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      Improving Classification of Cancer and Mining Biomarkers from Gene Expression Profiles Using Hybrid Optimization Algorithms and Fuzzy Support Vector Machine

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          Abstract

          Background:

          Gene expression data are characteristically high dimensional with a small sample size in contrast to the feature size and variability inherent in biological processes that contribute to difficulties in analysis. Selection of highly discriminative features decreases the computational cost and complexity of the classifier and improves its reliability for prediction of a new class of samples.

          Methods:

          The present study used hybrid particle swarm optimization and genetic algorithms for gene selection and a fuzzy support vector machine (SVM) as the classifier. Fuzzy logic is used to infer the importance of each sample in the training phase and decrease the outlier sensitivity of the system to increase the ability to generalize the classifier. A decision-tree algorithm was applied to the most frequent genes to develop a set of rules for each type of cancer. This improved the abilities of the algorithm by finding the best parameters for the classifier during the training phase without the need for trial-and-error by the user. The proposed approach was tested on four benchmark gene expression profiles.

          Results:

          Good results have been demonstrated for the proposed algorithm. The classification accuracy for leukemia data is 100%, for colon cancer is 96.67% and for breast cancer is 98%. The results show that the best kernel used in training the SVM classifier is the radial basis function.

          Conclusions:

          The experimental results show that the proposed algorithm can decrease the dimensionality of the dataset, determine the most informative gene subset, and improve classification accuracy using the optimal parameters of the classifier with no user interface.

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          Most cited references45

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          Quantitative monitoring of gene expression patterns with a complementary DNA microarray.

          A high-capacity system was developed to monitor the expression of many genes in parallel. Microarrays prepared by high-speed robotic printing of complementary DNAs on glass were used for quantitative expression measurements of the corresponding genes. Because of the small format and high density of the arrays, hybridization volumes of 2 microliters could be used that enabled detection of rare transcripts in probe mixtures derived from 2 micrograms of total cellular messenger RNA. Differential expression measurements of 45 Arabidopsis genes were made by means of simultaneous, two-color fluorescence hybridization.
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            Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays.

            Oligonucleotide arrays can provide a broad picture of the state of the cell, by monitoring the expression level of thousands of genes at the same time. It is of interest to develop techniques for extracting useful information from the resulting data sets. Here we report the application of a two-way clustering method for analyzing a data set consisting of the expression patterns of different cell types. Gene expression in 40 tumor and 22 normal colon tissue samples was analyzed with an Affymetrix oligonucleotide array complementary to more than 6,500 human genes. An efficient two-way clustering algorithm was applied to both the genes and the tissues, revealing broad coherent patterns that suggest a high degree of organization underlying gene expression in these tissues. Coregulated families of genes clustered together, as demonstrated for the ribosomal proteins. Clustering also separated cancerous from noncancerous tissue and cell lines from in vivo tissues on the basis of subtle distributed patterns of genes even when expression of individual genes varied only slightly between the tissues. Two-way clustering thus may be of use both in classifying genes into functional groups and in classifying tissues based on gene expression.
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              MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia.

              Acute lymphoblastic leukemias carrying a chromosomal translocation involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can clearly be separated from conventional acute lymphoblastic and acute myelogenous leukemias. We propose that they constitute a distinct disease, denoted here as MLL, and show that the differences in gene expression are robust enough to classify leukemias correctly as MLL, acute lymphoblastic leukemia or acute myelogenous leukemia. Establishing that MLL is a unique entity is critical, as it mandates the examination of selectively expressed genes for urgently needed molecular targets.
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                Author and article information

                Journal
                J Med Signals Sens
                J Med Signals Sens
                JMSS
                Journal of Medical Signals and Sensors
                Medknow Publications & Media Pvt Ltd (India )
                2228-7477
                Jan-Mar 2018
                : 8
                : 1
                : 1-11
                Affiliations
                [1] Department of Biomedical Engineering, Islamic Azad University, Science and Research Branch, Tehran, Iran
                [1 ] Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
                Author notes
                Address for correspondence: Dr. Keivan Maghooli, Department of Biomedical Engineering, Islamic Azad University, Science and Research Branch, Tehran, Iran. E-mail: k_maghooli@ 123456srbiau.ac.ir
                Article
                JMSS-8-1
                10.4103/jmss.JMSS_21_17
                5840891
                29535919
                2e0055cb-009f-442f-9053-d98f40b3037c
                Copyright: © 2018 Journal of Medical Signals & Sensors

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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                Categories
                Original Article

                Radiology & Imaging
                cancer classification,fuzzy support vector machine,gene expression,genetic algorithm,particle swarm optimization algorithm

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