Feature Alignment

Equivariant graph neural network (GNN) methods for antibody complementarity-determining region (CDR) design achieve the highest sequence recovery but suffer from severe vocabulary collapse. The current best GNN methods over-predict very few amino acids, such as tyrosine and glycine, while ignoring functionally important residues. We trace this failure to GNN encoders learning amino acid distributions de novo from limited structural data, discarding substitution patterns encoded in evolutionary databases. To resolve this, we propose EvoStruct, which bridges a frozen protein language model (PLM) with 3D structural context from an E(3)-equivariant GNN via a cross-attention adapter. Unlike prior PLM-structure adapters for general protein design, EvoStruct targets the vocabulary collapse problem specific to CDR design through progressive PLM unfreezing and R-Drop consistency regularization. On the CHIMERA-Bench dataset, EvoStruct achieves the highest amino acid recovery and lowest perplexity among several antibody design methods, improving sequence recovery by 16% and reducing perplexity by 43% relative to the best GNN baselines, while recovering 2.3x greater amino acid diversity and the highest binding-pair correlation with ground truth.

Direct Preference Optimization (DPO) has emerged as a popular alternative to Reinforcement Learning from Human Feedback (RLHF), offering theoretical equivalence with simpler implementation. We prove this equivalence is conditional rather than universal, depending on an implicit assumption frequently violated in practice: the RLHF-optimal policy must prefer human-preferred responses. When this assumption fails, DPO optimizes relative advantage over the reference policy rather than absolute alignment with human preferences, leading to pathological convergence where policies decrease DPO loss while preferring dispreferred responses. We characterize when this assumption is violated, show the existence of an undesirable solution space, and prove that DPO and RLHF optimize fundamentally different objectives in such cases. To address this, we introduce Constrained Preference Optimization (CPO), augmenting RLHF with constraints for provable alignment. We further provide a geometric interpretation through soft margin ranking, revealing that DPO implements margin ranking with potentially negative targets. Our theoretical analysis establishes when DPOs' guarantees hold and provides solutions preserving simplicity with provable alignment. Comprehensive experiments on standard benchmarks demonstrate that CPO achieves state-of-the-art performance. Code is available at: https://github.com/visitworld123/CPO.

Automatic speech recognition replaces typing only when correction costs less than manual entry - a threshold determined by error types, not counts: fixing a misrecognized domain term costs far more than inserting a comma. Word error rate (WER) fails on two fronts: it collapses distinct error categories into a single scalar, and it structurally penalizes agglutinative languages where valid sandhi merges inflate scores. We introduce SCRIBE, a diagnostic framework offering categorical error decomposition into lexical, punctuation, numeral, and domain-entity rates via sandhi-tolerant alignment with domain vocabulary injection. Human validation confirms SCRIBE aligns with expert judgment where WER does not. We release SCRIBE, an LLM curation pipeline, benchmarks, and open-weight rich transcription models for Hindi, Malayalam, and Kannada.

Audio-to-score alignment is a long-standing challenge in music information retrieval and arguably the most widely applicable alignment task for music research. Alignment algorithms match two versions of a piece of music, and for this to work these versions need to be in comparable formats. Audio-to-audio alignment matches audio features; when matching audio files to scores, they must either synthesize the score or derive audio-like features by means of piano rolls or similar feature sequences. Symbolic alignment, by contrast, matches symbolically encoded notes; in an audio-to-score scenario these would be obtained by a transcription of the audio file. In this article, we present an algorithm that bridges audio-like and symbol-level features directly. Sequential audio features encoding onset and spectral activation are matched to score positions by a bespoke dynamic programming-based matching algorithm derived from symbolic alignment methods. The resulting method is both precise - surpassing widely used audio-to-audio approaches based on synthesized scores -, and remains flexible in its digital signal processing components, i.e., the method is adaptable to diverse timbral characteristics without requiring a separate transcription model. Furthermore it inherits some of the symbolic alignment runtime advantages with an algorithmic complexity that is at worst linear in the length of the (typically short) symbolic score and (typically long) audio feature sequence. In the following sections, we provide a detailed algorithm description and evaluate its alignment quality on a large-scale dataset of solo piano recordings.

