提出无需假设的整合后推断方法,提升数据融合分析的可靠性。
Assumption-Lean Post-Integrated Inference with Surrogate Control Outcomes
- 用代理控制结果替代传统负向控制,增强对隐藏混杂因素的识别能力。
- 在模型误设和嵌入误差下仍保持统计有效性,且提供偏差量化与有限样本界。
- 适用于单细胞基因扰动等存在未测量混杂因子的数据集,支持机器学习自适应估计。
数据整合方法旨在从高维结果中提取低维嵌入,以消除异质数据集间的批次效应和未测协变量等干扰。然而,整合后的多重假设检验可能因数据依赖过程而产生偏差。本文提出一种鲁棒的后整合推断方法,通过利用控制结果来捕捉潜在异质性。基于因果解释,我们推导出使用负向控制结果的非参数可识别性。进一步引入代理控制结果作为负向控制的扩展,发展了投影直接效应估计量的半参数推断,能够处理隐藏中介、混杂和调节效应。这些估计量在模型误设及嵌入误差下仍具统计意义。我们提供了偏差量化与有限样本线性展开,并给出一致的均匀浓度界。所提出的双重稳健估计器在最小假设下具有相合性和高效性,支持结合机器学习算法进行数据自适应估计。通过随机森林的模拟和单细胞CRISPR扰动数据集分析验证了该方法的有效性,这些数据可能包含潜在未测量混杂因素。
原文摘要 · Abstract (English)
Data integration methods aim to extract low-dimensional embeddings from high-dimensional outcomes to remove unwanted variations, such as batch effects and unmeasured covariates, across heterogeneous datasets. However, multiple hypothesis testing after integration can be biased due to data-dependent processes. We introduce a robust post-integrated inference method that accounts for latent heterogeneity by utilizing control outcomes. Leveraging causal interpretations, we derive nonparametric identifiability of the direct effects using negative control outcomes. By utilizing surrogate control outcomes as an extension of negative control outcomes, we develop semiparametric inference on projected direct effect estimands, accounting for hidden mediators, confounders, and moderators. These estimands remain statistically meaningful under model misspecifications and with error-prone embeddings. We provide bias quantifications and finite-sample linear expansions with uniform concentration bounds. The proposed doubly robust estimators are consistent and efficient under minimal assumptions and potential misspecification, facilitating data-adaptive estimation with machine learning algorithms. Our proposal is evaluated using random forests through simulations and analysis of single-cell CRISPR perturbed datasets, which may contain potential unmeasured confounders.
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