NeurIPS 2023 Papers

Stabilizing proteins is a foundational step in protein engineering. However, the evolutionary pressure of all extant proteins makes identifying the scarce number of mutations that will improve thermodynamic stability challenging. Deep learning has recently emerged as a powerful tool for identifying promising mutations. Existing approaches, however, are computationally expensive, as the number of model inferences scales with the number of mutations queried. Our main contribution is a simple, parallel decoding algorithm. Mutate Everything is capable of predicting the effect of all single and double mutations in one forward pass. It is even versatile enough to predict higher-order mutations with minimal computational overhead. We build Mutate Everything on top of ESM2 and AlphaFold, neither of which were trained to predict thermodynamic stability. We trained on the Mega-Scale cDNA proteolysis dataset and achieved state-of-the-art performance on single and higher-order mutations on S669, ProTherm, and ProteinGym datasets. Our code is available at https://github.com/jozhang97/MutateEverything.

Question answering (QA) in the field of healthcare has received much attention due to significant advancements in natural language processing. However, existing healthcare QA datasets primarily focus on medical images, clinical notes, or structured electronic health record tables. This leaves the vast potential of combining electrocardiogram (ECG) data with these systems largely untapped. To address this gap, we present ECG-QA, the first QA dataset specifically designed for ECG analysis. The dataset comprises a total of 70 question templates that cover a wide range of clinically relevant ECG topics, each validated by an ECG expert to ensure their clinical utility. As a result, our dataset includes diverse ECG interpretation questions, including those that require a comparative analysis of two different ECGs. In addition, we have conducted numerous experiments to provide valuable insights for future research directions. We believe that ECG-QA will serve as a valuable resource for the development of intelligent QA systems capable of assisting clinicians in ECG interpretations.

The offline reinforcement learning (RL) problem is often motivated by the need to learn data-driven decision policies in financial, legal and healthcare applications. However, the learned policy could retain sensitive information of individuals in the training data (e.g., treatment and outcome of patients), thus susceptible to various privacy risks. We design offline RL algorithms with differential privacy guarantees which provably prevent such risks. These algorithms also enjoy strong instance-dependent learning bounds under both tabular and linear Markov Decision Process (MDP) settings. Our theory and simulation suggest that the privacy guarantee comes at (almost) no drop in utility comparing to the non-private counterpart for a medium-size dataset.

Visual Reinforcement Learning (RL) agents trained on limited views face significant challenges in generalizing their learned abilities to unseen views. This inherent difficulty is known as the problem of $\textit{view generalization}$. In this work, we systematically categorize this fundamental problem into four distinct and highly challenging scenarios that closely resemble real-world situations. Subsequently, we propose a straightforward yet effective approach to enable successful adaptation of visual $\textbf{Mo}$del-based policies for $\textbf{Vie}$w generalization ($\textbf{MoVie}$) during test time, without any need for explicit reward signals and any modification during training time. Our method demonstrates substantial advancements across all four scenarios encompassing a total of $\textbf{18}$ tasks sourced from DMControl, xArm, and Adroit, with a relative improvement of $\mathbf{33}$%, $\mathbf{86}$%, and $\mathbf{152}$% respectively. The superior results highlight the immense potential of our approach for real-world robotics applications. Code and videos are available at https://yangsizhe.github.io/MoVie/.

We present CELL-E 2, a novel bidirectional transformer that can generate images depicting protein subcellular localization from the amino acid sequences (and vice versa). Protein localization is a challenging problem that requires integrating sequence and image information, which most existing methods ignore. CELL-E 2 extends the work of CELL-E, not only capturing the spatial complexity of protein localization and produce probability estimates of localization atop a nucleus image, but also being able to generate sequences from images, enabling de novo protein design. We train and finetune CELL-E 2 on two large-scale datasets of human proteins. We also demonstrate how to use CELL-E 2 to create hundreds of novel nuclear localization signals (NLS). Results and interactive demos are featured at https://bohuanglab.github.io/CELL-E_2/.

