NeurIPS 2024 Papers

We present a unified likelihood ratio-based confidence sequence (CS) for *any* (self-concordant) generalized linear model (GLM) that is guaranteed to be convex and numerically tight. We show that this is on par or improves upon known CSs for various GLMs, including Gaussian, Bernoulli, and Poisson. In particular, for the first time, our CS for Bernoulli has a $\mathrm{poly}(S)$-free radius where $S$ is the norm of the unknown parameter. Our first technical novelty is its derivation, which utilizes a time-uniform PAC-Bayesian bound with a uniform prior/posterior, despite the latter being a rather unpopular choice for deriving CSs. As a direct application of our new CS, we propose a simple and natural optimistic algorithm called **OFUGLB**, applicable to *any* generalized linear bandits (**GLB**; Filippi et al. (2010)). Our analysis shows that the celebrated optimistic approach simultaneously attains state-of-the-art regrets for various self-concordant (not necessarily bounded) **GLB**s, and even $\mathrm{poly}(S)$-free for bounded **GLB**s, including logistic bandits. The regret analysis, our second technical novelty, follows from combining our new CS with a new proof technique that completely avoids the previously widely used self-concordant control lemma (Faury et al., 2020, Lemma 9). Numerically, **OFUGLB** outperforms or is at par with prior algorithms for logistic bandits.

Predicting molecular impact on cellular function is a core challenge in therapeutic design. Phenomic experiments, designed to capture cellular morphology, utilize microscopy based techniques and demonstrate a high throughput solution for uncovering molecular impact on the cell. In this work, we learn a joint latent space between molecular structures and microscopy phenomic experiments, aligning paired samples with contrastive learning. Specifically, we study the problem of Contrastive PhenoMolecular Retrieval, which consists of zero-shot molecular structure identification conditioned on phenomic experiments. We assess challenges in multi-modal learning of phenomics and molecular modalities such as experimental batch effect, inactive molecule perturbations, and encoding perturbation concentration. We demonstrate improved multi-modal learner retrieval through (1) a uni-modal pre-trained phenomics model, (2) a novel inter sample similarity aware loss, and (3) models conditioned on a representation of molecular concentration. Following this recipe, we propose MolPhenix, a molecular phenomics model. MolPhenix leverages a pre-trained phenomics model to demonstrate significant performance gains across perturbation concentrations, molecular scaffolds, and activity thresholds. In particular, we demonstrate an 8.1 times improvement in zero shot molecular retrieval of active molecules over the previous state-of-the-art, reaching 77.33% in top-1% accuracy. These results open the door for machine learning to be applied in virtual phenomics screening, which can significantly benefit drug discovery applications.

We present NeuralFluid, a novel framework to explore neural control and design of complex fluidic systems with dynamic solid boundaries. Our system features a fast differentiable Navier-Stokes solver with solid-fluid interface handling, a low-dimensional differentiable parametric geometry representation, a control-shape co-design algorithm, and gym-like simulation environments to facilitate various fluidic control design applications. Additionally, we present a benchmark of design, control, and learning tasks on high-fidelity, high-resolution dynamic fluid environments that pose challenges for existing differentiable fluid simulators. These tasks include designing the control of artificial hearts, identifying robotic end-effector shapes, and controlling a fluid gate. By seamlessly incorporating our differentiable fluid simulator into a learning framework, we demonstrate successful design, control, and learning results that surpass gradient-free solutions in these benchmark tasks.

We prove that single-parameter natural exponential families with subexponential tails are self-concordant with polynomial-sized parameters. For subgaussian natural exponential families we establish an exact characterization of the growth rate of the self-concordance parameter. Applying these findings to bandits allows us to fill gaps in the literature: We show that optimistic algorithms for generalized linear bandits enjoy regret bounds that are both second-order (scale with the variance of the optimal arm's reward distribution) and free of an exponential dependence on the bound of the problem parameter in the leading term. To the best of our knowledge, ours is the first regret bound for generalized linear bandits with subexponential tails, broadening the class of problems to include Poisson, exponential and gamma bandits.

