Convolutional neural networks (CNNs) allow for parameter sharing and translational equivariance by using convolutional kernels in their linear layers. By restricting these kernels to be SO(3)-steerable, CNNs can further improve parameter sharing. These rotationally-equivariant convolutional layers have several advantages over standard convolutional layers, including increased robustness to unseen poses, smaller network size, and improved sample efficiency. Despite this, most segmentation networks used in medical image analysis continue to rely on standard convolutional kernels. In this paper, we present a new family of segmentation networks that use equivariant voxel convolutions based on spherical harmonics. These networks are robust to data poses not seen during training, and do not require rotation-based data augmentation during training. In addition, we demonstrate improved segmentation performance in MRI brain tumor and healthy brain structure segmentation tasks, with enhanced robustness to reduced amounts of training data and improved parameter efficiency. Code to reproduce our results, and to implement the equivariant segmentation networks for other tasks is available at http://github.com/SCAN-NRAD/e3nn_Unet
We present e3nn, a generalized framework for creating E(3) equivariant trainable functions, also known as Euclidean neural networks. e3nn naturally operates on geometry and geometric tensors that describe systems in 3D and transform predictably under a change of coordinate system. The core of e3nn are equivariant operations such as the TensorProduct class or the spherical harmonics functions that can be composed to create more complex modules such as convolutions and attention mechanisms. These core operations of e3nn can be used to efficiently articulate Tensor Field Networks, 3D Steerable CNNs, Clebsch-Gordan Networks, SE(3) Transformers and other E(3) equivariant networks.
Understanding when the noise in stochastic gradient descent (SGD) affects generalization of deep neural networks remains a challenge, complicated by the fact that networks can operate in distinct training regimes. Here we study how the magnitude of this noise $T$ affects performance as the size of the training set $P$ and the scale of initialization $α$ are varied. For gradient descent, $α$ is a key parameter that controls if the network is `lazy'($α\gg1$) or instead learns features ($α\ll1$). For classification of MNIST and CIFAR10 images, our central results are: (i) obtaining phase diagrams for performance in the $(α,T)$ plane. They show that SGD noise can be detrimental or instead useful depending on the training regime. Moreover, although increasing $T$ or decreasing $α$ both allow the net to escape the lazy regime, these changes can have opposite effects on performance. (ii) Most importantly, we find that the characteristic temperature $T_c$ where the noise of SGD starts affecting the trained model (and eventually performance) is a power law of $P$. We relate this finding with the observation that key dynamical quantities, such as the total variation of weights during training, depend on both $T$ and $P$ as power laws. These results indicate that a key effect of SGD noise occurs late in training by affecting the stopping process whereby all data are fitted. Indeed, we argue that due to SGD noise, nets must develop a stronger `signal', i.e. larger informative weights, to fit the data, leading to a longer training time. A stronger signal and a longer training time are also required when the size of the training set $P$ increases. We confirm these views in the perceptron model, where signal and noise can be precisely measured. Interestingly, exponents characterizing the effect of SGD depend on the density of data near the decision boundary, as we explain.
We present Symphony, an $E(3)$-equivariant autoregressive generative model for 3D molecular geometries that iteratively builds a molecule from molecular fragments. Existing autoregressive models such as G-SchNet and G-SphereNet for molecules utilize rotationally invariant features to respect the 3D symmetries of molecules. In contrast, Symphony uses message-passing with higher-degree $E(3)$-equivariant features. This allows a novel representation of probability distributions via spherical harmonic signals to efficiently model the 3D geometry of molecules. We show that Symphony is able to accurately generate small molecules from the QM9 dataset, outperforming existing autoregressive models and approaching the performance of diffusion models.
Allan dos Santos Costa, Ilan Mitnikov, Mario Geiger et al.
