PLX043277

GSE94116: Predicting susceptibility to tuberculosis based on gene expression profiling in dendritic cells

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Tuberculosis is a deadly infectious disease, which kills millions of people every year. The causative pathogen, Mycobacterium tuberculosis (MTB), is estimated to have infected up to a third of the worlds population; however, only approximately 10% of healthy individuals progress to active TB disease. Despite evidence for heritability, it is not currently possible to predict whether a healthy person is susceptible to TB. To explore approaches to classify susceptibility to TB, we infected with MTB dendritic cells (DCs) from putatively resistant individuals diagnosed with latent TB, and from susceptible individuals that had recovered from a past episode of active TB. We measured genome-wide gene expression levels in infected and non-infected cells and found hundreds of differentially expressed genes between susceptible and resistant individuals in the non-infected cells. We further found that genetic polymorphisms in proximity to the differentially expressed genes between susceptible and resistant individuals are more likely to be associated with TB susceptibility in published GWAS data. By intersecting the gene expression and GWAS data, we identified two promising candidate genes: CCL1 and UNC13A. Lastly, we trained a classifier based on the gene expression levels in the non-infected cells, and demonstrated decent performance on our data and an independent data set. Overall, our promising results from this small study suggest that training a classifier on a larger cohort may enable us to accurately predict TB susceptibility. SOURCE: John,D,BlischakGilad University of Chicago