Selection of interdependent genes via dynamic relevance analysis for cancer diagnosis

Microarray analysis is widely accepted for human cancer diagnosis and classification. However the high dimensionality of microarray data poses a great challenge to classification. Gene selection plays a key role in identifying salient genes from thousands of genes in microarray data that can directly contribute to the symptom of disease. Although various excellent selection methods are currently available, one common problem of these methods is that genes which have strong discriminatory power as a group but are weak as individuals will be discarded. In this paper, a new gene selection method is proposed for cancer diagnosis and classification by retaining useful intrinsic groups of interdependent genes. The primary characteristic of this method is that the relevance between each gene and target will be dynamically updated when a new gene is selected. The effectiveness of our method is validated by experiments on six publicly available microarray data sets. Experimental results show that the classification performance and enrichment score achieved by our proposed method is better than those of other selection methods.     

An integrated algorithm for gene selection and classification applied to microarray data of ovarian cancer

OBJECTIVE: The type of data in microarray provides unprecedented amount of data. A typical microarray data of ovarian cancer consists of the expressions of tens of thousands of genes on a genomic scale, and there is no systematic procedure to analyze this information instantaneously. To avoid higher computational complexity, it needs to select the most likely differentially expressed gene markers to explain the effects of ovarian cancer. Traditionally, gene markers are selected by ranking genes according to statistics or machine learning algorithms. In this paper, an integrated algorithm is derived for gene selection and classification in microarray data of ovarian cancer. METHODS: First, regression analysis is applied to find target genes. Genetic algorithm (GA), particle swarm optimization (PSO), support vector machine (SVM), and analysis of variance (ANOVA) are hybridized to select gene markers from target genes. Finally, the improved fuzzy model is applied to classify cancer tissues. RESULTS: The microarray data of ovarian cancer, obtained from China Medical University Hospital, is used to test the performance of the proposed algorithm. In simulation, 200 target genes are obtained after regression analysis and six gene markers are selected from the hybrid process of GA, PCO, SVM and ANOVA. Additionally, these gene markers are used to classify cancer tissues. CONCLUSIONS: The proposed algorithm can be used to analyze gene expressions and has superior performance in microarray data of ovarian cancer, and it can be performed on other studies for cancer diagnosis.     

A hybrid feature selection method for DNA microarray data

Gene expression profiles, which represent the state of a cell at a molecular level, have great potential as a medical diagnosis tool. In cancer classification, available training data sets are generally of a fairly small sample size compared to the number of genes involved. Along with training data limitations, this constitutes a challenge to certain classification methods. Feature (gene) selection can be used to successfully extract those genes that directly influence classification accuracy and to eliminate genes which have no influence on it. This significantly improves calculation performance and classification accuracy. In this paper, correlation-based feature selection (CFS) and the Taguchi-genetic algorithm (TGA) method were combined into a hybrid method, and the K-nearest neighbor (KNN) with the leave-one-out cross-validation (LOOCV) method served as a classifier for eleven classification profiles to calculate the classification accuracy. Experimental results show that the proposed method reduced redundant features effectively and achieved superior classification accuracy. The classification accuracy obtained by the proposed method was higher in ten out of the eleven gene expression data set test problems when compared to other classification methods from the literature.     

A kernel-based clustering method for gene selection with gene expression data

Gene selection is important for cancer classification based on gene expression data, because of high dimensionality and small sample size. In this paper, we present a new gene selection method based on clustering, in which dissimilarity measures are obtained through kernel functions. It searches for best weights of genes iteratively at the same time to optimize the clustering objective function. Adaptive distance is used in the process, which is suitable to learn the weights of genes during the clustering process, improving the performance of the algorithm. The proposed algorithm is simple and does not require any modification or parameter optimization for each dataset. We tested it on eight publicly available datasets, using two classifiers (support vector machine, k-nearest neighbor), compared with other six competitive feature selectors. The results show that the proposed algorithm is capable of achieving better accuracies and may be an efficient tool for finding possible biomarkers from gene expression data.     