Three-dimensional native states of natural proteins display recurring and hierarchical patterns. Yet, traditional graph-based modeling of protein structures is often limited to operate within a single fine-grained resolution, and lacks hourglass neural architectures to learn those high-level building blocks. We narrow this gap by introducing Ophiuchus, an SO(3)-equivariant coarse-graining model that efficiently operates on all-atom protein structures. Our model departs from current approaches that employ graph modeling, instead focusing on local convolutional coarsening to model sequence-motif interactions with efficient time complexity in protein length. We measure the reconstruction capabilities of Ophiuchus across different compression rates, and compare it to existing models. We examine the learned latent space and demonstrate its utility through conformational interpolation. Finally, we leverage denoising diffusion probabilistic models (DDPM) in the latent space to efficiently sample protein structures. Our experiments demonstrate Ophiuchus to be a scalable basis for efficient protein modeling and generation.
Artificial Intelligence models encoding biology and chemistry are opening new routes to high-throughput and high-quality in-silico drug development. However, their training increasingly relies on computational scale, with recent protein language models (pLM) training on hundreds of graphical processing units (GPUs). We introduce the BioNeMo Framework to facilitate the training of computational biology and chemistry AI models across hundreds of GPUs. Its modular design allows the integration of individual components, such as data loaders, into existing workflows and is open to community contributions. We detail technical features of the BioNeMo Framework through use cases such as pLM pre-training and fine-tuning. On 256 NVIDIA A100s, BioNeMo Framework trains a three billion parameter BERT-based pLM on over one trillion tokens in 4.2 days. The BioNeMo Framework is open-source and free for everyone to use.
Recently, diffusion- and flow-based generative models of protein structures have emerged as a powerful tool for de novo protein design. Here, we develop Proteina, a new large-scale flow-based protein backbone generator that utilizes hierarchical fold class labels for conditioning and relies on a tailored scalable transformer architecture with up to 5x as many parameters as previous models. To meaningfully quantify performance, we introduce a new set of metrics that directly measure the distributional similarity of generated proteins with reference sets, complementing existing metrics. We further explore scaling training data to millions of synthetic protein structures and explore improved training and sampling recipes adapted to protein backbone generation. This includes fine-tuning strategies like LoRA for protein backbones, new guidance methods like classifier-free guidance and autoguidance for protein backbones, and new adjusted training objectives. Proteina achieves state-of-the-art performance on de novo protein backbone design and produces diverse and designable proteins at unprecedented length, up to 800 residues. The hierarchical conditioning offers novel control, enabling high-level secondary-structure guidance as well as low-level fold-specific generation.
Allan dos Santos Costa, Ilan Mitnikov, Franco Pellegrini et al.
Mapping the conformational dynamics of proteins is crucial for elucidating their functional mechanisms. While Molecular Dynamics (MD) simulation enables detailed time evolution of protein motion, its computational toll hinders its use in practice. To address this challenge, multiple deep learning models for reproducing and accelerating MD have been proposed drawing on transport-based generative methods. However, existing work focuses on generation through transport of samples from prior distributions, that can often be distant from the data manifold. The recently proposed framework of stochastic interpolants, instead, enables transport between arbitrary distribution endpoints. Building upon this work, we introduce EquiJump, a transferable SO(3)-equivariant model that bridges all-atom protein dynamics simulation time steps directly. Our approach unifies diverse sampling methods and is benchmarked against existing models on trajectory data of fast folding proteins. EquiJump achieves state-of-the-art results on dynamics simulation with a transferable model on all of the fast folding proteins.
Jesun Firoz, Franco Pellegrini, Mario Geiger et al.
Chemistry Foundation Models (CFMs) that leverage Graph Neural Networks (GNNs) operating on 3D molecular graph structures are becoming indispensable tools for computational chemists and materials scientists. These models facilitate the understanding of matter and the discovery of new molecules and materials. In contrast to GNNs operating on a large homogeneous graphs, GNNs used by CFMs process a large number of geometric graphs of varying sizes, requiring different optimization strategies than those developed for large homogeneous GNNs. This paper presents optimizations for two critical phases of CFM training: data distribution and model training, targeting MACE - a state-of-the-art CFM. We address the challenge of load balancing in data distribution by formulating it as a multi-objective bin packing problem. We propose an iterative algorithm that provides a highly effective, fast, and practical solution, ensuring efficient data distribution. For the training phase, we identify symmetric tensor contraction as the key computational kernel in MACE and optimize this kernel to improve the overall performance. Our combined approach of balanced data distribution and kernel optimization significantly enhances the training process of MACE. Experimental results demonstrate a substantial speedup, reducing per-epoch execution time for training from 12 to 2 minutes on 740 GPUs with a 2.6M sample dataset.