Computer-aided synthesis planning (CASP) algorithms have demonstrated expert-level abilities in planning retrosynthetic routes to molecules of low to moderate complexity. However, current search methods assume the sufficiency of reaching arbitrary building blocks, failing to address the common real-world constraint where using specific molecules is desired. To this end, we present a formulation of synthesis planning with starting material constraints. Under this formulation, we propose Double-Ended Synthesis Planning ($\texttt{DESP}$), a novel CASP algorithm under a _bidirectional graph search_ scheme that interleaves expansions from the target and from the goal starting materials to ensure constraint satisfiability. The search algorithm is guided by a goal-conditioned cost network learned offline from a partially observed hypergraph of valid chemical reactions. We demonstrate the utility of $\texttt{DESP}$ in improving solve rates and reducing the number of search expansions by biasing synthesis planning towards expert goals on multiple new benchmarks. $\texttt{DESP}$ can make use of existing one-step retrosynthesis models, and we anticipate its performance to scale as these one-step model capabilities improve.

Many applications today provide users with multiple auto-complete drafts as they type, including GitHub's code completion, Gmail's smart compose, and Apple's messaging auto-suggestions. Under the hood, language models support this by running an autoregressive inference pass to provide a draft. Consequently, providing $k$ drafts to the user requires running an expensive language model $k$ times. To alleviate the computation cost of running $k$ inference passes, we propose Superposed Decoding, a new decoding algorithm that generates $k$ drafts at the computation cost of one autoregressive inference pass. We achieve this by feeding a superposition of the most recent token embeddings from the $k$ drafts as input to the next decoding step of the language model. At every inference step we combine the $k$ drafts with the top-$k$ tokens to get $k^2$ new drafts and cache the $k$ most likely options, using an n-gram interpolation with minimal compute overhead to filter out incoherent generations. Our experiments show that $k$ drafts from Superposed Decoding are at least as coherent and factual as Nucleus Sampling and Greedy Decoding respectively, while being at least $2.44\times$ faster for $k\ge3$. In a compute-normalized setting, user evaluations demonstrably favor text generated by Superposed Decoding over Nucleus Sampling. Superposed Decoding can also be combined with other decoding strategies, resulting in universal coverage gains when scaling inference time compute. Code and more examples open-sourced at https://github.com/RAIVNLab/SuperposedDecoding.

Machine learning (ML) is playing an increasingly important role in scientific research. In conjunction with classical statistical approaches, ML-assisted analytical strategies have shown great promise in accelerating research findings. This has also opened a whole field of methodological research focusing on integrative approaches that leverage both ML and statistics to tackle data science challenges. One type of study that has quickly gained popularity employs ML to predict unobserved outcomes in massive samples, and then uses predicted outcomes in downstream statistical inference. However, existing methods designed to ensure the validity of this type of post-prediction inference are limited to very basic tasks such as linear regression analysis. This is because any extension of these approaches to new, more sophisticated statistical tasks requires task-specific algebraic derivations and software implementations, which ignores the massive library of existing software tools already developed for the same scientific problem given observed data. This severely constrains the scope of application for post-prediction inference. To address this challenge, we introduce a novel statistical framework named PSPS for task-agnostic ML-assisted inference. It provides a post-prediction inference solution that can be easily plugged into almost any established data analysis routines. It delivers valid and efficient inference that is robust to arbitrary choice of ML model, allowing nearly all existing statistical frameworks to be incorporated into the analysis of ML-predicted data. Through extensive experiments, we showcase our method’s validity, versatility, and superiority compared to existing approaches. Our software is available at https://github.com/qlu-lab/psps.

