A metagene based similarity network fusion approach for multi-omics data integration identified novel subtypes in renal cell carcinoma

Renal cell carcinoma (RCC) ranks among the most prevalent cancers worldwide, with both incidence and mortality rates increasing annually. The heterogeneity among RCC patients presents considerable challenges for developing universally effective treatment strategies, emphasizing the necessity of in-depth research into RCC's molecular mechanisms, understanding the variations among RCC patients and further identifying distinct molecular subtypes for precise treatment. We proposed a metagene-based similarity network fusion (Meta-SNF) method for RCC subtype identification with multi-omics data, using a non-negative matrix factorization technique to capture alternative structures inherent in the dataset as metagenes. These latent metagenes were then integrated to construct a fused network under the Similarity Network Fusion (SNF) framework for more precise subtyping. We conducted simulation studies and analyzed real-world data from two RCC datasets, namely kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) to demonstrate the utility of Meta-SNF. The simulation studies indicated that Meta-SNF achieved higher accuracy in subtype identification compared with the original SNF and other state-of-the-art methods. In analyses of real data, Meta-SNF produced more distinct and well-separated clusters, classifying both KIRC and KIRP into four subtypes with significant differences in survival outcomes. Subsequently, we performed comprehensive bioinformatics analyses focused on subtypes with poor prognoses in KIRC and KIRP and identified several potential biomarkers. Meta-SNF offers a novel strategy for subtype identification using multi-omics data, and its application to RCC datasets has yielded diverse biological insights which are highly valuable for informing clinical decision-making processes in the treatment of RCC.