We propose a novel neural network-based approach to modeling protein dynamics using an implicit representation of a protein's surface in 3D and time. Our method utilizes the zero-level set of signed distance functions (SDFs) to represent protein surfaces, enabling temporally and spatially continuous representations of protein dynamics. Our experimental results demonstrate that our model accurately captures protein dynamic trajectories and can interpolate and extrapolate in 3D and time. Importantly, this is the first study to introduce this method and successfully model large-scale protein dynamics. This approach offers a promising alternative to current methods, overcoming the limitations of first-principles-based and deep learning methods, and provides a more scalable and efficient approach to modeling protein dynamics. Additionally, our surface representation approach simplifies calculations and allows identifying movement trends and amplitudes of protein domains, making it a useful tool for protein dynamics research. Codes are available at https://github.com/Sundw-818/DSR,

Feature attribution methods, which explain an individual prediction made by a model as a sum of attributions for each input feature, are an essential tool for understanding the behavior of complex deep learning models. However, ensuring that models produce meaningful explanations, rather than ones that rely on noise, is not straightforward. Exacerbating this problem is the fact that attribution methods do not provide insight as to why features are assigned their attribution values, leading to explanations that are difficult to interpret. In real-world problems we often have sets of additional information for each feature that are predictive of that feature's importance to the task at hand. Here, we propose the deep attribution prior (DAPr) framework to exploit such information to overcome the limitations of attribution methods. Our framework jointly learns a relationship between prior information and feature importance, as well as biases models to have explanations that rely on features predicted to be important. We find that our framework both results in networks that generalize better to out of sample data and admits new methods for interpreting model behavior.

Thus, the robustness of 3D deep learning models against adversarial attacks becomes a major consideration. In this paper, we systematically study the impact of various self-supervised learning proxy tasks on different architectures and threat models for 3D point clouds with adversarial training. Specifically, we study MLP-based (PointNet), convolution-based (DGCNN), and transformer-based (PCT) 3D architectures. Through extensive experimentation, we demonstrate that appropriate applications of self-supervision can significantly enhance the robustness in 3D point cloud recognition, achieving considerable improvements compared to the standard adversarial training baseline. Our analysis reveals that local feature learning is desirable for adversarial robustness in point clouds since it limits the adversarial propagation between the point-level input perturbations and the model's final output. This insight also explains the success of DGCNN and the jigsaw proxy task in achieving stronger 3D adversarial robustness.

Deep learning systems frequently fail at out-of-context (OOC) prediction, the problem of making reliable predictions on uncommon or unusual inputs or subgroups of the training distribution. To this end, a number of benchmarks for measuring OOC performance have been recently introduced. In this work, we introduce a framework unifying the literature on OOC performance measurement, and demonstrate how rich auxiliary information can be leveraged to identify candidate sets of OOC examples in existing datasets. We present NOOCh: a suite of naturally-occurring challenge sets, and show how varying notions of context can be used to probe specific OOC failure modes. Experimentally, we explore the tradeoffs between various learning approaches on these challenge sets and demonstrate how the choices made in designing OOC benchmarks can yield varying conclusions.

While Attention has come to be an important mechanism in deep learning, there remains limited intuition for why it works so well. Here, we show that Transformer Attention can be closely related under certain data conditions to Kanerva's Sparse Distributed Memory (SDM), a biologically plausible associative memory model. We confirm that these conditions are satisfied in pre-trained GPT2 Transformer models. We discuss the implications of the Attention-SDM map and provide new computational and biological interpretations of Attention.