A critical challenge in single-cell RNA sequencing (scRNA-seq) integration is resolving the tension between eliminating batch effects and maintaining biological fidelity. While recent evidence indicates that batch effects manifest heterogeneously across genes, most existing methods process the transcriptome uniformly, frequently resulting in over-correction and loss of subtle biological signals. To address this, we present scHelix, a dataset-adaptive framework that fundamentally changes how features are processed by explicitly partitioning genes into domain-invariant Anchors and domain-sensitive Variants at the input level. scHelix utilizes a dual-stream sparse diffusion encoder equipped with stop-gradient graph caching to efficiently learn multi-scale structural representations. The core of our approach is a novel asymmetric Align-Refine-Fuse protocol: the unstable Variant stream is first aligned to the robust topology of the Anchor stream, followed by a conservative refinement phase where the Anchor stream absorbs denoised details via bounded residual gating. This divide-and-conquer architecture prevents shortcut learning and ensures robust batch removal without compromising the integrity of biological clusters. Extensive benchmarking demonstrates that scHelix outperforms state-of-the-art methods.

Expanding Large Language Models~(LLMs) to new languages is a costly endeavor, demanding extensive Continued Pre-Training~(CPT) and data-intensive alignment. While recent data-free merging techniques attempt to bypass alignment by fusing a multilingual CPT-enhanced model with its instruct counterpart, they are plagued by a critical trade-off: mitigating parameter conflicts to preserve original abilities inevitably dilutes new language acquisition, and vice-versa. To resolve this conflict, we introduce \method, which upcycles a dense model into a Mixture-of-Experts~(MoE) architecture, allocating different experts to different languages. Alignment ability is then transferred by grafting a MoE-expanded parameter delta~($Δ_{\text{post}}$) to the CPT-enhanced base model, bypassing the complex alignment phase. Experiments demonstrate \method's superiority even against baselines with similar FLOPs or number of parameters; it improves performance on expanded languages while effectively preserving original capabilities. We further show our approach is highly applicable across different models and Post-training deltas.

Predicting spatial gene expression from routine H&E enables large-scale molecular profiling, yet current models treat this as isolated pointwise tasks, thereby overlooking essential biological structures like gene coordination and spatial distribution. To preserve these relationships, we introduce \textbf{FLAG}, a diffusion-based framework that redefines this task as structured distribution modeling. At the same time, we identify the critical \textbf{Gene Dimension Curse}, where joint modeling gene expression and their spatial interactions fail in high-dimensional spaces, and FLAG solves this challenge by integrating a spatial graph encoder for topological consistency and utilizing Gene Foundation Model (GFM) alignment for gene-gene fidelity in the generation process. To rigorously assess model performance, we propose a set of novel structural evaluation metrics, including Gene Structural Correlation (\textbf{GSC}) and Spatial Structural Correlation (\textbf{SSC}). Our experiments demonstrate that FLAG is highly competitive in traditional accuracy (PCC/MSE) while achieving significantly enhanced structural fidelity in capturing both gene-gene and gene-spatial relationships. The code is available at https://github.com/darkflash03/FLAG.

