Construction of pan-cancer regulatory networks based on causal inference

Abstract

The pan-cancer initiative aims to study the origin patterns of cancer cell, the processes of carcinogenesis, and the signaling pathways from a perspective that spans across different types of cancer. The construction of the pan-cancer related gene regulatory network is helpful to excavate the commonalities in regulatory relationships among different types of cancers. It also aids in understanding the mechanisms behind cancer occurrence and development, which is of great scientific significance for cancer prevention and treatment. In light of the high dimension and large sample size of pan-cancer omics data, a causal pan-cancer gene regulation network inference algorithm based on stochastic complexity is proposed. With the network construction strategy of local first and then global, the stochastic complexity is used in the conditional independence test and causal direction inference for the candidate adjacent node set of the target nodes. This approach aims to decrease the time complexity and error rate of causal network learning. By applying this algorithm to the sample data of seven types of cancers in the TCGA database, including breast cancer, lung adenocarcinoma, and so on, the pan-cancer related causal regulatory networks are constructed, and their biological significance is verified. The experimental results show that this algorithm can eliminate the redundant regulatory relationships effectively and infer the pan-cancer regulatory network more accurately (https://github.com/LindeEugen/CNI-SC).