Deep learning models are increasingly popular in many machine learning applications where the training data may contain sensitive information. To provide formal and rigorous privacy guarantee, many learning systems now incorporate differential privacy by training their models with (differentially) private SGD. A key step in each private SGD update is gradient clipping that shrinks the gradient of an individual example whenever its l2 norm exceeds a certain threshold. We first demonstrate how gradient clipping can prevent SGD from converging to a stationary point. We then provide a theoretical analysis on private SGD with gradient clipping. Our analysis fully characterizes the clipping bias on the gradient norm, which can be upper bounded by the Wasserstein distance between the gradient distribution and a geometrically symmetric distribution. Our empirical evaluation further suggests that the gradient distributions along the trajectory of private SGD indeed exhibit such symmetric structure. Together, our results provide an explanation why private SGD with gradient clipping remains effective in practice despite its potential clipping bias. Finally, we develop a new perturbation-based technique that can provably correct the clipping bias even for instances with highly asymmetric gradient distributions.

Controlled feature selection aims to discover the features a response depends on while limiting the false discovery rate (FDR) to a predefined level. Recently, multiple deep-learning-based methods have been proposed to perform controlled feature selection through the Model-X knockoff framework. We demonstrate, however, that these methods often fail to control the FDR for two reasons. First, these methods often learn inaccurate models of features. Second, the swap property, which is required for knockoffs to be valid, is often not well enforced.

Research in Neuroscience, as in many scientific disciplines, is undergoing a renaissance based on deep learning. Unique to Neuroscience, deep learning models can be used not only as a tool but interpreted as models of the brain. The central claims of recent deep learning-based models of brain circuits are that they make novel predictions about neural phenomena or shed light on the fundamental functions being optimized. We show, through the case-study of grid cells in the entorhinal-hippocampal circuit, that one may get neither. We begin by reviewing the principles of grid cell mechanism and function obtained from first-principles modeling efforts, then rigorously examine the claims of deep learning models of grid cells. Using large-scale architectural and hyperparameter sweeps and theory-driven experimentation, we demonstrate that the results of such models may be more strongly driven by particular, non-fundamental, and post-hoc implementation choices than fundamental truths about neural circuits or the loss function(s) they might optimize. We discuss why these models cannot be expected to produce accurate models of the brain without the addition of substantial amounts of inductive bias, an informal No Free Lunch result for Neuroscience. Based on first principles work, we provide hypotheses for what additional loss functions will produce grid cells more robustly. In conclusion, circumspection and transparency, together with biological knowledge, are warranted in building and interpreting deep learning models in Neuroscience.

Unlike standard prediction tasks, survival analysis requires modeling right censored data, which must be treated with care. While deep neural networks excel in traditional supervised learning, it remains unclear how to best utilize these models in survival analysis. A key question asks which data-generating assumptions of traditional survival models should be retained and which should be made more flexible via the function-approximating capabilities of neural networks. Rather than estimating the survival function targeted by most existing methods, we introduce a Deep Extended Hazard (DeepEH) model to provide a flexible and general framework for deep survival analysis. The extended hazard model includes the conventional Cox proportional hazards and accelerated failure time models as special cases, so DeepEH subsumes the popular Deep Cox proportional hazard (DeepSurv) and Deep Accelerated Failure Time (DeepAFT) models. We additionally provide theoretical support for the proposed DeepEH model by establishing consistency and convergence rate of the survival function estimator, which underscore the attractive feature that deep learning is able to detect low-dimensional structure of data in high-dimensional space. Numerical experiments also provide evidence that the proposed methods outperform existing statistical and deep learning approaches to survival analysis.

We introduce a framework that abstracts Reinforcement Learning (RL) as a sequence modeling problem. This allows us to draw upon the simplicity and scalability of the Transformer architecture, and associated advances in language modeling such as GPT-x and BERT. In particular, we present Decision Transformer, an architecture that casts the problem of RL as conditional sequence modeling. Unlike prior approaches to RL that fit value functions or compute policy gradients, Decision Transformer simply outputs the optimal actions by leveraging a causally masked Transformer. By conditioning an autoregressive model on the desired return (reward), past states, and actions, our Decision Transformer model can generate future actions that achieve the desired return. Despite its simplicity, Decision Transformer matches or exceeds the performance of state-of-the-art model-free offline RL baselines on Atari, OpenAI Gym, and Key-to-Door tasks.