Marco Simnacher

Wei-Cheng Lai, Marco Simnacher, Christoph Lippert

Two-sample testing is a fundamental tool for detecting distributional differences across scientific domains, but classical tests (including kernel-based tests) can be ineffective on high-dimensional structured data such as images. Recent deep two-sample tests improve sensitivity in these settings by learning informative representations, yet they provide limited insight into which data features drive rejection of the null hypothesis $H_0$. To address this issue, we propose a counterfactual explanation framework for deep two-sample testing that generates sample-level edits moving observations from a source group toward a target group while explicitly reducing the discrepancy measured by the test. Our method combines a diffusion autoencoder with a pretrained deep two-sample test model and optimizes a maximum mean discrepancy (MMD) objective in the test model's representation space to produce plausible counterfactuals. We quantify distribution-level effects through changes in the test statistic and the resulting two-sample p-values. We evaluate the method on synthetic 2D shape datasets and two MRI cohorts. Across both settings, the counterfactual transformations consistently increase p-values relative to the original samples, indicating that the edited source set becomes statistically closer to the target distribution under the test. We measure minimality using LPIPS to ensure the counterfactuals remain close to the original samples. The resulting edits provide interpretable evidence of the features associated with the detected group differences. On MRI, the localized changes are consistent with known anatomical differences between cohorts.

Marco Simnacher, Xiangnan Xu, Hani Park et al.

Conditional independence tests (CITs) test for conditional dependence between random variables. As existing CITs are limited in their applicability to complex, high-dimensional variables such as images, we introduce deep nonparametric CITs (DNCITs). The DNCITs combine embedding maps, which extract feature representations of high-dimensional variables, with nonparametric CITs applicable to these feature representations. For the embedding maps, we derive general properties on their parameter estimators to obtain valid DNCITs and show that these properties include embedding maps learned through (conditional) unsupervised or transfer learning. For the nonparametric CITs, appropriate tests are selected and adapted to be applicable to feature representations. Through simulations, we investigate the performance of the DNCITs for different embedding maps and nonparametric CITs under varying confounder dimensions and confounder relationships. We apply the DNCITs to brain MRI scans and behavioral traits, given confounders, of healthy individuals from the UK Biobank (UKB), confirming null results from a number of ambiguous personality neuroscience studies with a larger data set and with our more powerful tests. In addition, in a confounder control study, we apply the DNCITs to brain MRI scans and a confounder set to test for sufficient confounder control, leading to a potential reduction in the confounder dimension under improved confounder control compared to existing state-of-the-art confounder control studies for the UKB. Finally, we provide an R package implementing the DNCITs.