Mikhail Plekhanov, Nora Kassner, Kashyap Popat et al.
Entity Linking is one of the most common Natural Language Processing tasks in practical applications, but so far efficient end-to-end solutions with multilingual coverage have been lacking, leading to complex model stacks. To fill this gap, we release and open source BELA, the first fully end-to-end multilingual entity linking model that efficiently detects and links entities in texts in any of 97 languages. We provide here a detailed description of the model and report BELA's performance on four entity linking datasets covering high- and low-resource languages.
Frédéric A. Dreyer, Radosław Grabarczyk, Pier Francesco Monni
A significant challenge in the tagging of boosted objects via machine-learning technology is the prohibitive computational cost associated with training sophisticated models. Nevertheless, the universality of QCD suggests that a large amount of the information learnt in the training is common to different physical signals and experimental setups. In this article, we explore the use of transfer learning techniques to develop fast and data-efficient jet taggers that leverage such universality. We consider the graph neural networks LundNet and ParticleNet, and introduce two prescriptions to transfer an existing tagger into a new signal based either on fine-tuning all the weights of a model or alternatively on freezing a fraction of them. In the case of $W$-boson and top-quark tagging, we find that one can obtain reliable taggers using an order of magnitude less data with a corresponding speed-up of the training process. Moreover, while keeping the size of the training data set fixed, we observe a speed-up of the training by up to a factor of three. This offers a promising avenue to facilitate the use of such tools in collider physics experiments.
Frédéric A. Dreyer, Daniel Cutting, Constantin Schneider et al.
We consider the problem of antibody sequence design given 3D structural information. Building on previous work, we propose a fine-tuned inverse folding model that is specifically optimised for antibody structures and outperforms generic protein models on sequence recovery and structure robustness when applied on antibodies, with notable improvement on the hypervariable CDR-H3 loop. We study the canonical conformations of complementarity-determining regions and find improved encoding of these loops into known clusters. Finally, we consider the applications of our model to drug discovery and binder design and evaluate the quality of proposed sequences using physics-based methods.
David Errington, Constantin Schneider, Cédric Bouysset et al.
The field of protein-ligand pose prediction has seen significant advances in recent years, with machine learning-based methods now being commonly used in lieu of classical docking methods or even to predict all-atom protein-ligand complex structures. Most contemporary studies focus on the accuracy and physical plausibility of ligand placement to determine pose quality, often neglecting a direct assessment of the interactions observed with the protein. In this work, we demonstrate that ignoring protein-ligand interaction fingerprints can lead to overestimation of model performance, most notably in recent protein-ligand cofolding models which often fail to recapitulate key interactions.
Joshua Southern, Changpeng Lu, Santrupti Nerli et al.
Multispecific antibodies offer transformative therapeutic potential by engaging multiple epitopes simultaneously, yet their efficacy is an emergent property governed by complex molecular architectures. Rational design is often bottlenecked by the inability to predict how subtle changes in domain topology influence functional outcomes, a challenge exacerbated by the scarcity of comprehensive experimental data. Here, we introduce a computational framework to address part of this gap. First, we present a generative method for creating large-scale, realistic synthetic functional landscapes that capture non-linear interactions where biological activity depends on domain connectivity. Second, we propose a graph neural network architecture that explicitly encodes these topological constraints, distinguishing between format configurations that appear identical to sequence-only models. We demonstrate that this model, trained on synthetic landscapes, recapitulates complex functional properties and, via transfer learning, has the potential to achieve high predictive accuracy on limited biological datasets. We showcase the model's utility by optimizing trade-offs between efficacy and toxicity in trispecific T-cell engagers and retrieving optimal common light chains. This work provides a robust benchmarking environment for disentangling the combinatorial complexity of multispecifics, accelerating the design of next-generation therapeutics.
The capabilities of natural language models trained on large-scale data have increased immensely over the past few years. Open source libraries such as HuggingFace have made these models easily available and accessible. While prior research has identified biases in large language models, this paper considers biases contained in the most popular versions of these models when applied `out-of-the-box' for downstream tasks. We focus on generative language models as they are well-suited for extracting biases inherited from training data. Specifically, we conduct an in-depth analysis of GPT-2, which is the most downloaded text generation model on HuggingFace, with over half a million downloads per month. We assess biases related to occupational associations for different protected categories by intersecting gender with religion, sexuality, ethnicity, political affiliation, and continental name origin. Using a template-based data collection pipeline, we collect 396K sentence completions made by GPT-2 and find: (i) The machine-predicted jobs are less diverse and more stereotypical for women than for men, especially for intersections; (ii) Intersectional interactions are highly relevant for occupational associations, which we quantify by fitting 262 logistic models; (iii) For most occupations, GPT-2 reflects the skewed gender and ethnicity distribution found in US Labor Bureau data, and even pulls the societally-skewed distribution towards gender parity in cases where its predictions deviate from real labor market observations. This raises the normative question of what language models should learn - whether they should reflect or correct for existing inequalities.
Henry Kenlay, Frédéric A. Dreyer, Aleksandr Kovaltsuk et al.
