Explaining the decision process of machine learning algorithms is nowadays crucial for both model’s performance enhancement and human comprehension. This can be achieved by assessing the variable importance of single variables, even for high-capacity non-linear methods, e.g. Deep Neural Networks (DNNs). While only removal-based approaches, such as Permutation Importance (PI), can bring statistical validity, they return misleading results when variables are correlated. Conditional Permutation Importance (CPI) bypasses PI’s limitations in such cases. However, in high-dimensional settings, where high correlations between the variables cancel their conditional importance, the use of CPI as well as other methods leads to unreliable results, besides prohibitive computation costs. Grouping variables statistically via clustering or some prior knowledge gains some power back and leads to better interpretations. In this work, we introduce BCPI (Block-Based Conditional Permutation Importance), a new generic framework for variable importance computation with statistical guarantees handling both single and group cases. Furthermore, as handling groups with high cardinality (such as a set of observations of a given modality) are both time-consuming and resource-intensive, we also introduce a new stacking approach extending the DNN architecture with sub-linear layers adapted to the group structure. We show that the ensuing approach extended with stacking controls the type-I error even with highly-correlated groups and shows top accuracy across benchmarks. Furthermore, we perform a real-world data analysis in a large-scale medical dataset where we aim to show the consistency between our results and the literature for a biomarker prediction.

Variable importance assessment has become a crucial step in machine-learning applications when using complex learners, such as deep neural networks, on large-scale data. Removal-based importance assessment is currently the reference approach, particularly when statistical guarantees are sought to justify variable inclusion. It is often implemented with variable permutation schemes. On the flip side, these approaches risk misidentifying unimportant variables as important in the presence of correlations among covariates. Here we develop a systematic approach for studying Conditional Permutation Importance (CPI) that is model agnostic and computationally lean, as well as reusable benchmarks of state-of-the-art variable importance estimators. We show theoretically and empirically that \textit{CPI} overcomes the limitations of standard permutation importance by providing accurate type-I error control. When used with a deep neural network, \textit{CPI} consistently showed top accuracy across benchmarks. An experiment on real-world data analysis in a large-scale medical dataset showed that \textit{CPI} provides a more parsimonious selection of statistically significant variables. Our results suggest that \textit{CPI} can be readily used as drop-in replacement for permutation-based methods.