### Detecting Statistical Interactions from Neural Network Weights

Interpreting neural networks is a crucial and challenging task in machine learning. In this paper, we develop a novel framework for detecting statistical interactions captured by a feedforward multilayer neural network by directly interpreting its learned weights. Depending on the desired interactions, our method can achieve significantly better or similar interaction detection performance compared to the state-of-the-art without searching an exponential solution space of possible interactions. We obtain this accuracy and efficiency by observing that interactions between input features are created by the non-additive effect of nonlinear activation functions, and that interacting paths are encoded in weight matrices. We demonstrate the performance of our method and the importance of discovered interactions via experimental results on both synthetic datasets and real-world application datasets.

### Interaction-aware Factorization Machines for Recommender Systems

Factorization Machine (FM) is a widely used supervised learning approach by effectively modeling of feature interactions. Despite the successful application of FM and its many deep learning variants, treating every feature interaction fairly may degrade the performance. For example, the interactions of a useless feature may introduce noises; the importance of a feature may also differ when interacting with different features. In this work, we propose a novel model named \emph{Interaction-aware Factorization Machine} (IFM) by introducing Interaction-Aware Mechanism (IAM), which comprises the \emph{feature aspect} and the \emph{field aspect}, to learn flexible interactions on two levels. The feature aspect learns feature interaction importance via an attention network while the field aspect learns the feature interaction effect as a parametric similarity of the feature interaction vector and the corresponding field interaction prototype. IFM introduces more structured control and learns feature interaction importance in a stratified manner, which allows for more leverage in tweaking the interactions on both feature-wise and field-wise levels. Besides, we give a more generalized architecture and propose Interaction-aware Neural Network (INN) and DeepIFM to capture higher-order interactions. To further improve both the performance and efficiency of IFM, a sampling scheme is developed to select interactions based on the field aspect importance. The experimental results from two well-known datasets show the superiority of the proposed models over the state-of-the-art methods.

### Neural Interaction Transparency (NIT): Disentangling Learned Interactions for Improved Interpretability

Neural networks are known to model statistical interactions, but they entangle the interactions at intermediate hidden layers for shared representation learning. We propose a framework, Neural Interaction Transparency (NIT), that disentangles the shared learning across different interactions to obtain their intrinsic lower-order and interpretable structure. This is done through a novel regularizer that directly penalizes interaction order. We show that disentangling interactions reduces a feedforward neural network to a generalized additive model with interactions, which can lead to transparent models that perform comparably to the state-of-the-art models. NIT is also flexible and efficient; it can learn generalized additive models with maximum $K$-order interactions by training only $O(1)$ models.

### Recovering Pairwise Interactions Using Neural Networks

Recovering pairwise interactions, i.e. pairs of input features whose joint effect on an output is different from the sum of their marginal effects, is central in many scientific applications. We conceptualize a solution to this problem as a two-stage procedure: first, we model the relationship between the features and the output using a flexible hybrid neural network; second, we detect feature interactions from the trained model. For the second step we propose a simple and intuitive interaction measure (IM), which has no specific requirements on the machine learning model used in the first step, only that it defines a mapping from an input to an output. And in a special case it reduces to the averaged Hessian of the input-output mapping. Importantly, our method upper bounds the interaction recovery error with the error of the learning model, which ensures that we can improve the recovered interactions by training a more accurate model. We present analyses of simulated and real-world data which demonstrate the benefits of our method compared to available alternatives, and theoretically analyse its properties and relation to other methods.

### PADME: A Deep Learning-based Framework for Drug-Target Interaction Prediction

In silico drug-target interaction (DTI) prediction is an important and challenging problem in biomedical research with a huge potential benefit to the pharmaceutical industry and patients. Most existing methods for DTI prediction including deep learning models generally have binary endpoints, which could be an oversimplification of the problem, and those methods are typically unable to handle cold-target problems, i.e., problems involving target protein that never appeared in the training set. Towards this, we contrived PADME (Protein And Drug Molecule interaction prEdiction), a framework based on Deep Neural Networks, to predict real-valued interaction strength between compounds and proteins. PADME takes both compound and protein information as inputs, so it is capable of solving cold-target (and cold-drug) problems. To our knowledge, we are the first to combine Molecular Graph Convolution (MGC) for compound featurization with protein descriptors for DTI prediction. We used multiple cross-validation split schemes and evaluation metrics to measure the performance of PADME on multiple datasets, including the ToxCast dataset, which we believe should be a standard benchmark for DTI problems, and PADME consistently dominates baseline methods. The results of a case study, which predicts the interactions between various compounds and androgen receptor (AR), suggest PADME's potential in drug development. The scalability of PADME is another advantage in the age of Big Data.