Batch Effects Are Causal Effects: Applications in Human Connectomics

Abstract

Batch effects, undesirable sources of variance across multiple experiments, present a substantial hurdle for scientific and clinical discoveries. Specifically, the presence of batch effects can create both spurious discoveries and hide veridical signals, contributing to the ongoing reproducibility crisis. Typical approaches to dealing with batch effects conceptualize `batches’ as an associational effect, rather than a causal effect, despite the fact that the sources of variance that comprise the batch – potentially including experimental design and population demographics – causally impact downstream inferences. We therefore cast batch effects as a causal problem rather than an associational problem. This reformulation enables us to make explicit the assumptions and limitations of existing approaches for dealing with batch effects. We therefore develop causal batch effect strategies – Causal Dcorr for discovery of batch effects and Causal ComBat for mitigating batch effects – which build upon existing statistical associational methods by incorporating modern causal inference techniques. We apply these strategies to a large mega-study of human connectomes assembled by the Consortium for Reliability and Reproducibility, consisting of 24 batches including over 1700 individuals to illustrate that existing approaches create more spurious discoveries (false positives) and miss more veridical signals (true positives) than our proposed approaches. Our work therefore introduces a conceptual framing, as well as open source code, for combining multiple distinct datasets to increase confidence in claims of scientific and clinical discoveries.

Sambit Panda

Ph.D. Candidate
Department of Biomedical Engineering

Graduate student at Johns Hopkins creating tools to understand human and animal intelligence.