This is the final version. It was first published by eLife at http://elifesciences.org/content/3/e03883. ; Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response. - See more at: http://elifesciences.org/content/3/e03883#sthash.UfINkh5T.dpuf ; This work was supported in part by the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, U.S Department of Homeland Security, and the Fogarty International Center, NIH. The findings and conclusions in this report are those of the authors and do not necessarily reflect the views of the Centers for Disease Control and Prevention, the Department of Health and Human Services or its components, or the United States Department of Agriculture.