Oncodrive-CIS

Oncodrive-CIS is a method aimed to identify those copy number alterations (CNAs) leading to larger in cis expression changes that may be useful in elucidating the role of these aberrations in cancer. This is based on the hypothesis that a gene driving oncogenesis through copy number changes is more prone to bias towards overexpression (or underexpression) as compared to bystanders. The effect of the gene dosage is assessed by observing expression changes not only among tumors but also taking into account normal samples data, when available./nOncodrive-CIS has several potential benefits: first, it did not examine the frequency of the CNAs across samples and therefore the detection of low-recurrent driver alterations was not impaired. Second, amplifications and deletions were evaluated separately to obtain a fair ranking of genes, because the expression change measured in deletions was lower than the one obtained from multi-copy amplifications. Third, the expression of genes in tumor samples was analyzed according to the copy number status but was also compared to normal samples, thus better revealing the gene misregulation role of CNAs in cancer cells. And finally, it should be emphasized that the relationship between expression changes and their functional impact is complex, thus Oncodrive-CIS is proposed as a method to elucidate the role of CNAs in cancer which may be complementary to analyses based on other criteria.