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spiky implements methods and model generation for cfMeDIP (cell-free methylated DNA immunoprecipitation) with spike-in controls. CfMeDIP is an enrichment protocol which avoids destructive conversion of scarce template, making it ideal as a "liquid biopsy," but creating certain challenges in comparing results across specimens, subjects, and experiments. The use of synthetic spike-in standard oligos allows diagnostics performed with cfMeDIP to quantitatively compare samples across subjects, experiments, and time points in both relative and absolute terms.