Gene Expression Signatures Characterized by Longitudinal Stability and Interindividual Variability Delineate Baseline...

Area of Science:

• Immunology
• Genomics
• Systems Biology

Background:

• Human immune responses vary significantly between individuals.
• Stable, individual-specific immune signatures exist within people.
• These signatures may predict responses to immune challenges.

Purpose of the Study:

• To explore if baseline immune signatures can predict immune response outcomes.
• To identify determinants of immune responsiveness by analyzing gene expression patterns.

Main Methods:

• Quantified global gene expression in CD4+ T-cells from healthy individuals at baseline and after stimulation.
• Defined molecular immune response signatures (MIRS) based on stable and differential gene expression.
• Performed iterative differential gene expression analyses across phenotypic groupings.

Main Results:

• Identified shared baseline and response phenotypic groupings, indicating baseline MIRS predicts responsiveness.
• Found significant numbers of shared phenotype-defining determinants across independent cohorts.
• Discovered over 6000 baseline immune phenotypic groups using the MIRS concept.

Conclusions:

• Baseline molecular immune response signatures (MIRS) contain determinants of immune responsiveness.
• Gene expression variability patterns can define immune phenotypes and predict responses.
• The MIRS concept is applicable to diverse immune perturbation contexts.