Spring 2008 Database Seminar

Thursday Jan 30th, 2008
CSE Room 305
12:00 - 1:00 PM

Inferring Progression Models for CGH Data

Jun Liu

Large scale evolutionary analysis across heterogeneous cancer types is one of the most critical tasks in cancer research. One of the mutational processes that can be monitored genome-wide is the occurrence of regional DNA Copy Number Alterations (CNAs), which may lead to deletion or over-expression of tumor suppressors or oncogenes, respectively. Recently, the descriptive analysis of oncogenomic summary data was able to point towards a concordance of imbalance profiles from entities of similar histological categories. However, the analysis of average imbalance profiles can not capture the diversity of aberration complexity in the different entities. There is a great need for efficient methods that can accurately model the progression of the cancer markers and reconstruct evolutionary relationship between multiple types of cancers. We have developed an automatic method to infer a graph model for the markers of multiple cancers from a large population of Comparative Genomic Hybridization (CGH) data. Our method identifies highly correlated markers across different cancer types. It then builds a directed acyclic graph that shows the evolutionary history of these markers based on how common each marker is in different cancer types. We demonstrated the use of this model in determining the importance of markers in cancer evolution. We have also developed a new method to measure the evolutionary distance between different cancers based on their markers. This method employs the graph model we developed for the individual markers to measure the distance between pairs of cancers. We used this measure to create an evolutionary tree for multiple cancers. Our experiments on Progenetix database show that our markers are largely consistent to the reported hot-spot imbalances and most frequent imbalances. The results show that our distance measure can accurately reconstruct the evolutionary relationship between multiple cancer types.

 


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