An Automatic Gridding and Contour Based Segmentation Approach Applied to DNA Microarray Image Analysis

DNA microarray technology is widely used by geneticists to diagnose or treat diseases through gene expression. This technology is based on the hybridization of a tissue-s DNA sequence into a substrate and the further analysis of the image formed by the thousands of genes in the DNA as green, red or yellow spots. The process of DNA microarray image analysis involves finding the location of the spots and the quantification of the expression level of these. In this paper, a tool to perform DNA microarray image analysis is presented, including a spot addressing method based on the image projections, the spot segmentation through contour based segmentation and the extraction of relevant information due to gene expression.

Evaluation of Clustering Based on Preprocessing in Gene Expression Data

Microarrays have become the effective, broadly used tools in biological and medical research to address a wide range of problems, including classification of disease subtypes and tumors. Many statistical methods are available for analyzing and systematizing these complex data into meaningful information, and one of the main goals in analyzing gene expression data is the detection of samples or genes with similar expression patterns. In this paper, we express and compare the performance of several clustering methods based on data preprocessing including strategies of normalization or noise clearness. We also evaluate each of these clustering methods with validation measures for both simulated data and real gene expression data. Consequently, clustering methods which are common used in microarray data analysis are affected by normalization and degree of noise and clearness for datasets.

Dynamical Analysis of Circadian Gene Expression

Microarrays technique allows the simultaneous measurements of the expression levels of thousands of mRNAs. By mining this data one can identify the dynamics of the gene expression time series. By recourse of principal component analysis, we uncover the circadian rhythmic patterns underlying the gene expression profiles from Cyanobacterium Synechocystis. We applied PCA to reduce the dimensionality of the data set. Examination of the components also provides insight into the underlying factors measured in the experiments. Our results suggest that all rhythmic content of data can be reduced to three main components.

Cutaneous Application of Royal Jelly Inhibits Skin Lesions in NC/Nga Mice, a Human-Like Mouse Model of Atopic Dermatitis

Anti-allergic effects of royal jelly were evaluated in a human-like mouse model of atopic dermatitis. NC/Nga mice were cutaneously applied with royal jelly for 6 weeks. Royal jelly-treated mice exhibited lower levels of serum total immunoglobulin E in comparison with controls. We found that the treatment decreased (11% to the control) expression of mRNA for aquaporin-3, which is involved in the modulation of epidermal hydration. Microarray analysis revealed more than 10-fold changes in the expression of several genes, such as transglutaminase 2, repetin, and keratins. In normal human epidermal keratinocytes, royal jelly extract suppressed interleukin-8 elevation induced by TNF-α and interferon-γ, suggesting direct anti-inflammatory activity in keratinocytes. Collectively, topical application of royal jelly may be useful for amelioration of lesions and inflammation in atopic dermatitis.

Carbon Sources Utilization Profiles of Thermophilic Phytase Producing Bacteria Isolated from Hot-spring in Malaysia

Phytases (myo-inositol hexakisphosphate phosphohydrolases; EC 3.1.3.8) catalyze the hydrolysis of phytic acid (myoinositol hexakisphosphate) to the mono-, di-, tri-, tetra-, and pentaphosphates of myo-inositol and inorganic phosphate. Therrmophilic bacteria isolated from water sampled from hot spring. About 120 isolates of bacteria were successfully isolated form hot spring water sample and tested for extracellular phytase producing. After 5 passages of the screening on the PSM media, 4 isolates were found stable in producing phytase enzyme. The 16s RDNA sequencing for identification of bacteria using molecular technique revealed that all isolates those positive in phytase producing are belong to Geobacillus spp. And Anoxybacillus spp. Anoxybacillus rupiensis UniSZA-7 were identified for their carbon source utilization using Phenotype Microarray Plate of Biolog and found they utilize several kind of carbon source provided.