Through an uncertainty quantification (UQ) perspective, we show that score-based generative models (SGMs) are provably robust to the multiple sources of error in practical implementation. Our primary tool is the Wasserstein uncertainty propagation (WUP) theorem, a *model-form UQ* bound that describes how the $L^2$ error from learning the score function propagates to a Wasserstein-1 ($\mathbf{d}_1$) ball around the true data distribution under the evolution of the Fokker-Planck equation. We show how errors due to (a) finite sample approximation, (b) early stopping, (c) score-matching objective choice, (d) score function parametrization expressiveness, and (e) reference distribution choice, impact the quality of the generative model in terms of a $\mathbf{d}_1$ bound of computable quantities. The WUP theorem relies on Bernstein estimates for Hamilton-Jacobi-Bellman partial differential equations (PDE) and the regularizing properties of diffusion processes. Specifically, *PDE regularity theory* shows that *stochasticity* is the key mechanism ensuring SGM algorithms are provably robust. The WUP theorem applies to integral probability metrics beyond $\mathbf{d}_1$, such as the total variation distance and the maximum mean discrepancy. Sample complexity and generalization bounds in $\mathbf{d}_1$ follow directly from the WUP theorem. Our approach requires minimal assumptions, is agnostic to the manifold hypothesis and avoids absolute continuity assumptions for the target distribution. Additionally, our results clarify the *trade-offs* among multiple error sources in SGMs.

We study learning-based approaches to semantic route planning, which concerns producing routes in response to rich queries that specify various criteria and preferences. Semantic routing is already widely found in industry applications, especially navigational services like Google Maps; however, existing implementations only support limited route criteria and narrow query sets as they rely on repurposing classical route optimization algorithms. We argue for a learning-based approach to semantic routing as a more scalable and general alternative. To foster interest in this important application of graph learning, we are releasing a large-scale publicly-licensed benchmark for semantic routing consisting of real-world multi-objective navigation problems---expressed via natural language queries---on the richly annotated road networks of US cities. In addition to being intractable with existing approaches to semantic routing, our benchmark poses a significant scaling challenge for graph learning methods. As a proof-of-concept, we show that---at scale---even a standard transformer network is a powerful semantic routing system and achieves non-trivial performance on our benchmark. In the process, we demonstrate a simple solution to the challenge of scaling up graph learning: an autoregressive approach that decomposes semantic routing into smaller ``next-edge'' prediction problems.

Analyzing inter-individual variability of physiological functions is particularly appealing in medical and biological contexts to describe or quantify health conditions. Such analysis can be done by comparing individuals to a reference one with time series as biomedical data. This paper introduces an unsupervised representation learning (URL) algorithm for time series tailored to inter-individual studies. The idea is to represent time series as deformations of a reference time series. The deformations are diffeomorphisms parameterized and learned by our method called TS-LDDMM. Once the deformations and the reference time series are learned, the vector representations of individual time series are given by the parametrization of their corresponding deformation. At the crossroads between URL for time series and shape analysis, the proposed algorithm handles irregularly sampled multivariate time series of variable lengths and provides shape-based representations of temporal data. In this work, we establish a representation theorem for the graph of a time series and derive its consequences on the LDDMM framework. We showcase the advantages of our representation compared to existing methods using synthetic data and real-world examples motivated by biomedical applications.

We introduce Poseidon, a foundation model for learning the solution operators of PDEs. It is based on a multiscale operator transformer, with time-conditioned layer norms that enable continuous-in-time evaluations. A novel training strategy leveraging the semi-group property of time-dependent PDEs to allow for significant scaling-up of the training data is also proposed. Poseidon is pretrained on a diverse, large scale dataset for the governing equations of fluid dynamics. It is then evaluated on a suite of 15 challenging downstream tasks that include a wide variety of PDE types and operators. We show that Poseidon exhibits excellent performance across the board by outperforming baselines significantly, both in terms of sample efficiency and accuracy. Poseidon also generalizes very well to new physics that is not seen during pretraining. Moreover, Poseidon scales with respect to model and data size, both for pretraining and for downstream tasks. Taken together, our results showcase the surprising ability of Poseidon to learn effective representations from a very small set of PDEs during pretraining in order to generalize well to unseen and unrelated PDEs downstream, demonstrating its potential as an effective, general purpose PDE foundation model. Finally, the Poseidon model as well as underlying pretraining and downstream datasets are open sourced, with code being available at https://github.com/camlab-ethz/poseidon and pretrained models and datasets at https://huggingface.co/camlab-ethz.

