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# Causal Effect Estimation

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  1. arXiv

    Instrumental variables move into continuous time: as confounding grows, discrete-time estimators drift while path-based moments hold

    Continuous-time stochastic processes had no instrumental-variable framework, and discrete-time methods place the structural sparsity on finite-step transitions rather than on the actual mechanism. The work writes relevance, exclusion and exogeneity directly at the infinitesimal level of a stochastic differential equation's drift and builds moment conditions from the whole instrument path, giving an identification condition and a consistent estimator in the linear case. On confounded Ornstein-Uhlenbeck simulations, maximum likelihood becomes systematically biased as confounding grows while this estimator stays stable, and a single instrument process identifies multi-dimensional effects.

  2. bioRxiv

    Pooling guides hides off-target bias: majority-agreement weighting pulls Perturb-seq target estimates near zero

    Perturb-seq often pools several guides per target as replicates, but a guide's off-target effects can bias the target-level estimate. PETRO assumes a strict majority of guides are valid for each outcome and uses robust weighting to downweight disagreeing guides, recovering the on-target perturbation effect without removing guides or using sequence annotations. In RPE-1 CRISPRa target-outcome pairs whose longest seed match was 13–18 bp, mean pooled bias was 0.087 and PETRO's residual bias was 0.005; in simulation, pooling stayed near 0.075 as cells increased while PETRO fell toward zero.

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