A novel network control model for identifying personalized driver genes in cancer

Although existing computational models have identified many common driver genes, it remains challenging to identify the personalized driver genes by using samples of an individual patient. Recently, the methods of exploiting the structure-based control principles of complex networks provide new clues for identifying minimum number of driver nodes to drive the state transition of large-scale complex networks from an initial state to the desired state. However, the structure-based network control methods cannot be directly applied to identify the personalized driver genes due to the unknown network dynamics of the personalized system. Here we proposed the personalized network control model (PNC) to identify the personalized driver genes by employing the structure-based network control principle on genetic data of individual patients. In PNC model, we firstly presented a paired single sample network construction method to construct the personalized state transition network for capturing the phenotype transitions between healthy and disease states. Then, we designed a novel structure-based network control method from the Feedback Vertex Sets-based control perspective to identify the personalized driver genes. The wide experimental results on 13 cancer datasets from The Cancer Genome Atlas firstly showed that PNC model outperforms current state-of-the-art methods, in terms of F-measures for identifying cancer driver genes enriched in the gold-standard cancer driver gene lists. Furthermore, these results showed that personalized driver genes can be explored by their network characteristics even when they are hidden factors in transcription and mutation profiles. Our PNC gives novel insights and useful tools into understanding the tumor heterogeneity in cancer. The PNC package and data resources used in this work can be freely downloaded from https://github.com/NWPU-903PR/PNC.