EEG-based visual decoding aims to establish a mapping between neural signals and visual semantics. However, it remains constrained by the dual challenges of severe information granularity mismatch and the low signal-to-noise ratio (SNR) of EEG signals. Existing approaches typically treat static visual features, ignoring the dynamic selectivity of human vision and the frequency specificity of neural oscillations. To bridge this gap, we propose CAIA, a Cognitive-guided Adaptive blurring with Information-Constrained Alignment framework for Neural-Visual decoding. On the visual side, it simulates selective attention to adaptively reduce redundancy. Meanwhile, on the EEG side, it leverages neural oscillation priors and the information bottleneck mechanism to enhance SNR. Specifically, we devise a cognitive-dynamics-based adaptive blurring mechanism that dynamically integrates center-biased and saliency-guided visual cues via cross-modal attention. Furthermore, we introduce a distribution-aware boundary calibration loss to robustly rectify alignment bias caused by outlier samples. Moreover, a cognitively-guided information-screening method is proposed to select task-relevant EEG oscillations. Extensive experiments demonstrate that CAIA improves both subject-dependent and subject-independent average Top-1 and Top-5 accuracy in zero-shot brain-to-image retrieval, significantly outperforming prior methods. Our work validates that optimizing visual information density to match neural granularity offers a more interpretable and robust pathway for neural decoding.

Periodic crystals repeatedly instantiate similar local coordination motifs across translated cells and chemically related structures, but current equivariant atomistic models usually encode these patterns only implicitly in dense edge features. We introduce PaMM, a periodic motif memory that augments the UMA eSCN-MD edge encoder with explicit pair and triplet lookup features. Pair motifs are keyed by $(Z_j, Z_i, b_r)$ and triplet motifs by $(Z_j, Z_i, Z_k, b_θ)$, hashed into fixed-size tables and fused with the baseline edge representation through lightweight gate-only and affine-equipped variants. We evaluate PaMM in a matched UMA-S OMAT setting and focus on a narrow question: whether explicit motif memory helps at a fixed intermediate training budget. At the 10k-step checkpoint, both PaMM variants improve over the plain baseline; gate-only gives the best energy MAE, while the affine-equipped variant gives the best force MAE. A matched 20k follow-up keeps the same operating-point picture. Aligned controls show that the gain weakens for pair-only, triplet-only, random-bucket, and parameter-matched MLP alternatives, suggesting that the benefit is tied to structured pair/triplet organization rather than generic added capacity. A within-OMAT24 source-family evaluation also shows small but consistent gains across held-out generation families. We therefore make a focused claim: in the studied UMA-S + OMAT regime, explicit pair/ triplet motif memory is a useful inductive bias for periodic atomistic modeling. We do not claim broad cross-dataset transfer, a uniquely preferred fusion variant, or strong scientific interpretability beyond a more inspectable local-structure interface.

Large language models (LLMs) often produce answers with high certainty even when they are incorrect, making reliable confidence estimation essential for deployment in real-world scenarios. Verbalized confidence, where models explicitly state their confidence in natural language, provides a flexible and user-facing uncertainty signal that can be applied even when token logits are unavailable. However, existing verbalized-confidence methods often optimize answer generation and confidence generation jointly, which can cause confidence-alignment objectives to interfere with answer accuracy. In this work, we propose a decoupled and order-aware framework for verbalized confidence calibration. Our method first generates an answer and then estimates confidence conditioned on the fixed question--answer pair, allowing confidence optimization without directly perturbing the answer-generation process. To align confidence with correctness likelihood, we construct a sampling-based surrogate from multiple model completions and optimize rank-based reinforcement learning objectives that encourage responses with higher estimated correctness likelihood to receive higher verbalized confidence. Experiments on reasoning and knowledge-intensive benchmarks show that our method improves calibration and failure prediction performance while largely preserving answer accuracy. These results demonstrate that verbalized confidence can be more reliably aligned by decoupling confidence estimation from answer generation and optimizing the relative ordering of confidence across responses.

