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S12 SYSTEMS BIOLOGY APPROACHES CHARACTERISE THE HOST RESPONSE TO TUBERCULOSIS
1M. P. R. Berry, 1C. M. Graham, 1S. J. Bloch, 1T. Oni, 1K. A. Wilkinson, 3R. J. Wilkinson, 2O. M. Kon, 4J. Banchereau, 4D. Chaussabel, 1A. O’Garra. 1National Institute For Medical Research, London, UK, 2Imperial College Healthcare NHS Trust, London, UK, 3University of Cape Town, Cape Town, Republic of South Africa, 4Baylor Institute for Immunology Research, Dallas, Texas, USA
Introduction Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. The immune response during TB is complex and incompletely characterised, hindering the development of new diagnostics, treatments and vaccines. Studies performed in different disease settings (intermediate vs high burden) have sometimes yielded divergent results, limiting advances in our understanding of TB. We used systems biology approaches to obtain an unbiased comprehensive survey of the host response to TB in both the UK and South Africa.
Methods We recruited 214 participants; 153 met the final inclusion criteria. Active TB patients were culture positive. Latent TB patients were positive by both tuberculin skin test (TST) and interferon γ release assay (IGRA), and healthy controls were negative by both TST and IGRA. Whole blood was collected before treatment. RNA was extracted and used for whole genome expression studies using Illumina HT-12 microarrays. This was complemented by multiplexed cytokine analysis using the MILLIPLEX Multi-Analyte Profiling system. Biological data were integrated with comprehensive clinical data including radiology. Data mining was performed using Genespring GX 7.3 and Ingenuity Pathways Analysis software in combination with a novel Genomic Modular Analysis Framework. A subset of patients was assessed at 2 and 12 months post-treatment.
Results 42 participants from London were used as a training set to explore the microarray data, using supervised and unsupervised analyses to define a transcriptional signature. Findings were then …