Norberto Díaz-Díaz

GO-based Functional Dissimilarity of Gene Sets

BackgroundThe 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.ResultsTo 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.ConclusionsResults 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.

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.

Gene network coherence based on prior knowledge using direct and indirect relationships

Gene networks (GNs) have become one of the most important approaches for modeling biological processes. They are very useful to understand the different complex biological processes that may occur in living organisms. Currently, one of the biggest challenge in any study related with GN is to assure the quality of these GNs. In this sense, recent works use artificial data sets or a direct comparison with prior biological knowledge. However, these approaches are not entirely accurate as they only take into account direct gene-gene interactions for validation, leaving aside the weak (indirect) relationships. We propose a new measure, named gene network coherence (GNC), to rate the coherence of an input network according to different biological databases. In this sense, the measure considers not only the direct gene-gene relationships but also the indirect ones to perform a complete and fairer evaluation of the input network. Hence, our approach is able to use the whole information stored in the networks. A GNC JAVA-based implementation is available at: http://fgomezvela.github.io/GNC/. The results achieved in this work show that GNC outperforms the classical approaches for assessing GNs by means of three different experiments using different biological databases and input networks. According to the results, we can conclude that the proposed measure, which considers the inherent information stored in the direct and indirect gene-gene relationships, offers a new robust solution to the problem of GNs biological validation.

CarGene: Characterisation of sets of genes based on metabolic pathways analysis

The great amount of biological information provides scientists with an incomparable framework for testing the results of new algorithms. Several tools have been developed for analysing gene-enrichment and most of them are Gene Ontology-based tools. We developed a Kyoto Encyclopedia of Genes and Genomes (Kegg)-based tool that provides a friendly graphical environment for analysing gene-enrichment. The tool integrates two statistical corrections and simultaneously analysing the information about many groups of genes in both visual and textual manner. We tested the usefulness of our approach on a previous analysis (Huttenshower et al.). Furthermore, our tool is freely available (http://www.upo.es/eps/bigs/cargene.html).

Gene Network Biological Validity Based on Gene-Gene Interaction Relevance

In recent years, gene networks have become one of the most useful tools for modeling biological processes. Many inference gene network algorithms have been developed as techniques for extracting knowledge from gene expression data. Ensuring the reliability of the inferred gene relationships is a crucial task in any study in order to prove that the algorithms used are precise. Usually, this validation process can be carried out using prior biological knowledge. The metabolic pathways stored in KEGG are one of the most widely used knowledgeable sources for analyzing relationships between genes. This paper introduces a new methodology, GeneNetVal, to assess the biological validity of gene networks based on the relevance of the gene-gene interactions stored in KEGG metabolic pathways. Hence, a complete KEGG pathway conversion into a gene association network and a new matching distance based on gene-gene interaction relevance are proposed. The performance of GeneNetVal was established with three different experiments. Firstly, our proposal is tested in a comparative ROC analysis. Secondly, a randomness study is presented to show the behavior of GeneNetVal when the noise is increased in the input network. Finally, the ability of GeneNetVal to detect biological functionality of the network is shown.

Incorporating biological knowledge for construction of fuzzy networks of gene associations

Graphical abstractDisplay Omitted HighlightsA novel fuzzy-based approach to generate gene association networks is developed.It is able to deal with data noise by incorporating biological.Its performance was proved by means of four thorough experiments.The method is able is able to obtain a high number of edges with biological meaning. Gene association networks have become one of the most important approaches to modelling of biological processes by means of gene expression data. According to the literature, co-expression-based methods are the main approaches to identification of gene association networks because such methods can identify gene expression patterns in a dataset and can determine relations among genes. These methods usually have two fundamental drawbacks. Firstly, they are dependent on quality of the input dataset for construction of reliable models because of the sensitivity to data noise. Secondly, these methods require that the user select a threshold to determine whether a relation is biologically relevant. Due to these shortcomings, such methods may ignore some relevant information.We present a novel fuzzy approach named FyNE (Fuzzy NEtworks) for modelling of gene association networks. FyNE has two fundamental features. Firstly, it can deal with data noise using a fuzzy-set-based protocol. Secondly, the proposed approach can incorporate prior biological knowledge into the modelling phase, through a fuzzy aggregation function. These features help to gain some insights into doubtful gene relations.The performance of FyNE was tested in four different experiments. Firstly, the improvement offered by FyNE over the results of a co-expression-based method in terms of identification of gene networks was demonstrated on different datasets from different organisms. Secondly, the results produced by FyNE showed its low sensitivity to noise data in a randomness experiment. Additionally, FyNE could infer gene networks with a biological structure in a topological analysis. Finally, the validity of our proposed method was confirmed by comparing its performance with that of some representative methods for identification of gene networks

Feature selection based on bootstrapping

The results of feature selection methods have a great influence on the success of data mining processes, especially when the data sets have high dimensionality. In order to find the optimal result from feature selection methods, we should check each possible subset of features to obtain the precision on classification, i.e., an exhaustive search through the search space. However, it is an unfeasible task due to its computational complexity. In this paper, we propose a novel method of feature selection based on bootstrapping techniques. Our approach shows that it is not necessary to try every subset of features, but only a very small subset of combinations to achieve the same performance as the exhaustive approach. The experiments have been carried out using very high-dimensional datasets (thousands of features) and they show that it is possible to maintain the precision at the same time that the complexity is reduced substantially

A measure for data set editing by ordered projections

In this paper we study a measure, named weakness of an example, which allows us to establish the importance of an example to find representative patterns for the data set editing problem. Our approach consists in reducing the database size without losing information, using algorithm patterns by ordered projections. The idea is to relax the reduction factor with a new parameter, λ, removing all examples of the database whose weakness verify a condition over this λ. We study how to establish this new parameter. Our experiments have been carried out using all databases from UCI-Repository and they show that is possible a size reduction in complex databases without notoriously increase of the error rate.

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.

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

Summary: 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 Contact: enrico.petretto@duke-nus.edu.sg Supplementary information: Supplementary data are available at Bioinformatics online.