In this paper, we design a regularization-free algorithm for high-dimensional support vector machines (SVMs) by integrating over-parameterization with Nesterov's smoothing method, and provide theoretical guarantees for the induced implicit regularization phenomenon. In particular, we construct an over-parameterized hinge loss function and estimate the true parameters by leveraging regularization-free gradient descent on this loss function. The utilization of Nesterov's method enhances the computational efficiency of our algorithm, especially in terms of determining the stopping criterion and reducing computational complexity. With appropriate choices of initialization, step size, and smoothness parameter, we demonstrate that unregularized gradient descent achieves a near-oracle statistical convergence rate. Additionally, we verify our theoretical findings through a variety of numerical experiments and compare the proposed method with explicit regularization. Our results illustrate the advantages of employing implicit regularization via gradient descent in conjunction with over-parameterization in sparse SVMs.

Mixup is an efficient data augmentation approach that improves the generalization of neural networks by smoothing the decision boundary with mixed data. Recently, dynamic mixup methods have improved previous \textit{static} policies effectively (e.g., linear interpolation) by maximizing target-related salient regions in mixed samples, but excessive additional time costs are not acceptable. These additional computational overheads mainly come from optimizing the mixed samples according to the mixed labels. However, we found that the extra optimizing step may be redundant because label-mismatched mixed samples are informative hard mixed samples for deep models to localize discriminative features. In this paper, we thus are not trying to propose a more complicated dynamic mixup policy but rather an efficient mixup objective function with decoupled regularizer, named decoupled mixup (DM). The primary effect is that DM can adaptively utilize those hard mixed samples to mine discriminative features without losing the original smoothness of mixup. As a result, DM enables static mixup methods to achieve comparable or even exceed the performance of dynamic methods without any extra computation. This also leads to an interesting objective design problem for mixup training that we need to focus on both smoothing the decision boundaries and identifying discriminative features. Extensive experiments on supervised and semi-supervised learning benchmarks across seven datasets validate the effectiveness of DM.

Diffusion MRI (dMRI) is a widely used imaging modality, but requires long scanning times to acquire high resolution datasets. By leveraging the unique geometry present within this domain, we present a novel approach to dMRI angular super-resolution that extends upon the parametric continuous convolution (PCConv) framework. We introduce several additions to the operation including a Fourier feature mapping, 'global' co-ordinates, and domain specific context. Using this framework, we build a fully parametric continuous convolution network (PCCNN) and compare against existing models. We demonstrate the PCCNN performs competitively while using significantly fewer parameters. Moreover, we show that this formulation generalises well to clinically relevant downstream analyses such as fixel-based analysis, and neurite orientation dispersion and density imaging.

Recently, there has been increased interest in fair generative models. In this work, we conduct, for the first time, an in-depth study on fairness measurement, a critical component in gauging progress on fair generative models. We make three contributions. First, we conduct a study that reveals that the existing fairness measurement framework has considerable measurement errors, even when highly accurate sensitive attribute (SA) classifiers are used. These findings cast doubts on previously reported fairness improvements. Second, to address this issue, we propose CLassifier Error-Aware Measurement (CLEAM), a new framework which uses a statistical model to account for inaccuracies in SA classifiers. Our proposed CLEAM reduces measurement errors significantly, e.g., 4.98%→0.62% for StyleGAN2 w.r.t. Gender. Additionally, CLEAM achieves this with minimal additional overhead. Third, we utilize CLEAM to measure fairness in important text-to-image generator and GANs, revealing considerable biases in these models that raise concerns about their applications. Code and more resources: https: //sutd-visual-computing-group.github.io/CLEAM/.

Recently, researchers have found that representations learned by large-scale pre-trained language models are useful in various downstream tasks. However, there is little theoretical understanding of how pre-training performance is related to downstream task performance. In this paper, we analyze how this performance transfer depends on the properties of the downstream task and the structure of the representations. We consider a log-linear model where a word can be predicted from its context through a network having softmax as its last layer. We show that even if the downstream task is highly structured and depends on a simple function of the hidden representation, there are still cases when a low pre-training loss cannot guarantee good performance on the downstream task. On the other hand, we propose and empirically validate the existence of an ``anchor vector'' in the representation space, and show that this assumption, together with properties of the downstream task, guarantees performance transfer.

