title: Immuno-Navigator, a batch-corrected coexpression database, reveals cell type-specific gene networks in the immune system.
abstract: High-throughput gene expression data are one of the primary resources for exploring complex intracellular dynamics in modern biology. The integration of large amounts of public data may allow us to examine general dynamical relationships between regulators and target genes. However, obstacles for such analyses are study-specific biases or batch effects in the original data. Here we present Immuno-Navigator, a batch-corrected gene expression and coexpression database for 24 cell types of the mouse immune system. We systematically removed batch effects from the underlying gene expression data and showed that this removal considerably improved the consistency between inferred correlations and prior knowledge. The data revealed widespread cell type-specific correlation of expression. Integrated analysis tools allow users to use this correlation of expression for the generation of hypotheses about biological networks and candidate regulators in specific cell types. We show several applications of Immuno-Navigator as examples. In one application we successfully predicted known regulators of importance in naturally occurring Treg cells from their expression correlation with a set of Treg-specific genes. For one high-scoring gene, integrin β8 (Itgb8), we confirmed an association between Itgb8 expression in forkhead box P3 (Foxp3)-positive T cells and Treg-specific epigenetic remodeling. Our results also suggest that the regulation of Treg-specific genes within Treg cells is relatively independent of Foxp3 expression, supporting recent results pointing to a Foxp3-independent component in the development of Treg cells.
authors.affiliation: Immuno-Genomics Research Unit, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan; alexisvdb@ifrec.osaka-u.ac.jp shimon@ifrec.osaka-u.ac.jp.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vandenbon
authors.affiliation: Immuno-Genomics Research Unit, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan;
authors.forename: Viet H
authors.initials: VH
authors.lastname: Dinh
authors.affiliation: Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan;
authors.forename: Norihisa
authors.initials: N
authors.lastname: Mikami
authors.affiliation: Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan;
authors.forename: Yohko
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Quantitative Immunology Research Unit, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan;
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Teraguchi
authors.affiliation: Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan; Frontier Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: Naganari
authors.initials: N
authors.lastname: Ohkura
authors.affiliation: Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan; alexisvdb@ifrec.osaka-u.ac.jp shimon@ifrec.osaka-u.ac.jp.
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
mesh_terms: D000818:Animals; D016208:Databases, Factual; D051858:Forkhead Transcription Factors / Q000235:genetics; D015870:Gene Expression; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005809:Genes, Regulator; D055106:Genome-Wide Association Study / Q000379:methods; D006410:Hematopoiesis; D007107:Immune System / Q000166:cytology; D051379:Mice; D050378:T-Lymphocytes, Regulatory
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse
keywords: database; gene expression; immune system; network inference; regulatory T cells