A survey of current software for network analysis in molecular biology
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A survey of current software for network analysis in molecular biology Sterling Thomas1 and Danail Bonchev1,2* 1
Center for the Study of Biological Complexity, Virginia Commonwealth University, PO Box 842030, Richmond, VA 23284-2030, USA Department of Mathematics and Applied Mathematics, Virginia Commonwealth University, Richmond, VA 23284, USA *Correspondence to: Tel: þ1 804 827 7375; Fax: þ1 804 828 1961; E-mail: [email protected]
2
Date received (in revised form): 22 April 2010
Abstract Software for network motifs and modules is briefly reviewed, along with programs for network comparison. The three major software packages for network analysis, CYTOSCAPE, INGENUITY and PATHWAY STUDIO, and their associated databases, are compared in detail. A comparative test evaluated how these software packages perform the search for key terms and the creation of network from those terms and from experimental expression data. Keywords: software, network analysis, microarray expression analysis
Introduction to network-related software tools Post-genomic biology makes extensive use of network analysis at all levels of the hierarchy of life. Networks are basic tools in systems biology for expressing the essence of living things as whole integrated systems.1 – 3 The explosive development of the theory of dynamic evolutionary networks during the past decade4 – 6 stimulated the creation of numerous algorithms and software programs for constructing, manipulating and analysing networks. Many of those are multi-purpose programs with applications to most of the available types of complex networks: social, transportation, communication, financial, etc. This review focuses on software for the analysis of networks in living cells, the nodes in which represent genes, proteins, metabolites and other cell components. Examples of such networks are protein –protein interaction networks (PPN), gene regulatory networks (GRN), and metabolic and signalling networks and pathways, as well as disease-related or cell function-related networks.
The detailed analysis in this review is devoted to several of the most comprehensive and multifunctional software packages for network analysis in molecular biology. Other essential types of software in this field, which solve more specific network tasks, are also listed. One such kind of software performs a substructure search for identifying over-represented sub-graphs called motifs.7,8 Viewed as the smallest building blocks of networks, motifs serve as a signature for distinguishing species, or different states of a single species, and are of interest for evolutionary and biomedical studies. The concept of motifs was developed in the Laboratory of Uri Alon from the Weizmann Institute in Israel, where a library of identification (ID) numbers of all motifs having three to eight nodes was created, along with the downloadable MFinder software for motif identification.9 Other groups followed with freely available software: MAVisto (Schreiber and Schwo¨bbermeyer)10 and FANMOD (Wernicke and Rasche).11 FANMOD is
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