Development and use of a Cytoscape app for GRNCOP2.

BACKGROUND AND OBJECTIVE: Gene regulatory networks (GRNs) are essential for understanding most molecular processes. In this context, the so-called model-free approaches have an advantage modeling the complex topologies behind these dynamic molecular networks, since most GRNs are difficult to map correctly by any other mathematical model. Abstract model-free approaches, also known as rule-based extraction methods, offer valuable benefits when performing data-driven analysis; such as requiring the least amount of data and simplifying the inference of large models at a faster analysis speed. In particular, GRNCOP2 is a combinatorial optimization method with an adaptive criterion for the discretization of gene expression data and high performance, in contrast to other rule-based extraction methods for discovering GRNs. However, the analysis of the large relational structures of the networks inferred by GRNCOP2 requires the support of effective tools for interactive network visualization and topological analysis of the extracted associations. This need motivated the possibility of integrating GRNCOP2 in the Cytoscape ecosystem in order to benefit from Cytoscapes core functionality, as well as all the other apps in its ecosystem. METHODS: In this paper, we introduce the implementation of a GRNCOP2 Cytoscape app. This incorporation to Cytoscape platform includes new functionality for GRN visualizations, dynamic user-interaction and integration with other apps for topological analysis of the networks. RESULTS: In order to demonstrate the usefulness of integrating GRNCOP2 in Cytoscape, the new app was used to tackle a novel use case for GRNCOP2: the analysis of crosstalk between pathways. In this regard, datasets associated with Alzheimer's disease (AD) were analyzed using GRNCOP2 app and other apps of the Cytoscape ecosystem by performing a topological analysis of the AD progression and its synchronization with the Ubiquitin Mediated Proteolysis pathway. Finally, the biological relevance of the findings achieved by this new app were evaluated by searching for evidence in the literature. CONCLUSIONS: The proposed crosstalk analysis with the new GRNCOP2 app focused on assessing the phase of the Alzheimer's disease progression where the coordination with the Ubiquitin Mediated Proteolysis pathway increase, and identifying the genes that explain the signalling between these cellular processes. Both questions were explored by topological contrastive analysis of the GRNs generated for the GRNCOP2 app, where several facilities of Cytoscape were exploited. The topological patterns inferred by this new App have been consistent with biological evidence reported in the scientic literature, illustrating the effectiveness of using this new GRNCOP2 App in pathway analysis. AVAILABILITY: The GRNCOP2 App is freely available at the official Cytoscape app store: http://apps.cytoscape.org/apps/grncop2.

GNC-app: A new Cytoscape app to rate gene networks biological coherence using gene-gene indirect relationships.

MOTIVATION: Gene networks are currently considered a powerful tool to model biological processes in the Bioinformatics field. A number of approaches to infer gene networks and various software tools to handle them in a visual simplified way have been developed recently. However, there is still a need to assess the inferred networks in order to prove their relevance. RESULTS: In this paper, we present the new GNC-app for Cytoscape. GNC-app implements the GNC methodology for assessing the biological coherence of gene association networks and integrates it into Cytoscape. Implemented de novo, GNC-app significantly improves the performance of the original algorithm in order to be able to analyse large gene networks more efficiently. It has also been integrated in Cytoscape to increase the tool accessibility for non-technical users and facilitate the visual analysis of the results. This integration allows the user to analyse not only the global biological coherence of the network, but also the biological coherence at the gene-gene relationship level. It also allows the user to leverage Cytoscape capabilities as well as its rich ecosystem of apps to perform further analyses and visualizations of the network using such data. AVAILABILITY: The GNC-app is freely available at the official Cytoscape app store: http://apps.cytoscape.org/apps/gnc.

GFD-Net: A novel semantic similarity methodology for the analysis of gene networks.

Since the popularization of biological network inference methods, it has become crucial to create methods to validate the resulting models. Here we present GFD-Net, the first methodology that applies the concept of semantic similarity to gene network analysis. GFD-Net combines the concept of semantic similarity with the use of gene network topology to analyze the functional dissimilarity of gene networks based on Gene Ontology (GO). The main innovation of GFD-Net lies in the way that semantic similarity is used to analyze gene networks taking into account the network topology. GFD-Net selects a functionality for each gene (specified by a GO term), weights each edge according to the dissimilarity between the nodes at its ends and calculates a quantitative measure of the network functional dissimilarity, i.e. a quantitative value of the degree of dissimilarity between the connected genes. The robustness of GFD-Net as a gene network validation tool was demonstrated by performing a ROC analysis on several network repositories. Furthermore, a well-known network was analyzed showing that GFD-Net can also be used to infer knowledge. The relevance of GFD-Net becomes more evident in Section "GFD-Net applied to the study of human diseases" where an example of how GFD-Net can be applied to the study of human diseases is presented. GFD-Net is available as an open-source Cytoscape app which offers a user-friendly interface to configure and execute the algorithm as well as the ability to visualize and interact with the results(http://apps.cytoscape.org/apps/gfdnet).

Web-based Gene Pathogenicity Analysis (WGPA): a web platform to interpret gene pathogenicity from personal genome data.

UNLABELLED: As the volume of patient-specific genome sequences increases the focus of biomedical research is switching from the detection of disease-mutations to their interpretation. To this end a number of techniques have been developed that use mutation data collected within a population to predict whether individual genes are likely to be disease-causing or not. As both sequence data and associated analysis tools proliferate, it becomes increasingly difficult for the community to make sense of these data and their implications. Moreover, no single analysis tool is likely to capture all relevant genomic features that contribute to the gene's pathogenicity. Here, we introduce Web-based Gene Pathogenicity Analysis (WGPA), a web-based tool to analyze genes impacted by mutations and rank them through the integration of existing prioritization tools, which assess different aspects of gene pathogenicity using population-level sequence data. Additionally, to explore the polygenic contribution of mutations to disease, WGPA implements gene set enrichment analysis to prioritize disease-causing genes and gene interaction networks, therefore providing a comprehensive annotation of personal genomes data in disease. AVAILABILITY AND IMPLEMENTATION: wgpa.systems-genetics.net.

Development and use of the Cytoscape app GFD-Net for measuring semantic dissimilarity of gene networks.

Gene networks are one of the main computational models used to study the interaction between different elements during biological processes being widely used to represent gene-gene, or protein-protein interaction complexes. We present GFD-Net, a Cytoscape app for visualizing and analyzing the functional dissimilarity of gene networks.