Benchmarking multi-omics integrative clustering methods for subtype identification in colorectal cancer

Abstract Background and objectives Colorectal cancer (CRC) represents a heterogeneous malignancy that has concerned global burden of incidence and mortality. The traditional tumor-node-metastasis staging system has exhibited certain limitations. With the advancement of omics technologies, researchers are directing their focus on developing a more precise multi-omics molecular classification. Therefore, the utilization of unsupervised multi-omics integrative clustering methods in CRC, advocating for the establishment of a comprehensive benchmark with practical guidelines. In this study, we obtained CRC multi-omics data, encompassing DNA methylation, gene expression, and protein expression from the TCGA database. We then generated interrelated CRC multi-omics data with various structures based on realistic multi-omics correlations, and performed a comprehensive evaluation of eight representative methods categorized as early integration, intermediate integration, and late integration using complementary benchmarks for subtype classification accuracy. Lastly, we employed these methods to integrate real-world CRC multi-omics data, survival and differential analysis were used to highlight differences among newly identified multi-omics subtypes. Results Through in-depth comparisons, we observed that similarity network fusion (SNF) exhibited exceptional performance in integrating multi-omics data derived from simulations. Additionally, SNF effectively distinguished CRC patients into five subgroups with the highest classification accuracy. Moreover, we found significant survival differences and molecular distinctions among SNF subtypes. Conclusions The findings consistently demonstrate that SNF outperforms other methods in CRC multi-omics integrative clustering. The significant survival differences and molecular distinctions among SNF subtypes provide novel insights into the multi-omics perspective on CRC heterogeneity with potential clinical treatment. The code and its implementation are available in GitHub https://github.com/zsbvb/Comparison-of-Multiomics-Integration-Methods-for-CRC.