustness to the specific structural properties of a regulatory network is an important yet unsolved problem in systems biology. It is widely believed that the topological characteristics of a biological control network largely determine its dynamic behavior, yet the actual mechanism is still poorly understood. Here, we define a novel structural feature of biological networks, termed ‘regulation entropy’, to quantitatively assess the influence of network topology on the robustness of the systems. Using the cell-cycle control networks of the budding yeast (Saccharomyces cerevisiae) and the fission yeast (Schizosaccharomyces pombe) as examples, we first demonstrate the correlation of this quantity with the dynamic stability of biological control networks, and then we establish a significant association between this quantity and the structural stability of the networks. And we further substantiate the generality of this approach with a broad spectrum of biological and random networks. We conclude that the regulation entropy is an effective order parameter in evaluating the robustness of biological control networks. Our work suggests a novel connection between the topological feature and the dynamic property of biological regulatory networks.  相似文献   

3.
Biological networks, such as those describing gene regulation, signal transduction, and neural synapses, are representations of large-scale dynamic systems. Discovery of organizing principles of biological networks can be enhanced by embracing the notion that there is a deep interplay between network structure and system dynamics. Recently, many structural characteristics of these non-random networks have been identified, but dynamical implications of the features have not been explored comprehensively. We demonstrate by exhaustive computational analysis that a dynamical property—stability or robustness to small perturbations—is highly correlated with the relative abundance of small subnetworks (network motifs) in several previously determined biological networks. We propose that robust dynamical stability is an influential property that can determine the non-random structure of biological networks.  相似文献   

4.
Robustness and evolvability are highly intertwined properties of biological systems. The relationship between these properties determines how biological systems are able to withstand mutations and show variation in response to them. Computational studies have explored the relationship between these two properties using neutral networks of RNA sequences (genotype) and their secondary structures (phenotype) as a model system. However, these studies have assumed every mutation to a sequence to be equally likely; the differences in the likelihood of the occurrence of various mutations, and the consequence of probabilistic nature of the mutations in such a system have previously been ignored. Associating probabilities to mutations essentially results in the weighting of genotype space. We here perform a comparative analysis of weighted and unweighted neutral networks of RNA sequences, and subsequently explore the relationship between robustness and evolvability. We show that assuming an equal likelihood for all mutations (as in an unweighted network), underestimates robustness and overestimates evolvability of a system. In spite of discarding this assumption, we observe that a negative correlation between sequence (genotype) robustness and sequence evolvability persists, and also that structure (phenotype) robustness promotes structure evolvability, as observed in earlier studies using unweighted networks. We also study the effects of base composition bias on robustness and evolvability. Particularly, we explore the association between robustness and evolvability in a sequence space that is AU-rich – sequences with an AU content of 80% or higher, compared to a normal (unbiased) sequence space. We find that evolvability of both sequences and structures in an AU-rich space is lesser compared to the normal space, and robustness higher. We also observe that AU-rich populations evolving on neutral networks of phenotypes, can access less phenotypic variation compared to normal populations evolving on neutral networks.  相似文献   

5.
As scientific advances in perturbing biological systems and technological advances in data acquisition allow the large-scale quantitative analysis of biological function, the robustness of organisms to both transient environmental stresses and inter-generational genetic changes is a fundamental impediment to the identifiability of mathematical models of these functions. An approach to overcoming this impediment is to reduce the space of possible models to take into account both types of robustness. However, the relationship between the two is still controversial. This work uncovers a network characteristic, transient responsiveness, for a specific function that correlates environmental imperturbability and genetic robustness. We test this characteristic extensively for dynamic networks of ordinary differential equations ranging up to 30 interacting nodes and find that there is a power-law relating environmental imperturbability and genetic robustness that tends to linearity as the number of nodes increases. Using our methods, we refine the classification of known 3-node motifs in terms of their environmental and genetic robustness. We demonstrate our approach by applying it to the chemotaxis signaling network. In particular, we investigate plausible models for the role of CheV protein in biochemical adaptation via a phosphorylation pathway, testing modifications that could improve the robustness of the system to environmental and/or genetic perturbation.  相似文献   

