Identifying the Immunological Gene Signatures of Immune Cell Subtypes

Abstract

The immune system is a complicated defensive system that comprises multiple functional cells and molecules acting against endogenous and exogenous pathogenic factors. Identifying immune cell subtypes and recognizing their unique immunological functions are difficult because of the complicated cellular components and immunological functions of the immune system. With the development of transcriptomics and high-throughput sequencing, the gene expression profiling of immune cells can provide a new strategy to explore the immune cell subtyping. On the basis of the new profiling data of mouse immune cell gene expression from the Immunological Genome Project (ImmGen), a novel computational pipeline was applied to identify different immune cell subtypes, including αβ T cells, B cells, γδ T cells, and innate lymphocytes. First, the profiling data was analyzed by a powerful feature selection method, Monte-Carlo Feature Selection, resulting in a feature list and some informative features. For the list, the two-stage incremental feature selection method, incorporating random forest as the classification algorithm, was applied to extract essential gene signatures and build an efficient classifier. On the other hand, a rule learning scheme was applied on the informative features to construct quantitative expression rules. A group of gene signatures was found as qualitatively related to the biological processes of four immune cell subtypes. The quantitative expression rules can efficiently cluster immune cells. This work provides a novel computational tool for immune cell quantitative subtyping and biomarker recognition.