Rotational symmetry is one of the most important structural principles in machine learning on 3D data. In applications ranging from physics and materials science to 3D computer vision, predictions should not depend on an arbitrary choice of coordinate frame. Rotational equivariance captures this requirement mathematically by enforcing that a rotation of the input induces a corresponding transformation of the model output. This tutorial provides a comprehensive introduction to rotational equivariance, starting from the physical and geometric intuition behind coordinate independence and building up the necessary machinery from geometric deep learning, group theory, and representation theory. We introduce message passing on Euclidean graphs, group actions and representations, spherical harmonics, Wigner matrices, tensor products, and Clebsch-Gordan decomposition, and explain how these ingredients give rise to modern equivariant architectures. We then survey the principal strategies for incorporating rotational equivariance in deep learning, including group convolutions, internal tensorial representations, and canonicalization-based methods, and discuss their practical strengths and limitations. The tutorial aims to lower the barrier to the subject by connecting the underlying mathematics to practical model design, by unifying ideas that are often expressed in different formal languages, and by helping practitioners choose among competing approaches through a clear discussion of their trade-offs.
Protein structure modeling rests on a single computational primitive: the interaction between what a residue is (sequence content) and where it sits (three-dimensional geometry). What is the expressive limit of this layer class? We show that the complete bilinear operator over content-geometry outer products--the sufficient statistic of all second-order interactions--is the expressive ceiling, while the additive message passing of mainstream geometric GNNs is provably blind to content-geometry binding. We then introduce Hyper-Fold, a rank-K separable convolutional backbone approaching this ceiling at message-passing cost: each radius neighborhood is organized into a sequence hyperedge and a contact hyperedge, modulated by an edge-conditioned matrix-valued operator factorized into K learned basis operators with geometry-generated coefficients. Across enzyme function prediction, fold classification, and ligand binding site detection, Hyper-Fold and its hierarchical variant Hyper-Fold-Deep achieve the best results among protein-specific structure encoders; Hyper-Fold-Pocket, an anchored set-prediction head, surpasses UniSite-3D on UniSite-DS and two zero-shot benchmarks with no sequence language model features, 68x fewer parameters, and 4.8x lower latency--suggesting that a sufficiently expressive 3D backbone recovers information that fusion architectures previously borrowed from evolution-scale pretraining.
Alessio Borgi, Mario Severino, Fabrizio Silvestri +1cs.LG cs.AI
Equivariant graph neural networks provide a principled way to model geometric systems, but efficient first-order architectures remain limited in how vector information can be transformed as it moves across a graph. We introduce \textsc{ESNN}, an Equivariant Sheaf Neural Network that enriches this interaction by learning directed, matrix-valued transport between neighboring vector features while preserving exact Euclidean equivariance. Rather than increasing the order of the representation, ESNN keeps scalar and vector features first-order and places the additional geometric flexibility in the edge transport itself. We characterize this transport theoretically, showing that when relative displacement is the only covariant geometric input, every linear $O(n)$-equivariant map decomposes into independent radial and tangential components, while learned covariant features enable richer feature-conditioned transformations. We also introduce controlled symmetry relaxation for systems with a preferred ambient direction, which may be prescribed or inferred from data while recovering full $E(n)$-equivariance when the directional pathway is inactive. Across particle dynamics, mesh-based simulation, point-cloud classification, and molecular property prediction, ESNN improves dynamics prediction, recovers the gravity axis when symmetry is broken, yields substantial gains on selected mesh tasks and long-horizon rollouts, and remains robust to unseen rotations. These results show that learning how geometric information is transported across edges offers a complementary route to expressive equivariant message passing without requiring higher-order representations.