In this work, we introduce a Tropical Axial Attention neural reasoning architecture that replaces vanilla softmax dot-product attention with max-plus operators, inducing a piecewise-linear structure aligned with dynamic programming formulations. From multi-species sequence alignments, our model learns all possible pairwise distances and is trained using a combination of $\ell_1$ and tropical symmetric distance metric losses with an ultrametric violation penalty. We leverage the well known isomorphic relationship between the space of all phylogenetic trees with $n$ species and tropical Grassmannian to show that tropical attention provides a natural geometric framework for phylogenetic inference. On empirical $DS1-DS11$ alignments, where true trees are unknown, the tropical model produces distance matrices that are substantially closer to their BME-induced tree metrics than the baseline models. These results suggest that tropical attention is a useful geometric inductive bias for neural phylogenetic inference, especially under distribution shift and when tree-metric consistency is important.

The design of RNA molecules that interact with specific proteins is a critical challenge in experimental and computational biology. Despite recent progress in natural language modeling and deep learning-based protein design, there remains significant room to improve the frequency of successful interactions and the authenticity of generated sequences for functional applications. In this work, we frame conditional RNA sequence generation as a multi-stage alignment problem, introducing Moirain: a suite of models optimized via multimodal supervised fine-tuning (SFT) and Direct Preference Optimization (DPO). Our approach begins with large-scale pretraining on diverse RNA corpora to capture the fundamental grammars of sequence plausibility. To achieve target-specific generation, we employ a multimodal SFT architecture that conditions RNA synthesis on protein structural and sequential features. Finally, we leverage DPO to refine the model using synthetic interaction data: taking advantage of DPO's unique ability to navigate non-aligned preference spaces, we improve functional fitness without collapsing the learned natural distribution. Extensive evaluation of the Moirain series (Moirain-Base, -Multi, and -DPO) demonstrates that our framework consistently produces novel, diverse, and biologically plausible RNA sequences with superior binding affinities compared to existing baselines.

Federated learning usually aggregates client updates using dataset size or gradient-level criteria, while overlooking internal signals about how each client model is organizing its input space during training. We introduce FedOUI, a simple aggregation rule based on the Overfitting-Underfitting Indicator (OUI), an activation-based and label-free metric. Each participating client sends its local update together with a OUI value computed on a fixed probe batch, and the server estimates the round-wise OUI distribution to assign lower weights to structurally atypical clients through a smooth reweighting rule. We evaluate FedOUI on CIFAR-10 under strong non-IID partitioning and noisy-client conditions, comparing it with FedAvg, FedProx, and a gradient-alignment baseline. The clearest gains appear under strong heterogeneity, where OUI-based weighting improves aggregation quality while remaining lightweight and interpretable. These results show that internal activation structure can provide useful information for federated aggregation beyond client size and gradient geometry.

We present Open Ontologies, an open-source ontology engineering system implemented in Rust that integrates LLM-driven construction with formal OWL reasoning and ontology alignment via the Model Context Protocol. Our primary finding is that stable 1-to-1 matching is the dominant factor in ontology alignment quality: on the OAEI Anatomy track, it achieves F1 = 0.832 (P = 0.963, R = 0.733), competitive with state-of-the-art systems and exceeding all in precision. Ablation across five weight configurations shows that signal weights are irrelevant when stable matching is applied (F1 varies by less than 0.004), while removing stable matching drops F1 to 0.728. On the Conference track, the same method achieves F1 = 0.438. On tool-augmented ontology interaction, we find a surprising result: an LLM reading a raw OWL file (F1 = 0.323) performs worse than the same LLM with no file at all (F1 = 0.431), while structured MCP tool access achieves F1 = 0.717. This demonstrates that tool structure provides a qualitatively different mode of access that the LLM cannot replicate by reading raw syntax. The system ships as a single binary under the MIT licence.