Gene and sample selection using T-score with sample selection

Gene selection from high-dimensional microarray gene-expression data is statistically a challenging problem. Filter approaches to gene selection have been popular because of their simplicity, efficiency, and accuracy. Due to small sample size, all samples are generally used to compute relevant ranking statistics and selection of samples in filter-based gene selection methods has not been addressed. In this paper, we extend previously-proposed simultaneous sample and gene selection approach. In a backward elimination method, a modified logistic regression loss function is used to select relevant samples at each iteration, and these samples are used to compute the T-score to rank genes. This method provides a compromise solution between T-score and other support vector machine (SVM) based algorithms. The performance is demonstrated on both simulated and real datasets with criteria such as classification performance, stability and redundancy. Results indicate that computational complexity and stability of the method are improved compared to SVM based methods without compromising the classification performance.     

New gene selection method for multiclass tumor classification by class centroid

In the analysis of gene expression profiles, the selection of genetic markers and precise diagnosis of cancer type are crucial for successful treatment. The selection of discriminatory genes is critical to improve the accuracy and decrease computational complexity and cost in microarray analysis. In this paper, we developed a new statistical parameter, the suitability score to filter genes which only utilize sample distances from the class centroid. The filtered genes are employed in the nearest centroid classification to classify cancer. To evaluate the performance of the new statistical parameter, the proposed approach is applied to three publicly available microarray datasets. In this paper we demonstrate that the proposed gene selection method is steady in handling classification tasks and is a useful tool for gene selection and mining high dimension data.     

Cancer classification and prediction using logistic regression with Bayesian gene selection

In microarray-based cancer classification and prediction, gene selection is an important research problem owing to the large number of genes and the small number of experimental conditions. In this paper, we propose a Bayesian approach to gene selection and classification using the logistic regression model. The basic idea of our approach is in conjunction with a logistic regression model to relate the gene expression with the class labels. We use Gibbs sampling and Markov chain Monte Carlo (MCMC) methods to discover important genes. To implement Gibbs Sampler and MCMC search, we derive a posterior distribution of selected genes given the observed data. After the important genes are identified, the same logistic regression model is then used for cancer classification and prediction. Issues for efficient implementation for the proposed method are discussed. The proposed method is evaluated against several large microarray data sets, including hereditary breast cancer, small round blue-cell tumors, and acute leukemia. The results show that the method can effectively identify important genes consistent with the known biological findings while the accuracy of the classification is also high. Finally, the robustness and sensitivity properties of the proposed method are also investigated.     

一种基于Gene Ontology注释信息的基因选择算法

基因选择算法是辅助生物学分析最重要的方法之一,但这类统计学算法受样本量相对基因数目过少的困扰.提出一种结合Gene Ontology(GO)注释信息的基因选择算法,用GO注释接近基因的方差的加权平均进行修正,增强小样本量下对总体的估计,进而寻找差异表达基因.将该算法与其他5种常见算法对比,以选择出的基因为特征构建分类器,以分类器的可靠性作为衡量算法的标准.3组芯片实验的结果表明,该算法在小样本情况下具有一定优势.亦有Pubmed文献证明,该算法可以鉴别出其他算法未曾发现的致病基因.该方法所建立起来的框架,是把生物学注释信息引入算法改进的一种有效尝试.     

Hybrid genetic algorithm-neural network: feature extraction for unpreprocessed microarray data

Objective

Suitable techniques for microarray analysis have been widely researched, particularly for the study of marker genes expressed to a specific type of cancer. Most of the machine learning methods that have been applied to significant gene selection focus on the classification ability rather than the selection ability of the method. These methods also require the microarray data to be preprocessed before analysis takes place. The objective of this study is to develop a hybrid genetic algorithm-neural network (GANN) model that emphasises feature selection and can operate on unpreprocessed microarray data.

