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).

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.

In the last few years, DNA microarray technology has attained a very important role in biological and biomedical research. It enables analyzing the relations among thousands of genes simultaneously, generating huge amounts of data. The gene networks represent, in a graph data structure, genes or gene products and the functional relationships between them. These models have been fully used in Bioinformatics because they provide an easy way to understand gene expression regulation. Nowadays, a lot of gene network algorithms have been developed as knowledge extraction techniques. A very important task in all these studies is to assure the network models reliability in order to prove that the methods used are precise. This validation process can be carried out by using the inherent information of the input data or by using public biological knowledge. In this last case, these sources of information provide a great opportunity of verifying the biological soundness of the generated networks. In this work, authors present a gene network validation methodology based on the information stored in Kegg database. With this aim, a complete Kegg pathway conversion to gene network is presented, and a global and functional validation process is proposed, where the whole metabolical information stored in Kegg is used at the same time.

In this paper, we propose a greedy clustering algorithm to identify groups of related genes and a new measure to improve the results of this algorithm. Clustering algorithms analyze genes in order to group those with similar behavior. Instead, our approach groups pairs of genes that present similar positive and/or negative interactions. In order to avoid noise in clusters, we apply a threshold, the neighbouring minimun index(λ), to know if a pair of genes have interaction enough or not. The algorithm allows the researcher to modify all the criteria: discretization mapping function, gene-gene mapping function and filtering function, and even the neighbouring minimun index, and provides much flexibility to obtain clusters based on the level of precision needed. We have carried out a deep experimental study in databases to obtain a good neighbouring minimun index, λ. The performance of our approach is experimentally tested on the yeast, yeast cell-cycle and malaria datasets. The final number of clusters has a very high level of customization and genes within show a significant level of cohesion, as it is shown graphically in the experiments.

BACKGROUND: The Gene Ontology (GO) provides a controlled vocabulary for describing the functions of genes and can be used to evaluate the functional coherence of gene sets. Many functional coherence measures consider each pair of gene functions in a set and produce an output based on all pairwise distances. A single gene can encode multiple proteins that may differ in function. For each functionality, other proteins that exhibit the same activity may also participate. Therefore, an identification of the most common function for all of the genes involved in a biological process is important in evaluating the functional similarity of groups of genes and a quantification of functional coherence can helps to clarify the role of a group of genes working together. RESULTS: To implement this approach to functional assessment, we present GFD (GO-based Functional Dissimilarity), a novel dissimilarity measure for evaluating groups of genes based on the most relevant functions of the whole set. The measure assigns a numerical value to the gene set for each of the three GO sub-ontologies. CONCLUSIONS: Results show that GFD performs robustly when applied to gene set of known functionality (extracted from KEGG). It performs particularly well on randomly generated gene sets. An ROC analysis reveals that the performance of GFD in evaluating the functional dissimilarity of gene sets is very satisfactory. A comparative analysis against other functional measures, such as GS2 and those presented by Resnik and Wang, also demonstrates the robustness of GFD.