Abstract
Cancer is a highly heterogeneous disease characterized by complex molecular changes. Subtypes identified through multi-omics data hold significant promise for improving prognosis and facilitating personalized precision treatment. Recent multi-omics integration methods have mostly focused on capturing complementary information from different data types, often overlooking potential interactions between omics data. Here we develop a novel method named interactive multi-kernel learning (iMKL), which incorporates omics-omics interactions alongside heterogeneous data types under the unsupervised multi-kernel learning framework, to improve subtype identification. Using the sample-similarity kernel for each dataset, we propose a joint Hadamard product strategy to capture higher-order interactive effects from different omics data types. We applied iMKL to two renal cell carcinoma (RCC) datasets-clear renal cell carcinoma (ccRCC) and type II papillary renal cell carcinoma (type II pRCC)-both including miRNA expression, mRNA expression, and DNA methylation data. Stability analysis through random sampling of patients or features demonstrated that iMKL exhibits strong robustness and accuracy in identifying patient subtypes. The identified subtypes revealed dramatic differences in patient survival, with both ccRCC and type II pRCC classified into three distinct subtypes. The findings in the real application highlight potential biomarkers associated with adverse patient outcomes and demonstrate substantial advancement in cancer subtype identification. The iMKL method effectively identifies tumor molecular subtypes that are strongly associated with clinical features and survival rates, providing valuable insights for accurate cancer subtyping, clinical decision-making, and the realization of personalized treatment strategies.