Performance Analysis of Genetic Algorithm with kNN and SVM for Feature Selection in Tumor Classification

Tumor classification is a key area of research in the field of bioinformatics. Microarray technology is commonly used in the study of disease diagnosis using gene expression levels. The main drawback of gene expression data is that it contains thousands of genes and a very few samples. Feature selection methods are used to select the informative genes from the microarray. These methods considerably improve the classification accuracy. In the proposed method, Genetic Algorithm (GA) is used for effective feature selection. Informative genes are identified based on the T-Statistics, Signal-to-Noise Ratio (SNR) and F-Test values. The initial candidate solutions of GA are obtained from top-m informative genes. The classification accuracy of k-Nearest Neighbor (kNN) method is used as the fitness function for GA. In this work, kNN and Support Vector Machine (SVM) are used as the classifiers. The experimental results show that the proposed work is suitable for effective feature selection. With the help of the selected genes, GA-kNN method achieves 100% accuracy in 4 datasets and GA-SVM method achieves in 5 out of 10 datasets. The GA with kNN and SVM methods are demonstrated to be an accurate method for microarray based tumor classification.

A Comparison of SVM-based Criteria in Evolutionary Method for Gene Selection and Classification of Microarray Data

An evolutionary method whose selection and recombination operations are based on generalization error-bounds of support vector machine (SVM) can select a subset of potentially informative genes for SVM classifier very efficiently [7]. In this paper, we will use the derivative of error-bound (first-order criteria) to select and recombine gene features in the evolutionary process, and compare the performance of the derivative of error-bound with the error-bound itself (zero-order) in the evolutionary process. We also investigate several error-bounds and their derivatives to compare the performance, and find the best criteria for gene selection and classification. We use 7 cancer-related human gene expression datasets to evaluate the performance of the zero-order and first-order criteria of error-bounds. Though both criteria have the same strategy in theoretically, experimental results demonstrate the best criterion for microarray gene expression data.

A Phenomic Algorithm for Reconstruction of Gene Networks

The goal of Gene Expression Analysis is to understand the processes that underlie the regulatory networks and pathways controlling inter-cellular and intra-cellular activities. In recent times microarray datasets are extensively used for this purpose. The scope of such analysis has broadened in recent times towards reconstruction of gene networks and other holistic approaches of Systems Biology. Evolutionary methods are proving to be successful in such problems and a number of such methods have been proposed. However all these methods are based on processing of genotypic information. Towards this end, there is a need to develop evolutionary methods that address phenotypic interactions together with genotypic interactions. We present a novel evolutionary approach, called Phenomic algorithm, wherein the focus is on phenotypic interaction. We use the expression profiles of genes to model the interactions between them at the phenotypic level. We apply this algorithm to the yeast sporulation dataset and show that the algorithm can identify gene networks with relative ease.

Multidimensional Visualization Tools for Analysis of Expression Data

Expression data analysis is based mostly on the statistical approaches that are indispensable for the study of biological systems. Large amounts of multidimensional data resulting from the high-throughput technologies are not completely served by biostatistical techniques and are usually complemented with visual, knowledge discovery and other computational tools. In many cases, in biological systems we only speculate on the processes that are causing the changes, and it is the visual explorative analysis of data during which a hypothesis is formed. We would like to show the usability of multidimensional visualization tools and promote their use in life sciences. We survey and show some of the multidimensional visualization tools in the process of data exploration, such as parallel coordinates and radviz and we extend them by combining them with the self-organizing map algorithm. We use a time course data set of transitional cell carcinoma of the bladder in our examples. Analysis of data with these tools has the potential to uncover additional relationships and non-trivial structures.

Systholic Boolean Orthonormalizer Network in Wavelet Domain for Microarray Denoising

We describe a novel method for removing noise (in wavelet domain) of unknown variance from microarrays. The method is based on the following procedure: We apply 1) Bidimentional Discrete Wavelet Transform (DWT-2D) to the Noisy Microarray, 2) scaling and rounding to the coefficients of the highest subbands (to obtain integer and positive coefficients), 3) bit-slicing to the new highest subbands (to obtain bit-planes), 4) then we apply the Systholic Boolean Orthonormalizer Network (SBON) to the input bit-plane set and we obtain two orthonormal otput bit-plane sets (in a Boolean sense), we project a set on the other one, by means of an AND operation, and then, 5) we apply re-assembling, and, 6) rescaling. Finally, 7) we apply Inverse DWT-2D and reconstruct a microarray from the modified wavelet coefficients. Denoising results compare favorably to the most of methods in use at the moment.

