Literature DB >> 27078110

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

Alexis Vandenbon1, Viet H Dinh2, Norihisa Mikami3, Yohko Kitagawa3, Shunsuke Teraguchi4, Naganari Ohkura5, Shimon Sakaguchi6.   

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.

Entities:  

Keywords:  database; gene expression; immune system; network inference; regulatory T cells

Mesh:

Substances:

Year:  2016        PMID: 27078110      PMCID: PMC4855614          DOI: 10.1073/pnas.1604351113

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  43 in total

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2.  T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.

Authors:  Naganari Ohkura; Masahide Hamaguchi; Hiromasa Morikawa; Kyoko Sugimura; Atsushi Tanaka; Yoshinaga Ito; Motonao Osaki; Yoshiaki Tanaka; Riu Yamashita; Naoko Nakano; Jochen Huehn; Hans Joerg Fehling; Tim Sparwasser; Kenta Nakai; Shimon Sakaguchi
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Review 4.  Tackling the widespread and critical impact of batch effects in high-throughput data.

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Journal:  Proc Natl Acad Sci U S A       Date:  2005-09-30       Impact factor: 11.205

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Journal:  EMBO J       Date:  2009-09-24       Impact factor: 11.598

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Authors:  Wenxian Fu; Ayla Ergun; Ting Lu; Jonathan A Hill; Sokol Haxhinasto; Marlys S Fassett; Roi Gazit; Stanley Adoro; Laurie Glimcher; Susan Chan; Philippe Kastner; Derrick Rossi; James J Collins; Diane Mathis; Christophe Benoist
Journal:  Nat Immunol       Date:  2012-09-09       Impact factor: 25.606

10.  A reanalysis of mouse ENCODE comparative gene expression data.

Authors:  Yoav Gilad; Orna Mizrahi-Man
Journal:  F1000Res       Date:  2015-05-19
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Review 2.  Single-Cell Genomics: Approaches and Utility in Immunology.

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