Identification of disease-causing genes using microarray data mining and gene ontology

Background: One of the best and most accurate methods for identifying disease-causing genes is monitoring gene expression values in different samples using microarray technology. One of the shortcomings of microarray data is that they provide a small quantity of samples with respect to the number of genes. This problem reduces the classification accuracy of the methods, so gene selection is essential to improve the predictive accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVMRFE) has become one of the leading methods, but its performance can be reduced because of the small sample size, noisy data and the fact that the method does not remove redundant genes. Methods: We propose a novel framework for gene selection which uses the advantageous features of conventional methods and addresses their weaknesses. In fact, we have combined the Fisher method and SVMRFE to utilize the advantages of a filtering method as well as an embedded method. Furthermore, we have added a redundancy reduction stage to address the weakness of the Fisher method and SVMRFE. In addition to gene expression values, the proposed method uses Gene Ontology which is a reliable source of information on genes. The use of Gene Ontology can compensate, in part, for the limitations of microarrays, such as having a small number of samples and erroneous measurement results. Results: The proposed method has been applied to colon, Diffuse Large B-Cell Lymphoma (DLBCL) and prostate cancer datasets. The empirical results show that our method has improved classification performance in terms of accuracy, sensitivity and specificity. In addition, the study of the molecular function of selected genes strengthened the hypothesis that these genes are involved in the process of cancer growth. Conclusions: The proposed method addresses the weakness of conventional methods by adding a redundancy reduction stage and utilizing Gene Ontology information. It predicts marker genes for colon, DLBCL and prostate cancer with a high accuracy. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help in the search for a cure for cancers

A lexicographic multi-objective genetic algorithm for multi-label correlation-based feature selection

This paper proposes a new Lexicographic multi-objective Genetic Algorithm for Multi-Label Correlation-based Feature Selection (LexGA-ML-CFS), which is an extension of the previous single-objective Genetic Algorithm for Multi-label Correlation-based Feature Selection (GA-ML-CFS). This extension uses a LexGA as a global search method for generating candidate feature subsets. In our experiments, we compare the results obtained by LexGA-ML-CFS with the results obtained by the original hill climbing-based ML-CFS, the single-objective GA-ML-CFS and a baseline Binary Relevance method, using ML-kNN as the multi-label classifier. The results from our experiments show that LexGA-ML-CFS improved predictive accuracy, by comparison with other methods, in some cases, but in general there was no statistically significant different between the results of LexGA-ML-CFS and other methods

NCBO Ontology Recommender 2.0: An Enhanced Approach for Biomedical Ontology Recommendation

Biomedical researchers use ontologies to annotate their data with ontology terms, enabling better data integration and interoperability. However, the number, variety and complexity of current biomedical ontologies make it cumbersome for researchers to determine which ones to reuse for their specific needs. To overcome this problem, in 2010 the National Center for Biomedical Ontology (NCBO) released the Ontology Recommender, which is a service that receives a biomedical text corpus or a list of keywords and suggests ontologies appropriate for referencing the indicated terms. We developed a new version of the NCBO Ontology Recommender. Called Ontology Recommender 2.0, it uses a new recommendation approach that evaluates the relevance of an ontology to biomedical text data according to four criteria: (1) the extent to which the ontology covers the input data; (2) the acceptance of the ontology in the biomedical community; (3) the level of detail of the ontology classes that cover the input data; and (4) the specialization of the ontology to the domain of the input data. Our evaluation shows that the enhanced recommender provides higher quality suggestions than the original approach, providing better coverage of the input data, more detailed information about their concepts, increased specialization for the domain of the input data, and greater acceptance and use in the community. In addition, it provides users with more explanatory information, along with suggestions of not only individual ontologies but also groups of ontologies. It also can be customized to fit the needs of different scenarios. Ontology Recommender 2.0 combines the strengths of its predecessor with a range of adjustments and new features that improve its reliability and usefulness. Ontology Recommender 2.0 recommends over 500 biomedical ontologies from the NCBO BioPortal platform, where it is openly available.Comment: 29 pages, 8 figures, 11 table

Modeling cumulative biological phenomena with Suppes-Bayes Causal Networks

Several diseases related to cell proliferation are characterized by the accumulation of somatic DNA changes, with respect to wildtype conditions. Cancer and HIV are two common examples of such diseases, where the mutational load in the cancerous/viral population increases over time. In these cases, selective pressures are often observed along with competition, cooperation and parasitism among distinct cellular clones. Recently, we presented a mathematical framework to model these phenomena, based on a combination of Bayesian inference and Suppes' theory of probabilistic causation, depicted in graphical structures dubbed Suppes-Bayes Causal Networks (SBCNs). SBCNs are generative probabilistic graphical models that recapitulate the potential ordering of accumulation of such DNA changes during the progression of the disease. Such models can be inferred from data by exploiting likelihood-based model-selection strategies with regularization. In this paper we discuss the theoretical foundations of our approach and we investigate in depth the influence on the model-selection task of: (i) the poset based on Suppes' theory and (ii) different regularization strategies. Furthermore, we provide an example of application of our framework to HIV genetic data highlighting the valuable insights provided by the inferred

Resampling methods for parameter-free and robust feature selection with mutual information

Combining the mutual information criterion with a forward feature selection strategy offers a good trade-off between optimality of the selected feature subset and computation time. However, it requires to set the parameter(s) of the mutual information estimator and to determine when to halt the forward procedure. These two choices are difficult to make because, as the dimensionality of the subset increases, the estimation of the mutual information becomes less and less reliable. This paper proposes to use resampling methods, a K-fold cross-validation and the permutation test, to address both issues. The resampling methods bring information about the variance of the estimator, information which can then be used to automatically set the parameter and to calculate a threshold to stop the forward procedure. The procedure is illustrated on a synthetic dataset as well as on real-world examples