The purpose of the Funding Opportunity Announcement (FOA) is to support research that employs systems biology approaches to human pathogens. The approach will generate and integrate large datasets into models that guide in vitro, in vivo and clinical studies, with the goals of predicting disease severity, predicting responses to vaccines and therapeutics, and identifying candidate targets for interventions.
The integration of systems-level data (genomics, transcriptomics, and other “omics” technologies) in combination with behavioral, environmental, and clinical data lay the foundation for models of host-pathogen interactions and disease progression. These systems biology applications have progressed over the last decade, yet limited strategies integrate discordant data types. Many current workflows for data integration and interpretation rely on human intelligence (i.e., “by eye”), a method that is not conducive to iterative hypothesis testing and experimentation. Therefore, additional work is required to develop models which leverage statistical methods, machine learning and artificial intelligence that have high accuracy and can move towards clinical application. In this re-issue, the Centers will continue to advance the systems biology field in infectious diseases by developing and applying models that identify drivers of disease and candidate interventions. This initiative will further establish these platforms across bacteria, viruses, fungi, parasites and their vectors, where applicable, that cause human disease.
In 2008 NIAID/DMID launched the Systems Biology Program for Infectious Diseases Research to encourage a paradigm shift in strategies for basic infectious diseases research by adopting less traditional approaches, including a combination of HTP “omics” technology platforms, high-performance computing infrastructure, and increasingly sophisticated data processing and modeling algorithms. Most recently, Systems Biology for Infectious Diseases: The Next Generation, supported research projects on both bacterial and viral pathogens (RFA-AI-16-080). The Next Generation Program:
- established a network of Centers focused on building predictive models of infectious diseases leveraging Systems Biology. The necessity for rapid research on SARS-CoV-2 illustrates the value of systems analyses. The Systems Biology Centers have defined global protein interaction networks to identify drug targets and leveraged high throughput assays for SARS-CoV-2 drug discovery. In clinical samples, the Centers have described serological signatures associated with mortality and survival, and transcriptomic signatures distinct for SARS-CoV-2 pneumonia. The Centers have integrated genomic epidemiology with molecular modeling.
- developed high throughput CRISPR tools for bacterial pathogenesis and animal models for M. tuberculosis that more closely replicate human disease.
- developed and improved experimental methods, technologies, bioinformatics and computational tools, machine learning software, and statistical inference methods. Major accomplishments include novel discoveries across high-impact publications; release of large datasets following the Findable, Accessible, Interoperable, Reusable (FAIR) data-sharing best practices, network models and analysis software; and robust technological advances.
The re-issue builds upon this program history and will apply systems approaches to both fundamental research and clinical applications, transforming clinical data/metadata into models that predict severity and guide interventions and countermeasures.
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Filed Under: Funding Opportunities