Alam Noor, Luis Almeida, Mohamed Daoudics.CV cs.AI
Deep learning systems perform mainly within the 2D for a single image domain and take the face as a single-dimension representation, losing sight of the 3D anatomy of sheep and cross-landmark spatial relationships that are intrinsic to the clinically proven Sheep Pain Facial Expression Scale (SPFES). This paper presents the \textbf{3D Sheep Pain Facial Expression System (3D-SPFES)}, a novel, monocular depth-aware geometric graph neural network system that integrates each SPFES facial landmark, such as the ears, eyes, and nose, into 3D Euclidean space estimated from a single RGB camera by using VideoDepthAnything, thus preventing the need for specialized depth hardware. Each landmark node includes a feature vector containing its 3D spatial coordinates, estimated surface normal, and facial attribute class embedding. Edges linked to nodes are assigned weights based on an aggregate metric that combines both Euclidean distance and surface co-planarity in a 3D space. A Weighted Geometric Graph Neural Network (WG-GNN) studies this graph using $\mathcal{K} = 3$ geometry-aware message-passing layers enhanced by a scaled dot-product attention method that selectively enhances anatomically relevant inter-landmark messages. The resultant node embeddings are combined into $\mathcal{O} = 3$ pain-level clusters and integrated into a Normalized Pain Score (NPS) within the range of $[0, 100%]$ a confidence-weighted, SPFES-derived scoring method.
Over the last decade, neural networks have been applied to an increasingly diverse range of applications, including data with rich geometric, topological, or symmetry-related structure. As a result, researchers have increasingly drawn inspiration from topology, algebra, and geometry. Despite this rich algorithmic development, the supporting software ecosystem remains fragmented. Many important methods exist only as research prototypes in unmaintained repositories. We address this by introducing Topology, Algebra, and Geometry Torch (TAGTorch), an open-source, PyTorch-based library that unifies tools inspired by topology, algebra, and geometry, including data-preprocessing methods, architectures, training techniques, and model analysis tools. We describe the design philosophy of TAGTorch and then discuss its current architecture and capabilities, highlighting areas where it can fill gaps in the current software ecosystem. We conclude with a discussion of our future development priorities for the library.
This work proposes an adaptation of the attention mechanism for triangle meshes. The core observation is that endowing the attention mechanism with critical properties for learning over meshes -- intrinsicality and triangulation-agnosticism -- enables it to attain state-of-the-art results over several learning-based tasks in geometry-processing. The above is achieved by modifying the attention mechanism from the bottom up based on simple principles from geometry-processing. Namely, the quantities used within attention -- queries, keys and values -- are created by an intrinsic, triangulation-agnostic network, and treated as discretizations of continuous functions. From that, we devise an appropriate attention mechanism that operates over triangle meshes through standard FEM discretization of the resulting integrals of the above functions. Surprisingly, as far as we know, this straightforward approach has not been utilized for learning over meshes. Experiments show our method exceeds current state of the art, including both mesh-based architectures as well as point cloud transformers. Namely, we show significant improvements on several common benchmarks and tasks -- predicting canonical high-frequency signals; predicting deformations; computing dense correspondences, both between full shapes and partial ones; and predicting feature descriptors.
Deep neural networks on manifold-valued representations have attracted growing interest, but many basic components remain tied to specific manifolds, rely on Euclidean approximations, or require costly and numerically fragile geometric operations. This thesis develops a unified framework for Riemannian deep learning from three complementary perspectives: reusable neural modules, manifold-specific network architectures, and the design of underlying geometries. It generalizes batch normalization from Euclidean spaces and individual manifolds to broad classes of Lie groups and gyrogroups, and extends multinomial logistic regression from Euclidean space to SPD manifolds and then to general Riemannian manifolds. It further develops neural networks for several important geometric representations, including an unconstrained model of hyperbolic space, Busemann-based hyperbolic learning, and full-rank correlation matrices. Finally, it introduces adaptive and computationally efficient Riemannian metrics on SPD manifolds, including learnable Log-Euclidean geometries and fast, stable Cholesky-based geometries. The proposed methods are supported by theoretical analysis and validated through numerical experiments and applications in vision, signal processing, graph learning, and genomics.
