Constrained clusters of gene expression profiles with pathological features.
BACKGROUND
Gene expression profiles should be useful in distinguishing variations in disease, since they reflect accurately the status of cells. The primary clustering of gene expression reveals the genotypes that are responsible for the proximity of members within each cluster, while further clustering elucidates the pathological features of the individual members of each cluster. However, since the first clustering process and the second classification step, in which the features are associated with clusters, are performed independently, the initial set of clusters may omit genes that are associated with pathologically meaningful features. Therefore, it is important to devise a way of identifying gene expression clusters that are associated with pathological features.


RESULTS
We present the novel technique of 'itemset constrained clustering' (IC-Clustering), which computes the optimal cluster that maximizes the interclass variance of gene expression between groups, which are divided according to the restriction that only divisions that can be expressed using common features are allowed. This constraint automatically labels each cluster with a set of pathological features which characterize that cluster. When applied to liver cancer datasets, IC-Clustering revealed informative gene expression clusters, which could be annotated with various pathological features, such as 'tumor' and 'man', or 'except tumor' and 'normal liver function'. In contrast, the k-means method overlooked these clusters.
Sese
Jun
J
Undergraduate Program for Bioinformatics and Systems Biology, Graduate School of Frontier Sciences, University of Tokyo, Bunkyo, Tokyo, Japan. sesejun@gi.k.u-tokyo.ac.jp
Kurokawa
Yukinori
Y
Monden
Morito
M
Kato
Kikuya
K
Morishita
Shinichi
S
D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016000:Cluster Analysis; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000145:classification* / Q000175:diagnosis* / Q000378:metabolism; D010363:Pattern Recognition, Automated / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor