Blood-informative transcripts define nine common axes of peripheral blood gene expression
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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.
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Molecular indicators of human well-being such as the CTRA and blood-informative transcripts (BIT) may add a new dimension to social, cultural, and political discourse by providing objective leading indicators of human biological well-being that can help gauge the extent to which particular social conditions are congruent with basic human nature and help realize our genomically endowed potential.
“molecular indicators of human well-being such as the CTRA and blood-informative transcripts (BIT) [12], [64] may add a new dimension to social, cultural, and political discourse by providing objective leading indicators of human biological well-being”
From Human Social Genomics (2014) · cites this paper as [64]
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- Authors
- Preininger, M., Arafat, D., Kim, J., Nath, A. P., Idaghdour, Y., Brigham, K. L., & Gibson, G.
- Affiliations
- Georgia Institute of Technology (US)
- Université de Montréal (CA)
- Emory University (US)
- Corresponding author
- Gibson, Greg
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-03-14
- Volume
- 9
- Issue
- 3
- Pages
- e1003362
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3597511
- OpenAlex
- W1999418667
- Cited by
- 59
- References
- 28
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 2 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 8 · 2016: 6 · 2015: 13 · 2014: 8 · 2013: 5
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Research Institute, Georgia Institute of Technology
- Georgia Institute of Technology
- Emory University
- Academy of Finland (118065)
- National Institute of General Medical Sciences (P01GM099568)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- peripheral blood gene expression, immune function, innate and adaptive immunity, tuberculosis infection, body mass index, heritability, gene expression profiling, personalized medicine, respiratory viral infections, lifestyle differences
- MeSH terms
- Adult, Australia, B-Lymphocytes, Blood Proteins, Female, Georgia, Humans, Morocco, Gene Expression, Body Mass Index, Gene Expression Profiling, Microarray Analysis, Precision Medicine
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