Abstract
Compendia of large-scale datasets made available in public repositories provide an opportunity to identify and fill gaps in biomedical knowledge. But first, these data need to be made readily accessible to research investigators for interpretation. Here we make available a collection of transcriptome datasets to investigate the functional programming of human hematopoietic cells in early life. Thirty two datasets were retrieved from the NCBI Gene Expression Omnibus (GEO) and loaded in a custom web application called the Gene Expression Browser (GXB), which was designed for interactive query and visualization of integrated large-scale data. Quality control checks were performed. Multiple sample groupings and gene rank lists were created allowing users to reveal age-related differences in transcriptome profiles, changes in the gene expression of neonatal hematopoietic cells to a variety of immune stimulators and modulators, as well as during cell differentiation. Available demographic, clinical, and cell phenotypic information can be overlaid with the gene expression data and used to sort samples. Web links to customized graphical views can be generated and subsequently inserted in manuscripts to report novel findings. GXB also enables browsing of a single gene across projects, thereby providing new perspectives on age- and developmental stage-specific expression of a given gene across the human hematopoietic system. This dataset collection is available at: http://developmentalimmunology.gxbsidra.org/dm3/geneBrowser/list.
Highlights
Human immune defenses are highly dynamic and vary with age, reflecting the different environmental challenges and needs for adaptation during the fetal, neonatal and postnatal period, and throughout life
An increasing number of studies have been designed to gain a deeper understanding of immunity in early life, and to reveal the underlying immune defense and regulatory mechanisms that determine the clinical outcome of primary infections, and responses to early childhood vaccination[1,2,3]
Aside from the limited repertoire of memory B and T lymphocytes in neonates, such studies have revealed substantial gestational- and postnatal age-dependent differences in the phenotype and function of a variety of hematopoietic cell types upon in vitro stimulation of cord/peripheral blood and isolated blood mononuclear cells with a variety of immune stimulators and modulators, including purified Toll-like receptor (TLR) and RIG-I-like receptor (RLR) agonists, cytokines, and whole pathogens, which engage a variety of pattern recognition receptors (PRRs) and signaling pathways[5,6,7,8,9,10,11,12,13,14]
Summary
Human immune defenses are highly dynamic and vary with age, reflecting the different environmental challenges and needs for adaptation during the fetal, neonatal and postnatal period, and throughout life. The ability to pool and analyze samples across various age and risk groups, and across various hematopoietic cell types, offers a unique opportunity to define common denominators of early life immunity and to reveal critical differences in the functional programming of fetal and neonatal hematopoietic cells To this date, over 65,000 high-throughput functional genomics studies have been deposited in the NCBI Gene Expression Omnibus (GEO), a public repository of transcriptome profiles. Users can customize data plots by adding multiple layers of information (such as postnatal age, weeks of gestation at birth, and gender), modify the ordering of samples and genes, change the plot type, and generate links (mini URLs) capturing the user’s settings, which can be inserted in email communications or in publications These user-generated mini URLs provide access the transcription data and to rich contextual information and data interpretation, including gene information, relevant literature, a description of the study design, as well as detailed sample information that was supplied along with the transcriptome data submission to GEO
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