Zhonglin Cao, Mario Geiger, Allan dos Santos Costa et al.
Fast and accurate generation of molecular conformers is desired for downstream computational chemistry and drug discovery tasks. Currently, training and sampling state-of-the-art diffusion or flow-based models for conformer generation require significant computational resources. In this work, we build upon flow-matching and propose two mechanisms for accelerating training and inference of generative models for 3D molecular conformer generation. For fast training, we introduce the SO(3)-Averaged Flow training objective, which leads to faster convergence to better generation quality compared to conditional optimal transport flow or Kabsch-aligned flow. We demonstrate that models trained using SO(3)-Averaged Flow can reach state-of-the-art conformer generation quality. For fast inference, we show that the reflow and distillation methods of flow-based models enable few-steps or even one-step molecular conformer generation with high quality. The training techniques proposed in this work show a path towards highly efficient molecular conformer generation with flow-based models.
Reductive Lie Groups, such as the orthogonal groups, the Lorentz group, or the unitary groups, play essential roles across scientific fields as diverse as high energy physics, quantum mechanics, quantum chromodynamics, molecular dynamics, computer vision, and imaging. In this paper, we present a general Equivariant Neural Network architecture capable of respecting the symmetries of the finite-dimensional representations of any reductive Lie Group G. Our approach generalizes the successful ACE and MACE architectures for atomistic point clouds to any data equivariant to a reductive Lie group action. We also introduce the lie-nn software library, which provides all the necessary tools to develop and implement such general G-equivariant neural networks. It implements routines for the reduction of generic tensor products of representations into irreducible representations, making it easy to apply our architecture to a wide range of problems and groups. The generality and performance of our approach are demonstrated by applying it to the tasks of top quark decay tagging (Lorentz group) and shape recognition (orthogonal group).
Reinforcement learning is generally difficult for partially observable Markov decision processes (POMDPs), which occurs when the agent's observation is partial or noisy. To seek good performance in POMDPs, one strategy is to endow the agent with a finite memory, whose update is governed by the policy. However, policy optimization is non-convex in that case and can lead to poor training performance for random initialization. The performance can be empirically improved by constraining the memory architecture, then sacrificing optimality to facilitate training. Here we study this trade-off in a two-hypothesis testing problem, akin to the two-arm bandit problem. We compare two extreme cases: (i) the random access memory where any transitions between $M$ memory states are allowed and (ii) a fixed memory where the agent can access its last $m$ actions and rewards. For (i), the probability $q$ to play the worst arm is known to be exponentially small in $M$ for the optimal policy. Our main result is to show that similar performance can be reached for (ii) as well, despite the simplicity of the memory architecture: using a conjecture on Gray-ordered binary necklaces, we find policies for which $q$ is exponentially small in $2^m$, i.e. $q\simα^{2^m}$ with $α< 1$. In addition, we observe empirically that training from random initialization leads to very poor results for (i), and significantly better results for (ii) thanks to the constraints on the memory architecture.
Oliver T. Unke, Mihail Bogojeski, Michael Gastegger et al.
Machine learning has enabled the prediction of quantum chemical properties with high accuracy and efficiency, allowing to bypass computationally costly ab initio calculations. Instead of training on a fixed set of properties, more recent approaches attempt to learn the electronic wavefunction (or density) as a central quantity of atomistic systems, from which all other observables can be derived. This is complicated by the fact that wavefunctions transform non-trivially under molecular rotations, which makes them a challenging prediction target. To solve this issue, we introduce general SE(3)-equivariant operations and building blocks for constructing deep learning architectures for geometric point cloud data and apply them to reconstruct wavefunctions of atomistic systems with unprecedented accuracy. Our model achieves speedups of over three orders of magnitude compared to ab initio methods and reduces prediction errors by up to two orders of magnitude compared to the previous state-of-the-art. This accuracy makes it possible to derive properties such as energies and forces directly from the wavefunction in an end-to-end manner. We demonstrate the potential of our approach in a transfer learning application, where a model trained on low accuracy reference wavefunctions implicitly learns to correct for electronic many-body interactions from observables computed at a higher level of theory. Such machine-learned wavefunction surrogates pave the way towards novel semi-empirical methods, offering resolution at an electronic level while drastically decreasing computational cost. Additionally, the predicted wavefunctions can serve as initial guess in conventional ab initio methods, decreasing the number of iterations required to arrive at a converged solution, thus leading to significant speedups without any loss of accuracy or robustness.
