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This volume constitutes the refereed proceedings of the 6th International Symposium on Bioinformatics Research and Applications, ISBRA 2010, held in Storrs, CT, USA, in May 2010.§The 20 revised full papers and 6 invited talks presented were carefully reviewed and selected out of 57 submissions. Topics presented span all areas of bioinformatics and computational biology, including the development of experimental or commercial systems.