19,400 research outputs found
Graph Theory and Networks in Biology
In this paper, we present a survey of the use of graph theoretical techniques
in Biology. In particular, we discuss recent work on identifying and modelling
the structure of bio-molecular networks, as well as the application of
centrality measures to interaction networks and research on the hierarchical
structure of such networks and network motifs. Work on the link between
structural network properties and dynamics is also described, with emphasis on
synchronization and disease propagation.Comment: 52 pages, 5 figures, Survey Pape
Finding undetected protein associations in cell signaling by belief propagation
External information propagates in the cell mainly through signaling cascades
and transcriptional activation, allowing it to react to a wide spectrum of
environmental changes. High throughput experiments identify numerous molecular
components of such cascades that may, however, interact through unknown
partners. Some of them may be detected using data coming from the integration
of a protein-protein interaction network and mRNA expression profiles. This
inference problem can be mapped onto the problem of finding appropriate optimal
connected subgraphs of a network defined by these datasets. The optimization
procedure turns out to be computationally intractable in general. Here we
present a new distributed algorithm for this task, inspired from statistical
physics, and apply this scheme to alpha factor and drug perturbations data in
yeast. We identify the role of the COS8 protein, a member of a gene family of
previously unknown function, and validate the results by genetic experiments.
The algorithm we present is specially suited for very large datasets, can run
in parallel, and can be adapted to other problems in systems biology. On
renowned benchmarks it outperforms other algorithms in the field.Comment: 6 pages, 3 figures, 1 table, Supporting Informatio
The Physics of Communicability in Complex Networks
A fundamental problem in the study of complex networks is to provide
quantitative measures of correlation and information flow between different
parts of a system. To this end, several notions of communicability have been
introduced and applied to a wide variety of real-world networks in recent
years. Several such communicability functions are reviewed in this paper. It is
emphasized that communication and correlation in networks can take place
through many more routes than the shortest paths, a fact that may not have been
sufficiently appreciated in previously proposed correlation measures. In
contrast to these, the communicability measures reviewed in this paper are
defined by taking into account all possible routes between two nodes, assigning
smaller weights to longer ones. This point of view naturally leads to the
definition of communicability in terms of matrix functions, such as the
exponential, resolvent, and hyperbolic functions, in which the matrix argument
is either the adjacency matrix or the graph Laplacian associated with the
network. Considerable insight on communicability can be gained by modeling a
network as a system of oscillators and deriving physical interpretations, both
classical and quantum-mechanical, of various communicability functions.
Applications of communicability measures to the analysis of complex systems are
illustrated on a variety of biological, physical and social networks. The last
part of the paper is devoted to a review of the notion of locality in complex
networks and to computational aspects that by exploiting sparsity can greatly
reduce the computational efforts for the calculation of communicability
functions for large networks.Comment: Review Article. 90 pages, 14 figures. Contents: Introduction;
Communicability in Networks; Physical Analogies; Comparing Communicability
Functions; Communicability and the Analysis of Networks; Communicability and
Localization in Complex Networks; Computability of Communicability Functions;
Conclusions and Prespective
Network-based approaches to explore complex biological systems towards network medicine
Network medicine relies on different types of networks: from the molecular level of proteinâprotein interactions to gene regulatory network and correlation studies of gene expression. Among network approaches based on the analysis of the topological properties of proteinâprotein interaction (PPI) networks, we discuss the widespread DIAMOnD (disease module detection) algorithm. Starting from the assumption that PPI networks can be viewed as maps where diseases can be identified with localized perturbation within a specific neighborhood (i.e., disease modules), DIAMOnD performs a systematic analysis of the human PPI network to uncover new disease-associated genes by exploiting the connectivity significance instead of connection density. The past few years have witnessed the increasing interest in understanding the molecular mechanism of post-transcriptional regulation with a special emphasis on non-coding RNAs since they are emerging as key regulators of many cellular processes in both physiological and pathological states. Recent findings show that coding genes are not the only targets that microRNAs interact with. In fact, there is a pool of different RNAsâincluding long non-coding RNAs (lncRNAs) âcompeting with each other to attract microRNAs for interactions, thus acting as competing endogenous RNAs (ceRNAs). The framework of regulatory networks provides a powerful tool to gather new insights into ceRNA regulatory mechanisms. Here, we describe a data-driven model recently developed to explore the lncRNA-associated ceRNA activity in breast invasive carcinoma. On the other hand, a very promising example of the co-expression network is the one implemented by the software SWIM (switch miner), which combines topological properties of correlation networks with gene expression data in order to identify a small pool of genesâcalled switch genesâcritically associated with drastic changes in cell phenotype. Here, we describe SWIM tool along with its applications to cancer research and compare its predictions with DIAMOnD disease genes
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
Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks
The idea of 'date' and 'party' hubs has been influential in the study of
protein-protein interaction networks. Date hubs display low co-expression with
their partners, whilst party hubs have high co-expression. It was proposed that
party hubs are local coordinators whereas date hubs are global connectors. Here
we show that the reported importance of date hubs to network connectivity can
in fact be attributed to a tiny subset of them. Crucially, these few, extremely
central, hubs do not display particularly low expression correlation,
undermining the idea of a link between this quantity and hub function. The
date/party distinction was originally motivated by an approximately bimodal
distribution of hub co-expression; we show that this feature is not always
robust to methodological changes. Additionally, topological properties of hubs
do not in general correlate with co-expression. Thus, we suggest that a
date/party dichotomy is not meaningful and it might be more useful to conceive
of roles for protein-protein interactions rather than individual proteins. We
find significant correlations between interaction centrality and the functional
similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure
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