6.
Distributed robustness versus redundancy as causes of mutational robustness   总被引:15,自引:0,他引:15  
A biological system is robust to mutations if it continues to function after genetic changes in its parts. Such robustness is pervasive on different levels of biological organization, from macromolecules to genetic networks and whole organisms. I here ask which of two possible causes of such robustness are more important on a genome-wide scale, for systems whose parts are genes, such as metabolic and genetic networks. The first of the two causes is redundancy of a system's parts: A gene may be dispensable if the genome contains redundant, back-up copies of the gene. The second cause, distributed robustness, is more poorly understood. It emerges from the distributed nature of many biological systems, where many (and different) parts contribute to system functions. I will here discuss evidence suggesting that distributed robustness is equally or more important for mutational robustness than gene redundancy. This evidence comes from the functional divergence of redundant genes, as well as from large-scale gene deletion studies. I also ask whether one can quantify the extent to which redundancy or distributed robustness contribute to mutational robustness.  相似文献   

7.
8.
9.
Transposable elements as the key to a 21st century view of evolution   总被引:8,自引:0,他引:8  
Shapiro JA 《Genetica》1999,107(1-3):171-179
  相似文献   

10.
The study of gene relationships and their effect on biological function and phenotype is a focal point in systems biology. Gene co-expression networks built using microarray expression profiles are one technique for discovering and interpreting gene relationships. A knowledge-independent thresholding technique, such as Random Matrix Theory (RMT), is useful for identifying meaningful relationships. Highly connected genes in the thresholded network are then grouped into modules that provide insight into their collective functionality. While it has been shown that co-expression networks are biologically relevant, it has not been determined to what extent any given network is functionally robust given perturbations in the input sample set. For such a test, hundreds of networks are needed and hence a tool to rapidly construct these networks. To examine functional robustness of networks with varying input, we enhanced an existing RMT implementation for improved scalability and tested functional robustness of human (Homo sapiens), rice (Oryza sativa) and budding yeast (Saccharomyces cerevisiae). We demonstrate dramatic decrease in network construction time and computational requirements and show that despite some variation in global properties between networks, functional similarity remains high. Moreover, the biological function captured by co-expression networks thresholded by RMT is highly robust.  相似文献   

11.
12.
13.
We give in this paper indications about the dynamical impact (as phenotypic changes) coming from the main sources of perturbation in biological regulatory networks. First, we define the boundary of the interaction graph expressing the regulations between the main elements of the network (genes, proteins, metabolites, ...). Then, we search what changes in the state values on the boundary could cause some changes of states in the core of the system (robustness to boundary conditions). After, we analyse the role of the mode of updating (sequential, block sequential or parallel) on the asymptotics of the network, essentially on the occurrence of limit cycles (robustness to updating methods). Finally, we show the influence of some topological changes (e.g. suppression or addition of interactions) on the dynamical behaviour of the system (robustness to topology perturbations).  相似文献   

14.
Many biological systems are composed of unreliable components which self-organize effectively into systems that achieve a balance between efficiency and robustness. One such example is the true slime mold Physarum polycephalum which is an amoeba-like organism that seeks and connects food sources and efficiently distributes nutrients throughout its cell body. The distribution of nutrients is accomplished by a self-assembled resource distribution network of small tubes with varying diameter which can evolve with changing environmental conditions without any global control. In this paper, we exploit two different mechanisms of the slime mold??s tubular network formation process via laboratory experiments and mathematical behavior modeling to design two corresponding localized routing protocols for wireless sensor networks (WSNs) that take both efficiency and robustness into account. In the first mechanism of path growth, slime mold explores its immediate surroundings to discover and connect new food sources during its growth cycle. We adapt this mechanism for a path growth routing protocol by treating data sources and sinks as singular potentials to establish routes from the sinks to all the data sources. The second mechanism of path evolution is the temporal evolution of existing tubes through nonlinear feedback in order to distribute nutrients efficiently throughout the organism. Specifically, the diameters of tubes carrying large fluxes of nutrients grow to expand their capacities, and tubes that are not used decline and disappear entirely. We adapt the tube dynamics of the slime mold for a path evolution routing protocol. In our protocol, we identify one key adaptation parameter to adjust the tradeoff between efficiency and robustness of network routes. Through extensive realistic network simulations and ideal closed form or numerical computations, we validate the effectiveness of both protocols, as well as the efficiency and robustness of the resulting network connectivity.  相似文献   

