img2net: Automated network-based analysis of imaged phenotypes

Automated analysis of imaged phenotypes enables fast and reproducible quantification of biologically relevant features. Despite recent developments, recordings of complex, networked structures, such as: leaf venation patterns, cytoskeletal structures, or traffic networks, remain challenging to analyze. Here we illustrate the applicability of img2net to automatedly analyze such structures by reconstructing the underlying network, computing relevant network properties, and statistically comparing networks of different types or under different conditions. The software can be readily used for analyzing image data of arbitrary 2D and 3D network-like structures. img2net is open-source software under the GPL and can be downloaded from http://mathbiol.mpimp-golm.mpg.de/img2net/, where supplementary information and data sets for testing are provided.Comment: Bioinformatics, 2014, btu50

Graph-theoretic Approach To Modeling Propagation And Control Of Network Worms

In today\u27s network-dependent society, cyber attacks with network worms have become the predominant threat to confidentiality, integrity, and availability of network computing resources. Despite ongoing research efforts, there is still no comprehensive network-security solution aimed at controling large-scale worm propagation. The aim of this work is fivefold: (1) Developing an accurate combinatorial model of worm propagation that can facilitate the analysis of worm control strategies, (2) Building an accurate epidemiological model for the propagation of a worm employing local strategies, (3) Devising distributed architecture and algorithms for detection of worm scanning activities, (4) Designing effective control strategies against the worm, and (5) Simulation of the developed models and strategies on large, scale-free graphs representing real-world communication networks. The proposed pair-approximation model uses the information about the network structure--order, size, degree distribution, and transitivity. The empirical study of propagation on large scale-free graphs is in agreement with the theoretical analysis of the proposed pair-approximation model. We, then, describe a natural generalization of the classical cops-and-robbers game--a combinatorial model of worm propagation and control. With the help of this game on graphs, we show that the problem of containing the worm is NP-hard. Six novel near-optimal control strategies are devised: combination of static and dynamic immunization, reactive dynamic and invariant dynamic immunization, soft quarantining, predictive traffic-blocking, and contact-tracing. The analysis of the predictive dynamic traffic-blocking, employing only local information, shows that the worm can be contained so that 40\% of the network nodes are not affected. Finally, we develop the Detection via Distributed Blackholes architecture and algorithm which reflect the propagation strategy used by the worm and the salient properties of the network. Our distributed detection algorithm can detect the worm scanning activity when only 1.5% of the network has been affected by the propagation. The proposed models and algorithms are analyzed with an individual-based simulation of worm propagation on realistic scale-free topologies

Dynamic regulatory on/off minimization for biological systems under internal temporal perturbations

<p>Abstract</p> <p>Background</p> <p>Flux balance analysis (FBA) together with its extension, dynamic FBA, have proven instrumental for analyzing the robustness and dynamics of metabolic networks by employing only the stoichiometry of the included reactions coupled with adequately chosen objective function. In addition, under the assumption of minimization of metabolic adjustment, dynamic FBA has recently been employed to analyze the transition between metabolic states.</p> <p>Results</p> <p>Here, we propose a suite of novel methods for analyzing the dynamics of (internally perturbed) metabolic networks and for quantifying their robustness with limited knowledge of kinetic parameters. Following the biochemically meaningful premise that metabolite concentrations exhibit smooth temporal changes, the proposed methods rely on minimizing the significant fluctuations of metabolic profiles to predict the time-resolved metabolic state, characterized by both fluxes and concentrations. By conducting a comparative analysis with a kinetic model of the Calvin-Benson cycle and a model of plant carbohydrate metabolism, we demonstrate that the principle of regulatory on/off minimization coupled with dynamic FBA can accurately predict the changes in metabolic states.</p> <p>Conclusions</p> <p>Our methods outperform the existing dynamic FBA-based modeling alternatives, and could help in revealing the mechanisms for maintaining robustness of dynamic processes in metabolic networks over time.</p

The Choice between MapMan and Gene Ontology for Automated Gene Function Prediction in Plant Science

