Identification of ovarian cancer driver genes by using module network integration of multi-omics data.

The increasing availability of multi-omics cancer datasets has created a new opportunity for data integration that promises a more comprehensive understanding of cancer. The challenge is to develop mathematical methods that allow the integration and extraction of knowledge from large datasets such as The Cancer Genome Atlas (TCGA). This has led to the development of a variety of omics profiles that are highly correlated with each other; however, it remains unknown which profile is the most meaningful and how to efficiently integrate different omics profiles. We developed AMARETTO, an algorithm to identify cancer drivers by integrating a variety of omics data from cancer and normal tissue. AMARETTO first models the effects of genomic/epigenomic data on disease-specific gene expression. AMARETTO's second step involves constructing a module network to connect the cancer drivers with their downstream targets. We observed that more gene expression variation can be explained when using disease-specific gene expression data. We applied AMARETTO to the ovarian cancer TCGA data and identified several cancer driver genes of interest, including novel genes in addition to known drivers of cancer. Finally, we showed that certain modules are predictive of good versus poor outcome, and the associated drivers were related to DNA repair pathways.