The traditional "one drug, one target" paradigm of structure-based drug design (SBDD) frequently proves inadequate for treating multifactorial diseases such as cancer and neurodegenerative disorders, owing to compensatory signaling pathways and the emergence of drug resistance. While polypharmacology offers a synergistic therapeutic strategy, the rational design of ligands capable of simultaneously satisfying the geometric constraints imposed by multiple targets remains a major computational bottleneck. This review positions geometric deep learning (GDL) as a powerful integrative approach to overcome these limitations. We systematically survey GDL architectures ranging from invariant graph neural networks to SE(3)-equivariant diffusion models that harness non-Euclidean molecular data to capture intrinsic three-dimensional (3D) structural interdependencies. We critically analyze GDL applications across three core dimensions, including the characterization of shared binding pockets via geometric embeddings, multi-target bioactivity prediction through heterogeneous graph fusion, and de novo generation of dual-target ligands. Particular emphasis is placed on emerging structure-conditioned generative algorithms that integrate diffusion models with reinforcement learning to autonomously resolve complex geometric conflicts between competing binding sites. Furthermore, we evaluate the pivotal role of multimodal omics integration and specialized geometric benchmarking infrastructures in validating these models. By synthesizing these methodological advances, this review elucidates the paradigm shift in drug discovery from serendipitous exploration to rational, structure-driven polypharmacological molecular engineering, thereby providing a clear, structured guide for navigating the complexities of next-generation therapeutics.
Understanding the geometric structure of pre-trained language model embeddings matters for interpretability and safety. We ask whether sentence-level classification signal lives in the Riemannian geometry of contextual token embeddings, and probe it by extracting per-token pullback metrics from a learned encoder's analytical Jacobian and aggregating them with the Fréchet mean on the symmetric positive definite (SPD) manifold; we call this procedure Riemannian Mean Pooling (RMP). Across three datasets with non-trivial linguistic structure (CoLA, CREAK, RTE), RMP outperforms Euclidean mean pooling, while on FEVER-Symmetric, a benchmark constructed to remove annotation-driven lexical artifacts, the method correctly stays at chance. Ablations show that a randomly initialised encoder combined with Fréchet aggregation already beats Euclidean pooling on two of the three signal-bearing datasets, localising the source of the gain to the geometric aggregation rather than to learned manifold structure; the trained encoder contributes additional signal specifically on CREAK, the most knowledge-heavy of the three signal-bearing datasets.
Eli N. Weinstein, David M. Bleistat.ML cs.LG q-bio.BM
Scientists often seek to draw causal inferences from structured data that is not independently and identically distributed, such as spatial data, network data, or molecular data. We develop geometric causal models (GCMs), a framework for causal inference from dependent data that exploits underlying symmetries of the data generating process. For example, in spatial data, we consider processes that are symmetric under translations, or in graph data, symmetric under permutations of the nodes. We show how symmetries, formalized with group theory, can enable causal identification and estimation. We deploy ergodic theory for amenable groups to establish identification, and combine geometric deep learning with scalable Bayesian inference for estimation. We recover i.i.d. causal models and do-calculus when the data is a sequence and the symmetry is permutation equivariance, and find novel types of causal models when we use alternate structures and symmetries. As an example, we construct a causal model that satisfies the symmetries of DNA. This GCM enables new estimators for the effects of genetic variation, combining deep functional genomics models to describe outcomes and DNA language models to describe propensities. We illustrate on semisynthetic data.
Symmetry is everywhere in nature and society. Geometric deep learning builds architectures respecting group symmetries, whereas topological deep learning organizes computation through cells, incidence relations, and local-to-global structure. In this paper, we extend geometric deep learning beyond simple group actions and unify it with topological deep learning. Specifically, we develop order-equivariant neural networks (OENN), which generalize standard graph message passing and sheaf neural networks via the theory of equivariant vector bundles over face posets (or face categories). We (i) characterize all linear order-equivariant maps, (ii) build OENN layers, and (iii) prove universal approximation theorems (UATs) for continuous order-equivariant maps, which are new results even when restricted to sheaf neural networks. We illustrate the framework on graph and sheaf models. Our results can also be seen as extending the known UAT for graph neural networks to a more general setting that subsumes sheaf neural networks as well. In the appendix, we show that OENN can be connected, via the action groupoid Grothendieck construction, to CENN (category-equivariant neural network), which gives the categorical general form of equivariant neural networks, allowing us to leverage categorical symmetry in data and extending geometric deep learning from groups of symmetries to categories of transformations.