Existing metrics for reinforcement learning (RL) such as regret, PAC bounds, or uniform-PAC (Dann et al., 2017), typically evaluate the cumulative performance, while allowing the play of an arbitrarily bad policy at any finite time t. Such a behavior can be highly detrimental in high-stakes applications. This paper introduces a stronger metric, uniform last-iterate (ULI) guarantee, capturing both cumulative and instantaneous performance of RL algorithms. Specifically, ULI characterizes the instantaneous performance since it ensures that the per-round suboptimality of the played policy is bounded by a function, monotonically decreasing w.r.t. (large) round t, preventing revisits to bad policies when sufficient samples are available. We demonstrate that a near-optimal ULI guarantee directly implies near-optimal cumulative performance across aforementioned metrics, but not the other way around. To examine the achievability of ULI, we first provide two positive results for bandit problems with finite arms, showing that some elimination-based algorithms and high-probability adversarial algorithms with stronger analysis or additional designs, can attain near-optimal ULI guarantees. We also provide a negative result, indicating that optimistic algorithms cannot achieve a near-optimal ULI guarantee. Furthermore, we propose an efficient algorithm for linear bandits with infinitely many arms, which achieves the ULI guarantee, given access to an optimization oracle. Finally, we propose an algorithm that achieves a near-optimal ULI guarantee for the online reinforcement learning setting.

Optimizing neural networks with loss that contain high-dimensional and high-order differential operators is expensive to evaluate with back-propagation due to $\mathcal{O}(d^{k})$ scaling of the derivative tensor size and the $\mathcal{O}(2^{k-1}L)$ scaling in the computation graph, where $d$ is the dimension of the domain, $L$ is the number of ops in the forward computation graph, and $k$ is the derivative order. In previous works, the polynomial scaling in $d$ was addressed by amortizing the computation over the optimization process via randomization. Separately, the exponential scaling in $k$ for univariate functions ($d=1$) was addressed with high-order auto-differentiation (AD). In this work, we show how to efficiently perform arbitrary contraction of the derivative tensor of arbitrary order for multivariate functions, by properly constructing the input tangents to univariate high-order AD, which can be used to efficiently randomize any differential operator. When applied to Physics-Informed Neural Networks (PINNs), our method provides >1000$\times$ speed-up and >30$\times$ memory reduction over randomization with first-order AD, and we can now solve 1-million-dimensional PDEs in 8 minutes on a single NVIDIA A100 GPU. This work opens the possibility of using high-order differential operators in large-scale problems.

Data-driven deep learning models are transforming global weather forecasting. It is an open question if this success can extend to climate modeling, where the complexity of the data and long inference rollouts pose significant challenges. Here, we present the first conditional generative model that produces accurate and physically consistent global climate ensemble simulations by emulating a coarse version of the United States' primary operational global forecast model, FV3GFS. Our model integrates the dynamics-informed diffusion framework (DYffusion) with the Spherical Fourier Neural Operator (SFNO) architecture, enabling stable 100-year simulations at 6-hourly timesteps while maintaining low computational overhead compared to single-step deterministic baselines. The model achieves near gold-standard performance for climate model emulation, outperforming existing approaches and demonstrating promising ensemble skill. This work represents a significant advance towards efficient, data-driven climate simulations that can enhance our understanding of the climate system and inform adaptation strategies. Code is available at [https://github.com/Rose-STL-Lab/spherical-dyffusion](https://github.com/Rose-STL-Lab/spherical-dyffusion).

Species range maps (SRMs) are essential tools for research and policy-making in ecology, conservation, and environmental management. However, traditional SRMs rely on the availability of environmental covariates and high-quality observational data, both of which can be challenging to obtain due to geographic inaccessibility and resource constraints. We propose a novel approach combining millions of citizen science species observations with textual descriptions from Wikipedia, covering habitat preferences and range descriptions for tens of thousands of species. Our framework maps location, species, and text descriptions into a common space, facilitating the learning of rich spatial covariates at a global scale and enabling zero-shot range estimation from textual descriptions. Evaluated on held-out species, our zero-shot SRMs significantly outperform baselines and match the performance of SRMs obtained using tens of observations. Our approach also acts as a strong prior when combined with observational data, resulting in more accurate range estimation with less data. We present extensive quantitative and qualitative analyses of the learned representations in the context of range estimation and other spatial tasks, demonstrating the effectiveness of our approach.

