Cancer classification using ensemble of neural networks with multiple significant gene subsets

Molecular level diagnostics based on microarray technologies can offer the methodology of precise, objective, and systematic cancer classification. Genome-wide expression patterns generally consist of thousands of genes. It is desirable to extract some significant genes for accurate diagnosis of cancer because not all genes are associated with a cancer. In this paper, we have used representative gene vectors that are highly discriminatory for cancer classes and extracted multiple significant gene subsets based on those representative vectors respectively. Also, an ensemble of neural networks learned from the multiple significant gene subsets is proposed to classify a sample into one of several cancer classes. The performance of the proposed method is systematically evaluated using three different cancer types: Leukemia, colon, and B-cell lymphoma.     

基于主成份分析的肿瘤分类检测算法研究

基于基因表达谱的肿瘤诊断方法有望成为临床医学上一种快速而有效的诊断方法,但由于基因表达数据存在维数过高、样本量很小以及噪音大等特点,使得提取与肿瘤有关的信息基因成为一件有挑战性的工作。因此,在分析了目前肿瘤分类检测所采用方法的基础上,本文提出了一种结合基因特征记分和主成份分析的混合特征抽取方法。实验表明明,这种方法能够有效地提取分类特征信息,并在保持较高的肿瘤识别准确率的前提下大幅度地降低基因表达数据的维数,使得分类器性能得到很大提高。实验采用了两种与肿瘤有关的基因表达数据集来验证这种混合特征抽取方法的有效性,采用支持向量机的分类实验结果表明,所提出的混合方法不仅交叉验证识别准确率高而且分类结果能够可
可视化。对于结肠癌组织样本集,其交叉验证识别准确率高这95．16％;而对于急性白血病组织样本集,其交叉验证识别准确率高这100％。     

A novel approach to feature extraction from classification models based on information gene pairs

Various microarray experiments are now done in many laboratories, resulting in the rapid accumulation of microarray data in public repositories. One of the major challenges of analyzing microarray data is how to extract and select efficient features from it for accurate cancer classification. Here we introduce a new feature extraction and selection method based on information gene pairs that have significant change in different tissue samples. Experimental results on five public microarray data sets demonstrate that the feature subset selected by the proposed method performs well and achieves higher classification accuracy on several classifiers. We perform extensive experimental comparison of the features selected by the proposed method and features selected by other methods using different evaluation methods and classifiers. The results confirm that the proposed method performs as well as other methods on acute lymphoblastic-acute myeloid leukemia, adenocarcinoma and breast cancer data sets using a fewer information genes and leads to significant improvement of classification accuracy on colon and diffuse large B cell lymphoma cancer data sets.     

WEKA平台在肿瘤分类研究中的应用

采用传统的病理学诊断方法对肿瘤进行分类存在一定的局限性,基因芯片等高通量技术的问世为肿瘤研究带来了革命性的进展,在肿瘤分类中发挥了积极作用。该文以weka数据挖掘平台作为特征基因选择与样本分类模型建立的工具,解决了肿瘤分类理论性强,操作难度高的问题。该文以97名乳腺肿瘤患者的基因表达谱数据进行实验,实验结果表明,weka平台可以有效降低基因表达谱数据的维度,对肿瘤的精确诊断具有较高应用价值。     

基于粗糙集的基因表达数据分类研究

从微阵列得到的基因表达数据可以用于癌症的分类。该文介绍了基于粗糙集的基因表达数据分类方法,并在急性白血病的数据集上验证了该方法的有效性。实验表明,该方法能取得较高的预测准确率,可以成为生物信息学研究领域的有力工具。     

Extracting gene regulation information for cancer classification

In this paper, we address the problem of extracting gene regulation information from microarray data for cancer classification. From the biological viewpoint, a model of gene regulation probability is established where three types of gene regulation states in a tissue sample are assumed and then two regulation events correlated with the class distinction are defined. Different from the previous approaches, the proposed algorithm uses gene regulation probabilities as carriers of regulation information to select genes and construct classifiers. The proposed approach is successfully applied to two public available microarray data sets, the leukemia data and the prostate data. Experimental results suggest that gene selection based on regulation information can greatly improve cancer classification, and the classifier based on regulation information is more efficient and more stable than several previous classification algorithms.     

Gene selection using genetic algorithm and support vectors machines

In this paper, we present a gene selection method based on genetic algorithm (GA) and support vector machines (SVM) for cancer classification. First, the Wilcoxon rank sum test is used to filter noisy and redundant genes in high dimensional microarray data. Then, the different highly informative genes subsets are selected by GA/SVM using different training sets. The final subset, consisting of highly discriminating genes, is obtained by analyzing the frequency of appearance of each gene in the different gene subsets. The proposed method is tested on three open datasets: leukemia, breast cancer, and colon cancer data. The results show that the proposed method has excellent selection and classification performance, especially for breast cancer data, which can yield 100% classification accuracy using only four genes.     

