Evaluation and comparison of gene clustering methods in microarray analysis.
BACKGROUND
Microarray technology has been widely applied in biological and clinical studies for simultaneous monitoring of gene expression in thousands of genes. Gene clustering analysis is found useful for discovering groups of correlated genes potentially co-regulated or associated to the disease or conditions under investigation. Many clustering methods including hierarchical clustering, K-means, PAM, SOM, mixture model-based clustering and tight clustering have been widely used in the literature. Yet no comprehensive comparative study has been performed to evaluate the effectiveness of these methods.


RESULTS
In this paper, six gene clustering methods are evaluated by simulated data from a hierarchical log-normal model with various degrees of perturbation as well as four real datasets. A weighted Rand index is proposed for measuring similarity of two clustering results with possible scattered genes (i.e. a set of noise genes not being clustered). Performance of the methods in the real data is assessed by a predictive accuracy analysis through verified gene annotations. Our results show that tight clustering and model-based clustering consistently outperform other clustering methods both in simulated and real data while hierarchical clustering and SOM perform among the worst. Our analysis provides deep insight to the complicated gene clustering problem of expression profile and serves as a practical guideline for routine microarray cluster analysis.
Thalamuthu
Anbupalam
A
Department of Human Genetics, University of Pittsburgh, PA, USA.
Mukhopadhyay
Indranil
I
Zheng
Xiaojing
X
Tseng
George C
GC
D000465:Algorithms; D001185:Artificial Intelligence; D016000:Cluster Analysis; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods*; D008957:Models, Genetic; D015233:Models, Statistical; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012984:Software; D012986:Software Validation