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Machine learning (ML) models are powerful tools for detecting complex patterns within data, yet their "black box" nature limits their interpretability, hindering their use in critical domains like healthcare and finance. To address this challenge, interpretable ML methods have been developed to explain how features influence model predictions. However, these methods often focus on univariate feature importance, overlooking the complex interactions between features that ML models are capable of capturing. Recognizing this limitation, recent efforts have aimed to extend these methods to discover feature interactions, but existing approaches struggle with robustness and error control, especially under data perturbations. In this study, we introduce Diamond, a novel method for trustworthy feature interaction discovery. Diamond uniquely integrates the model-X knockoffs framework to control the false discovery rate (FDR), ensuring that the proportion of falsely discovered interactions remains low. We further address the challenges of using off-the-shelf interaction importance measures by proposing a calibration procedure that refines these measures to maintain the desired FDR. Diamond's applicability spans a wide range of ML models, including deep neural networks, tree-based models, and factorization-based models. Our empirical evaluations on both simulated and real datasets across various biomedical studies demonstrate Diamond's utility in enabling more reliable data-driven scientific discoveries. This method represents a significant step forward in the deployment of ML models for scientific innovation and hypothesis generation.

The complexity of deep neural networks (DNNs) makes them powerful but also makes them challenging to interpret, hindering their applicability in error-intolerant domains. Existing methods attempt to reason about the internal mechanism of DNNs by identifying feature interactions that influence prediction outcomes. However, such methods typically lack a systematic strategy to prioritize interactions while controlling confidence levels, making them difficult to apply in practice for scientific discovery and hypothesis validation. In this paper, we introduce a method, called DeepROCK, to address this limitation by using knockoffs, which are dummy variables that are designed to mimic the dependence structure of a given set of features while being conditionally independent of the response. Together with a novel DNN architecture involving a pairwise-coupling layer, DeepROCK jointly controls the false discovery rate (FDR) and maximizes statistical power. In addition, we identify a challenge in correctly controlling FDR using off-the-shelf feature interaction importance measures. DeepROCK overcomes this challenge by proposing a calibration procedure applied to existing interaction importance measures to make the FDR under control at a target level. Finally, we validate the effectiveness of DeepROCK through extensive experiments on simulated and real datasets.

Deep learning has become increasingly popular in both supervised and unsupervised machine learning thanks to its outstanding empirical performance. However, because of their intrinsic complexity, most deep learning methods are largely treated as black box tools with little interpretability. Even though recent attempts have been made to facilitate the interpretability of deep neural networks (DNNs), existing methods are susceptible to noise and lack of robustness. Therefore, scientists are justifiably cautious about the reproducibility of the discoveries, which is often related to the interpretability of the underlying statistical models. In this paper, we describe a method to increase the interpretability and reproducibility of DNNs by incorporating the idea of feature selection with controlled error rate. By designing a new DNN architecture and integrating it with the recently proposed knockoffs framework, we perform feature selection with a controlled error rate, while maintaining high power. This new method, DeepPINK (Deep feature selection using Paired-Input Nonlinear Knockoffs), is applied to both simulated and real data sets to demonstrate its empirical utility.

Genome and metagenome comparisons based on large amounts of next-generation sequencing (NGS) data pose significant challenges for alignment-based approaches due to the huge data size and the relatively short length of the reads. Alignment-free approaches based on the counts of word patterns in NGS data do not depend on the complete genome and are generally computationally efficient. Thus, they contribute significantly to genome and metagenome comparison. Recently, novel statistical approaches have been developed for the comparison of both long and shotgun sequences. These approaches have been applied to many problems including the comparison of gene regulatory regions, genome sequences, metagenomes, binning contigs in metagenomic data, identification of virus-host interactions, and detection of horizontal gene transfers. We provide an updated review of these applications and other related developments of word-count based approaches for alignment-free sequence analysis.