Consistency of Feature Attribution in Deep Learning Architectures for Multi-Omics (2507.22877v1)

Abstract: Machine and deep learning have grown in popularity and use in biological research over the last decade but still present challenges in interpretability of the fitted model. The development and use of metrics to determine features driving predictions and increase model interpretability continues to be an open area of research. We investigate the use of Shapley Additive Explanations (SHAP) on a multi-view deep learning model applied to multi-omics data for the purposes of identifying biomolecules of interest. Rankings of features via these attribution methods are compared across various architectures to evaluate consistency of the method. We perform multiple computational experiments to assess the robustness of SHAP and investigate modeling approaches and diagnostics to increase and measure the reliability of the identification of important features. Accuracy of a random-forest model fit on subsets of features selected as being most influential as well as clustering quality using only these features are used as a measure of effectiveness of the attribution method. Our findings indicate that the rankings of features resulting from SHAP are sensitive to the choice of architecture as well as different random initializations of weights, suggesting caution when using attribution methods on multi-view deep learning models applied to multi-omics data. We present an alternative, simple method to assess the robustness of identification of important biomolecules.