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Reasons from perturbation as causal probe, genotype-to-phenotype linkage, library representation, and effect-size-plus-FDR statistics through MAGeCK/BAGEL/CERES-Chronos, CRISPRcleanR, CRISPResso2, MPRAnalyze, and Perturb-seq pipelines while treating MOI/bottleneck artifacts, copy-number and p53/DSB toxicity, RNAi seed effects, and guide-assignment or gating errors as first-class failure modes.