The rapid scaling of over-parameterized machine learning architectures, particularly LLMs, raises a profound crisis: do these systems exhibit genuine intelligence, or are they merely sophisticated statistical pattern matchers? Classical flat Euclidean statistics cannot differentiate continuous interpolation from the autonomous discovery of novel causal laws. To resolve this, we introduce Statistically Meaningful Geometry (SMG), a framework modeling over-parameterized learning systems as infinite-dimensional non-parametric Orlicz fiber bundles. We prove that under persistent out-of-distribution (OOD) stimuli governed by unmodeled causal mechanisms, continuous optimization fails. Unmodeled variance is rejected by the visible horizontal base manifold, leaking into the unobservable vertical fiber space and generating an accumulation of Active Acausal Tension. Driven by the statistical manifold's non-linear curvature, this tension inevitably strikes a conjugate focal boundary ($T_{\text{crit}} = π^2 / K_{\text{max}}$), triggering localized volumetric collapse and a catastrophic matrix singularity ($[G_f]^{-1} \to \infty$). We demonstrate this geometric breakdown acts as the strict non-equilibrium trigger for a Gauge Symmetry Break (GSB). The system purges hidden tension from unobservable gauge redundancies, spontaneously crystallizing a new, mathematically independent horizontal coordinate axis. This non-parametric phase transition registers as a discrete $+1.0$ integer step-jump in observable Structural G-Entropy. By decoupling parameter charts and subjecting emergent axes to a Minimal Energy Path Criterion and a Causal Invariance Filter, we distinguish genuine discovery from malignant hallucinations. Ultimately, SMG provides a parameter-free, falsifiable dashboard to mathematically certify true intelligence, transforming AI for Science into an engine of autonomous paradigm shifts.
We place the attention token on the group: a token is an element $g_i$ of a matrix Lie group $G$ -- a bare transformation, with no feature payload and no external action $ρ(g)$ carrying it. To our knowledge this is the first attention construction whose tokens are bare matrix Lie group elements: their score is the closed-form algebra norm of the relative pose rather than a learned kernel, and it reaches the affine full-frame groups that every irrep- or surjective-exp-based method must exclude. We call it Lie-Algebra Attention. Once tokens are group elements, the rest follows with none of the usual representation-theoretic machinery. The relative geometry of a pair is canonical, $g_i^{-1} g_j$, so the pairwise invariant $w_{ij} = \log(g_i^{-1} g_j)$ is intrinsic rather than designed; equivariance under the diagonal $G$-action is tautological, and the cocycle condition holds automatically. The attention score is the negative squared algebra norm, $s_{ij} = -\|\log(g_i^{-1} g_j)\|_λ^2/τ$: the canonical proximity kernel under a block-weighted Frobenius inner product, with no irreducible representations, spherical harmonics, Clebsch-Gordan products, or learned kernel. The construction applies to any matrix Lie group on a chosen logarithm chart containing the relative poses, including the non-compact non-abelian affine groups with scale and shear that no vector-token attention method reaches: neither the irrep tradition nor surjective-exp methods. Three sequence-completion experiments, on SE(2), SO(3), and Aff(2), bear this out: the closed-form score matches a learned MLP kernel on the same invariant and outperforms it on SE(2), using 50 to 80x fewer score parameters, while a vector-token baseline breaks invariance by five to twelve orders of magnitude.
T. Mitchell Roddenberry, Richard G. Baraniukcs.LG eess.SP math.DG stat.ML
Graph neural network architectures based on the graph Laplacian approximate the Laplace-Beltrami operator, thus limiting their application to isotropic operators. As a nonlinear alternative to the Laplace-Beltrami operator, we consider estimates of the Finsler Laplacian on point clouds sampled from a manifold. We prove that these discrete estimates converge to the true operator on the manifold as the number of point samples grows. Moreover, we show that this operator can be expressed as a graph neural network layer, which we use to define a family of Finslerian graph neural networks constrained to express Finsler geometry. We show that Finslerian graph neural networks recover the geometry underlying nonlinear diffusion equations in practice.