Method

The GANN is a hybrid model where the fitness value of the genetic algorithm (GA) is based upon the number of samples correctly labelled by a standard feedforward artificial neural network (ANN). The model is evaluated by using two benchmark microarray datasets with different array platforms and differing number of classes (a 2-class oligonucleotide microarray data for acute leukaemia and a 4-class complementary DNA (cDNA) microarray dataset for SRBCTs (small round blue cell tumours)). The underlying concept of the GANN algorithm is to select highly informative genes by co-evolving both the GA fitness function and the ANN weights at the same time.

Results

The novel GANN selected approximately 50% of the same genes as the original studies. This may indicate that these common genes are more biologically significant than other genes in the datasets. The remaining 50% of the significant genes identified were used to build predictive models and for both datasets, the models based on the set of genes extracted by the GANN method produced more accurate results. The results also suggest that the GANN method not only can detect genes that are exclusively associated with a single cancer type but can also explore the genes that are differentially expressed in multiple cancer types.

Conclusions

The results show that the GANN model has successfully extracted statistically significant genes from the unpreprocessed microarray data as well as extracting known biologically significant genes. We also show that assessing the biological significance of genes based on classification accuracy may be misleading and though the GANN's set of extra genes prove to be more statistically significant than those selected by other methods, a biological assessment of these genes is highly recommended to confirm their functionality.     

Selection of relevant genes in cancer diagnosis based on their prediction accuracy

MOTIVATIONS: One of the main problems in cancer diagnosis by using DNA microarray data is selecting genes relevant for the pathology by analyzing their expression profiles in tissues in two different phenotypical conditions. The question we pose is the following: how do we measure the relevance of a single gene in a given pathology? METHODS: A gene is relevant for a particular disease if we are able to correctly predict the occurrence of the pathology in new patients on the basis of its expression level only. In other words, a gene is informative for the disease if its expression levels are useful for training a classifier able to generalize, that is, able to correctly predict the status of new patients. In this paper we present a selection bias free, statistically well founded method for finding relevant genes on the basis of their classification ability. RESULTS: We applied the method on a colon cancer data set and produced a list of relevant genes, ranked on the basis of their prediction accuracy. We found, out of more than 6500 available genes, 54 overexpressed in normal tissues and 77 overexpressed in tumor tissues having prediction accuracy greater than 70% with p-value 相似文献   

Ensemble gene selection by grouping for microarray data classification

Selecting relevant and discriminative genes for sample classification is a common and critical task in gene expression analysis (e.g. disease diagnostic). It is desirable that gene selection can improve classification performance of learning algorithm effectively. In general, for most gene selection methods widely used in reality, an individual gene subset will be chosen according to its discriminative power. One of deficiencies of individual gene subset is that its contribution to classification purpose is limited. This issue can be alleviated by ensemble gene selection based on random selection to some extend. However, the random one requires an unnecessary large number of candidate gene subsets and its reliability is a problem. In this study, we propose a new ensemble method, called ensemble gene selection by grouping (EGSG), to select multiple gene subsets for the classification purpose. Rather than selecting randomly, our method chooses salient gene subsets from microarray data by virtue of information theory and approximate Markov blanket. The effectiveness and accuracy of our method is validated by experiments on five publicly available microarray data sets. The experimental results show that our ensemble gene selection method has comparable classification performance to other gene selection methods, and is more stable than the random one.     

Genetic diagnosis of cancer by fuzzy-rough gene selection and the complementary hierarchical fuzzy classifier

Gene expression data have extremely high dimensionality with respect to traditional classifiers which causes not to be used efficiently. In this paper a Fuzzy-Rough Gene Selection and Complementary Hierarchical Fuzzy classifier (FRGS-CHF) to classify the gene expression data as a new methodology is proposed. First, some relevant genes are selected using fuzzy-rough attribute selection method. After removing redundant genes, a new complementary hierarchical fuzzy classifier is proposed. The complementary learning mechanism refers to positive and negative learning which are found in the human brain hippocampus. FRGS-CHF is made-up of two parallel hierarchical fuzzy systems; the first is trained with positive samples whilst the other is treated with negative samples. In contrast to many other methods such as statistical or neural networks, FRGS-CHF provides greater interpretability. It does not rely on the assumption of underlying data distribution. Using complementary and hierarchical approaches, the proposed method exploits the lateral inhibition between output classes and considers the problem as a multidimensional problem. Benchmarked datasets are used to demonstrate the validity and advantages of the proposed method over the other existing methods in terms of the accuracy, better transparency, time efficiency together with fewer fuzzy rules and parameters.     

