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

An integrated approach of particle swarm optimization and support vector machine for gene signature selection and cancer prediction

To improve cancer diagnosis and drug development, the classification of tumor types based on genomic information is important. As DNA micro array studies produce a large amount of data, expression data are highly redundant and noisy, and most genes are believed to be uninformative with respect to the studied classes. Only a fraction of genes may present distinct profiles for different classes of samples. Classification tools to deal with these issues are thus important. These tools should learn to robustly identify a subset of informative genes embedded in a large dataset that is contaminated with high dimensional noises. In this paper, an integrated approach of support vector machine (SVM) and particle swarm optimization (PSO) is proposed for this purpose. The proposed approach can simultaneously optimize the selection of feature subset and the classifier through a common solution coding mechanism. As an illustration, the proposed approach is applied to search the combinational gene signatures for predicting histologic response to chemotherapy of osteosarcoma patients. Cross validation results show that the proposed approach outperforms other existing methods in terms of classification accuracy. Further validation using an independent dataset shows misclassification of only one out of fourteen patient samples, suggesting that the selected gene signatures can reflect the chemoresistance in osteosarcoma

Semi-automatic 3D reconstruction of atheroma plaques from intravascular ultrasound images using an ad-hoc algorithm

The occurrence of atheroma plaques in the arteries can eventually obstruct them, leading to diseases such as atherosclerosis, which can cause, among others, a myocardial infarction or a stroke. As a consequence, it is necessary to shorten the time spent in locating and reconstructing the atheroma plaque that can be developed in an artery. This localization is usually conducted manually from the contours located on the cross-sectional radiographs of the artery and then reconstructed by creating the volumes using different techniques. This paper presents a 3-D reconstruction of the atheroma plaque by applying an image processing algorithm ad-hoc developed in order to obtain the boundaries of the atheroma, from a set of intravascular ultrasound images. The advantage of the approach developed in this paper is that it can be implemented in common medical procedures, as an important complementary decision-support tool. By reconstructing the atheroma instead of the artery, this work provides a different approach to improve its location and treatment. Results presented herein can be implemented in machine-learning-based algorithms, able to predict the growth and extent of incipient atheroma plaques, which ultimately contribute to an early detection of this pathology

Kernel methods in genomics and computational biology

Support vector machines and kernel methods are increasingly popular in genomics and computational biology, due to their good performance in real-world applications and strong modularity that makes them suitable to a wide range of problems, from the classification of tumors to the automatic annotation of proteins. Their ability to work in high dimension, to process non-vectorial data, and the natural framework they provide to integrate heterogeneous data are particularly relevant to various problems arising in computational biology. In this chapter we survey some of the most prominent applications published so far, highlighting the particular developments in kernel methods triggered by problems in biology, and mention a few promising research directions likely to expand in the future

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