Modeling continuous-time dynamics on irregular time series is critical to account for data evolution and correlations that occur continuously. Traditional methods including recurrent neural networks or Transformer models leverage inductive bias via powerful neural architectures to capture complex patterns. However, due to their discrete characteristic, they have limitations in generalizing to continuous-time data paradigms. Though neural ordinary differential equations (Neural ODEs) and their variants have shown promising results in dealing with irregular time series, they often fail to capture the intricate correlations within these sequences. It is challenging yet demanding to concurrently model the relationship between input data points and capture the dynamic changes of the continuous-time system. To tackle this problem, we propose ContiFormer that extends the relation modeling of vanilla Transformer to the continuous-time domain, which explicitly incorporates the modeling abilities of continuous dynamics of Neural ODEs with the attention mechanism of Transformers. We mathematically characterize the expressive power of ContiFormer and illustrate that, by curated designs of function hypothesis, many Transformer variants specialized in irregular time series modeling can be covered as a special case of ContiFormer. A wide range of experiments on both synthetic and real-world datasets have illustrated the superior modeling capacities and prediction performance of ContiFormer on irregular time series data. The project link is https://seqml.github.io/contiformer/.

Categorical encoders transform categorical features into numerical representations that are indispensable for a wide range of machine learning models. Existing encoder benchmark studies lack generalizability because of their limited choice of (1) encoders, (2) experimental factors, and (3) datasets. Additionally, inconsistencies arise from the adoption of varying aggregation strategies. This paper is the most comprehensive benchmark of categorical encoders to date, including an extensive evaluation of 32 configurations of encoders from diverse families, with 36 combinations of experimental factors, and on 50 datasets. The study shows the profound influence of dataset selection, experimental factors, and aggregation strategies on the benchmark's conclusions~---~aspects disregarded in previous encoder benchmarks. Our code is available at \url{https://github.com/DrCohomology/EncoderBenchmarking}.

Ordinal classification (OC), i.e., labeling instances along classes with a natural ordering, is common in multiple applications such as size or budget based recommendations and disease severity labeling. Often in practical scenarios, it is desirable to obtain a small set of likely classes with a guaranteed high chance of including the true class. Recent works on conformal prediction (CP) address this problem for the classification setting with non-ordered labels but the resulting prediction sets (PS) are often non-contiguous and unsuitable for ordinal classification. In this work, we propose a framework to adapt existing CP methods to generate contiguous sets with guaranteed coverage and minimal cardinality. Our framework employs a novel non-parametric approach for modeling unimodal distributions. Empirical results on both synthetic and real-world datasets demonstrate our method outperforms SOTA baselines by 4% on Accuracy@K and 8% on PS size.

Generative Adversarial Networks (GANs) are powerful tools for image synthesis. However, they require access to vast amounts of training data, which is often costly and prohibitive. Limited data affects GANs, leading to discriminator overfitting and training instability. In this paper, we present a novel approach called NoIse-modulated Consistency rEgularization (NICE) to overcome these challenges. To this end, we introduce an adaptive multiplicative noise into the discriminator to modulate its latent features. We demonstrate the effectiveness of such a modulation in preventing discriminator overfitting by adaptively reducing the Rademacher complexity of the discriminator. However, this modulation leads to an unintended consequence of increased gradient norm, which can undermine the stability of GAN training. To mitigate this undesirable effect, we impose a constraint on the discriminator, ensuring its consistency for the same inputs under different noise modulations. The constraint effectively penalizes the first and second-order gradients of latent features, enhancing GAN stability. Experimental evidence aligns with our theoretical analysis, demonstrating the reduction of generalization error and gradient penalization of NICE. This substantiates the efficacy of NICE in reducing discriminator overfitting and improving stability of GAN training. NICE achieves state-of-the-art results on CIFAR-10, CIFAR-100, ImageNet and FFHQ datasets when trained with limited data, as well as in low-shot generation tasks.

We study the problem of Inverse Reinforcement Learning (IRL) with an average-reward criterion. The goal is to recover an unknown policy and a reward function when the agent only has samples of states and actions from an experienced agent. Previous IRL methods assume that the expert is trained in a discounted environment, and the discount factor is known. This work alleviates this assumption by proposing an average-reward framework with efficient learning algorithms. We develop novel stochastic first-order methods to solve the IRL problem under the average-reward setting, which requires solving an Average-reward Markov Decision Process (AMDP) as a subproblem. To solve the subproblem, we develop a Stochastic Policy Mirror Descent (SPMD) method under general state and action spaces that needs $\mathcal{O}(1/\varepsilon)$ steps of gradient computation. Equipped with SPMD, we propose the Inverse Policy Mirror Descent (IPMD) method for solving the IRL problem with a $\mathcal{O}(1/\varepsilon^2)$ complexity. To the best of our knowledge, the aforementioned complexity results are new in IRL with the average reward criterion. Finally, we corroborate our analysis with numerical experiments using the MuJoCo benchmark and additional control tasks.

