According to the National Institute of Allergy and Infectious Diseases, in the past 20 years, out of the newly recognized pathogens that impact human and animal health, approximately 44 percent are viruses. Many of these pathogens, particularly RNA viruses, are characterized by a high mutation rate that allows them to rapidly adapt to a changing environment, as occurred in the 2009 H1N1 pandemic. Additionally, many viruses undergo more widespread genetic events (e.g., rearrangements, reassortments) that significantly alter the viral genome. These changes can produce virions capable of evading existing vaccine-acquired and convalescent immunity in humans and animals.

darpavirus

The goal of DARPA’s Prophecy (Pathogen Defeat) program 1 was to organize a team of researchers that could identify how genetic events significantly alter the viral genome. Researchers from Stanford University UCSF and the Tauber Bioinformatics Research Center at Haifa University teamed up to develop a biological method (CirSeq) and computational approaches to investigate viral adaptation and interaction with hosts(host-pathogen circuitry). As a result, the funding from DARPA helped create the CirSeq method published in Nature in 2014 2 and the T-BioInfo platform’s section dedicated to Virology.

virology-pipeline-explained

One of the outcomes of the DARPA project was a close collaboration between researchers studying viral SNVs, host data, including protein-protein interactions and post translational modifications of proteins. The computational challenges in analyzing this heterogenous datasets helped define the concept of “fitness” that can characterize a viral mutation into beneficial, neutral, detrimental and lethal. These characteristics can be mapped onto the protein surfaces to show which areas are highly conserved and are better targets for intervention, enabling a more precise way for vaccine and drug development.

virology-visualization-mol
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The DARPA project was addressing an important challenge posed by Dengue, a virus that is characterized by similar symptoms, even though 4 defined virus types have been studied.3

Next: Read about Host-Pathogen Circuitry

  1.  Hepburn, Matthew, MD,”Prophecy (Pathogen Defeat).” Prophecy (Pathogen Defeat). DARPA, n.d. Web. 16 Feb. 2016.
  2.  Acevedo, Ashley, Leonid Brodsky, and Raul Andino. “Mutational and Fitness Landscapes of an RNA Virus Revealed through Population Sequencing.” Nature 505.7485 (2013): 686-90. Web. 16 Feb. 2016.
  3. Dengue Viruses.” Nature.com. Nature Publishing Group, n.d. Web. 15 Feb. 2016.