BatMan: Mitigating Batch Effects via Stratification for Survival Outcome Prediction

TL;DR

This paper introduces BatMan, a new method for mitigating batch effects in survival outcome prediction from transcriptomics data, outperforming existing methods like ComBat especially when data normalization is also applied.

Contribution

The paper proposes BatMan, a novel stratification-based approach for batch effect correction in survival analysis, addressing limitations of existing methods like ComBat.

Findings

BatMan outperforms ComBat in most simulated scenarios with batch effects.

Adding data normalization can worsen prediction performance.

BatMan demonstrates superior performance on ovarian cancer microRNA data.

Abstract

Reproducible translation of transcriptomics data has been hampered by the ubiquitous presence of batch effects. Statistical methods for managing batch effects were initially developed in the setting of sample group comparison and later borrowed for other settings such as survival outcome prediction. The most notable such method is ComBat, which adjusts for batches by including it as a covariate alongside sample groups in a linear regression. In survival prediction, however, ComBat is used without definable groups for survival outcome and is done sequentially with survival regression for a potentially confounded outcome. To address these issues, we propose a new method, called BatMan ("BATch MitigAtion via stratificatioN"). It adjusts batches as strata in survival regression and utilize variable selection methods such as LASSO to handle high dimensionality. We assess the performance of BatMan in comparison with ComBat, each used either alone or in conjunction with data normalization, in a re-sampling-based simulation study under various levels of predictive signal strength and patterns of batch-outcome association. Our simulations show that (1) BatMan outperforms ComBat in nearly all scenarios when there are batch effects in the data, and (2) their performance can be worsened by the addition of data normalization. We further evaluate them using microRNA data for ovarian cancer from the Cancer Genome Atlas, and find that BatMan outforms ComBat while the addition of data normalization worsens the prediction. Our study thus shows the advantage of BatMan and raises caution about the naive use of data normalization in the context of developing survival prediction models. The BatMan method and the simulation tool for performance assessment are implemented in R and publicly available at https://github.com/LXQin/PRECISION.survival.