Immune profiling and network modeling of Chikungunya infections

Project: Research project

Project Details

Description

This IOF proposal presents an excellent and timely opportunity to leverage the infrastructure for human systems immunology that is being put in place for analysis of dengue in the DHIPC and to apply it to an emerging epidemic disease, chikungunya (CHIK), in the Americas via our study sites in Nicaragua. Few publications to date describe the innate immune response to chikungunya virus infection, and none are as comprehensive or as large as the immune profiling study we are proposing. We will use the same analysis pipeline built for dengue, which will enable reduction in personnel costs, in turn maximizing the sample number and thus the power and reach of the study. This will also permit a comparative analysis with dengue, which causes a disease with similar initial clinical presentation, once the equivalent data is generated for dengue virus infections as part of the parent HIPC. The choice of timepoints is such that the acute timepoint will reflect the immediate response to the disease while the patient is viremic, and the convalescent phase will reflect the height of the adaptive immune response. CyTOF analysis (performed by Core D, Mount Sinai) will allow a detailed description of the frequencies and phenotype of all major circulating immune cells, together with information regarding CHIKV infection. In parallel, Luminex assays will provide information about the systemic cytokine and chemokine balance of patients at both phases of infection. Core B at Northwestern University will use RNA-seq data to identify differences in mRNA and lncRNA transcript structure and abundance to characterize the diverse states of the human innate immune system following CHIKV infection. To integrate the data for network modeling, Cores E/F at Mount Sinai will use network approaches consisting of WGCENA, differential connectivity analysis, dynamic Bayesian networks, and key driver analysis, which are completely data-driven and present global, unbiased maps of regulatory relationships among hundreds of thousands of interactions, with significantly improved power to uncover novel host-virus pathways and driver genes. Project 1 at UC Berkeley will coordinate the project.
Importantly, this pilot project demonstrates how versatile and relevant the DHIPC can be, responding to an ongoing epidemic of global and domestic concern. The data will be available to other HIPC centers and the greater scientific community and will enable additional comparative studies with other human febrile illnesses.
StatusFinished
Effective start/end date12/1/155/31/16

Funding

  • Icahn School of Medicine at Mount Sinai (U255-8624-4609//1U19AI118610-10)
  • National Institute of Allergy and Infectious Diseases (U255-8624-4609//1U19AI118610-10)

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