Immuno-Navigator, a batch-corrected coexpression database, reveals cell type-specific gene networks in the immune system

Alexis Vandenbon, Viet H. Dinh, Norihisa Mikami, Yohko Kitagawa, Shunsuke Teraguchi, Naganari Ohkura, Shimon Sakaguchi

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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 studyspecific 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 Tregspecific 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.

Original languageEnglish
Pages (from-to)E2393-2402
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number17
DOIs
Publication statusPublished - 2016 Apr 26

Keywords

  • Database
  • Gene expression
  • Immune system
  • Network inference
  • Regulatory T cells

ASJC Scopus subject areas

  • General

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