A Novel Microarray Biclustering Algorithm

Biclustering aims at identifying several biclusters that reveal potential local patterns from a microarray matrix. A bicluster is a sub-matrix of the microarray consisting of only a subset of genes co-regulates in a subset of conditions. In this study, we extend the motif of subspace clustering to present a K-biclusters clustering (KBC) algorithm for the microarray biclustering issue. Besides minimizing the dissimilarities between genes and bicluster centers within all biclusters, the objective function of the KBC algorithm additionally takes into account how to minimize the residues within all biclusters based on the mean square residue model. In addition, the objective function also maximizes the entropy of conditions to stimulate more conditions to contribute the identification of biclusters. The KBC algorithm adopts the K-means type clustering process to efficiently make the partition of K biclusters be optimized. A set of experiments on a practical microarray dataset are demonstrated to show the performance of the proposed KBC algorithm.

Microarrays Denoising via Smoothing of Coefficients in Wavelet Domain

We describe a novel method for removing noise (in wavelet domain) of unknown variance from microarrays. The method is based on a smoothing of the coefficients of the highest subbands. Specifically, we decompose the noisy microarray into wavelet subbands, apply smoothing within each highest subband, and reconstruct a microarray from the modified wavelet coefficients. This process is applied a single time, and exclusively to the first level of decomposition, i.e., in most of the cases, it is not necessary a multirresoltuion analysis. Denoising results compare favorably to the most of methods in use at the moment.

Improved Wavelet Neural Networks for Early Cancer Diagnosis Using Clustering Algorithms

Wavelet neural networks (WNNs) have emerged as a vital alternative to the vastly studied multilayer perceptrons (MLPs) since its first implementation. In this paper, we applied various clustering algorithms, namely, K-means (KM), Fuzzy C-means (FCM), symmetry-based K-means (SBKM), symmetry-based Fuzzy C-means (SBFCM) and modified point symmetry-based K-means (MPKM) clustering algorithms in choosing the translation parameter of a WNN. These modified WNNs are further applied to the heterogeneous cancer classification using benchmark microarray data and were compared against the conventional WNN with random initialization method. Experimental results showed that a WNN classifier with the MPKM algorithm is more precise than the conventional WNN as well as the WNNs with other clustering algorithms.

Novel Hybrid Method for Gene Selection and Cancer Prediction

Microarray data profiles gene expression on a whole genome scale, therefore, it provides a good way to study associations between gene expression and occurrence or progression of cancer. More and more researchers realized that microarray data is helpful to predict cancer sample. However, the high dimension of gene expressions is much larger than the sample size, which makes this task very difficult. Therefore, how to identify the significant genes causing cancer becomes emergency and also a hot and hard research topic. Many feature selection algorithms have been proposed in the past focusing on improving cancer predictive accuracy at the expense of ignoring the correlations between the features. In this work, a novel framework (named by SGS) is presented for stable gene selection and efficient cancer prediction . The proposed framework first performs clustering algorithm to find the gene groups where genes in each group have higher correlation coefficient, and then selects the significant genes in each group with Bayesian Lasso and important gene groups with group Lasso, and finally builds prediction model based on the shrinkage gene space with efficient classification algorithm (such as, SVM, 1NN, Regression and etc.). Experiment results on real world data show that the proposed framework often outperforms the existing feature selection and prediction methods, say SAM, IG and Lasso-type prediction model.

A Hybrid Approach for Selection of Relevant Features for Microarray Datasets

Developing an accurate classifier for high dimensional microarray datasets is a challenging task due to availability of small sample size. Therefore, it is important to determine a set of relevant genes that classify the data well. Traditionally, gene selection method often selects the top ranked genes according to their discriminatory power. Often these genes are correlated with each other resulting in redundancy. In this paper, we have proposed a hybrid method using feature ranking and wrapper method (Genetic Algorithm with multiclass SVM) to identify a set of relevant genes that classify the data more accurately. A new fitness function for genetic algorithm is defined that focuses on selecting the smallest set of genes that provides maximum accuracy. Experiments have been carried on four well-known datasets1. The proposed method provides better results in comparison to the results found in the literature in terms of both classification accuracy and number of genes selected.