We study the problem of exploration in Reinforcement Learning and present a novel model-free solution. We adopt an information-theoretical viewpoint and start from the instance-specific lower bound of the number of samples that have to be collected to identify a nearly-optimal policy. Deriving this lower bound along with the optimal exploration strategy entails solving an intricate optimization problem and requires a model of the system. In turn, most existing sample optimal exploration algorithms rely on estimating the model. We derive an approximation of the instance-specific lower bound that only involves quantities that can be inferred using model-free approaches. Leveraging this approximation, we devise an ensemble-based model-free exploration strategy applicable to both tabular and continuous Markov decision processes. Numerical results demonstrate that our strategy is able to identify efficient policies faster than state-of-the-art exploration approaches.

Distributed training of Deep Learning models has been critical to many recent successes in the field. Current standard methods primarily rely on synchronous centralized algorithms which induce major communication bottlenecks and synchronization locks at scale. Decentralized asynchronous algorithms are emerging as a potential alternative but their practical applicability still lags. In order to mitigate the increase in communication cost that naturally comes with scaling the number of workers, we introduce a principled asynchronous, randomized, gossip-based optimization algorithm which works thanks to a continuous local momentum named $\textbf{A}^2\textbf{CiD}^2$. Our method allows each worker to continuously process mini-batches without stopping, and run a peer-to-peer averaging routine in parallel, reducing idle time. In addition to inducing a significant communication acceleration at no cost other than adding a local momentum variable, minimal adaptation is required to incorporate $\textbf{A}^2\textbf{CiD}^2$ to standard asynchronous approaches. Our theoretical analysis proves accelerated rates compared to previous asynchronous decentralized baselines and we empirically show that using our $\textbf{A}^2\textbf{CiD}^2$ momentum significantly decrease communication costs in poorly connected networks. In particular, we show consistent improvement on the ImageNet dataset using up to 64 asynchronous workers (A100 GPUs) and various communication network topologies.

Whenever a clinician reflects on the efficacy of a sequence of treatment decisions for a patient, they may try to identify critical time steps where, had they made different decisions, the patient's health would have improved. While recent methods at the intersection of causal inference and reinforcement learning promise to aid human experts, as the clinician above, to *retrospectively* analyze sequential decision making processes, they have focused on environments with finitely many discrete states. However, in many practical applications, the state of the environment is inherently continuous in nature. In this paper, we aim to fill this gap. We start by formally characterizing a sequence of discrete actions and continuous states using finite horizon Markov decision processes and a broad class of bijective structural causal models. Building upon this characterization, we formalize the problem of finding counterfactually optimal action sequences and show that, in general, we cannot expect to solve it in polynomial time. Then, we develop a search method based on the A* algorithm that, under a natural form of Lipschitz continuity of the environment’s dynamics, is guaranteed to return the optimal solution to the problem. Experiments on real clinical data show that our method is very efficient in practice, and it has the potential to offer interesting insights for sequential decision making tasks.

Learning rich skills under the option framework without supervision of external rewards is at the frontier of reinforcement learning research. Existing works mainly fall into two distinctive categories: variational option discovery that maximizes the diversity of the options through a mutual information loss (while ignoring coverage) and Laplacian-based methods that focus on improving the coverage of options by increasing connectivity of the state space (while ignoring diversity). In this paper, we show that diversity and coverage in unsupervised option discovery can indeed be unified under the same mathematical framework. To be specific, we explicitly quantify the diversity and coverage of the learned options through a novel use of Determinantal Point Process (DPP) and optimize these objectives to discover options with both superior diversity and coverage. Our proposed algorithm, ODPP, has undergone extensive evaluation on challenging tasks created with Mujoco and Atari. The results demonstrate that our algorithm outperforms state-of-the-art baselines in both diversity- and coverage-driven categories.