Since the introduction of the Gene Ontology (GO), the analysis of high-throughput data has become tightly coupled with the use of ontologies to establish associations between knowledge and data in an automated fashion. Ontologies provide a systematic description of knowledge by a controlled vocabulary of defined structure in which ontological concepts are connected by pre-defined relationships. In plant science, MapMan and GO offer two alternatives for ontology-driven analyses. Unlike GO, initially developed to characterize microbial systems, MapMan was specifically designed to cover plant-specific pathways and processes. While the dependencies between concepts in MapMan are modeled as a tree, in GO these are captured in a directed acyclic graph. Therefore, the difference in ontologies may cause discrepancies in data reduction, visualization, and hypothesis generation. Here provide the first systematic comparative analysis of GO and MapMan for the case of the model plant species Arabidopsis thaliana (Arabidopsis) with respect to their structural properties and difference in distributions of information content. In addition, we investigate the effect of the two ontologies on the specificity and sensitivity of automated gene function prediction via the coupling of co-expression networks and the guilt-by-association principle. Automated gene function prediction is particularly needed for the model plant Arabidopsis in which only half of genes have been functionally annotated based on sequence similarity to known genes. The results highlight the need for structured representation of species-specific biological knowledge, and warrants caution in the design principles employed in future ontologies

Mass-balanced randomization of metabolic networks

Motivation: Network-centered studies in systems biology attempt to integrate the topological properties of biological networks with experimental data in order to make predictions and posit hypotheses. For any topology-based prediction, it is necessary to first assess the significance of the analyzed property in a biologically meaningful context. Therefore, devising network null models, carefully tailored to the topological and biochemical constraints imposed on the network, remains an important computational problem

Evolutionary significance of metabolic network properties

Complex networks have been successfully employed to represent different levels of biological systems, ranging from gene regulation to protein–protein interactions and metabolism. Network-based research has mainly focused on identifying unifying structural properties, such as small average path length, large clustering coefficient, heavy-tail degree distribution and hierarchical organization, viewed as requirements for efficient and robust system architectures. However, for biological networks, it is unclear to what extent these properties reflect the evolutionary history of the represented systems. Here, we show that the salient structural properties of six metabolic networks from all kingdoms of life may be inherently related to the evolution and functional organization of metabolism by employing network randomization under mass balance constraints. Contrary to the results from the common Markov-chain switching algorithm, our findings suggest the evolutionary importance of the small-world hypothesis as a fundamental design principle of complex networks. The approach may help us to determine the biologically meaningful properties that result from evolutionary pressure imposed on metabolism, such as the global impact of local reaction knockouts. Moreover, the approach can be applied to test to what extent novel structural properties can be used to draw biologically meaningful hypothesis or predictions from structure alone

Relative flux trade-offs and optimization of metabolic network functionalities

Trade-offs between traits are present across different levels of biological systems and ultimately reflect constraints imposed by physicochemical laws and the structure of underlying biochemical networks. Yet, mechanistic explanation of how trade-offs between molecular traits arise and how they relate to optimization of fitness-related traits remains elusive. Here, we introduce the concept of relative flux trade-offs and propose a constraint-based approach, termed FluTOr, to identify metabolic reactions whose fluxes are in relative trade-off with respect to an optimized fitness-related cellular task, like growth. We then employed FluTOr to identify relative flux trade-offs in the genome-scale metabolic networks of Escherichia coli, Saccharomyces cerevisiae, and Arabidopsis thaliana. For the metabolic models of E. coli and S. cerevisiae we showed that: (i) the identified relative flux trade-offs depend on the carbon source used and that (ii) reactions that participated in relative trade-offs in both species were implicated in cofactor biosynthesis. In contrast to the two microorganisms, the relative flux trade-offs for the metabolic model of A. thaliana did not depend on the available nitrogen sources, reflecting the differences in the underlying metabolic network as well as the considered environments. Lastly, the established connection between relative flux trade-offs allowed us to identify overexpression targets that can be used to optimize fitness-related traits. Altogether, our computational approach and findings demonstrate how relative flux trade-offs can shape optimization of metabolic tasks, important in biotechnological applications. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.Peer reviewe