21,330 research outputs found
ModuLand plug-in for Cytoscape: determination of hierarchical layers of overlapping network modules and community centrality
Summary: The ModuLand plug-in provides Cytoscape users an algorithm for
determining extensively overlapping network modules. Moreover, it identifies
several hierarchical layers of modules, where meta-nodes of the higher
hierarchical layer represent modules of the lower layer. The tool assigns
module cores, which predict the function of the whole module, and determines
key nodes bridging two or multiple modules. The plug-in has a detailed
JAVA-based graphical interface with various colouring options. The ModuLand
tool can run on Windows, Linux, or Mac OS. We demonstrate its use on protein
structure and metabolic networks. Availability: The plug-in and its user guide
can be downloaded freely from: http://www.linkgroup.hu/modules.php. Contact:
[email protected] Supplementary information: Supplementary
information is available at Bioinformatics online.Comment: 39 pages, 1 figure and a Supplement with 9 figures and 10 table
Methods for protein complex prediction and their contributions towards understanding the organization, function and dynamics of complexes
Complexes of physically interacting proteins constitute fundamental
functional units responsible for driving biological processes within cells. A
faithful reconstruction of the entire set of complexes is therefore essential
to understand the functional organization of cells. In this review, we discuss
the key contributions of computational methods developed till date
(approximately between 2003 and 2015) for identifying complexes from the
network of interacting proteins (PPI network). We evaluate in depth the
performance of these methods on PPI datasets from yeast, and highlight
challenges faced by these methods, in particular detection of sparse and small
or sub- complexes and discerning of overlapping complexes. We describe methods
for integrating diverse information including expression profiles and 3D
structures of proteins with PPI networks to understand the dynamics of complex
formation, for instance, of time-based assembly of complex subunits and
formation of fuzzy complexes from intrinsically disordered proteins. Finally,
we discuss methods for identifying dysfunctional complexes in human diseases,
an application that is proving invaluable to understand disease mechanisms and
to discover novel therapeutic targets. We hope this review aptly commemorates a
decade of research on computational prediction of complexes and constitutes a
valuable reference for further advancements in this exciting area.Comment: 1 Tabl
Diffusion Model Based Spectral Clustering for Protein-Protein Interaction Networks
BACKGROUND: A goal of systems biology is to analyze large-scale molecular networks including gene expressions and protein-protein interactions, revealing the relationships between network structures and their biological functions. Dividing a protein-protein interaction (PPI) network into naturally grouped parts is an essential way to investigate the relationship between topology of networks and their functions. However, clear modular decomposition is often hard due to the heterogeneous or scale-free properties of PPI networks. METHODOLOGY/PRINCIPAL FINDINGS: To address this problem, we propose a diffusion model-based spectral clustering algorithm, which analytically solves the cluster structure of PPI networks as a problem of random walks in the diffusion process in them. To cope with the heterogeneity of the networks, the power factor is introduced to adjust the diffusion matrix by weighting the transition (adjacency) matrix according to a node degree matrix. This algorithm is named adjustable diffusion matrix-based spectral clustering (ADMSC). To demonstrate the feasibility of ADMSC, we apply it to decomposition of a yeast PPI network, identifying biologically significant clusters with approximately equal size. Compared with other established algorithms, ADMSC facilitates clear and fast decomposition of PPI networks. CONCLUSIONS/SIGNIFICANCE: ADMSC is proposed by introducing the power factor that adjusts the diffusion matrix to the heterogeneity of the PPI networks. ADMSC effectively partitions PPI networks into biologically significant clusters with almost equal sizes, while being very fast, robust and appealing simple
Disordered proteins and network disorder in network descriptions of protein structure, dynamics and function. Hypotheses and a comprehensive review
During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here we review the links between disordered proteins and the associated networks, and describe the consequences of local, mesoscopic and global network disorder on changes in protein structure and dynamics. We introduce a new classification of protein networks into ‘cumulus-type’, i.e., those similar to puffy (white) clouds, and ‘stratus-type’, i.e., those similar to flat, dense (dark) low-lying clouds, and relate these network types to protein disorder dynamics and to differences in energy transmission processes. In the first class, there is limited overlap between the modules, which implies higher rigidity of the individual units; there the conformational changes can be described by an ‘energy transfer’ mechanism. In the second class, the topology presents a compact structure with significant overlap between the modules; there the conformational changes can be described by ‘multi-trajectories’; that is, multiple highly populated pathways. We further propose that disordered protein regions evolved to help other protein segments reach ‘rarely visited’ but functionally-related states. We also show the role of disorder in ‘spatial games’ of amino acids; highlight the effects of intrinsically disordered proteins (IDPs) on cellular networks and list some possible studies linking protein disorder and protein structure networks
From Network Structure to Dynamics and Back Again: Relating dynamical stability and connection topology in biological complex systems
The recent discovery of universal principles underlying many complex networks
occurring across a wide range of length scales in the biological world has
spurred physicists in trying to understand such features using techniques from
statistical physics and non-linear dynamics. In this paper, we look at a few
examples of biological networks to see how similar questions can come up in
very different contexts. We review some of our recent work that looks at how
network structure (e.g., its connection topology) can dictate the nature of its
dynamics, and conversely, how dynamical considerations constrain the network
structure. We also see how networks occurring in nature can evolve to modular
configurations as a result of simultaneously trying to satisfy multiple
structural and dynamical constraints. The resulting optimal networks possess
hubs and have heterogeneous degree distribution similar to those seen in
biological systems.Comment: 15 pages, 6 figures, to appear in Proceedings of "Dynamics On and Of
Complex Networks", ECSS'07 Satellite Workshop, Dresden, Oct 1-5, 200
Allo-network drugs: Extension of the allosteric drug concept to protein-protein interaction and signaling networks
Allosteric drugs are usually more specific and have fewer side effects than orthosteric drugs targeting the same
protein. Here, we overview the current knowledge on allosteric signal transmission from the network point of view, and show that most intra-protein conformational changes may be dynamically transmitted across protein-protein interaction and signaling networks of the cell. Allo-network drugs influence the pharmacological target protein indirectly using specific inter-protein network pathways. We show that allo-network drugs may have a higher efficiency to change the networks of human cells than those of other organisms, and can be designed to have specific effects on cells in a diseased state. Finally, we summarize possible methods to identify allo-network drug targets and sites, which may develop to a promising new area of systems-based drug design
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