Blood-Informative Transcripts Define Nine Common Axes of Peripheral Blood Gene Expression

Marcela Preininger, Dalia Arafat, Jinhee Kim, Artika P. Nath, Youssef Idaghdhour, Kenneth L. Brigham, Greg Gibson

    Research output: Contribution to journalArticle

    Abstract

    We describe a novel approach to capturing the covariance structure of peripheral blood gene expression that relies on the identification of highly conserved Axes of variation. Starting with a comparison of microarray transcriptome profiles for a new dataset of 189 healthy adult participants in the Emory-Georgia Tech Center for Health Discovery and Well-Being (CHDWB) cohort, with a previously published study of 208 adult Moroccans, we identify nine Axes each with between 99 and 1,028 strongly co-regulated transcripts in common. Each axis is enriched for gene ontology categories related to sub-classes of blood and immune function, including T-cell and B-cell physiology and innate, adaptive, and anti-viral responses. Conservation of the Axes is demonstrated in each of five additional population-based gene expression profiling studies, one of which is robustly associated with Body Mass Index in the CHDWB as well as Finnish and Australian cohorts. Furthermore, ten tightly co-regulated genes can be used to define each Axis as "Blood Informative Transcripts" (BITs), generating scores that define an individual with respect to the represented immune activity and blood physiology. We show that environmental factors, including lifestyle differences in Morocco and infection leading to active or latent tuberculosis, significantly impact specific axes, but that there is also significant heritability for the Axis scores. In the context of personalized medicine, reanalysis of the longitudinal profile of one individual during and after infection with two respiratory viruses demonstrates that specific axes also characterize clinical incidents. This mode of analysis suggests the view that, rather than unique subsets of genes marking each class of disease, differential expression reflects movement along the major normal Axes in response to environmental and genetic stimuli.

    Original languageEnglish (US)
    Article numbere1003362
    JournalPLoS Genetics
    Volume9
    Issue number3
    DOIs
    StatePublished - Apr 15 2013

    Fingerprint

    gene expression
    blood
    Gene Expression
    Blood Physiological Phenomena
    Latent Tuberculosis
    physiology
    gene
    Cell Physiological Phenomena
    Morocco
    Precision Medicine
    Gene Ontology
    Health
    Gene Expression Profiling
    Infection
    Transcriptome
    cell physiology
    Genes
    tuberculosis
    genes
    Life Style

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Molecular Biology
    • Genetics
    • Genetics(clinical)
    • Cancer Research

    Cite this

    Preininger, M., Arafat, D., Kim, J., Nath, A. P., Idaghdhour, Y., Brigham, K. L., & Gibson, G. (2013). Blood-Informative Transcripts Define Nine Common Axes of Peripheral Blood Gene Expression. PLoS Genetics, 9(3), [e1003362]. https://doi.org/10.1371/journal.pgen.1003362

    Blood-Informative Transcripts Define Nine Common Axes of Peripheral Blood Gene Expression. / Preininger, Marcela; Arafat, Dalia; Kim, Jinhee; Nath, Artika P.; Idaghdhour, Youssef; Brigham, Kenneth L.; Gibson, Greg.

    In: PLoS Genetics, Vol. 9, No. 3, e1003362, 15.04.2013.

    Research output: Contribution to journalArticle

    Preininger, M, Arafat, D, Kim, J, Nath, AP, Idaghdhour, Y, Brigham, KL & Gibson, G 2013, 'Blood-Informative Transcripts Define Nine Common Axes of Peripheral Blood Gene Expression', PLoS Genetics, vol. 9, no. 3, e1003362. https://doi.org/10.1371/journal.pgen.1003362
    Preininger M, Arafat D, Kim J, Nath AP, Idaghdhour Y, Brigham KL et al. Blood-Informative Transcripts Define Nine Common Axes of Peripheral Blood Gene Expression. PLoS Genetics. 2013 Apr 15;9(3). e1003362. https://doi.org/10.1371/journal.pgen.1003362
    Preininger, Marcela ; Arafat, Dalia ; Kim, Jinhee ; Nath, Artika P. ; Idaghdhour, Youssef ; Brigham, Kenneth L. ; Gibson, Greg. / Blood-Informative Transcripts Define Nine Common Axes of Peripheral Blood Gene Expression. In: PLoS Genetics. 2013 ; Vol. 9, No. 3.
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