Leonardo Petrini, Alessandro Favero, Mario Geiger et al.
Understanding why deep nets can classify data in large dimensions remains a challenge. It has been proposed that they do so by becoming stable to diffeomorphisms, yet existing empirical measurements support that it is often not the case. We revisit this question by defining a maximum-entropy distribution on diffeomorphisms, that allows to study typical diffeomorphisms of a given norm. We confirm that stability toward diffeomorphisms does not strongly correlate to performance on benchmark data sets of images. By contrast, we find that the stability toward diffeomorphisms relative to that of generic transformations $R_f$ correlates remarkably with the test error $ε_t$. It is of order unity at initialization but decreases by several decades during training for state-of-the-art architectures. For CIFAR10 and 15 known architectures, we find $ε_t\approx 0.2\sqrt{R_f}$, suggesting that obtaining a small $R_f$ is important to achieve good performance. We study how $R_f$ depends on the size of the training set and compare it to a simple model of invariant learning.
This work presents Neural Equivariant Interatomic Potentials (NequIP), an E(3)-equivariant neural network approach for learning interatomic potentials from ab-initio calculations for molecular dynamics simulations. While most contemporary symmetry-aware models use invariant convolutions and only act on scalars, NequIP employs E(3)-equivariant convolutions for interactions of geometric tensors, resulting in a more information-rich and faithful representation of atomic environments. The method achieves state-of-the-art accuracy on a challenging and diverse set of molecules and materials while exhibiting remarkable data efficiency. NequIP outperforms existing models with up to three orders of magnitude fewer training data, challenging the widely held belief that deep neural networks require massive training sets. The high data efficiency of the method allows for the construction of accurate potentials using high-order quantum chemical level of theory as reference and enables high-fidelity molecular dynamics simulations over long time scales.
Deep learning algorithms are responsible for a technological revolution in a variety of tasks including image recognition or Go playing. Yet, why they work is not understood. Ultimately, they manage to classify data lying in high dimension -- a feat generically impossible due to the geometry of high dimensional space and the associated curse of dimensionality. Understanding what kind of structure, symmetry or invariance makes data such as images learnable is a fundamental challenge. Other puzzles include that (i) learning corresponds to minimizing a loss in high dimension, which is in general not convex and could well get stuck bad minima. (ii) Deep learning predicting power increases with the number of fitting parameters, even in a regime where data are perfectly fitted. In this manuscript, we review recent results elucidating (i,ii) and the perspective they offer on the (still unexplained) curse of dimensionality paradox. We base our theoretical discussion on the $(h,α)$ plane where $h$ is the network width and $α$ the scale of the output of the network at initialization, and provide new systematic measures of performance in that plane for MNIST and CIFAR 10. We argue that different learning regimes can be organized into a phase diagram. A line of critical points sharply delimits an under-parametrised phase from an over-parametrized one. In over-parametrized nets, learning can operate in two regimes separated by a smooth cross-over. At large initialization, it corresponds to a kernel method, whereas for small initializations features can be learnt, together with invariants in the data. We review the properties of these different phases, of the transition separating them and some open questions. Our treatment emphasizes analogies with physical systems, scaling arguments and the development of numerical observables to quantitatively test these results empirically.
Benjamin Kurt Miller, Mario Geiger, Tess E. Smidt et al.
