20 research outputs found
Modular co-evolution of metabolic networks
The architecture of biological networks has been reported to exhibit high
level of modularity, and to some extent, topological modules of networks
overlap with known functional modules. However, how the modular topology of the
molecular network affects the evolution of its member proteins remains unclear.
In this work, the functional and evolutionary modularity of Homo sapiens (H.
sapiens) metabolic network were investigated from a topological point of view.
Network decomposition shows that the metabolic network is organized in a highly
modular core-periphery way, in which the core modules are tightly linked
together and perform basic metabolism functions, whereas the periphery modules
only interact with few modules and accomplish relatively independent and
specialized functions. Moreover, over half of the modules exhibit
co-evolutionary feature and belong to specific evolutionary ages. Peripheral
modules tend to evolve more cohesively and faster than core modules do. The
correlation between functional, evolutionary and topological modularity
suggests that the evolutionary history and functional requirements of metabolic
systems have been imprinted in the architecture of metabolic networks. Such
systems level analysis could demonstrate how the evolution of genes may be
placed in a genome-scale network context, giving a novel perspective on
molecular evolution.Comment: 26 pages, 7 figure
Model validation of simple-graph representations of metabolism
The large-scale properties of chemical reaction systems, such as the
metabolism, can be studied with graph-based methods. To do this, one needs to
reduce the information -- lists of chemical reactions -- available in
databases. Even for the simplest type of graph representation, this reduction
can be done in several ways. We investigate different simple network
representations by testing how well they encode information about one
biologically important network structure -- network modularity (the propensity
for edges to be cluster into dense groups that are sparsely connected between
each other). To reach this goal, we design a model of reaction-systems where
network modularity can be controlled and measure how well the reduction to
simple graphs capture the modular structure of the model reaction system. We
find that the network types that best capture the modular structure of the
reaction system are substrate-product networks (where substrates are linked to
products of a reaction) and substance networks (with edges between all
substances participating in a reaction). Furthermore, we argue that the
proposed model for reaction systems with tunable clustering is a general
framework for studies of how reaction-systems are affected by modularity. To
this end, we investigate statistical properties of the model and find, among
other things, that it recreate correlations between degree and mass of the
molecules.Comment: to appear in J. Roy. Soc. Intefac
Complexity and robustness in hypernetwork models of metabolism
Metabolic reaction data is commonly modelled using a complex network approach, whereby nodes represent the chemical species present within the organism of interest, and connections are formed between those nodes participating in the same chemical reaction. Unfortunately, such an approach provides an inadequate description of the metabolic process in general, as a typical chemical reaction will involve more than two nodes, thus risking over-simplification of the the system of interest in a potentially significant way. In this paper, we employ a complex hypernetwork formalism to investigate the robustness of bacterial metabolic hypernetworks by extending the concept of a percolation process to hypernetworks. Importantly, this provides a novel method for determining the robustness of these systems and thus for quantifying their resilience to random attacks/errors. Moreover, we performed a site percolation analysis on a large cohort of bacterial metabolic networks and found that hypernetworks that evolved in more variable enviro nments displayed increased levels of robustness and topological complexity
Extracting the abstraction pyramid from complex networks
<p>Abstract</p> <p>Background</p> <p>At present, the organization of system modules is typically limited to either a multilevel hierarchy that describes the "vertical" relationships between modules at different levels (e.g., module A at level two is included in module B at level one), or a single-level graph that represents the "horizontal" relationships among modules (e.g., genetic interactions between module A and module B). Both types of organizations fail to provide a broader and deeper view of the complex systems that arise from an integration of vertical and horizontal relationships.