Clustering gene expression data using a graph-theoretic approach: an application of minimum spanning trees.

Massive amounts of gene expression data are generated using microarrays for functional studies of genes and gene expression data clustering is a useful tool for studying the functional relationship among genes in a biological process. We have developed a computer package EXCAVATOR for clustering gene expression profiles based on our new framework for representing gene expression data as a minimum spanning tree. EXCAVATOR uses a number of rigorous and efficient clustering algorithms. This program has a number of unique features, including capabilities for: (i) data- constrained clustering; (ii) identification of genes with similar expression profiles to pre-specified seed genes; (iii) cluster identification from a noisy background; (iv) computational comparison between different clustering results of the same data set. EXCAVATOR can be run from a Unix/Linux/DOS shell, from a Java interface or from a Web server. The clustering results can be visualized as colored figures and 2-dimensional plots. Moreover, EXCAVATOR provides a wide range of options for data formats, distance measures, objective functions, clustering algorithms, methods to choose number of clusters, etc. The effectiveness of EXCAVATOR has been demonstrated on several experimental data sets. Its performance compares favorably against the popular K-means clustering method in terms of clustering quality and computing time.

Classifying the gene expression levels of normal and cancerous cells and identifying the genes most contributing to this distinction propose an alternative means of diagnosis. We have investigated the effect of feature extraction and feature selection on clustering of the expression data on two different data sets for ovarian cancer. One data set consisted of 2176 transcripts from 30 samples, nine from normal ovarian epithelial cells and 21 from cancerous ones. The other data set had 7129 transcripts coming from 27 tumor and four normal ovarian tissues. Hierarchical clustering algorithms employing complete-link, average-link and Ward's method were implemented for comparative evaluation. Principal component analysis was applied for feature extraction and resulted in 100% segregation. Feature selection was performed to identify the most distinguishing genes using CART/spl reg/ software. Selected features were able to cluster the data with 100% success. The results suggest that adoption of feature extraction and selection enhances the quality of clustering of gene expression data for ovarian cancer. Identification of distinguishing genes is a more complex problem that requires incorporating pathway knowledge with statistical and machine learning methods.

Based on the previously proposed Quantum-behaved Particle Swarm Optimization (QPSO) algorithm, in this paper, we focus on the application of QPSO in gene expression data clustering which can be reduced to an optimization problem. The proposed clustering algorithm partitions the N patterns of the gene expression dataset into user-defined K categories to minimize the fitness function of Total Within-Cluster Variation. Thus a partition with high performance is obtained. The experiment results on four gene expression data sets show that our QPSO-based clustering algorithm will be an effective and promising tool for gene expression data analysis.

Clustering gene expression data are an important problem in bioinformatics because understanding which genes behave similarly can lead to the discovery of important biological information. Many clustering methods have been used in the field of gene clustering. This paper proposed a new method for gene expression data clustering based on an improved expectation maximization(EM) method of multivariate Gaussian mixture models. To solve the problem of over-reliance on the initialization, we propose a remove and add initialization for the classical EM, and make a random perturbation on the solution before continuing EM iterations. The number of clusters is estimated with the Quasi Akaike’s information criterion in this paper. The improved EM method is tested and compared with some other clustering methods; the performance of our clustering algorithm has been extensively compared over several simulated and real gene expression data sets. Our results indicated that improved EM clustering method is superior than other clustering algorithms and can be widely used for gene clustering.

In order to understand even the simplest cellular processes, we need to integrate proteomic, gene expression and other biomolecular data. To date, most computational approaches aimed at integrating proteomics and gene expression data use direct gene/protein correlation measures. However, due to post-transcriptional and translational regulations, the correspondence between the expression of a gene and its protein is complicated. We apply a multivariate statistical method, co-inertia analysis (CIA), to visualise gene and proteomic expression data stemming from the same biological samples. Principal components analysis or correspondence analysis can be used for data exploration on single datasets. CIA is then used to explore the relationships between two or more datasets. We further explore the data by projecting gene ontology (GO) information onto these plots to describe the cellular processes in action. We apply these techniques to gene expression and protein abundance data from studies of the human malarial parasite life cycle and the NCI-60 cancer cell lines. In each case, we visualise gene expression, protein abundance and GO classes in the same low dimensional projections and identify GO classes that are likely to be of biological importance.