Equivariant neural networks (ENNs) are graph neural networks embedded in $\mathbb{R}^3$ and are well suited for predicting molecular properties. The ENN library e3nn has customizable convolutions, which can be designed to depend only on distances between points, or also on angular features, making them rotationally invariant, or equivariant, respectively. This paper studies the practical value of including angular dependencies for molecular property prediction directly via an ablation study with \texttt{e3nn} and the QM9 data set. We find that, for fixed network depth and parameter count, adding angular features decreased test error by an average of 23%. Meanwhile, increasing network depth decreased test error by only 4% on average, implying that rotationally equivariant layers are comparatively parameter efficient. We present an explanation of the accuracy improvement on the dipole moment, the target which benefited most from the introduction of angular features.
Mario Geiger, Arthur Jacot, Stefano Spigler et al.
Supervised deep learning involves the training of neural networks with a large number $N$ of parameters. For large enough $N$, in the so-called over-parametrized regime, one can essentially fit the training data points. Sparsity-based arguments would suggest that the generalization error increases as $N$ grows past a certain threshold $N^{*}$. Instead, empirical studies have shown that in the over-parametrized regime, generalization error keeps decreasing with $N$. We resolve this paradox through a new framework. We rely on the so-called Neural Tangent Kernel, which connects large neural nets to kernel methods, to show that the initialization causes finite-size random fluctuations $\|f_{N}-\bar{f}_{N}\|\sim N^{-1/4}$ of the neural net output function $f_{N}$ around its expectation $\bar{f}_{N}$. These affect the generalization error $ε_{N}$ for classification: under natural assumptions, it decays to a plateau value $ε_{\infty}$ in a power-law fashion $\sim N^{-1/2}$. This description breaks down at a so-called jamming transition $N=N^{*}$. At this threshold, we argue that $\|f_{N}\|$ diverges. This result leads to a plausible explanation for the cusp in test error known to occur at $N^{*}$. Our results are confirmed by extensive empirical observations on the MNIST and CIFAR image datasets. Our analysis finally suggests that, given a computational envelope, the smallest generalization error is obtained using several networks of intermediate sizes, just beyond $N^{*}$, and averaging their outputs.
We present a general theory of Group equivariant Convolutional Neural Networks (G-CNNs) on homogeneous spaces such as Euclidean space and the sphere. Feature maps in these networks represent fields on a homogeneous base space, and layers are equivariant maps between spaces of fields. The theory enables a systematic classification of all existing G-CNNs in terms of their symmetry group, base space, and field type. We also consider a fundamental question: what is the most general kind of equivariant linear map between feature spaces (fields) of given types? Following Mackey, we show that such maps correspond one-to-one with convolutions using equivariant kernels, and characterize the space of such kernels.
Mario Geiger, Stefano Spigler, Stéphane d'Ascoli et al.
Deep learning has been immensely successful at a variety of tasks, ranging from classification to AI. Learning corresponds to fitting training data, which is implemented by descending a very high-dimensional loss function. Understanding under which conditions neural networks do not get stuck in poor minima of the loss, and how the landscape of that loss evolves as depth is increased remains a challenge. Here we predict, and test empirically, an analogy between this landscape and the energy landscape of repulsive ellipses. We argue that in FC networks a phase transition delimits the over- and under-parametrized regimes where fitting can or cannot be achieved. In the vicinity of this transition, properties of the curvature of the minima of the loss are critical. This transition shares direct similarities with the jamming transition by which particles form a disordered solid as the density is increased, which also occurs in certain classes of computational optimization and learning problems such as the perceptron. Our analysis gives a simple explanation as to why poor minima of the loss cannot be encountered in the overparametrized regime, and puts forward the surprising result that the ability of fully connected networks to fit random data is independent of their depth. Our observations suggests that this independence also holds for real data. We also study a quantity $Δ$ which characterizes how well ($Δ<0$) or badly ($Δ>0$) a datum is learned. At the critical point it is power-law distributed, $P_+(Δ)\simΔ^θ$ for $Δ>0$ and $P_-(Δ)\sim(-Δ)^{-γ}$ for $Δ<0$, with $θ\approx0.3$ and $γ\approx0.2$. This observation suggests that near the transition the loss landscape has a hierarchical structure and that the learning dynamics is prone to avalanche-like dynamics, with abrupt changes in the set of patterns that are learned.
