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At diagnosis, the clonal burden within the B cell compartment was found to be 55% (pt1) and 86% (pt2) for the dominant clones. At 16 months following treatment these clones still constituted 66% and 89%, respectively. Utilizing multi\u2010omic methodologies at the DNA and RNA levels, including single\u2010cell transcriptomics, we aimed to establish a comprehensive framework for multi\u2010omics analysis for longitudinal ibrutinib response evaluation. 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