A two step method to identify clinical outcome relevant genes with microarray data

With advances in microarray technology, many biomarkers selection approaches have been proposed for cancer diagnosis. Marker sets are selected by scoring genes for how well they can discriminate between different classes of diseases [1-4] or are ranked by significance analysis without reference to classification tasks. However there is a pressing need for methods integrating biological priori knowledge in the gene selection process. In this study, we proposed to identify genes primarily in terms of diagnostic outcome relevance. As gene expression is a combination effect, with the help of SVD, the microarray data is decomposed, the eigenvectors correspond to the biological effect of clinical outcomes are identified. Genes which play important roles in determining this biological effect are detected. Therefore, genes are essentially identified in terms of the strength of association with clinical outcomes and the relationship of genes and clinical outcomes is analyzed. Monte Carlo simulations are then used to fine tune the selected gene set in terms of classification accuracy. The approach was tested on four public data sets. Comparative studies show that the selected genes achieved higher classification accuracies. Graphical analysis visualizes that they have close relationship with the cancer class. Statistical simulation shows that the gene set found by the proposed method is also less variable and comparatively invariant to external influences. The biological relevance of the selected genes is further discussed and validated with the literature study and analysis of biological databases.     

An efficient statistical feature selection approach for classification of gene expression data

Classification of gene expression data plays a significant role in prediction and diagnosis of diseases. Gene expression data has a special characteristic that there is a mismatch in gene dimension as opposed to sample dimension. All genes do not contribute for efficient classification of samples. A robust feature selection algorithm is required to identify the important genes which help in classifying the samples efficiently. In order to select informative genes (features) based on relevance and redundancy characteristics, many feature selection algorithms have been introduced in the past. Most of the earlier algorithms require computationally expensive search strategy to find an optimal feature subset. Existing feature selection methods are also sensitive to the evaluation measures. The paper introduces a novel and efficient feature selection approach based on statistically defined effective range of features for every class termed as ERGS (Effective Range based Gene Selection). The basic principle behind ERGS is that higher weight is given to the feature that discriminates the classes clearly. Experimental results on well-known gene expression datasets illustrate the effectiveness of the proposed approach. Two popular classifiers viz. Nave Bayes Classifier (NBC) and Support Vector Machine (SVM) have been used for classification. The proposed feature selection algorithm can be helpful in ranking the genes and also is capable of identifying the most relevant genes responsible for diseases like leukemia, colon tumor, lung cancer, diffuse large B-cell lymphoma (DLBCL), prostate cancer.     

Sequential local least squares imputation estimating missing value of microarray data

Missing values in microarray data can significantly affect subsequent analysis, thus it is important to estimate these missing values accurately. In this paper, a sequential local least squares imputation (SLLSimpute) method is proposed to solve this problem. It estimates missing values sequentially from the gene containing the fewest missing values and partially utilizes these estimated values. In addition, an automatic parameter selection algorithm, which can generate an appropriate number of neighboring genes for each target gene, is presented for parameter estimation. Experimental results confirmed that SLLSimpute method exhibited better estimation ability compared with other currently used imputation methods.     

A multiple kernel support vector machine scheme for feature selection and rule extraction from gene expression data of cancer tissue