Antibodies are proteins produced by the immune system that can identify and neutralise a wide variety of antigens with high specificity and affinity, and constitute the most successful class of biotherapeutics. With the advent of next-generation sequencing, billions of antibody sequences have been collected in recent years, though their application in the design of better therapeutics has been constrained by the sheer volume and complexity of the data. To address this challenge, we present IgBert and IgT5, the best performing antibody-specific language models developed to date which can consistently handle both paired and unpaired variable region sequences as input. These models are trained comprehensively using the more than two billion unpaired sequences and two million paired sequences of light and heavy chains present in the Observed Antibody Space dataset. We show that our models outperform existing antibody and protein language models on a diverse range of design and regression tasks relevant to antibody engineering. This advancement marks a significant leap forward in leveraging machine learning, large scale data sets and high-performance computing for enhancing antibody design for therapeutic development.
Daniel Cutting, Frédéric A. Dreyer, David Errington et al.
We introduce IgDiff, an antibody variable domain diffusion model based on a general protein backbone diffusion framework which was extended to handle multiple chains. Assessing the designability and novelty of the structures generated with our model, we find that IgDiff produces highly designable antibodies that can contain novel binding regions. The backbone dihedral angles of sampled structures show good agreement with a reference antibody distribution. We verify these designed antibodies experimentally and find that all express with high yield. Finally, we compare our model with a state-of-the-art generative backbone diffusion model on a range of antibody design tasks, such as the design of the complementarity determining regions or the pairing of a light chain to an existing heavy chain, and show improved properties and designability.
Frédéric A. Dreyer, Jan Ludwiczak, Karolis Martinkus et al.
We introduce Ibex, a pan-immunoglobulin structure prediction model that achieves state-of-the-art accuracy in modeling the variable domains of antibodies, nanobodies, and T-cell receptors. Unlike previous approaches, Ibex explicitly distinguishes between bound and unbound protein conformations by training on labeled apo and holo structural pairs, enabling accurate prediction of both states at inference time. Using a comprehensive private dataset of high-resolution antibody structures, we demonstrate superior out-of-distribution performance compared to existing specialized and general protein structure prediction tools. Ibex combines the accuracy of cutting-edge models with significantly reduced computational requirements, providing a robust foundation for accelerating large molecule design and therapeutic development.
Mattia Atzeni, Mikhail Plekhanov, Frédéric A. Dreyer et al.
Entity linking methods based on dense retrieval are an efficient and widely used solution in large-scale applications, but they fall short of the performance of generative models, as they are sensitive to the structure of the embedding space. In order to address this issue, this paper introduces DUCK, an approach to infusing structural information in the space of entity representations, using prior knowledge of entity types. Inspired by duck typing in programming languages, we propose to define the type of an entity based on the relations that it has with other entities in a knowledge graph. Then, porting the concept of box embeddings to spherical polar coordinates, we propose to represent relations as boxes on the hypersphere. We optimize the model to cluster entities of similar type by placing them inside the boxes corresponding to their relations. Our experiments show that our method sets new state-of-the-art results on standard entity-disambiguation benchmarks, it improves the performance of the model by up to 7.9 F1 points, outperforms other type-aware approaches, and matches the results of generative models with 18 times more parameters.
The identification of boosted heavy particles such as top quarks or vector bosons is one of the key problems arising in experimental studies at the Large Hadron Collider. In this article, we introduce LundNet, a novel jet tagging method which relies on graph neural networks and an efficient description of the radiation patterns within a jet to optimally disentangle signatures of boosted objects from background events. We apply this framework to a number of different benchmarks, showing significantly improved performance for top tagging compared to existing state-of-the-art algorithms. We study the robustness of the LundNet taggers to non-perturbative and detector effects, and show how kinematic cuts in the Lund plane can mitigate overfitting of the neural network to model-dependent contributions. Finally, we consider the computational complexity of this method and its scaling as a function of kinematic Lund plane cuts, showing an order of magnitude improvement in speed over previous graph-based taggers.
We introduce a generative model to simulate radiation patterns within a jet using the Lund jet plane. We show that using an appropriate neural network architecture with a stochastic generation of images, it is possible to construct a generative model which retrieves the underlying two-dimensional distribution to within a few percent. We compare our model with several alternative state-of-the-art generative techniques. Finally, we show how a mapping can be created between different categories of jets, and use this method to retroactively change simulation settings or the underlying process on an existing sample. These results provide a framework for significantly reducing simulation times through fast inference of the neural network as well as for data augmentation of physical measurements.
We introduce a novel implementation of a reinforcement learning (RL) algorithm which is designed to find an optimal jet grooming strategy, a critical tool for collider experiments. The RL agent is trained with a reward function constructed to optimize the resulting jet properties, using both signal and background samples in a simultaneous multi-level training. We show that the grooming algorithm derived from the deep RL agent can match state-of-the-art techniques used at the Large Hadron Collider, resulting in improved mass resolution for boosted objects. Given a suitable reward function, the agent learns how to train a policy which optimally removes soft wide-angle radiation, allowing for a modular grooming technique that can be applied in a wide range of contexts. These results are accessible through the corresponding GroomRL framework.