Unsupervised fuzzy pattern discovery in gene expression data

Discovering patterns from gene expression levels is regarded as a classification problem when tissue classes of the samples are given and solved as a discrete-data problem by discretizing the expression levels of each gene into intervals maximizing the interdependence between that gene and the class labels. However, when class information is unavailable, discovering gene expression patterns becomes difficult.

For a gene pool with large number of genes, we first cluster the genes into smaller groups. In each group, we use the representative gene, one with highest interdependence with others in the group, to drive the discretization of the gene expression levels of other genes. Treating intervals as discrete events, association patterns of events can be discovered. If the gene groups obtained are crisp gene clusters, significant patterns overlapping different gene clusters cannot be found. This paper presents a new method of "fuzzifying" the crisp gene clusters to overcome such problem.

To evaluate the effectiveness of our approach, we first apply the above described procedure on a synthetic data set and then a gene expression data set with known class labels. The class labels are not being used in both analyses but used later as the ground truth in a classificatory problem for assessing the algorithm's effectiveness in fuzzy gene clustering and discretization. The results show the efficacy of the proposed method. The existence of correlation among continuous valued gene expression levels suggests that certain genes in the gene groups have high interdependence with other genes in the group. Fuzzification of a crisp gene cluster allows the cluster to take in genes from other clusters so that overlapping relationship among gene clusters could be uncovered. Hence, previously unknown hidden patterns resided in overlapping gene clusters are discovered. From the experimental results, the high order patterns discovered reveal multiple gene interaction patterns in cancerous tissues not found in normal tissues. It was also found that for the colon cancer experiment, 70% of the top patterns and most of the discriminative patterns between cancerous and normal tissues are among those spanning across different crisp gene clusters.

We show that the proposed method for analyzing the error-prone microarray is effective even without the presence of tissue class information. A unified framework is presented, allowing fast and accurate pattern discovery for gene expression data. For a large gene set, to discover a comprehensive set of patterns, gene clustering, gene expression discretization and gene cluster fuzzification are absolutely necessary.