Ensemble Rough Hypercuboid Approach for Classifying Cancers

Cancer classification is the critical basis for patient-tailored therapy. Conventional histological analysis tends to be unreliable because different tumors may have similar appearance. The advances in microarray technology make individualized therapy possible. Various machine learning methods can be employed to classify cancer tissue samples based on microarray data. However, few methods can be elegantly adopted for generating accurate and reliable as well as biologically interpretable rules. In this paper, we introduce an approach for classifying cancers based on the principle of minimal rough fringe. For training rough hypercuboid classifiers from gene expression data sets, the method dynamically evaluates all available genes and sifts the genes with the smallest implicit regions as the dimensions of implicit hypercuboids. An unseen object is predicted to be a certain class if it falls within the corresponding class hypercuboid. Based upon the method, ensemble rough hypercuboid classifiers are subsequently constructed. Experimental results on some open cancer gene expression data sets show that the proposed method is capable of generating accurate and interpretable rules compared with some other machine learning methods. Hence, it is a feasible way of classifying cancer tissues in biomedical applications.     

肿瘤信息基因启发式宽度优先搜索算法研究

基于基因表达谱的肿瘤检测方法有望成为临床医学上一种快速而有效的肿瘤分子诊断方法,但由于基因表达谱数据存在维数过高、样本量很小以及噪音很大等特点,使得肿瘤信息基因选择成为一件有挑战性的工作.根据肿瘤基因表达谱样本集的特点,提出了一种以支持向量机分类性能为评估准则的寻找信息基因的启发式宽度优先搜索算法,其优点是能够同时搜索到基因数量尽可能少而分类能力尽可能强的多个信息基因子集.实验采用了3种肿瘤样本集以验证新算法的可行性和有效性,对于急性白血病、难以分类的结肠癌和多肿瘤亚型的小圆蓝细胞瘤样本集,分别只需2,4和4个信息基因就能获得100%的4-折交叉验证识别准确率.与其它优秀的肿瘤分类方法相比,实验结果在信息基因数量及其分类性能方面具有明显的优越性.为避免样本集的不同划分对分类性能的影响,提出了一种能够更加客观地反映信息基因子集分类性能的全折交叉验证评估方法.     

gene-CBR: A CASE-BASED REASONIG TOOL FOR CANCER DIAGNOSIS USING MICROARRAY DATA SETS

Gene expression profiles are composed of thousands of genes at the same time, representing the complex relationships between them. One of the well-known constraints specifically related to microarray data is the large number of genes in comparison with the small number of available experiments or cases. In this context, the ability of design methods capable of overcoming current limitations of state-of-the-art algorithms is crucial to the development of successful applications. This paper presents gene -CBR, a hybrid model that can perform cancer classification based on microarray data. The system employs a case-based reasoning model that incorporates a set of fuzzy prototypes, a growing cell structure network and a set of rules to provide an accurate diagnosis. The hybrid model has been implemented and tested with microarray data belonging to bone marrow cases from forty-three adult patients with cancer plus a group of six cases corresponding to healthy persons.     

Cascade of genetic algorithm and decision tree for cancer classification on gene expression data

Abstract: Cancer classification, through gene expression data analysis, has produced remarkable results, and has indicated that gene expression assays could significantly aid in the development of efficient cancer diagnosis and classification platforms. However, cancer classification, based on DNA array data, remains a difficult problem. The main challenge is the overwhelming number of genes relative to the number of training samples, which implies that there are a large number of irrelevant genes to be dealt with. Another challenge is from the presence of noise inherent in the data set. It makes accurate classification of data more difficult when the sample size is small. We apply genetic algorithms (GAs) with an initial solution provided by t statistics, called t‐GA, for selecting a group of relevant genes from cancer microarray data. The decision‐tree‐based cancer classifier is built on the basis of these selected genes. The performance of this approach is evaluated by comparing it to other gene selection methods using publicly available gene expression data sets. Experimental results indicate that t‐GA has the best performance among the different gene selection methods. The Z‐score figure also shows that some genes are consistently preferentially chosen by t‐GA in each data set.     

