Aidan N. Gomez’s research while affiliated with University of Oxford and other places

We introduce the Aya Expanse model family, a new generation of 8B and 32B parameter multilingual language models, aiming to address the critical challenge of developing highly performant multilingual models that match or surpass the capabilities of monolingual models. By leveraging several years of research at Cohere For AI and Cohere, including advancements in data arbitrage, multilingual preference training, and model merging, Aya Expanse sets a new state-of-the-art in multilingual performance. Our evaluations on the Arena-Hard-Auto dataset, translated into 23 languages, demonstrate that Aya Expanse 8B and 32B outperform leading open-weight models in their respective parameter classes, including Gemma 2, Qwen 2.5, and Llama 3.1, achieving up to a 76.6% win-rate. Notably, Aya Expanse 32B outperforms Llama 3.1 70B, a model with twice as many parameters, achieving a 54.0% win-rate. In this short technical report, we present extended evaluation results for the Aya Expanse model family and release their open-weights, together with a new multilingual evaluation dataset m-ArenaHard.

Training on web-scale data can take months. But much computation and time is wasted on redundant and noisy points that are already learnt or not learnable. To accelerate training, we introduce Reducible Holdout Loss Selection (RHO-LOSS), a simple but principled technique which selects approximately those points for training that most reduce the model's generalization loss. As a result, RHO-LOSS mitigates the weaknesses of existing data selection methods: techniques from the optimization literature typically select 'hard' (e.g. high loss) points, but such points are often noisy (not learnable) or less task-relevant. Conversely, curriculum learning prioritizes 'easy' points, but such points need not be trained on once learned. In contrast, RHO-LOSS selects points that are learnable, worth learning, and not yet learnt. RHO-LOSS trains in far fewer steps than prior art, improves accuracy, and speeds up training on a wide range of datasets, hyperparameters, and architectures (MLPs, CNNs, and BERT). On the large web-scraped image dataset Clothing-1M, RHO-LOSS trains in 18x fewer steps and reaches 2% higher final accuracy than uniform data shuffling.

The ability to accurately model the fitness landscape of protein sequences is critical to a wide range of applications, from quantifying the effects of human variants on disease likelihood, to predicting immune-escape mutations in viruses and designing novel biotherapeutic proteins. Deep generative models of protein sequences trained on multiple sequence alignments have been the most successful approaches so far to address these tasks. The performance of these methods is however contingent on the availability of sufficiently deep and diverse alignments for reliable training. Their potential scope is thus limited by the fact many protein families are hard, if not impossible, to align. Large language models trained on massive quantities of non-aligned protein sequences from diverse families address these problems and show potential to eventually bridge the performance gap. We introduce Tranception, a novel transformer architecture leveraging autoregressive predictions and retrieval of homologous sequences at inference to achieve state-of-the-art fitness prediction performance. Given its markedly higher performance on multiple mutants, robustness to shallow alignments and ability to score indels, our approach offers significant gain of scope over existing approaches. To enable more rigorous model testing across a broader range of protein families, we develop ProteinGym -- an extensive set of multiplexed assays of variant effects, substantially increasing both the number and diversity of assays compared to existing benchmarks.

Quantifying the pathogenicity of protein variants in human disease-related genes would have a marked effect on clinical decisions, yet the overwhelming majority (over 98%) of these variants still have unknown consequences1,2,3. In principle, computational methods could support the large-scale interpretation of genetic variants. However, state-of-the-art methods4,5,6,7,8,9,10 have relied on training machine learning models on known disease labels. As these labels are sparse, biased and of variable quality, the resulting models have been considered insufficiently reliable¹¹. Here we propose an approach that leverages deep generative models to predict variant pathogenicity without relying on labels. By modelling the distribution of sequence variation across organisms, we implicitly capture constraints on the protein sequences that maintain fitness. Our model EVE (evolutionary model of variant effect) not only outperforms computational approaches that rely on labelled data but also performs on par with, if not better than, predictions from high-throughput experiments, which are increasingly used as evidence for variant classification12,13,14,15,16. We predict the pathogenicity of more than 36 million variants across 3,219 disease genes and provide evidence for the classification of more than 256,000 variants of unknown significance. Our work suggests that models of evolutionary information can provide valuable independent evidence for variant interpretation that will be widely useful in research and clinical settings.