Scene graphs (SGs) represent objects and their relationships as structured graphs, enabling applications in image generation, robotics, and 3D understanding. Recent work suggests that conditioning image generation on scene graphs improves compositional fidelity compared to text-only prompting. However, since users typically provide text rather than structured graphs, a key challenge is to generate scene graphs from natural language. Prior work on discrete diffusion has demonstrated success in generating generic graphs such as molecules and circuits, but fails to account for the hierarchical structure and strong dependencies between objects, edges, and relations in scene graphs. We address this limitation by introducing a dependency-aware, hierarchically constrained discrete diffusion model for scene graph generation. Our approach decouples structure and semantics across the forward and reverse processes, enabling the model to capture conditional dependencies. At inference time, we perform training-free conditioning to sample text-aligned scene graphs. We evaluate our method on standard SG benchmarks and demonstrate improvements over both continuous and discrete graph generation baselines across graph and layout metrics. When fed to downstream image generation, our approach yields improved compositional alignment compared to text-to-image models, particularly in multi-object scenarios.

Zero-shot 3D anomaly detection aims to identify anomalies without access to training data from target categories. However, existing methods mainly rely on projecting 3D observations into multi-view representations that primarily capture geometric cues rather than realistic visual semantics and process them with vision encoders pretrained on RGB data, leading to a significant domain gap between the encoder and the projected representations. To address this issue, we propose Align3D-AD, a unified two-stage framework that leverages the RGB modality from auxiliary categories as cross-modal guidance for zero-shot 3D anomaly detection. First, we introduce a cross-modal feature alignment paradigm that maps rendering features into the RGB semantic space. Unlike prior works that implicitly rely on pretrained encoders, our method enables direct semantic transfer from RGB observations. A semantic consistency reweighting strategy is further introduced to refine feature alignment by reweighting local regions according to holistic semantic consistency. Second, we propose a modality-aware prompt learning framework with dual-prompt contrastive alignment. By assigning independent prompts to RGB-aligned and rendering features, our method captures complementary semantics across modalities, while the contrastive alignment further enhances prompt representations to improve discriminability. Extensive experiments on MVTec3D-AD, Eyecandies, and Real3D-AD demonstrate that Align3D-AD consistently outperforms existing zero-shot methods under both one-vs-rest and cross-dataset settings, highlighting its generalization capability and robustness. Code and the dataset will be made available once our paper is accepted.

Text-to-image generation has advanced rapidly with diffusion models, progressing from CLIP and T5 conditioning to unified systems where a single LLM backbone handles both visual understanding and generation. Despite the architectural unification, these systems frequently fail to faithfully align complex prompts during synthesis, even though they remain highly accurate at verifying whether an image satisfies those same prompts. We formalize this as the \emph{understanding-generation gap} and propose UniReasoner, a framework that leverages the LLM as a universal reasoner to convert its understanding strength into direct generation guidance. Given a prompt, the LLM first produces a coarse visual draft composed of discrete vision tokens. It then performs a self-critique by evaluating the draft for prompt consistency, producing a grounded textual evaluation that pinpoints what needs to be corrected. Finally, a diffusion model is conditioned jointly on the prompt, the visual draft, and the evaluation, ensuring that generation is guided by explicit corrective signals. Each signal addresses a limitation of the other: the draft provides a concrete, scene-level anchor that reduces under-specification in text-only conditioning, while the evaluation turns verification into grounded, actionable constraints that correct omissions, hallucinations, and relational errors. Experiments show that UniReasoner improves compositional alignment and semantic faithfulness under the same diffusion backbone while maintaining image quality, demonstrating a practical way to exploit LLM reasoning to close the understanding-generation gap.

Ancestral sequence reconstruction (ASR) aims to infer extinct protein sequences at internal nodes of a phylogenetic tree. Classical ASR methods are typically based on continuous-time Markov substitution models, but they treat sites largely independently and handle insertions and deletions only weakly or not at all. We introduce a tree-conditioned edit-flow model for variable-length ASR. Given two descendant sequences and their branch distances to a shared ancestor, the model reconstructs the ancestor through paired bidirectional edit trajectories constrained to agree on a common ancestral state. On a benchmark of experimentally evolved sequences with only context-independent substitutions, the model does not match the accuracy of the best classical method, yet still achieves reasonable performance despite being trained on natural sequences that include insertions, deletions, and substitutions. On a benchmark of natural homologous sequences with abundant insertions and deletions, the model most accurately localizes inferred evolutionary change.