OBJECTIVE: Recently, gene expression profiling using microarray techniques has been shown as a promising tool to improve the diagnosis and treatment of cancer. Gene expression data contain high level of noise and the overwhelming number of genes relative to the number of available samples. It brings out a great challenge for machine learning and statistic techniques. Support vector machine (SVM) has been successfully used to classify gene expression data of cancer tissue. In the medical field, it is crucial to deliver the user a transparent decision process. How to explain the computed solutions and present the extracted knowledge becomes a main obstacle for SVM. MATERIAL AND METHODS: A multiple kernel support vector machine (MK-SVM) scheme, consisting of feature selection, rule extraction and prediction modeling is proposed to improve the explanation capacity of SVM. In this scheme, we show that the feature selection problem can be translated into an ordinary multiple parameters learning problem. And a shrinkage approach: 1-norm based linear programming is proposed to obtain the sparse parameters and the corresponding selected features. We propose a novel rule extraction approach using the information provided by the separating hyperplane and support vectors to improve the generalization capacity and comprehensibility of rules and reduce the computational complexity. RESULTS AND CONCLUSION: Two public gene expression datasets: leukemia dataset and colon tumor dataset are used to demonstrate the performance of this approach. Using the small number of selected genes, MK-SVM achieves encouraging classification accuracy: more than 90% for both two datasets. Moreover, very simple rules with linguist labels are extracted. The rule sets have high diagnostic power because of their good classification performance.     

Simultaneous genes and training samples selection by modified particle swarm optimization for gene expression data classification

Gene expression datasets is a means to classify and predict the diagnostic categories of a patient. Informative genes and representative samples selection are two important aspects for reducing gene expression data. Identifying and pruning redundant genes and samples simultaneously can improve the performance of classification and circumvent the local optima problem. In the present paper, the modified particle swarm optimization was applied to selecting optimal genes and samples simultaneously and support vector machine was used as an objective function to determine the optimum set of genes and samples. To evaluate the performance of the new proposed method, it was applied to three publicly available microarray datasets. It has been demonstrated that the proposed method for gene and sample selection is a useful tool for mining high dimension data.     

A new classification model with simple decision rule for discovering optimal feature gene pairs

Classifiers have been widely used to select an optimal subset of feature genes from microarray data for accurate classification of cancer samples and cancer-related studies. However, the classification rules derived from most classifiers are complex and difficult to understand in biological significance. How to solve this problem is a new challenge. In this paper, a new classification model based on gene pair is proposed to address the problem. The experimental results on several microarray data demonstrate that the proposed classification model performs well in finding a large number of excellent feature gene pairs. A 100% LOOCV classification accuracy can be achieved using a single classification model based on optimal feature gene pair or combining multiple top-ranked classification models. Using the proposed method, we successfully identified important cancer-related genes that had been validated in previous biological studies while they were not discovered by the other methods.     

Gene extraction for cancer diagnosis by support vector machines--an improvement

OBJECTIVE: To improve the performance of gene extraction for cancer diagnosis by recursive feature elimination with support vector machines (RFE-SVMs): A cancer diagnosis by using the DNA microarray data faces many challenges the most serious one being the presence of thousands of genes and only several dozens (at the best) of patient's samples. Thus, making any kind of classification in high-dimensional spaces from a limited number of data is both an extremely difficult and a prone to an error procedure. The improved RFE-SVMs is introduced and used here for an elimination of less relevant genes and just for a reduction of the overall number of genes used in a medical diagnostic. METHODS: The paper shows why and how the, usually neglected, penalty parameter C and some standard data preprocessing techniques (normalizing and scaling) influence classification results and the gene selection of RFE-SVMs. The gene selected by RFE-SVMs is compared with eight other gene selection algorithms implemented in the Rankgene software to investigate whether there is any consensus among the algorithms, so the scope of finding the right set of genes can be reduced. RESULTS: The improved RFE-SVMs is applied on the two benchmarking colon and lymphoma cancer data sets with various C parameters and different standard preprocessing techniques. Here, decreasing C leads to the smaller diagnosis error in comparisons to other known methods applied to the benchmarking data sets. With an appropriate parameter C and with a proper preprocessing procedure, the reduction in a diagnosis error is as high as 36%. CONCLUSIONS: The results suggest that with a properly chosen parameter C, the extracted genes and the constructed classifier will ensure less overfitting of the training data leading to an increased accuracy in selecting relevant genes. Finally, comparison in gene ranking obtained by different algorithms shows that there is a significant consensus among the various algorithms as to which set of genes is relevant.