Dataset Information

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 ?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.

SUBMITTER: Vandenbon A

PROVIDER: S-EPMC4855614 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Vandenbon Alexis A Dinh Viet H VH Mikami Norihisa N Kitagawa Yohko Y Teraguchi Shunsuke S Ohkura Naganari N Sakaguchi Shimon S

Proceedings of the National Academy of Sciences of the United States of America 20160413 17

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 mous ...[more]

PMID: 27078110

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Project description:BackgroundBiological processes are carried out by coordinated modules of interacting molecules. As clustering methods demonstrate that genes with similar expression display increased likelihood of being associated with a common functional module, networks of coexpressed genes provide one framework for assigning gene function. This has informed the guilt-by-association (GBA) heuristic, widely invoked in functional genomics. Yet although the idea of GBA is accepted, the breadth of GBA applicability is uncertain.ResultsWe developed methods to systematically explore the breadth of GBA across a large and varied corpus of expression data to answer the following question: To what extent is the GBA heuristic broadly applicable to the transcriptome and conversely how broadly is GBA captured by a priori knowledge represented in the Gene Ontology (GO)? Our study provides an investigation of the functional organization of five coexpression networks using data from three mammalian organisms. Our method calculates a probabilistic score between each gene and each Gene Ontology category that reflects coexpression enrichment of a GO module. For each GO category we use Receiver Operating Curves to assess whether these probabilistic scores reflect GBA. This methodology applied to five different coexpression networks demonstrates that the signature of guilt-by-association is ubiquitous and reproducible and that the GBA heuristic is broadly applicable across the population of nine hundred Gene Ontology categories. We also demonstrate the existence of highly reproducible patterns of coexpression between some pairs of GO categories.ConclusionWe conclude that GBA has universal value and that transcriptional control may be more modular than previously realized. Our analyses also suggest that methodologies combining coexpression measurements across multiple genes in a biologically-defined module can aid in characterizing gene function or in characterizing whether pairs of functions operate together.

Project description:PurposeTo develop a motion estimation and correction method for motion-robust three-dimensional (3D) quantitative imaging with 3D-echo-planar time-resolved imaging.Theory and methodsThe 3D-echo-planar time-resolved imaging technique was designed with additional four-dimensional navigator acquisition (x-y-z-echoes) to achieve fast and motion-robust quantitative imaging of the human brain. The four-dimensional-navigator is inserted into the relaxation-recovery deadtime of the sequence in every pulse TR (∼2 s) to avoid extra scan time, and to provide continuous tracking of the 3D head motion and B0 -inhomogeneity changes. By using an optimized spatiotemporal encoding combined with a partial-Fourier scheme, the navigator acquires a large central k-t data block for accurate motion estimation using only four small-flip-angle excitations and readouts, resulting in negligible signal-recovery reduction to the 3D-echo-planar time-resolved imaging acquisition. By incorporating the estimated motion and B0 -inhomogeneity changes into the reconstruction, multi-contrast images can be recovered with reduced motion artifacts.ResultsSimulation shows the cost to the SNR efficiency from the added navigator acquisitions is <1%. Both simulation and in vivo retrospective experiments were conducted, that demonstrate the four-dimensional navigator provided accurate estimation of the 3D motion and B0 -inhomogeneity changes, allowing effective reduction of image artifacts in quantitative maps. Finally, in vivo prospective undersampling acquisition was performed with and without head motion, in which the motion corrupted data after correction show close image quality and consistent quantifications to the motion-free scan, providing reliable quantitative measurements even with head motion.ConclusionThe proposed four-dimensional navigator acquisition provides reliable tracking of the head motion and B0 change with negligible SNR cost, equips the 3D-echo-planar time-resolved imaging technique for motion-robust and efficient quantitative imaging.

Dataset Information

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

Publications

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

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