Out-of-Distribution Detection Methods Answer the Wrong Questions

To detect distribution shifts and improve model safety, many out-of-distribution (OOD) detection methods rely on the predictive uncertainty or features of supervised models trained on in-distribution data. In this paper, we critically re-examine this popular family of OOD detection procedures, and we argue that these methods are fundamentally answering the wrong questions for OOD detection. There is no simple fix to this misalignment, since a classifier trained only on in-distribution classes cannot be expected to identify OOD points; for instance, a cat-dog classifier may confidently misclassify an airplane if it contains features that distinguish cats from dogs, despite generally appearing nothing alike. We find that uncertainty-based methods incorrectly conflate high uncertainty with being OOD, while feature-based methods incorrectly conflate far feature-space distance with being OOD. We show how these pathologies manifest as irreducible errors in OOD detection and identify common settings where these methods are ineffective. Additionally, interventions to improve OOD detection such as feature-logit hybrid methods, scaling of model and data size, epistemic uncertainty representation, and outlier exposure also fail to address this fundamental misalignment in objectives. We additionally consider unsupervised density estimation and generative models for OOD detection, which we show have their own fundamental limitations.

Scaling Collapse Reveals Universal Dynamics in Compute-Optimally Trained Neural Networks

What scaling limits govern neural network training dynamics when model size and training time grow in tandem? We show that despite the complex interactions between architecture, training algorithms, and data, compute-optimally trained models exhibit a remarkably precise universality. Specifically, loss curves from models of varying sizes collapse onto a single universal curve when training compute and loss are normalized to unity at the end of training. With learning rate decay, the collapse becomes so tight that differences in the normalized curves across models fall below the noise floor of individual loss curves across random seeds, a phenomenon we term supercollapse. We observe supercollapse across learning rate schedules, datasets, and architectures, including transformers trained on next-token prediction, and find it breaks down when hyperparameters are scaled suboptimally, providing a precise and practical indicator of good scaling. We explain these phenomena by connecting collapse to the power-law structure in typical neural scaling laws, and analyzing a simple yet surprisingly effective model of SGD noise dynamics that accurately predicts loss curves across various learning rate schedules and quantitatively explains the origin of supercollapse.

Training Flexible Models of Genetic Variant Effects from Functional Annotations using Accelerated Linear Algebra

To understand how genetic variants in human genomes manifest in phenotypes -- traits like height or diseases like asthma -- geneticists have sequenced and measured hundreds of thousands of individuals. Geneticists use this data to build models that predict how a genetic variant impacts phenotype given genomic features of the variant, like DNA accessibility or the presence of nearby DNA-bound proteins. As more data and features become available, one might expect predictive models to improve. Unfortunately, training these models is bottlenecked by the need to solve expensive linear algebra problems because variants in the genome are correlated with nearby variants, requiring inversion of large matrices. Previous methods have therefore been restricted to fitting small models, and fitting simplified summary statistics, rather than the full likelihood of the statistical model. In this paper, we leverage modern fast linear algebra techniques to develop DeepWAS (Deep genome Wide Association Studies), a method to train large and flexible neural network predictive models to optimize likelihood. Notably, we find that larger models only improve performance when using our full likelihood approach; when trained by fitting traditional summary statistics, larger models perform no better than small ones. We find larger models trained on more features make better predictions, potentially improving disease predictions and therapeutic target identification.

Why Masking Diffusion Works: Condition on the Jump Schedule for Improved Discrete Diffusion

Discrete diffusion models, like continuous diffusion models, generate high-quality samples by gradually undoing noise applied to datapoints with a Markov process. Gradual generation in theory comes with many conceptual benefits; for example, inductive biases can be incorporated into the noising Markov process, and access to improved sampling algorithms. In practice, however, the consistently best performing discrete diffusion model is, surprisingly, masking diffusion, which does not denoise gradually. Here we explain the superior performance of masking diffusion by noting that it makes use of a fundamental difference between continuous and discrete Markov processes: discrete Markov processes evolve by discontinuous jumps at a fixed rate and, unlike other discrete diffusion models, masking diffusion builds in the known distribution of jump times and only learns where to jump to. We show that we can similarly bake in the known distribution of jump times into any discrete diffusion model. The resulting models - schedule-conditioned discrete diffusion (SCUD) - generalize classical discrete diffusion and masking diffusion. By applying SCUD to models with noising processes that incorporate inductive biases on images, text, and protein data, we build models that outperform masking.

Compute-Optimal LLMs Provably Generalize Better With Scale

Why do larger language models generalize better? To investigate this question, we develop generalization bounds on the pretraining objective of large language models (LLMs) in the compute-optimal regime, as described by the Chinchilla scaling laws. We introduce a novel, fully empirical Freedman-type martingale concentration inequality that tightens existing bounds by accounting for the variance of the loss function. This generalization bound can be decomposed into three interpretable components: the number of parameters per token, the loss variance, and the quantization error at a fixed bitrate. As compute-optimal language models are scaled up, the number of parameters per data point remains constant; however, both the loss variance and the quantization error decrease, implying that larger models should have smaller generalization gaps. We examine why larger models tend to be more quantizable from an information theoretic perspective, showing that the rate at which they can integrate new information grows more slowly than their capacity on the compute-optimal frontier. From these findings we produce a scaling law for the generalization gap, with bounds that become predictably stronger with scale.

