TPQCI: A Topology Potential-Based Method to Quantify Functional Influence of Copy Number Variations.

Abstract Copy number variation (CNV) is a major type of chromosomal structural variation that plays important roles in many diseases including cancers. Due to genome instability, a large number of CNV events can be detected in diseases such as cancer. Therefore, it is important to identify the functionally important CNVs in diseases, which currently still poses a challenge in genomics. One of the critical steps to solve the problem is to define the influence of CNV. In this paper, we provide a topology potential based method, TPQCI, to quantify this kind of influence by integrating statistics, gene regulatory associations, and biological function information. We used this metric to detect functionally enriched genes on genomic segments with CNV in breast cancer and multiple myeloma and discovered biological functions influenced by CNV. Our results demonstrate that, by using our proposed TPQCI metric, we can detect disease-specific genes that are influenced by CNVs.