Statistical issues in the analysis of the array CGH data

The development of solid tumors is associated with acquisition of complex genetic alterations, indicating that failures in the mechanisms that maintain the integrity of the genome contribute to tumor evolution. Thus, one expects that the particular types of genomic derangement seen in tumors reflect underlying failures in maintenance of genetic stability, as well as selection for changes that provide growth advantage. In order to investigate genomic alterations we are using microarray-based comparative genomic hybridization (array CGH). The computational task is to map and characterize the number and types of copy number alterations present in the tumors, and so define copy number phenotypes as well as to associate them with known biological markers. To utilize the spatial coherence between nearby clones, we use unsupervised HiddenMarkovModels approach. The clones are partitioned into the states which represent underlying copy number of the group of clones. The method is demonstrated on the two cell line datasets with known copy number alterations for one of them. The biological conclusions drawn from the analyses are discussed.