Progression to Latent Infection Following Exposure to Mtb

These results were obtained in a controlled longitudinal experiment in which a group of rhesus macaques were exposed to a low dose of Mtb to study their progression to latent infection or active disease. Subsets of the animals were euthanized at scheduled time points, and granulomas taken from their lungs were assayed for gene expression. The clinical profiles associated with the animals following Mtb exposure revealed considerable variability, and we developed models for the disease trajectory for each subject using a Bayesian hierarchical B-spline approach. Disease severity estimates were derived from these fitted curves and included as covariates in linear models to identify genes significantly associated with disease progression. Our results demonstrate that the incorporation of clinical data increases the value of information extracted from the expression profiles and contributes to the identification of predictive biomarkers for TB susceptibility. Samples from 21 animals were included in this study. 18 rhesus macaques were exposed to Mtb and euthanisized according to a pre-defined schedule, and at least two granulomas were extracted from their lungs during necropsy. The remaining three animals were healthy controls and samples represent control lung tissues. The samples were arrayed using an extended loop design with animals grouped according to similar clinical profiles. Biological replication is provided in the form of at least two granuloma samples per animal.