Privacy-Preserving Identification of Cancer Subtype-Specific Driver Genes Based on Multigenomics Data with Privatedriver.

Abstract

Identifying cancer subtype-specific driver genes from a large number of irrelevant passengers is crucial for targeted therapy in cancer treatment. Recently, the rapid accumulation of large-scale cancer genomics data from multiple institutions has presented remarkable opportunities for identification of cancer subtype-specific driver genes. However, the insufficient subtype samples, privacy issues, and heterogenous of aberration events pose great challenges in precisely identifying cancer subtype-specific driver genes. To address this, we introduce privatedriver, the first model for identifying subtype-specific driver genes that integrates genomics data from multiple institutions in a data privacy-preserving collaboration manner. The process of identifying subtype-specific cancer driver genes using privatedriver involves the following two steps: genomics data integration and collaborative training. In the integration process, the aberration events from multiple genomics data sources are combined for each institution using the forward and backward propagation method of NetICS. In the collaborative training process, each institution utilizes the federated learning framework to upload encrypted model parameters instead of raw data of all institutions to train a global model by using the non-negative matrix factorization algorithm. We applied privatedriver on head and neck squamous cell and colon cancer from The Cancer Genome Atlas website and evaluated it with two benchmarks using macro-Fscore. The comparison analysis demonstrates that privatedriver achieves comparable results to centralized learning models and outperforms most other nonprivacy preserving models, all while ensuring the confidentiality of patient information. We also demonstrate that, for varying predicted driver gene distributions in subtype, our model fully considers the heterogeneity of subtype and identifies subtype-specific driver genes corresponding to the given prognosis and therapeutic effect. The success of privatedriver reveals the feasibility and effectiveness of identifying cancer subtype-specific driver genes in a data protection manner, providing new insights for future privacy-preserving driver gene identification studies.