Peng-Fei Sun, Chuan-Xian Ren, Hong Yancs.LG q-bio.BM
Accurate prediction of protein-ligand binding affinity is essential for structure-based drug discovery. Recent geometric deep learning methods have achieved promising performance by representing protein-ligand complexes as three-dimensional graphs. However, most existing approaches mainly rely on static interaction geometry from a single bound conformation, while neglecting molecular flexibility and binding-induced conformational changes. To address this limitation, we propose a curvature-informed potential energy surface (CPES) graph neural network for protein-ligand binding affinity prediction, which incorporates physics-informed curvature representations to model conformational flexibility. CPES first derives curvature spectral descriptors from the Hessian of the potential energy surface evaluated at equilibrium configurations, whose eigenvalues define the local principal curvatures of the potential energy surface. It then uses spectral cross-attention to compare the unbound ligand and protein with the bound complex, thereby capturing binding-induced changes in conformational dynamics. In parallel, hierarchical protein-ligand interaction representations are learned from static structural features through geometry-aware message passing, soft clustering, and bidirectional cross-attention. Finally, CPES fuses the curvature-informed dynamic representations with static interaction representations for affinity regression. Extensive evaluations on multiple benchmark datasets demonstrate that CPES achieves improved predictive performance and offers physical interpretability.
Shuai Li, Chuan-Xian Ren, Yuhao Li +4cs.LG q-bio.BM
Protein-ligand binding affinity (PLA) prediction is critical in drug discovery. Despite the notable advancements in machine learning-based approaches, existing methods struggle to jointly characterize local geometric organization and globally coordinated cross-molecular interactions, limiting their ability to model complex binding mechanisms. Here, we propose RicciBind, a geometric representation framework that integrates curvature-guided hierarchical structure learning with optimal transport (OT)-based cross-domain alignment to model molecular interactions. Specifically, RicciBind leverages Ricci curvature to capture local interaction tightness within molecular structures, enhancing structural awareness and organizing atomic interactions into curvature-aware hierarchical representations. An OT-based cluster matching mechanism then aligns protein and ligand clusters across heterogeneous domains under geometric constraints, enabling globally consistent correspondences and revealing higher-order interaction patterns beyond local neighborhoods. By coupling curvature-guided structure encoding with OT-driven cross-domain alignment, RicciBind effectively models complex interaction semantics and substantially improves both the accuracy and interpretability of binding affinity prediction. Extensive experiments demonstrate that RicciBind achieved superior predictive performance and generalization across PLA benchmarks and virtual screening tasks. Ablation studies further confirmed the essential role of Ricci curvature in enhancing molecular interaction representations.
Many important observables in physics and geometry are cup products of cochains. The adjusted cup product neural layer has been introduced in this paper. It is a neural primitive that hard wires the cup product with an adjustment term from higher gauge theory. This creates a readout that is gauge invariant by design. Their main theoretical result shows that on a closed cycle the output relies entirely on the adjustment coefficient. Setting this coefficient to zero removes the output completely regardless of other parameters. Thus the adjustment is the only source of gauge invariant signal. They prove this observable is a nonzero quadratic form and is exactly invariant under one and two gauge transformations.
We introduce Kuramoto attention, a self-attention layer in which each hidden coordinate is an angle. The layer scores tokens by gated cosine similarity, attends over previous phase states, and updates each token by the tangent component of the attention-weighted circular mean. Because the values are the raw phase states, this update is exactly the Kuramoto coupling term $\sum_u A_{t,u}\sin(θ_u-θ_t)$, with the attention matrix acting as an adaptive, content-dependent coupling kernel. Equivalently, the gated score is a learned metric on the torus that selects which tokens couple, and the update pulls each token toward the circular mean of the tokens it selects, tightening their phase agreement. The same two ingredients, an invariant similarity score and an on-manifold mean, define such a layer on any compact group; the torus is the abelian case, where both are closed-form. The softmax weights solve an entropy-regularized phase-retrieval problem, and rotary position enters as a position-dependent phase drift in the score. On enwiki8 character-level language modeling, the layer trains as a functional language model whose bits-per-character stays close to a strong matched RoPE+SwiGLU transformer: within $0.02$ BPC at one million parameters ($1.637\pm0.010$ versus $1.616\pm0.004$) and level on the median at five million ($1.448$ versus $1.452$ over five seeds) with the transformer ahead on the mean ($1.468$ versus $1.456$). These experiments establish that the constrained geometric structure is a viable language model at this scale; the structure itself, and its synchronization reading, is the contribution. Ablations isolate the load-bearing components, and the result gives a compact bridge between self-attention and phase synchronization.
