Driver pattern identification over the gene co-expression of drug response in ovarian cancer by integrating high throughput genomics data

Abstract

The multiple types of high throughput genomics data create a potential opportunity to identify driver pattern in ovarian cancer, which will acquire some novel and clinical biomarkers for appropriate diagnosis and treatment to cancer patients. However, it is a great challenging work to integrate omics data, including somatic mutations, Copy Number Variations (CNVs) and gene expression profiles, to distinguish interactions and regulations which are hidden in drug response dataset of ovarian cancer. To distinguish the candidate driver genes and the corresponding driving pattern for resistant and sensitive tumor from the heterogeneous data, we combined gene co-expression modules and mutation modulators and proposed the identification driver patterns method. Firstly, co-expression network analysis is applied to explore gene modules for gene expression profiles via weighted correlation network analysis (WGCNA). Secondly, mutation matrix is generated by integrating the CNVs and somatic mutations, and a mutation network is constructed from this mutation matrix. The candidate modulators are selected from the significant genes by clustering the vertex of the mutation network. At last, regression tree model is utilized for module networks learning in which the achieved gene modules and candidate modulators are trained for the driving pattern identification and modulator regulatory exploring. Many of the candidate modulators identified are known to be involved in biological meaningful processes associated with ovarian cancer, which can be regard as potential driver genes, such as CCL11, CCL16, CCL18, CCL23, CCL8, CCL5, APOB, BRCA1, SLC18A1, FGF22, GADD45B, GNA15, GNA11 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.