Inferring cancer common and specific gene networks via multi-layer joint graphical model

Abstract

Cancer is a complex disease caused primarily by genetic variants. Reconstructing gene networks within tumors is essential for understanding the functional regulatory mechanisms of carcinogenesis. Advances in high-throughput sequencing technologies have provided tremendous opportunities for inferring gene networks via computational approaches. However, due to the heterogeneity of the same cancer type and the similarities between different cancer types, it remains a challenge to systematically investigate the commonalities and specificities between gene networks of different cancer types, which is a crucial step towards precision cancer diagnosis and treatment. In this study, we propose a new sparse regularized multi-layer decomposition graphical model to jointly estimate the gene networks of multiple cancer types. Our model can handle various types of gene expression data and decomposes each cancer-type-specific network into three components, i.e., globally shared, partially shared and cancer-type-unique components. By identifying the globally and partially shared gene network components, our model can explore the heterogeneous similarities between different cancer types, and our identified cancer-type-unique components can help to reveal the regulatory mechanisms unique to each cancer type. Extensive experiments on synthetic data illustrate the effectiveness of our model in joint estimation of multiple gene networks. We also apply our model to two real data sets to infer the gene networks of multiple cancer subtypes or cell lines. By analyzing our estimated globally shared, partially shared, and cancer-type-unique components, we identified a number of important genes associated with common and specific regulatory mechanisms across different cancer types.

Keywords

• Gene network inference
• Gaussian graphical models
• Single-cell RNA sequencing
• Sparse penalty