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A transcriptome-based approach to identify functional modules within and across primary human immune cells.

ABSTRACT: Genome-wide transcriptomic analyses have provided valuable insight into fundamental biology and disease pathophysiology. Many studies have taken advantage of the correlation in the expression patterns of the transcriptome to infer a potential biologic function of uncharacterized genes, and multiple groups have examined the relationship between co-expression, co-regulation, and gene function on a broader scale. Given the unique characteristics of immune cells circulating in the blood, we were interested in determining whether it was possible to identify functional co-expression modules in human immune cells. Specifically, we sequenced the transcriptome of nine immune cell types from peripheral blood cells of healthy donors and, using a combination of global and targeted analyses of genes within co-expression modules, we were able to determine functions for these modules that were cell lineage-specific or shared among multiple cell lineages. In addition, our analyses identified transcription factors likely important for immune cell lineage commitment and/or maintenance.

SUBMITTER: Mola S

PROVIDER: S-EPMC7259617 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A transcriptome-based approach to identify functional modules within and across primary human immune cells.

Mola Saraï S Foisy Sylvain S Boucher Gabrielle G Major François F Beauchamp Claudine C Karaky Mohamad M Goyette Philippe P Lesage Sylvie S Rioux John D JD

PloS one 20200529 5

Genome-wide transcriptomic analyses have provided valuable insight into fundamental biology and disease pathophysiology. Many studies have taken advantage of the correlation in the expression patterns of the transcriptome to infer a potential biologic function of uncharacterized genes, and multiple groups have examined the relationship between co-expression, co-regulation, and gene function on a broader scale. Given the unique characteristics of immune cells circulating in the blood, we were int ...[more]

PMID: 32469933

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Project description:BACKGROUND: Plants respond to diverse environmental cues including microbial perturbations by coordinated regulation of thousands of genes. These intricate transcriptional regulatory interactions depend on the recognition of specific promoter sequences by regulatory transcription factors. The combinatorial and cooperative action of multiple transcription factors defines a regulatory network that enables plant cells to respond to distinct biological signals. The identification of immune-related modules in large-scale transcriptional regulatory networks can reveal the mechanisms by which exposure to a pathogen elicits a precise phenotypic immune response. RESULTS: We have generated a large-scale immune co-expression network using a comprehensive set of Arabidopsis thaliana (hereafter Arabidopsis) transcriptomic data, which consists of a wide spectrum of immune responses to pathogens or pathogen-mimicking stimuli treatments. We employed both linear and non-linear models to generate Arabidopsis immune co-expression regulatory (AICR) network. We computed network topological properties and ascertained that this newly constructed immune network is densely connected, possesses hubs, exhibits high modularity, and displays hallmarks of a "real" biological network. We partitioned the network and identified 156 novel modules related to immune functions. Gene Ontology (GO) enrichment analyses provided insight into the key biological processes involved in determining finely tuned immune responses. We also developed novel software called OCCEAN (One Click Cis-regulatory Elements ANalysis) to discover statistically enriched promoter elements in the upstream regulatory regions of Arabidopsis at a whole genome level. We demonstrated that OCCEAN exhibits higher precision than the existing promoter element discovery tools. In light of known and newly discovered cis-regulatory elements, we evaluated biological significance of two key immune-related functional modules and proposed mechanism(s) to explain how large sets of diverse GO genes coherently function to mount effective immune responses. CONCLUSIONS: We used a network-based, top-down approach to discover immune-related modules from transcriptomic data in Arabidopsis. Detailed analyses of these functional modules reveal new insight into the topological properties of immune co-expression networks and a comprehensive understanding of multifaceted plant defense responses. We present evidence that our newly developed software, OCCEAN, could become a popular tool for the Arabidopsis research community as well as potentially expand to analyze other eukaryotic genomes.

Dataset Information

A transcriptome-based approach to identify functional modules within and across primary human immune cells.

Publications

A transcriptome-based approach to identify functional modules within and across primary human immune cells.

Similar Datasets

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