Deep learning models for drug--target interaction (DTI) prediction often achieve strong benchmark performance without necessarily relying on mechanistically meaningful molecular features, a limitation that standard accuracy-based evaluation cannot detect. We introduce ISAAC (Intervention-based Structural Auditing Approach for Causal Reasoning), a post-hoc framework that evaluates prior-relative structural sensitivity by probing frozen models through matched mechanistic and spurious input-level interventions, independently of predictive accuracy. Applied to three sequence-based DTI architectures on the Davis benchmark, ISAAC reveals approximately 25\% relative differences in reasoning scores across models with comparable AUROC (within around 3\%), stable across training and intervention seeds and two distinct perturbation operators. These discrepancies, undetectable under conventional accuracy metrics, motivate the use of post-hoc structural auditing as a complement to standard performance evaluation in scientific machine learning for molecular modeling.

In this paper, we prove a conjecture published in 1989 and also partially address an open problem announced at the Conference on Learning Theory (COLT) 2015. With no unrealistic assumption, we first prove the following statements for the squared loss function of deep linear neural networks with any depth and any widths: 1) the function is non-convex and non-concave, 2) every local minimum is a global minimum, 3) every critical point that is not a global minimum is a saddle point, and 4) there exist "bad" saddle points (where the Hessian has no negative eigenvalue) for the deeper networks (with more than three layers), whereas there is no bad saddle point for the shallow networks (with three layers). Moreover, for deep nonlinear neural networks, we prove the same four statements via a reduction to a deep linear model under the independence assumption adopted from recent work. As a result, we present an instance, for which we can answer the following question: how difficult is it to directly train a deep model in theory? It is more difficult than the classical machine learning models (because of the non-convexity), but not too difficult (because of the nonexistence of poor local minima). Furthermore, the mathematically proven existence of bad saddle points for deeper models would suggest a possible open problem. We note that even though we have advanced the theoretical foundations of deep learning and non-convex optimization, there is still a gap between theory and practice.

However, acquiring large-scale annotated datasets is both a costly and time-consuming endeavor. To address this challenge, dataset expansion technologies aim to automatically augment datasets, unlocking the full potential of deep models. Current data expansion techniques include image transformation and image synthesis methods. Transformation-based methods introduce only local variations, leading to limited diversity. In contrast, synthesis-based methods generate entirely new content, greatly enhancing informativeness. However, existing synthesis methods carry the risk of distribution deviations, potentially degrading model performance with out-of-distribution samples. In this paper, we propose DistDiff, a training-free data expansion framework based on the distribution-aware diffusion model.

Detecting test samples drawn sufficiently far away from the training distribution statistically or adversarially is a fundamental requirement for deploying a good classifier in many real-world machine learning applications. However, deep neural networks with the softmax classifier are known to produce highly overconfident posterior distributions even for such abnormal samples. In this paper, we propose a simple yet effective method for detecting any abnormal samples, which is applicable to any pre-trained softmax neural classifier. We obtain the class conditional Gaussian distributions with respect to (low-and upper-level) features of the deep models under Gaussian discriminant analysis, which result in a confidence score based on the Mahalanobis distance. While most prior methods have been evaluated for detecting either out-of-distribution or adversarial samples, but not both, the proposed method achieves the state-of-the-art performances for both cases in our experiments. Moreover, we found that our proposed method is more robust in harsh cases, e.g., when the training dataset has noisy labels or small number of samples. Finally, we show that the proposed method enjoys broader usage by applying it to class-incremental learning: whenever out-of-distribution samples are detected, our classification rule can incorporate new classes well without further training deep models.

Deep learning with noisy labels is practically challenging, as the capacity of deep models is so high that they can totally memorize these noisy labels sooner or later during training. Nonetheless, recent studies on the memorization effects of deep neural networks show that they would first memorize training data of clean labels and then those of noisy labels. Therefore in this paper, we propose a new deep learning paradigm called ''Co-teaching'' for combating with noisy labels. Namely, we train two deep neural networks simultaneously, and let them teach each other given every mini-batch: firstly, each network feeds forward all data and selects some data of possibly clean labels; secondly, two networks communicate with each other what data in this mini-batch should be used for training; finally, each network back propagates the data selected by its peer network and updates itself. Empirical results on noisy versions of MNIST, CIFAR-10 and CIFAR-100 demonstrate that Co-teaching is much superior to the state-of-the-art methods in the robustness of trained deep models.

Molecular Property Prediction (MPP) is a critical task in computational drug discovery, aimed at identifying molecules with desirable pharmacological and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties. Machine learning models have been widely used in this fast-growing field, with two types of models being commonly employed: traditional non-deep models and deep models.

Uncertainty estimation in large deep-learning models is a computationally challenging task, where it is difficult to form even a Gaussian approximation to the posteriordistribution.

Neural Information Processing Systems http://nips.cc/