Combinatorial group testing reduces screening costs and turnaround time but remains challenging to apply due to design complexity, varying applicability, and lack of implementation tools. Here we present PoolPy, a unified end-to-end framework and web platform to benchmark, automate and decode combinatorial group testing strategies tailored to application-specific constraints across assay modalities. We demonstrate PoolPy utility for protein-ligand interaction screening and genome-wide molecular profiling, enabling the scaling up of multi-readout functional assays.

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