Here a systems genetics approach is applied to elucidate the mechanism and interactive host response pathways involved in modulating susceptibility and severity of necrotizing soft tissue infections (NSTIs).
Systems genetics approaches entail the assessment of relative variations in informative disease phenotypes across a large genetically heterogeneous population with well-characterized genomic differences. Specialized bioinformatics and modeling tools are then used to analyze relative variations in each assessed disease phenotype in the context of genomic differences across the study population, and to link networks of genes to networks of traits. As conducting such studies in humans can be logistically prohibitive, partner 15 have developed and optimized robust translational mouse models that are ideal for systems approaches. These systems approaches will be complemented by verifying the discoveries using focused approaches that will help verify or refute the involvement of specific genes or pathways in NSTI. The data generated in this WP will enable to estimate model parameters and to refine the models developed in WP4. The data generated in this WP will provide data to direct and focus the studies of host susceptibility genes in patient samples (WP3, 4 and 5; partners 1, 8, 9 and 10).