Nello Blaser, Odin Hoff Gardaa, Lars M. Salbu +2cs.LG math.AT
The Euler Characteristic Curve (ECC) records the Euler characteristic of a linearly embedded cell complex as a function of filtration height in a given direction, and the Euler Characteristic Transform (ECT) is the injective shape descriptor obtained by collecting ECCs over many directions. How the ECT is encoded for a neural network is itself an inductive bias, conventionally fixed by discretizing each ECC. We introduce a continuous encoding: for each direction and each vertex it records the net Euler-characteristic change attributed to that vertex, producing a per-direction token sequence that a small transformer maps to a feature vector. We separate the resulting pipeline into two stages on orthogonal axes: an ECC encoder that acts within each direction, mapping its curve to a fixed-length vector, and an ECT representation that acts across directions, aggregating the per-direction vectors into one. We study six ECT representation architectures spanning a range of inductive biases, from a structure-agnostic feedforward baseline to convolutional and complex-valued models that preserve equivariance under planar rotations. Across six classification benchmarks covering point clouds, graphs, cubical complexes, and meshes, the continuous encoding improves accuracy on five of six datasets, and control experiments attribute the gain to the tokenization itself rather than to the added transformer capacity. The representation architecture matters less than the encoding, and the payoff from its inductive biases depends on the encoding: a feedforward network performs best under continuous encoding but is less robust under discretization than convolutional architectures.
Md Sadek Hossain Asif, Tanzila Khan, Md. Mosaddek Khancs.LG cs.AI
We introduce Temporal Sheaf Neural Networks (TSNN), a temporal link prediction framework that equips each node with a time-varying orthogonal frame and compares node states only after explicit transport between local coordinate systems. In contrast to existing continuous-time graph models that operate in a shared global embedding space, TSNN models node-specific and evolving interaction semantics through dynamic local frames. The model parameterizes per-node frames via efficient low-rank Householder products, preserves stored hidden states exactly under frame updates, and uses a geometric-residual decoder that anchors predictions on transported distances while learning residual corrections. All computations are strictly causal and use only the pre-event history. We show that the symmetric degree-normalized sheaf Laplacian is orthogonally similar to the symmetric normalized graph Laplacian, with the random-walk normalized form similar in the corresponding degree metric; the full-active, feature-scaled diffusion used by TSNN is exactly a metric-gradient step on the combinatorial sheaf Dirichlet energy, with a degree-free monotone-descent and non-expansiveness guarantee. Frame drift perturbs updates only linearly. Across TGB v2 link-prediction and temporal-heterogeneous leaderboards, together with the DGB benchmark suite, TSNN matches or surpasses the strongest prior methods on most benchmarks, with the largest improvements on graphs exhibiting strong node-role heterogeneity. Ablations confirm the distinct benefit of dynamic frames, orthogonal transport, and geometric-residual decoding.
Traditional UV unwrapping relies on direct optimization of geometric distortion energies and can fail through invalid initialization, local minima, or topological foldovers. We recast fixed-chart UV unwrapping as continuous neural reparameterization: an untrained SIREN maps per-vertex mesh features to UV coordinates, and its weights are optimized for a geometric objective. The practical contribution is a robust chart-solver recipe, combining Laplace--Beltrami spectral inputs, Tutte residual warm-up, a $C^2$ determinant extension, an injectivity barrier, and validity-checked retry/fallback routing, rather than a claim that any single component guarantees validity or that recutting methods should be replaced. NTK--LBO diagnostics show that spectral conditioning changes update geometry, especially at initialization and mid-rank subspaces, but does not by itself predict chart success. On compact pre-cut charts and a 47-chart stratified Thingi10K/xatlas-cut benchmark, the neural solver produces zero flips on all compact charts and 42/47 valid zero-flip stratified solves. BFF and OptCuts comparisons sharpen the scope: recutting can be faster and lower-distortion when allowed, while the neural solver targets supplied-chart validity and validation-first atlas construction. On Amara Spatial generated meshes, the full atlas construction path gives packed-atlas coverage on a 25-asset set and 1000/1000 strict locally valid atlases with zero UV flips in a large-scale Rust atlas run after fallback routing.