Gene Selection for Cancer Classification using Support Vector Machines

DNA micro-arrays now permit scientists to screen thousands of genes simultaneously and determine whether those genes are active, hyperactive or silent in normal or cancerous tissue. Because these new micro-array devices generate bewildering amounts of raw data, new analytical methods must be developed to sort out whether cancer tissues have distinctive signatures of gene expression over normal tissues or other types of cancer tissues.In this paper, we address the problem of selection of a small subset of genes from broad patterns of gene expression data, recorded on DNA micro-arrays. Using available training examples from cancer and normal patients, we build a classifier suitable for genetic diagnosis, as well as drug discovery. Previous attempts to address this problem select genes with correlation techniques. We propose a new method of gene selection utilizing Support Vector Machine methods based on Recursive Feature Elimination (RFE). We demonstrate experimentally that the genes selected by our techniques yield better classification performance and are biologically relevant to cancer.In contrast with the baseline method, our method eliminates gene redundancy automatically and yields better and more compact gene subsets. In patients with leukemia our method discovered 2 genes that yield zero leave-one-out error, while 64 genes are necessary for the baseline method to get the best result (one leave-one-out error). In the colon cancer database, using only 4 genes our method is 98% accurate, while the baseline method is only 86% accurate.     

Ensemble gene selection for cancer classification

Cancer diagnosis is an important emerging clinical application of microarray data. Its accurate prediction to the type or size of tumors relies on adopting powerful and reliable classification models, so as to patients can be provided with better treatment or response to therapy. However, the high dimensionality of microarray data may bring some disadvantages, such as over-fitting, poor performance and low efficiency, to traditional classification models. Thus, one of the challenging tasks in cancer diagnosis is how to identify salient expression genes from thousands of genes in microarray data that can directly contribute to the phenotype or symptom of disease. In this paper, we propose a new ensemble gene selection method (EGS) to choose multiple gene subsets for classification purpose, where the significant degree of gene is measured by conditional mutual information or its normalized form. After different gene subsets have been obtained by setting different starting points of the search procedure, they will be used to train multiple base classifiers and then aggregated into a consensus classifier by the manner of majority voting. The proposed method is compared with five popular gene selection methods on six public microarray datasets and the comparison results show that our method works well.     

Multiple-kernel SVM based multiple-task oriented data mining system for gene expression data analysis

Gene expression profiling using DNA microarray technique has been shown as a promising tool to improve the diagnosis and treatment of cancer. Recently, many computational methods have been used to discover maker genes, make class prediction and class discovery based on gene expression data of cancer tissue. However, those techniques fall short on some critical areas. These included (a) interpretation of the solution and extracted knowledge. (b) Integrating various sources data and incorporating the prior knowledge into the system. (c) Giving a global understanding of biological complex systems by a complete knowledge discovery framework. This paper proposes a multiple-kernel SVM based data mining system. Multiple tasks, including feature selection, data fusion, class prediction, decision rule extraction, associated rule extraction and subclass discovery, are incorporated in an integrated framework. ALL-AML Leukemia dataset is used to demonstrate the performance of this system.     

Empirical characterization of random forest variable importance measures

Microarray studies yield data sets consisting of a large number of candidate predictors (genes) on a small number of observations (samples). When interest lies in predicting phenotypic class using gene expression data, often the goals are both to produce an accurate classifier and to uncover the predictive structure of the problem. Most machine learning methods, such as k-nearest neighbors, support vector machines, and neural networks, are useful for classification. However, these methods provide no insight regarding the covariates that best contribute to the predictive structure. Other methods, such as linear discriminant analysis, require the predictor space be substantially reduced prior to deriving the classifier. A recently developed method, random forests (RF), does not require reduction of the predictor space prior to classification. Additionally, RF yield variable importance measures for each candidate predictor. This study examined the effectiveness of RF variable importance measures in identifying the true predictor among a large number of candidate predictors. An extensive simulation study was conducted using 20 levels of correlation among the predictor variables and 7 levels of association between the true predictor and the dichotomous response. We conclude that the RF methodology is attractive for use in classification problems when the goals of the study are to produce an accurate classifier and to provide insight regarding the discriminative ability of individual predictor variables. Such goals are common among microarray studies, and therefore application of the RF methodology for the purpose of obtaining variable importance measures is demonstrated on a microarray data set.     