Sequential image segmentation based on minimum spanning tree representation

Clustering is a useful exploratory technique for the analysis of gene expression data. Many different heuristic clustering algorithms have been proposed in this context. Clustering algorithms based on probability models offer a principled alternative to heuristic algorithms. In particular, model-based clustering assumes that the data is generated by a finite mixture of underlying probability distributions such as multivariate normal distributions. The issues of selecting a 'good' clustering method and determining the 'correct' number of clusters are reduced to model selection problems in the probability framework. Gaussian mixture models have been shown to be a powerful tool for clustering in many applications. We benchmarked the performance of model-based clustering on several synthetic and real gene expression data sets for which external evaluation criteria were available. The model-based approach has superior performance on our synthetic data sets, consistently selecting the correct model and the number of clusters. On real expression data, the model-based approach produced clusters of quality comparable to a leading heuristic clustering algorithm, but with the key advantage of suggesting the number of clusters and an appropriate model. We also explored the validity of the Gaussian mixture assumption on different transformations of real data. We also assessed the degree to which these real gene expression data sets fit multivariate Gaussian distributions both before and after subjecting them to commonly used data transformations. Suitably chosen transformations seem to result in reasonable fits. MCLUST is available at http://www.stat.washington.edu/fraley/mclust. The software for the diagonal model is under development. kayee@cs.washington.edu. http://www.cs.washington.edu/homes/kayee/model.

The combined interpretation of gene expression data and gene sequences offers a valuable approach to investigate the intricate relationships involving gene transcriptional regulation. The highly interactive expression data produced by microarray hybridization experiments allow us to find the clusters of coexpressed genes. By analyzing the upstream regions of the identified coexpressed genes, we can discover the regulatory patterns characterized by transcription factor binding sites, which govern the process of transcriptional regulation. This paper presents a generic clustering algorithm that uses a Hybrid GA approach to discover clusters in gene expression data. The advantage of this method is that large search space can be effectively explored by utilizing the evolutionary algorithm techniques. Moreover, it is able to discover underlying patterns in noisy gene expression data for meaningful data groupings, and also statistically significant patterns hidden in each cluster can be extracted at the same time. Since the proposed method can handle both continuous-and discrete-valued data, it can be used with different microarray and biomedical data. To test its effectiveness, we have used it on real expression data. The experimental results reveal meaningful groupings and uncover many known transcription factor binding sites.

Clustering is one of the most important techniques, which group genes of similar expression pattern into a small number of meaningful homogeneous groups or clusters. Gene expression data has certain special characteristics and is a challenging research problem. There are many applications for clustering gene expression data. Clustering can be applied for genes called gene clustering. Hard clustering allows a gene to get placed in exactly one cluster and converges in local optima. Soft clustering approach allows gene to get placed in all the clusters with some membership values. As the hard clustering approach converges in local optimum, an evolutionary computation technique like swarm clustering is required to find the global optimum solution. This chapter studies swarm clustering techniques such as Particle Swarm Clustering K-Means, Cuckoo Search Clustering, Cuckoo Search Clustering with levy flight, harmony search, Fuzzy PSO and Ant Colony Optimization based Clustering for clustering gene expression data. Evaluation measures for clustering gene expression data are also discussed.

We present the use of KICA to perform clustering of gene expression data. Comparison experiments between KICA and two other methods, PCA and ICA, are performed. Three clustering algorithms, including weighted graph partitioning, k-means and agglomerative hierarchical clustering, and two similarity measures, including Euclidean and Pearson correlation, are also evaluated. The results indicate that KICA is an efficient feature extraction approach for gene expression data clustering. Our empirical study showed that clustering with the components instead of the original variables does improve cluster quality. In particular, the first few components by KICA capture most of the cluster structure. We also showed that clustering with components has different impact on different algorithms and different similarity metrics. Overall, we would recommend KICA before clustering gene expression data.