When Should We Orchestrate Multiple Agents?

Strategies for orchestrating the interactions between multiple agents, both human and artificial, can wildly overestimate performance and underestimate the cost of orchestration. We design a framework to orchestrate agents under realistic conditions, such as inference costs or availability constraints. We show theoretically that orchestration is only effective if there are performance or cost differentials between agents. We then empirically demonstrate how orchestration between multiple agents can be helpful for selecting agents in a simulated environment, picking a learning strategy in the infamous Rogers' Paradox from social science, and outsourcing tasks to other agents during a question-answer task in a user study.

Deep Learning is Not So Mysterious or Different

Deep neural networks are often seen as different from other model classes by defying conventional notions of generalization. Popular examples of anomalous generalization behaviour include benign overfitting, double descent, and the success of overparametrization. We argue that these phenomena are not distinct to neural networks, or particularly mysterious. Moreover, this generalization behaviour can be intuitively understood, and rigorously characterized using long-standing generalization frameworks such as PAC-Bayes and countable hypothesis bounds. We present soft inductive biases as a key unifying principle in explaining these phenomena: rather than restricting the hypothesis space to avoid overfitting, embrace a flexible hypothesis space, with a soft preference for simpler solutions that are consistent with the data. This principle can be encoded in many model classes, and thus deep learning is not as mysterious or different from other model classes as it might seem. However, we also highlight how deep learning is relatively distinct in other ways, such as its ability for representation learning, phenomena such as mode connectivity, and its relative universality.

Transformers Boost the Performance of Decision Trees on Tabular Data across Sample Sizes

Large language models (LLMs) perform remarkably well on tabular datasets in zero- and few-shot settings, since they can extract meaning from natural language column headers that describe features and labels. Similarly, TabPFN, a recent non-LLM transformer pretrained on numerous tables for in-context learning, has demonstrated excellent performance for dataset sizes up to a thousand samples. In contrast, gradient-boosted decision trees (GBDTs) are typically trained from scratch on each dataset without benefiting from pretraining data and must learn the relationships between columns from their entries alone since they lack natural language understanding. LLMs and TabPFN excel on small tabular datasets where a strong prior is essential, yet they are not competitive with GBDTs on medium or large datasets, since their context lengths are limited. In this paper, we propose a simple and lightweight approach for fusing large language models and TabPFN with gradient-boosted decision trees, which allows scalable GBDTs to benefit from the natural language capabilities and pretraining of transformers. We name our fusion methods LLM-Boost and PFN-Boost, respectively. While matching or surpassing the performance of the transformer at sufficiently small dataset sizes and GBDTs at sufficiently large sizes, LLM-Boost and PFN-Boost outperform both standalone components on a wide range of dataset sizes in between. We demonstrate state-of-the-art performance against numerous baselines and ensembling algorithms. We find that PFN-Boost achieves the best average performance among all methods we test for all but very small dataset sizes. We release our code at http://github.com/MayukaJ/LLM-Boost .

Bayesian Optimization of Antibodies Informed by a Generative Model of Evolving Sequences

To build effective therapeutics, biologists iteratively mutate antibody sequences to improve binding and stability. Proposed mutations can be informed by previous measurements or by learning from large antibody databases to predict only typical antibodies. Unfortunately, the space of typical antibodies is enormous to search, and experiments often fail to find suitable antibodies on a budget. We introduce Clone-informed Bayesian Optimization (CloneBO), a Bayesian optimization procedure that efficiently optimizes antibodies in the lab by teaching a generative model how our immune system optimizes antibodies. Our immune system makes antibodies by iteratively evolving specific portions of their sequences to bind their target strongly and stably, resulting in a set of related, evolving sequences known as a clonal family. We train a large language model, CloneLM, on hundreds of thousands of clonal families and use it to design sequences with mutations that are most likely to optimize an antibody within the human immune system. We propose to guide our designs to fit previous measurements with a twisted sequential Monte Carlo procedure. We show that CloneBO optimizes antibodies substantially more efficiently than previous methods in realistic in silico experiments and designs stronger and more stable binders in in vitro wet lab experiments.

Enhancing Foundation Models for Time Series Forecasting via Wavelet-based Tokenization

How to best develop foundational models for time series forecasting remains an important open question. Tokenization is a crucial consideration in this effort: what is an effective discrete vocabulary for a real-valued sequential input? To address this question, we develop WaveToken, a wavelet-based tokenizer that allows models to learn complex representations directly in the space of time-localized frequencies. Our method first scales and decomposes the input time series, then thresholds and quantizes the wavelet coefficients, and finally pre-trains an autoregressive model to forecast coefficients for the forecast horizon. By decomposing coarse and fine structures in the inputs, wavelets provide an eloquent and compact language for time series forecasting that simplifies learning. Empirical results on a comprehensive benchmark, including 42 datasets for both in-domain and zero-shot settings, show that WaveToken: i) provides better accuracy than recently proposed foundation models for forecasting while using a much smaller vocabulary (1024 tokens), and performs on par or better than modern deep learning models trained specifically on each dataset; and ii) exhibits superior generalization capabilities, achieving the best average rank across all datasets for three complementary metrics. In addition, we show that our method can easily capture complex temporal patterns of practical relevance that are challenging for other recent pre-trained models, including trends, sparse spikes, and non-stationary time series with varying frequencies evolving over time.