ABSTRACT The mission of the Genomics Core of the Memorial Sloan Kettering Cancer Center SPORE in Leukemia is to lead the analysis and interpretation of studies investigating the genetic, transcriptional, and epigenetic mechanisms contributing to AML development and resistance to therapy, and to identify potential therapeutic synergies and vulnerabilities through the integration of both targeted and unbiased genomic data. Achieving the transformative advances required for each Research Project to meet its goals will be greatly reliant on access to cutting-edge bioinformatics expertise. This expertise will be utilized to simultaneously focus a wide range of genome-wide data types on specific biological questions from each Project while also being broad enough to capture potentially shared mechanisms of response and resistance between the four Research Projects. Prior to the initiation of all studies, Core staff will consult with SPORE investigators to discuss the underlying scientific premise and translational goals of the project, to help the investigators select the ideal genomic techniques, sequencing parameters, and robust analytical methods. We will also coordinate with the investigators of the Biostatistics core to estimate sample sizes to ensure adequate power to address study objectives. In laboratory experiments, Core members will assist in the formulation of the experimental design and in the analysis and interpretation of the data at the conclusion of the study. For molecular studies using primary human and mouse tissues, Core members will closely interface with the members of the Biospecimen Repository Core, and will have primary responsibility for merging molecular and clinical data, and for performing appropriate bioinformatics analyses. The members of the Genomics Core will also work with SPORE investigators to format data for publication and assist with deposition of genomic data into public repositories to facilitate validation of results by external investigators using their own analytical methods. We believe that this experienced and collaborative Core is well configured to provide the Leukemia SPORE with a high level of bioinformatics leadership and support that will enhance the quality and quantitative rigor of its science.