Batch-effect correction with sample remeasurement in highly confounded case-control studies

Batch effects are pervasive in biomedical studies. One approach to address the batch effects is repeatedly measuring a subset of samples in each batch. These remeasured samples are used to estimate and correct the batch effects. However, rigorous statistical methods for batch-effect correction with remeasured samples are severely underdeveloped. Here we developed a framework for batch-effect correction using remeasured samples in highly confounded case-control studies. We provided theoretical analyses of the proposed procedure, evaluated its power characteristics and provided a power calculation tool to aid in the study design. We found that the number of samples that need to be remeasured depends strongly on the between-batch correlation. When the correlation is high, remeasuring a small subset of samples is possible to rescue most of the power. Batch effects pose great statistical challenges to the analysis of biomedical data. One approach to address batch effects is through sample remeasurement in each batch. In this work, the researchers developed a rigorous batch-effect correction procedure based on remeasured samples.