BackgroundCancer subtype identification is important for the early diagnosis of cancer and the provision of adequate treatment. Prior to identifying the subtype of cancer in a patient, feature selection is also crucial for reducing the dimensionality of the data by detecting genes that contain important information about the cancer subtype. Numerous cancer subtyping methods have been developed, and their performance has been compared. However, combinations of feature selection and subtype identification methods have rarely been considered. This study aimed to identify the best combination of variable selection and subtype identification methods in single omics data analysis.ResultsCombinations of six filter-based methods and six unsupervised subtype identification methods were investigated using The Cancer Genome Atlas (TCGA) datasets for four cancers. The number of features selected varied, and several evaluation metrics were used. Although no single combination was found to have a distinctively good performance, Consensus Clustering (CC) and Neighborhood-Based Multi-omics Clustering (NEMO) used with variance-based feature selection had a tendency to show lowerp-values, and nonnegative matrix factorization (NMF) stably showed good performance in many cases unless the Dip test was used for feature selection. In terms of accuracy, the combination of NMF and similarity network fusion (SNF) with Monte Carlo Feature Selection (MCFS) and Minimum-Redundancy Maximum Relevance (mRMR) showed good overall performance. NMF always showed among the worst performances without feature selection in all datasets, but performed much better when used with various feature selection methods. iClusterBayes (ICB) had decent performance when used without feature selection.ConclusionsRather than a single method clearly emerging as optimal, the best methodology was different depending on the data used, the number of features selected, and the evaluation method. A guideline for choosing the best combination method under various situations is provided.