Since the inception of our planet, the meteorological environment, as reflected through spatio-temporal data, has always been a fundamental factor influencing human life, socio-economic progress, and ecological conservation. A comprehensive exploration of this data is thus imperative to gain a deeper understanding and more accurate forecasting of these environmental shifts. Despite the success of deep learning techniques within the realm of spatio-temporal data and earth science, existing public datasets are beset with limitations in terms of spatial scale, temporal coverage, and reliance on limited time series data. These constraints hinder their optimal utilization in practical applications. To address these issues, we introduce **Terra**, a multimodal spatio-temporal dataset spanning the earth. This dataset encompasses hourly time series data from 6,480,000 grid areas worldwide over the past 45 years, while also incorporating multimodal spatial supplementary information including geo-images and explanatory text. Through a detailed data analysis and evaluation of existing deep learning models within earth sciences, utilizing our constructed dataset. we aim to provide valuable opportunities for enhancing future research in spatio-temporal data mining, thereby advancing towards more spatio-temporal general intelligence. Our source code and data can be accessed at https://github.com/CityMind-Lab/NeurIPS24-Terra.

Effectively designing molecular geometries is essential to advancing pharmaceutical innovations, a domain, which has experienced great attention through the success of generative models and, in particular, diffusion models. However, current molecular diffusion models are tailored towards a specific downstream task and lack adaptability. We introduce UniGuide, a framework for controlled geometric guidance of unconditional diffusion models that allows flexible conditioning during inference without the requirement of extra training or networks. We show how applications such as structure-based, fragment-based, and ligand-based drug design are formulated in the UniGuide framework and demonstrate on-par or superior performance compared to specialised models. Offering a more versatile approach, UniGuide has the potential to streamline the development of molecular generative models, allowing them to be readily used in diverse application scenarios.

Molecular learning is pivotal in many real-world applications, such as drug discovery. Supervised learning requires heavy human annotation, which is particularly challenging for molecular data, e.g., the commonly used density functional theory (DFT) is highly computationally expensive. Active learning (AL) automatically queries labels for most informative samples, thereby remarkably alleviating the annotation hurdle. In this paper, we present a principled AL paradigm for molecular learning, where we treat molecules as 3D molecular graphs. Specifically, we propose a new diversity sampling method to eliminate mutual redundancy built on distributions of 3D geometries. We first propose a set of new 3D graph isometries for 3D graph isomorphism analysis. Our method is provably at least as expressive as the Geometric Weisfeiler-Lehman (GWL) test. The moments of the distributions of the associated geometries are then extracted for efficient diversity computing. To ensure our AL paradigm selects samples with maximal uncertainties, we carefully design a Bayesian geometric graph neural network to compute uncertainties specifically for 3D molecular graphs. We pose active sampling as a quadratic programming (QP) problem using the proposed components. Experimental results demonstrate the effectiveness of our AL paradigm, as well as the proposed diversity and uncertainty methods.

Neural wave functions accomplished unprecedented accuracies in approximating the ground state of many-electron systems, though at a high computational cost. Recent works proposed amortizing the cost by learning generalized wave functions across different structures and compounds instead of solving each problem independently. Enforcing the permutation antisymmetry of electrons in such generalized neural wave functions remained challenging as existing methods require discrete orbital selection via non-learnable hand-crafted algorithms. This work tackles the problem by defining overparametrized, fully learnable neural wave functions suitable for generalization across molecules. We achieve this by relying on Pfaffians rather than Slater determinants. The Pfaffian allows us to enforce the antisymmetry on arbitrary electronic systems without any constraint on electronic spin configurations or molecular structure. Our empirical evaluation finds that a single neural Pfaffian calculates the ground state and ionization energies with chemical accuracy across various systems. On the TinyMol dataset, we outperform the `gold-standard' CCSD(T) CBS reference energies by 1.9m$E_h$ and reduce energy errors compared to previous generalized neural wave functions by up to an order of magnitude.