We introduce Goldilocks Selection, a technique for faster model training which selects a sequence of training points that are "just right". We propose an information-theoretic acquisition function -- the reducible validation loss -- and compute it with a small proxy model -- GoldiProx -- to efficiently choose training points that maximize information about a validation set. We show that the "hard" (e.g. high loss) points usually selected in the optimization literature are typically noisy, while the "easy" (e.g. low noise) samples often prioritized for curriculum learning confer less information. Further, points with uncertain labels, typically targeted by active learning, tend to be less relevant to the task. In contrast, Goldilocks Selection chooses points that are "just right" and empirically outperforms the above approaches. Moreover, the selected sequence can transfer to other architectures; practitioners can share and reuse it without the need to recreate it.

We challenge a common assumption underlying most supervised deep learning: that a model makes a prediction depending only on its parameters and the features of a single input. To this end, we introduce a general-purpose deep learning architecture that takes as input the entire dataset instead of processing one datapoint at a time. Our approach uses self-attention to reason about relationships between datapoints explicitly, which can be seen as realizing non-parametric models using parametric attention mechanisms. However, unlike conventional non-parametric models, we let the model learn end-to-end from the data how to make use of other datapoints for prediction. Empirically, our models solve cross-datapoint lookup and complex reasoning tasks unsolvable by traditional deep learning models. We show highly competitive results on tabular data, early results on CIFAR-10, and give insight into how the model makes use of the interactions between points.

Existing generalization measures that aim to capture a model's simplicity based on parameter counts or norms fail to explain generalization in overparameterized deep neural networks. In this paper, we introduce a new, theoretically motivated measure of a network's simplicity which we call prunability: the smallest \emph{fraction} of the network's parameters that can be kept while pruning without adversely affecting its training loss. We show that this measure is highly predictive of a model's generalization performance across a large set of convolutional networks trained on CIFAR-10, does not grow with network size unlike existing pruning-based measures, and exhibits high correlation with test set loss even in a particularly challenging double descent setting. Lastly, we show that the success of prunability cannot be explained by its relation to known complexity measures based on models' margin, flatness of minima and optimization speed, finding that our new measure is similar to -- but more predictive than -- existing flatness-based measures, and that its predictions exhibit low mutual information with those of other baselines.

Quantifying the pathogenicity of protein variants in human disease-related genes would have a profound impact on clinical decisions, yet the overwhelming majority (over 98%) of these variants still have unknown consequences. In principle, computational methods could support the large-scale interpretation of genetic variants. However, prior methods have relied on training machine learning models on available clinical labels. Since these labels are sparse, biased, and of variable quality, the resulting models have been considered insufficiently reliable. By contrast, our approach leverages deep generative models to predict the clinical significance of protein variants without relying on labels. The natural distribution of protein sequences we observe across organisms is the result of billions of evolutionary experiments. By modeling that distribution, we implicitly capture constraints on the protein sequences that maintain fitness. Our model EVE (Evolutionary model of Variant Effect) not only outperforms computational approaches that rely on labelled data, but also performs on par, if not better than, high-throughput assays which are increasingly used as strong evidence for variant classification. After thorough validation on clinical labels, we predict the pathogenicity of 11 million variants across 1,081 disease genes, and assign high-confidence reclassification for 72k Variants of Unknown Significance. Our work suggests that models of evolutionary information can provide a strong source of independent evidence for variant interpretation and that the approach will be widely useful in research and clinical settings.

The number of parameters in state of the art neural networks has drastically increased in recent years. This surge of interest in large scale neural networks has motivated the development of new distributed training strategies enabling such models. One such strategy is model-parallel distributed training. Unfortunately, model-parallelism suffers from poor resource utilisation, which leads to wasted resources. In this work, we improve upon recent developments in an idealised model-parallel optimisation setting: local learning. Motivated by poor resource utilisation, we introduce a class of intermediary strategies between local and global learning referred to as interlocking backpropagation. These strategies preserve many of the compute-efficiency advantages of local optimisation, while recovering much of the task performance achieved by global optimisation. We assess our strategies on both image classification ResNets and Transformer language models, finding that our strategy consistently out-performs local learning in terms of task performance, and out-performs global learning in training efficiency.