期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 17, 页码 E2393-E2402出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1604351113
关键词
gene expression; network inference; database; immune system; regulatory T cells
资金
- World Premier Inter-national Research Center Initiative of the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- MEXT [26253030]
- Japan Science and Technology Agency [15652235]
- Japan Society for the Promotion of Science [15H04744]
- Grants-in-Aid for Scientific Research [16H06295, 15H04744, 26253030] Funding Source: KAKEN
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 beta 8 (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.
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