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New DNA sequencing technologies presents an exceptional opportunity for novel and creative applications with the potential for breakthrough discoveries. To support such research efforts, the Cornell University Life Sciences Core Laboratories Center has implemented the Illumina Solexa Genome Analyzer IIx and the Roche 454 Genome Sequencer FLX platforms as academic core facility shared research resources. We have established sample handling methods, wikiLIMS tools and informatics analysis pipelines in support of these new technologies. Our DNA sequencing and genotyping core laboratory provides sample preparation and data generation services and in collaboration with the microarrays and informatics core facilities, provides both project consultation and analysis support for a wide range of possible applications, including de novo or reference based genome assembly, detection of genetic variation, transcriptome sequencing, small RNA profiling, and genome-wide epigenomic measurements of protein-nucleic interactions. Implementation of next generation sequencing platforms as shared resources with multi-disciplinary core facility support enables cost effective access and broad based use of these technologies.