Vandenbon Alexis, Dinh Viet H, Mikami Norihisa, Kitagawa Yohko, Teraguchi Shunsuke, Ohkura Naganari, Sakaguchi Shimon
Immuno-Genomics Research Unit, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan;
Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan;
Proc Natl Acad Sci U S A. 2016 Apr 26;113(17):E2393-402. doi: 10.1073/pnas.1604351113. Epub 2016 Apr 13.
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.
高通量基因表达数据是现代生物学中探索复杂细胞内动态的主要资源之一。整合大量公共数据可能使我们能够研究调节因子与靶基因之间的一般动态关系。然而,此类分析的障碍是原始数据中特定于研究的偏差或批次效应。在此,我们展示了Immuno-Navigator,这是一个针对小鼠免疫系统24种细胞类型的经过批次校正的基因表达和共表达数据库。我们系统地消除了基础基因表达数据中的批次效应,并表明这种消除极大地提高了推断的相关性与先验知识之间的一致性。数据揭示了广泛的细胞类型特异性表达相关性。集成分析工具允许用户利用这种表达相关性来生成关于特定细胞类型中生物网络和候选调节因子的假设。我们展示了Immuno-Navigator的几个应用示例。在一个应用中,我们从与一组调节性T细胞(Treg)特异性基因的表达相关性成功预测了天然存在的Treg细胞中重要的已知调节因子。对于一个高分基因,整合素β8(Itgb8),我们证实了叉头框P3(Foxp3)阳性T细胞中Itgb8表达与Treg特异性表观遗传重塑之间的关联。我们的结果还表明,Treg细胞内Treg特异性基因的调节相对独立于Foxp3表达,支持了最近指向Treg细胞发育中Foxp3非依赖性成分的结果。