A Simple Affymetrix Ratio-transformation Method Yields Comparable Expression Level Quantifications with cDNA Data

Gene expression profiling is rapidly evolving into a powerful technique for investigating tumor malignancies. The researchers are overwhelmed with the microarray-based platforms and methods that confer them the freedom to conduct large-scale gene expression profiling measurements. Simultaneously, investigations into cross-platform integration methods have started gaining momentum due to their underlying potential to help comprehend a myriad of broad biological issues in tumor diagnosis, prognosis, and therapy. However, comparing results from different platforms remains to be a challenging task as various inherent technical differences exist between the microarray platforms. In this paper, we explain a simple ratio-transformation method, which can provide some common ground for cDNA and Affymetrix platform towards cross-platform integration. The method is based on the characteristic data attributes of Affymetrix- and cDNA- platform. In the work, we considered seven childhood leukemia patients and their gene expression levels in either platform. With a dataset of 822 differentially expressed genes from both these platforms, we carried out a specific ratio-treatment to Affymetrix data, which subsequently showed an improvement in the relationship with the cDNA data.

Influence of Noise on the Inference of Dynamic Bayesian Networks from Short Time Series

In this paper we investigate the influence of external noise on the inference of network structures. The purpose of our simulations is to gain insights in the experimental design of microarray experiments to infer, e.g., transcription regulatory networks from microarray experiments. Here external noise means, that the dynamics of the system under investigation, e.g., temporal changes of mRNA concentration, is affected by measurement errors. Additionally to external noise another problem occurs in the context of microarray experiments. Practically, it is not possible to monitor the mRNA concentration over an arbitrary long time period as demanded by the statistical methods used to learn the underlying network structure. For this reason, we use only short time series to make our simulations more biologically plausible.

Iterative Clustering Algorithm for Analyzing Temporal Patterns of Gene Expression

Microarray experiments are information rich; however, extensive data mining is required to identify the patterns that characterize the underlying mechanisms of action. For biologists, a key aim when analyzing microarray data is to group genes based on the temporal patterns of their expression levels. In this paper, we used an iterative clustering method to find temporal patterns of gene expression. We evaluated the performance of this method by applying it to real sporulation data and simulated data. The patterns obtained using the iterative clustering were found to be superior to those obtained using existing clustering algorithms.

Analysis of DNA Microarray Data using Association Rules: A Selective Study

DNA microarrays allow the measurement of expression levels for a large number of genes, perhaps all genes of an organism, within a number of different experimental samples. It is very much important to extract biologically meaningful information from this huge amount of expression data to know the current state of the cell because most cellular processes are regulated by changes in gene expression. Association rule mining techniques are helpful to find association relationship between genes. Numerous association rule mining algorithms have been developed to analyze and associate this huge amount of gene expression data. This paper focuses on some of the popular association rule mining algorithms developed to analyze gene expression data.

Ranking Genes from DNA Microarray Data of Cervical Cancer by a local Tree Comparison

The major objective of this paper is to introduce a new method to select genes from DNA microarray data. As criterion to select genes we suggest to measure the local changes in the correlation graph of each gene and to select those genes whose local changes are largest. More precisely, we calculate the correlation networks from DNA microarray data of cervical cancer whereas each network represents a tissue of a certain tumor stage and each node in the network represents a gene. From these networks we extract one tree for each gene by a local decomposition of the correlation network. The interpretation of a tree is that it represents the n-nearest neighbor genes on the n-th level of a tree, measured by the Dijkstra distance, and, hence, gives the local embedding of a gene within the correlation network. For the obtained trees we measure the pairwise similarity between trees rooted by the same gene from normal to cancerous tissues. This evaluates the modification of the tree topology due to tumor progression. Finally, we rank the obtained similarity values from all tissue comparisons and select the top ranked genes. For these genes the local neighborhood in the correlation networks changes most between normal and cancerous tissues. As a result we find that the top ranked genes are candidates suspected to be involved in tumor growth. This indicates that our method captures essential information from the underlying DNA microarray data of cervical cancer.