Breast cancer outcome can be predicted using models derived from gene expression data or clinical data. Only a few studies have created a single prediction model using both gene expression and clinical data. These studies often remain inconclusive regarding an obtained improvement in prediction performance. We rigorously compare three different integration strategies (early, intermediate, and late integration) as well as classifiers employing no integration (only one data type) using five classifiers of varying complexity. We perform our analysis on a set of 295 breast cancer samples, for which gene expression data and an extensive set of clinical parameters are available as well as four breast cancer datasets containing 521 samples that we used as independent validation.mOn the 295 samples, a nearest mean classifier employing a logical OR operation (late integration) on clinical and expression classifiers significantly outperforms all other classifiers. Moreover, regardless of the integration strategy, the nearest mean classifier achieves the best performance. All five classifiers achieve their best performance when integrating clinical and expression data. Repeating the experiments using the 521 samples from the four independent validation datasets also indicated a significant performance improvement when integrating clinical and gene expression data. Whether integration also improves performances on other datasets (e.g. other tumor types) has not been investigated, but seems worthwhile pursuing. Our work suggests that future models for predicting breast cancer outcome should exploit both data types by employing a late OR or intermediate integration strategy based on nearest mean classifiers.

In view of today's unprecedented diverse and discrete mass text data processing, this paper presents a distributed MST (minimum spanning tree) algorithm based on MapReduce programming model. And with this MST algorithm, a distributed MST text clustering algorithm is designed and implemented. In this paper, this clustering algorithm is analyzed in three aspects: text feature vector extraction, graph construction and MST construction. And some data was used to experimentally compare this algorithm with ordinary MST clustering algorithm and MapReduce-based K-means clustering algorithm.

BackgroundA complete understanding of the regulatory mechanisms of gene expression is the next important issue of genomics. Many bioinformaticians have developed methods and algorithms for predicting transcriptional regulatory mechanisms from sequence, gene expression, and binding data. However, most of these studies involved the use of yeast which has much simpler regulatory networks than human and has many genome wide binding data and gene expression data under diverse conditions. Studies of genome wide transcriptional networks of human genomes currently lag behind those of yeast.ResultsWe report herein a new method that combines gene expression data analysis with promoter analysis to infer transcriptional regulatory elements of human genes. The Z scores from the application of gene set analysis with gene sets of transcription factor binding sites (TFBSs) were successfully used to represent the activity of TFBSs in a given microarray data set. A significant correlation between the Z scores of gene sets of TFBSs and individual genes across multiple conditions permitted successful identification of many known human transcriptional regulatory elements of genes as well as the prediction of numerous putative TFBSs of many genes which will constitute a good starting point for further experiments. Using Z scores of gene sets of TFBSs produced better predictions than the use of mRNA levels of a transcription factor itself, suggesting that the Z scores of gene sets of TFBSs better represent diverse mechanisms for changing the activity of transcription factors in the cell. In addition, cis-regulatory modules, combinations of co-acting TFBSs, were readily identified by our analysis.ConclusionBy a strategic combination of gene set level analysis of gene expression data sets and promoter analysis, we were able to identify and predict many transcriptional regulatory elements of human genes. We conclude that this approach will aid in decoding some of the important transcriptional regulatory elements of human genes.

Clustering of gene expression data is a standard exploratory technique used to identify closely related genes. Many other sources of data are also likely to be of great assistance in the analysis of gene expression data. This data provides a mean to begin elucidating the large-scale modular organization of the cell. The authors consider the challenging task of developing exploratory analytical techniques to deal with multiple complete and incomplete information sources. The Multi-Source Clustering (MSC) algorithm developed performs clustering with multiple, but complete, sources of data. To deal with incomplete data sources, the authors adopted the MPCK-means clustering algorithms to perform exploratory analysis on one complete source and other potentially incomplete sources provided in the form of constraints. This paper presents a new clustering algorithm MSC to perform exploratory analysis using two or more diverse but complete data sources, studies the effectiveness of constraints sets and robustness of the constrained clustering algorithm using multiple sources of incomplete biological data, and incorporates such incomplete data into constrained clustering algorithm in form of constraints sets.

As data mining having attracted a significant amount of research attention, many clustering algorithms have been proposed in the past decades. However, most of existing clustering methods have high computational time or are not suitable for discovering clusters with non-convex shape. In this paper, an efficient clustering algorithm CHSMST is proposed, which is based on clustering based on hyper surface (CHS) and minimum spanning tree. In the first step, CHSMST applies CHS to obtain initial clusters immediately. Thereafter, minimum spanning tree is intro- duced to handle locally dense data which is hard for CHS to deal with. The experiments show that CHSMST can discover clusters with arbitrary shape. Moreover, CHSMST is insensitive to the order of input samples and the run time of the algorithm increases moderately as the scale of dataset becomes large.