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There presently are a number of “next generation” sequencing technologies that are, or soon will be, commercially available. While there is much promise for applying these technologies in the near term, careful consideration of several critical aspects of implementation must be made. I will present our experiences to date, highlighting several unique applications of next-generation technology platforms that are underway at the Genome Sequencing Center. I also will describe the bioinformatics and IT infrastructure considerations of applying these technologies that are commonly overlooked.