Mansoor Ahmed, Huirong Chai, Haoxin Wang +2q-bio.QM cs.LG
Antibodies neutralize foreign antigens by binding to specific surface regions called epitopes. Computational epitope prediction is critical for understanding immune recognition and guiding antibody engineering. However, existing methods face three fundamental challenges: antibody-aware models encode each chain independently and combine them only at a late stage, failing to capture co-dependent structural features that define binding interfaces, whereas severe class imbalance and scarcity of known antibody-antigen complexes render standard training objectives ineffective. We propose EpiFormer, a general encoder-decoder framework that addresses these challenges jointly. Our key design principle is interleaved cross-attention within GNN encoding layers, enabling bidirectional antigen-antibody information flow throughout representation learning rather than only at the output. This early-fusion principle is backbone-agnostic, providing consistent gains across GNN architectures from simple GCNs to equivariant models. We further show that sparsity-aware objectives are effective when paired with early-fusion architectures for the epitope prediction task. EpiFormer improves over the previous best method by over 40% in F1 score on standard benchmarks, demonstrating generalizability and cross-dataset transferability. Notably, EpiFormer discovers known biological principles as emergent behaviors of end-to-end training, where the learned cross-attention gates favor antigen-to-antibody information flow, consistent with the asymmetric roles of the two chains at the binding interface, and the model's preference for geometric over evolutionary features aligns with the established finding that epitope residues are not evolutionarily conserved. The source code is available at: https://github.com/mansoor181/epiformer.git
We introduce Lie groupoid equivariant neural networks as a specialization of recently proposed topological category-equivariant neural networks to the differentiable setting. Lie groupoid equivariant neural networks are composed from Lie groupoid lifting convolutions and Lie groupoid convolution layers, and we show how for suitable Lie groupoids they are equivalent to certain Lie algebroid-equivariant neural networks. We additionally describe groupoid invariant global pooling as a generalization of group invariant global pooling. Furthermore, we show that each of the aforementioned layers is a special case of recently introduced admissible category-equivariant layers by demonstrating that they define continuous natural transformations between continuous feature functors.
Deep residual architectures are modeled as products of near-identity Jacobians. This paper proves deterministic quotient-geometric estimates for singular spectra of Frobenius-normalized layer factors, emphasizing a normalized top-radial Cartan coordinate and fitted power-law chart. Full-rank factors are mapped from $\mathrm{GL}(d)$ to the positive cone by $A\mapsto A^\top A$, then to ordered eigenvalue data. Under Frobenius normalization, exact power-law spectra form a trace-normalized Cartan orbit. This orbit is a Gibbs family on ranks, a Fisher information line, and a Bures--Wasserstein curve with line element $d/4$ times Fisher information. The main rigidity theorem is a slack-aware margin inequality: interface radial amplitude, non-backtracking slack, and signed residual variation control displacement of the fitted Cartan coordinate. In the exact-chart zero-slack case, a depth-$L$ budget gives exponent drift of order $(\log M)/L$; generally, slack and residual increments augment the bound. We separate scalar top-radial from full-Cartan spectral control, which also needs Bures/Hellinger residual variation. We prove approximate-power-law and metric-chart versions, converse lower bounds, Fisher--KL/Bures action estimates, and near-identity expansions for normalized residual chains. Near-identity results verify transport budgets; chart quality remains measurable. Effective rank is a spectral-energy quantile, giving finite-width power-law tail bounds and robust rank-window transition estimates. Empirical static-weight exponent profiles serve as diagnostics; full verification also requires interface budgets, slacks, and residuals for the same operator chain.