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We have demonstrated the synergy of a wide-area SLASH2 file system with remote bioinformatics workflows between Extreme Science and Engineering Discovery Environment sites using the Galaxy Project’s web-based platform for reproducible data analysis. Wide-area Galaxy workflows were enabled by establishing a geographically-distributed SLASH2 instance between the Greenfield system at Pittsburgh Supercomputing Center and virtual machines incorporating storage within the Corral file system at the Texas Advanced Computing Center. Analysis tasks submitted through a single Galaxy instance seamlessly leverage data available from either site. In this paper, we explore the advantages of SLASH2 for enabling workflows from Galaxy Main.