15.
Similar to intelligent multicellular neural networks controlling human brains, even single cells, surprisingly, are able to make intelligent decisions to classify several external stimuli or to associate them. This happens because of the fact that gene regulatory networks can perform as perceptrons, simple intelligent schemes known from studies on Artificial Intelligence. We study the role of genetic noise in intelligent decision making at the genetic level and show that noise can play a constructive role helping cells to make a proper decision. We show this using the example of a simple genetic classifier able to classify two external stimuli.  相似文献   

16.
It is system dynamics that determines the function of cells, tissues and organisms. To develop mathematical models and estimate their parameters are an essential issue for studying dynamic behaviors of biological systems which include metabolic networks, genetic regulatory networks and signal transduction pathways, under perturbation of external stimuli. In general, biological dynamic systems are partially observed. Therefore, a natural way to model dynamic biological systems is to employ nonlinear state-space equations. Although statistical methods for parameter estimation of linear models in biological dynamic systems have been developed intensively in the recent years, the estimation of both states and parameters of nonlinear dynamic systems remains a challenging task. In this report, we apply extended Kalman Filter (EKF) to the estimation of both states and parameters of nonlinear state-space models. To evaluate the performance of the EKF for parameter estimation, we apply the EKF to a simulation dataset and two real datasets: JAK-STAT signal transduction pathway and Ras/Raf/MEK/ERK signaling transduction pathways datasets. The preliminary results show that EKF can accurately estimate the parameters and predict states in nonlinear state-space equations for modeling dynamic biochemical networks.  相似文献   

17.
Branching networks are ubiquitous in nature and their growth often responds to environmental cues dynamically. Using the antibiotic-producing soil bacterium Streptomyces as a model we have developed a flexible mathematical model platform for the study of branched biological networks. Streptomyces form large aggregates in liquid culture that can impair industrial antibiotic fermentations. Understanding the features of these could aid improvement of such processes. The model requires relatively few experimental values for parameterisation, yet delivers realistic simulations of Streptomyces pellet and is able to predict features, such as the density of hyphae, the number of growing tips and the location of antibiotic production within a pellet in response to pellet size and external nutrient supply. The model is scalable and will find utility in a range of branched biological networks such as angiogenesis, plant root growth and fungal hyphal networks.  相似文献   

18.
19.
20.
In the ongoing evolutionary process, biological systems have displayed a fundamental and remarkable property of robustness, i.e., the property allows the system to maintain its functions despite external and internal perturbations. Redundancy and degeneracy are thought to be the underlying structural mechanisms of biological robustness. Inspired by this, we explored the proximate cause of the immunity of the synthetic evolved digital circuits to ESD interference and discussed the biological characteristics behind the evolutionary circuits. First, we proposed an evolutionary method for intrinsic immune circuit design. The circuits' immunity was evaluated using the functional fault models based on probability distributions. Then, several benchmark circuits, including ADDER, MAJORITY, and C17, were evolved for high intrinsic immunity. Finally, using the quantitative definitions based on information theory, we measured the topological characteristics of redundancy and degeneracy in the evolved circuits and compared their contributions to the immunity. The results show that redundant elements are necessary for the ESD immune circuit design, whereas degeneracy is the key to making use of the redundancy robustly and efficiently.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号