Nodes and 22347 edges that include 18398 activation edges (positive edges) and 3949 inhibitory edges (negative edges). Finally, we generated 6 different sizes of signaling networks by selecting the signaling pathways as shown in Table 1. (See File S4).Table 1. Signaling networks generated from the integration of signaling pathways.Network name SN1 SN2 SN3 SN4 SN5 SNNumber of pathways 1 2 14 20 150Number of nodes 68 137 510 1052 2746Number of edges 89 169 1356 2364 10959doi:10.1371/journal.pone.0068407.tRMOD: Regulatory Motif Detection ToolFigure 5. RMOD system architecture. The Web server hosts the RMOD Web application and accepts user requests via standard Web inhibitor browsers. The RMOD server handles user requests for network and query management, run the network analysis pipeline and presents the result of analyzed input via network viewer. The file management Autophagy module stores all network, regulatory motif and job-related data. doi:10.1371/journal.pone.0068407.gSystem ArchitectureFigure 5 shows the system architecture of RMOD. It comprises of a Web application server (RMOD server) that provides an easyto-use graphical user interfaces (GUIs) accessible via a Web browser, an embedded file management module for storing network, regulatory motif and other job-related data, and network analysis pipeline for regulatory motif identification. The RMOD server and network analysis pipeline can be accessed by multiple users through the RMOD server GUI using standard Web browsers. The RMOD GUI 1315463 provides four main functions to the users: (i) network management for uploading and manipulating input network; (ii) query management for manipulating and generating query regulatory motif; (iii) job submission for running the network analysis pipeline; (iv) graphical visualization of the analyzed input network. The network analysis pipeline is a standalone application that is initiated by the RMOD server at the user’s request and run in batch mode. As shown in Figure 3, the network analysis pipeline includes regulatory motif identification module and additional analysis modules for characterizing structural features of detected regulatory motif. The structural property analysis module calculates the sign, the length of the path and the size of individual regulatory motifs. The path search module, which is used for searching regulatory motif in user-defined path, finds the shortest paths that connect two nodes in network using Floyd algorithm [26] and selects regulatory motifs included in user-defined path. The RMOD system has been designed for easy integration with future network analysis module. The RMOD server was developed using Perl on a Linux platform with an Apache webserver. The Web interface was designed and implemented using Perl, HTML and Asynchronous Javascript and XML (AJAX). Cytoscape Web was also used in the Web interface for network and regulatory motif visualization [27]. AJAX was adopted for controlling the execution of various functions of Cytoscape Web and making Web pages more interactive without page reloading. The core functionalities in the network analysis pipeline wereimplemented using C++ programming language and standard template library. Availability and Requirements Project name: RMOD Project home page: http://pks.kaist.ac.kr/rmod Operating system: LinuxExperimentsAmong the several steps in identifying regulatory motifs, the search for subgraphs in the second step is a key factor in determining the performance of regulatory motif identi.Nodes and 22347 edges that include 18398 activation edges (positive edges) and 3949 inhibitory edges (negative edges). Finally, we generated 6 different sizes of signaling networks by selecting the signaling pathways as shown in Table 1. (See File S4).Table 1. Signaling networks generated from the integration of signaling pathways.Network name SN1 SN2 SN3 SN4 SN5 SNNumber of pathways 1 2 14 20 150Number of nodes 68 137 510 1052 2746Number of edges 89 169 1356 2364 10959doi:10.1371/journal.pone.0068407.tRMOD: Regulatory Motif Detection ToolFigure 5. RMOD system architecture. The Web server hosts the RMOD Web application and accepts user requests via standard Web browsers. The RMOD server handles user requests for network and query management, run the network analysis pipeline and presents the result of analyzed input via network viewer. The file management module stores all network, regulatory motif and job-related data. doi:10.1371/journal.pone.0068407.gSystem ArchitectureFigure 5 shows the system architecture of RMOD. It comprises of a Web application server (RMOD server) that provides an easyto-use graphical user interfaces (GUIs) accessible via a Web browser, an embedded file management module for storing network, regulatory motif and other job-related data, and network analysis pipeline for regulatory motif identification. The RMOD server and network analysis pipeline can be accessed by multiple users through the RMOD server GUI using standard Web browsers. The RMOD GUI 1315463 provides four main functions to the users: (i) network management for uploading and manipulating input network; (ii) query management for manipulating and generating query regulatory motif; (iii) job submission for running the network analysis pipeline; (iv) graphical visualization of the analyzed input network. The network analysis pipeline is a standalone application that is initiated by the RMOD server at the user’s request and run in batch mode. As shown in Figure 3, the network analysis pipeline includes regulatory motif identification module and additional analysis modules for characterizing structural features of detected regulatory motif. The structural property analysis module calculates the sign, the length of the path and the size of individual regulatory motifs. The path search module, which is used for searching regulatory motif in user-defined path, finds the shortest paths that connect two nodes in network using Floyd algorithm [26] and selects regulatory motifs included in user-defined path. The RMOD system has been designed for easy integration with future network analysis module. The RMOD server was developed using Perl on a Linux platform with an Apache webserver. The Web interface was designed and implemented using Perl, HTML and Asynchronous Javascript and XML (AJAX). Cytoscape Web was also used in the Web interface for network and regulatory motif visualization [27]. AJAX was adopted for controlling the execution of various functions of Cytoscape Web and making Web pages more interactive without page reloading. The core functionalities in the network analysis pipeline wereimplemented using C++ programming language and standard template library. Availability and Requirements Project name: RMOD Project home page: http://pks.kaist.ac.kr/rmod Operating system: LinuxExperimentsAmong the several steps in identifying regulatory motifs, the search for subgraphs in the second step is a key factor in determining the performance of regulatory motif identi.
