Classification of Widely and Rarely Expressed Genes with Recurrent Neural Network

Comput Struct Biotechnol J. 2018 Dec 14:17:49-60. doi: 10.1016/j.csbj.2018.12.002. eCollection 2019.

Abstract

A tissue-specific gene expression shapes the formation of tissues, while gene expression changes reflect the immune response of the human body to environmental stimulations or pressure, particularly in disease conditions, such as cancers. A few genes are commonly expressed across tissues or various cancers, while others are not. To investigate the functional differences between widely and rarely expressed genes, we defined the genes that were expressed in 32 normal tissues/cancers (i.e., called widely expressed genes; FPKM >1 in all samples) and those that were not detected (i.e., called rarely expressed genes; FPKM <1 in all samples) based on the large gene expression data set provided by Uhlen et al. Each gene was encoded using the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment scores. Minimum redundancy maximum relevance (mRMR) was used to measure and rank these features on the mRMR feature list. Thereafter, we applied the incremental feature selection method with a supervised classifier recurrent neural network (RNN) to select the discriminate features for classifying widely expressed genes from rarely expressed genes and construct an optimum RNN classifier. The Youden's indexes generated by the optimum RNN classifier and evaluated using a 10-fold cross validation were 0.739 for normal tissues and 0.639 for cancers. Furthermore, the underlying mechanisms of the key discriminate GO and KEGG features were analyzed. Results can facilitate the identification of the expression landscape of genes and elucidation of how gene expression shapes tissues and the microenvironment of cancers.

Keywords: Enrichment theory; Incremental feature selection; Minimum redundancy maximum relevance; Rarely expressed gene; Recurrent neural network; Widely expressed gene.