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CDCOCA: A statistical method to define complexity dependence of co-occuring chromosomal aberrations

Nitin Kumar,H. Rehrauer,Haoyang Cai,M. Baudis

Published 2011 in BMC Medical Genomics

ABSTRACT

BackgroundCopy number alterations (CNA) play a key role in cancer development and progression. Since more than one CNA can be detected in most tumors, frequently co-occurring genetic CNA may point to cooperating cancer related genes. Existing methods for co-occurrence evaluation so far have not considered the overall heterogeneity of CNA per tumor, resulting in a preferential detection of frequent changes with limited specificity for each association due to the high genetic instability of many samples.MethodWe hypothesize that in cancer some linkage-independent CNA may display a non-random co-occurrence, and that these CNA could be of pathogenetic relevance for the respective cancer. We also hypothesize that the statistical relevance of co-occurring CNA may depend on the sample specific CNA complexity. We verify our hypotheses with a simulation based algorithm CDCOCA (complexity dependence of co-occurring chromosomal aberrations).ResultsApplication of CDCOCA to example data sets identified co-occurring CNA from low complex background which otherwise went unnoticed. Identification of cancer associated genes in these co-occurring changes can provide insights of cooperative genes involved in oncogenesis.ConclusionsWe have developed a method to detect associations of regional copy number abnormalities in cancer data. Along with finding statistically relevant CNA co-occurrences, our algorithm points towards a generally low specificity for co-occurrence of regional imbalances in CNA rich samples, which may have negative impact on pathway modeling approaches relying on frequent CNA events.

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