We present a convolutional network that is equivariant to rigid body motions. The model uses scalar-, vector-, and tensor fields over 3D Euclidean space to represent data, and equivariant convolutions to map between such representations. These SE(3)-equivariant convolutions utilize kernels which are parameterized as a linear combination of a complete steerable kernel basis, which is derived analytically in this paper. We prove that equivariant convolutions are the most general equivariant linear maps between fields over R^3. Our experimental results confirm the effectiveness of 3D Steerable CNNs for the problem of amino acid propensity prediction and protein structure classification, both of which have inherent SE(3) symmetry.
Group equivariant and steerable convolutional neural networks (regular and steerable G-CNNs) have recently emerged as a very effective model class for learning from signal data such as 2D and 3D images, video, and other data where symmetries are present. In geometrical terms, regular G-CNNs represent data in terms of scalar fields ("feature channels"), whereas the steerable G-CNN can also use vector or tensor fields ("capsules") to represent data. In algebraic terms, the feature spaces in regular G-CNNs transform according to a regular representation of the group G, whereas the feature spaces in Steerable G-CNNs transform according to the more general induced representations of G. In order to make the network equivariant, each layer in a G-CNN is required to intertwine between the induced representations associated with its input and output space. In this paper we present a general mathematical framework for G-CNNs on homogeneous spaces like Euclidean space or the sphere. We show, using elementary methods, that the layers of an equivariant network are convolutional if and only if the input and output feature spaces transform according to an induced representation. This result, which follows from G.W. Mackey's abstract theory on induced representations, establishes G-CNNs as a universal class of equivariant network architectures, and generalizes the important recent work of Kondor & Trivedi on the intertwiners between regular representations.
We analyze numerically the training dynamics of deep neural networks (DNN) by using methods developed in statistical physics of glassy systems. The two main issues we address are (1) the complexity of the loss landscape and of the dynamics within it, and (2) to what extent DNNs share similarities with glassy systems. Our findings, obtained for different architectures and datasets, suggest that during the training process the dynamics slows down because of an increasingly large number of flat directions. At large times, when the loss is approaching zero, the system diffuses at the bottom of the landscape. Despite some similarities with the dynamics of mean-field glassy systems, in particular, the absence of barrier crossing, we find distinctive dynamical behaviors in the two cases, showing that the statistical properties of the corresponding loss and energy landscapes are different. In contrast, when the network is under-parametrized we observe a typical glassy behavior, thus suggesting the existence of different phases depending on whether the network is under-parametrized or over-parametrized.
Convolutional Neural Networks (CNNs) have become the method of choice for learning problems involving 2D planar images. However, a number of problems of recent interest have created a demand for models that can analyze spherical images. Examples include omnidirectional vision for drones, robots, and autonomous cars, molecular regression problems, and global weather and climate modelling. A naive application of convolutional networks to a planar projection of the spherical signal is destined to fail, because the space-varying distortions introduced by such a projection will make translational weight sharing ineffective. In this paper we introduce the building blocks for constructing spherical CNNs. We propose a definition for the spherical cross-correlation that is both expressive and rotation-equivariant. The spherical correlation satisfies a generalized Fourier theorem, which allows us to compute it efficiently using a generalized (non-commutative) Fast Fourier Transform (FFT) algorithm. We demonstrate the computational efficiency, numerical accuracy, and effectiveness of spherical CNNs applied to 3D model recognition and atomization energy regression.
The success of convolutional networks in learning problems involving planar signals such as images is due to their ability to exploit the translation symmetry of the data distribution through weight sharing. Many areas of science and egineering deal with signals with other symmetries, such as rotation invariant data on the sphere. Examples include climate and weather science, astrophysics, and chemistry. In this paper we present spherical convolutional networks. These networks use convolutions on the sphere and rotation group, which results in rotational weight sharing and rotation equivariance. Using a synthetic spherical MNIST dataset, we show that spherical convolutional networks are very effective at dealing with rotationally invariant classification problems.