Sequential reinforcement active feature learning for gene signature identification in renal cell carcinoma

Renal cell carcinoma (RCC) is one of the deadliest cancers and mainly consists of three subtypes: kidney clear cell carcinoma (KIRC), kidney papillary cell carcinoma (KIRP), and kidney chromophobe (KICH). Gene signature identification plays an important role in the precise classification of RCC subtypes and personalized treatment. However, most of the existing gene selection methods focus on statically selecting the same informative genes for each subtype, and fail to consider the heterogeneity of patients which causes pattern differences in each subtype. In this work, to explore different informative gene subsets for each subtype, we propose a novel gene selection method, named sequential reinforcement active feature learning (SRAFL), which dynamically acquire the different genes in each sample to identify the different gene signatures for each subtype. The proposed SRAFL method combines the cancer subtype classifier with the reinforcement learning (RL) agent, which sequentially select the active genes in each sample from three mixed RCC subtypes in a cost-sensitive manner. Moreover, the module-based gene filtering is run before gene selection to filter the redundant genes. We mainly evaluate the proposed SRAFL method based on mRNA and long non-coding RNA (lncRNA) expression profiles of RCC datasets from The Cancer Genome Atlas (TCGA). The experimental results demonstrate that the proposed method can automatically identify different gene signatures for different subtypes to accurately classify RCC subtypes. More importantly, we here for the first time show the proposed SRAFL method can consider the heterogeneity of samples to select different gene signatures for different RCC subtypes, which shows more potential for the precision-based RCC care in the future.