Project Summary/Abstract The purpose of Core 4 Biostatistics is to provide statistical support to all the Projects in this P01. For the association between clinical outcome and the comprehensive molecular and proteomic dissection of Richter's syndrome (RS), as performed by Project 1, the Core will assemble and curate the clinical data provided by internal and external collaborators and perform all analyses of association between these novel findings and appropriate clinical parameters. This will include working closely with Project to assess in cfDNA any RS-specific alternations that may predict this transformation. For all laboratory and animal studies of Projects 2 and 3, the Core will assure that the design, conduct, and analysis of experiments use robust statistical techniques that are appropriately implemented. For Project 2 this includes the single cell analyses of the tumor-intrinsic and tumor- extrinsic features, as well as the longitudinal assessment of these features. The mice developing RS with combinations of common CLL mutations (generated through this P01) will be assessed for response and resistance to novel therapies and analyzed by this Core. DBP studies are performed through Project 3, and the use of the Core for clinical association will permit Project 3 to remain blinded to clinical outcomes when performing their assays, assuring an unbiased assessment of their predictive ability. Through these aims, this central resource for the Projects will coordinate our insights into the trajectories from CLL to RS and support our ability to identify rational and personalized therapeutic strategies that will offer patients an improved chance of cure.