Bayesian binary kernel probit model for microarray based cancer classification and gene selection

With the arrival of gene expression microarrays a new challenge has opened up for identification or classification of cancer tissues. Due to the large number of genes providing valuable information simultaneously compared to very few available tissue samples the cancer staging or classification becomes very tricky.In this paper we introduce a hierarchical Bayesian probit model for two class cancer classification. Instead of assuming a linear structure for the function that relates the gene expressions with the cancer types we only assume that the relationship is explained by an unknown function which belongs to an abstract functional space like the reproducing kernel Hilbert space. Our formulation automatically reduces the dimension of the problem from the large number of covariates or genes to a small sample size. We incorporate a Bayesian gene selection scheme with the automatic dimension reduction to adaptively select important genes and classify cancer types under an unified model. Our model is highly flexible in terms of explaining the relationship between the cancer types and gene expression measurements and picking up the differentially expressed genes. The proposed model is successfully tested on three simulated data sets and three publicly available leukemia cancer, colon cancer, and prostate cancer real life data sets.     

Cloud computing-based parallel genetic algorithm for gene selection in cancer classification

Cancer classification is one of the main steps during patient healing process. This fact enforces modern clinical researchers to use advanced bioinformatics methods for cancer classification. Cancer classification is usually performed using gene expression data gained in microarray experiment and advanced machine learning methods. Microarray experiment generates huge amount of data, and its processing via machine learning methods represents a big challenge. In this study, two-step classification paradigm which merges genetic algorithm feature selection and machine learning classifiers is utilized. Genetic algorithm is built in MapReduce programming spirit which makes this algorithm highly scalable for Hadoop cluster. In order to improve the performance of the proposed algorithm, it is extended into a parallel algorithm which process on microarray data in distributed manner using the Hadoop MapReduce framework. In this paper, the algorithm was tested on eleven GEMS data sets (9 tumors, 11 tumors, 14 tumors, brain tumor 1, lung cancer, brain tumor 2, leukemia 1, DLBCL, leukemia 2, SRBCT, and prostate tumor) and its accuracy reached 100% for less than 25 selected features. The proposed cloud computing-based MapReduce parallel genetic algorithm performed well on gene expression data. In addition, the scalability of the suggested algorithm is unlimited because of underlying Hadoop MapReduce platform. The presented results indicate that the proposed method can be effectively implemented for real-world microarray data in the cloud environment. In addition, the Hadoop MapReduce framework demonstrates substantial decrease in the computation time.

     

Multiclass sparse logistic regression for classification of multiple cancer types using gene expression data

Monitoring gene expression profiles is a novel approach to cancer diagnosis. Several studies have showed that the sparse logistic regression is a useful classification method for gene expression data. Not only does it give a sparse solution with high accuracy, it provides the user with explicit probabilities of classification apart from the class information. However, its optimal extension to more than two classes is not obvious. In this paper, we propose a multiclass extension of sparse logistic regression. Analysis of five publicly available gene expression data sets shows that the proposed method outperforms the standard multinomial logistic model in prediction accuracy as well as gene selectivity.     

Cancer classification using gene expression data

The classification of different tumor types is of great importance in cancer diagnosis and drug discovery. However, most previous cancer classification studies are clinical based and have limited diagnostic ability. Cancer classification using gene expression data is known to contain the keys for addressing the fundamental problems relating to cancer diagnosis and drug discovery. The recent advent of DNA microarray technique has made simultaneous monitoring of thousands of gene expressions possible. With this abundance of gene expression data, researchers have started to explore the possibilities of cancer classification using gene expression data. Quite a number of methods have been proposed in recent years with promising results. But there are still a lot of issues which need to be addressed and understood.In order to gain a deep insight into the cancer classification problem, it is necessary to take a closer look at the problem, the proposed solutions and the related issues all together. In this survey paper, we present a comprehensive overview of various proposed cancer classification methods and evaluate them based on their computation time, classification accuracy and ability to reveal biologically meaningful gene information. We also introduce and evaluate various proposed gene selection methods which we believe should be an integral preprocessing step for cancer classification. In order to obtain a full picture of cancer classification, we also discuss several issues related to cancer classification, including the biological significance vs. statistical significance of a cancer classifier, the asymmetrical classification errors for cancer classifiers, and the gene contamination problem.     

Artificial neural network model for effective cancer classification using microarray gene expression data

Microarray gene expression profile shall be exploited for the efficient and effective classification of cancers. This is a computationally challenging task because of large quantity of genes and relatively small amount of experiments in gene expression data. The repercussion of this work is to devise a framework of techniques based on supervised machine learning for discrimination of acute lymphoblastic leukemia and acute myeloid leukemia using microarray gene expression profiles. Artificial neural network (ANN) technique was employed for this classification. Moreover, ANN was compared with other five machine learning techniques. These methods were assessed on eight different classification performance measures. This article reports a significant classification accuracy of 98% using ANN with no error in identification of acute lymphoblastic leukemia and only one error in identification of acute myeloid leukemia on tenfold cross-validation and leave-one-out approach. Furthermore, models were validated on independent test data, and all samples were correctly classified.