</p> <p>Results</p> <p>We propose a complex network analysis tool, Pyramabs, which was developed to integrate vertical and horizontal relationships and extract information at various granularities to create a pyramid from a complex system of interacting objects. The pyramid depicts the nested structure implied in a complex system, and shows the vertical relationships between abstract networks at different levels. In addition, at each level the abstract network of modules, which are connected by weighted links, represents the modules' horizontal relationships. We first tested Pyramabs on hierarchical random networks to verify its ability to find the module organization pre-embedded in the networks. We later tested it on a protein-protein interaction (PPI) network and a metabolic network. According to Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), the vertical relationships identified from the PPI and metabolic pathways correctly characterized the <it>inclusion </it>(i.e., <it>part-of</it>) relationship, and the horizontal relationships provided a good indication of the functional closeness between modules. Our experiments with Pyramabs demonstrated its ability to perform knowledge mining in complex systems.</p> <p>Conclusions</p> <p>Networks are a flexible and convenient method of representing interactions in a complex system, and an increasing amount of information in real-world situations is described by complex networks. We considered the analysis of a complex network as an iterative process for extracting meaningful information at multiple granularities from a system of interacting objects. The quality of the interpretation of the networks depends on the completeness and expressiveness of the extracted knowledge representations. Pyramabs was designed to interpret a complex network through a disclosure of a pyramid of abstractions. The abstraction pyramid is a new knowledge representation that combines vertical and horizontal viewpoints at different degrees of abstraction. Interpretations in this form are more accurate and more meaningful than multilevel dendrograms or single-level graphs. Pyramabs can be accessed at <url>http://140.113.166.165/pyramabs.php/</url>.</p
Opportunities at the interface of network science and metabolic modeling
Metabolism plays a central role in cell physiology because it provides the molecular machinery for growth. At the genome-scale, metabolism is made up of thousands of reactions interacting with one another. Untangling this complexity is key to understand how cells respond to genetic, environmental, or therapeutic perturbations. Here we discuss the roles of two complementary strategies for the analysis of genome-scale metabolic models: Flux Balance Analysis (FBA) and network science. While FBA estimates metabolic flux on the basis of an optimization principle, network approaches reveal emergent properties of the global metabolic connectivity. We highlight how the integration of both approaches promises to deliver insights on the structure and function of metabolic systems with wide-ranging implications in discovery science, precision medicine and industrial biotechnology
Top-Down Causation by Information Control: From a Philosophical Problem to a Scientific Research Program
It has been claimed that different types of causes must be considered in
biological systems, including top-down as well as same-level and bottom-up
causation, thus enabling the top levels to be causally efficacious in their own
right. To clarify this issue, important distinctions between information and
signs are introduced here and the concepts of information control and
functional equivalence classes in those systems are rigorously defined and used
to characterise when top down causation by feedback control happens, in a way
that is testable. The causally significant elements we consider are equivalence
classes of lower level processes, realised in biological systems through
different operations having the same outcome within the context of information
control and networks.Comment: Revised version to meet referee's comments, and responding to a paper
by Wegscheid et al that was not mentioned in the previous version. 23 pages,
9 figure
Evidence for the additions of clustered interacting nodes during the evolution of protein interaction networks from network motifs
<p>Abstract</p> <p>Background</p> <p>High-throughput screens have revealed large-scale protein interaction networks defining most cellular functions. How the proteins were added to the protein interaction network during its growth is a basic and important issue. Network motifs represent the simplest building blocks of cellular machines and are of biological significance.</p> <p>Results</p> <p>Here we study the evolution of protein interaction networks from the perspective of network motifs. We find that in current protein interaction networks, proteins of the same age class tend to form motifs and such co-origins of motif constituents are affected by their topologies and biological functions. Further, we find that the proteins within motifs whose constituents are of the same age class tend to be densely interconnected, co-evolve and share the same biological functions, and these motifs tend to be within protein complexes.</p> <p>Conclusions</p> <p>Our findings provide novel evidence for the hypothesis of the additions of clustered interacting nodes and point out network motifs, especially the motifs with the dense topology and specific function may play important roles during this process. Our results suggest functional constraints may be the underlying driving force for such additions of clustered interacting nodes.</p