Activation-alignment measures such as Representational Similarity Analysis (RSA), Canonical Correlation Analysis (CCA), and Centered Kernel Alignment (CKA) are widely used to compare biological and artificial neural representations. Recent theoretical work interprets many of these methods as assessing agreement between optimal linear readouts over broad families of global tasks. However, agreement at the level of global readouts does not determine how a system uses local stimulus evidence. Specifically, representations may align in activation space yet differ in their sensitivity to small perturbations. To address this challenge, we introduce a complementary framework based on local decodable information, which focuses on a representation's ability, under noise, to discriminate small perturbations within a specified stimulus-coordinate subspace. Building on Fisher information and local representation geometry, we summarize each representation using the expected projected pullback/Fisher metric over that subspace. This formulation induces a second-moment family of local discrimination tasks, for which the resulting operator provides a minimal, complete dataset-level summary of expected discriminability. We compare these regularized signatures using a log-spectral distance on the manifold of symmetric positive definite (SPD) matrices, yielding the Spectral Riemannian Alignment Score (S-RAS) and a uniform multiplicative certificate over the corresponding family of lifted task values. Empirically, this framework enables the recovery of corresponding layers across independently trained artificial neural networks, supports transferable class-conditional probes, reveals controlled dissociations between standard and robust training, and uncovers stimulus-coordinate family effects across mouse visual cortex using the Allen Brain Observatory static gratings dataset.

Unified multimodal models (UMMs) integrate visual understanding and generation within a single framework. For text-to-image (T2I) tasks, this unified capability allows UMMs to refine outputs after their initial generation, potentially extending the performance upper bound. Current UMM-based refinement methods primarily follow a refinement-via-editing (RvE) paradigm, where UMMs produce editing instructions to modify misaligned regions while preserving aligned content. However, editing instructions often describe prompt-image misalignment only coarsely, leading to incomplete refinement. Moreover, pixel-level preservation, though necessary for editing, unnecessarily restricts the effective modification space for refinement. To address these limitations, we propose Refinement via Regeneration (RvR), a novel framework that reformulates refinement as conditional image regeneration rather than editing. Instead of relying on editing instructions and enforcing strict content preservation, RvR regenerates images conditioned on the target prompt and the semantic tokens of the initial image, enabling more complete semantic alignment with a larger modification space. Extensive experiments demonstrate the effectiveness of RvR, improving Geneval from 0.78 to 0.91, DPGBench from 84.02 to 87.21, and UniGenBench++ from 61.53 to 77.41.

Agent benchmarks remain largely English-centric, while their multilingual versions are often built with machine translation (MT) and limited post-editing. We argue that, for agentic tasks, this minimal workflow can easily break benchmark validity through query-answer misalignment or culturally off-target context. We propose a refined workflow for adapting English benchmarks into multiple languages with explicit functional alignment, cultural alignment, and difficulty calibration using both automated checks and human review. Using this workflow, we introduce GAIA-v2-LILT, a re-audited multilingual extension of GAIA covering five non-English languages. In experiments, our workflow improves agent success rates by up to 32.7% over minimally translated versions, bringing the closest audited setting to within 3.1% of English performance while substantial gaps remain in many other cases. This indicates that a substantial share of the multilingual performance gap is benchmark-induced measurement error, motivating task-level alignment when adapting English benchmarks across languages. The data is available as part of the MAPS package at https://huggingface.co/datasets/Fujitsu-FRE/MAPS/viewer/GAIA-v2-LILT. We also release the code used in our experiments at https://github.com/lilt/gaia-v2-lilt.

Multi-Objective Alignment aims to align Large Language Models (LLMs) with diverse and often conflicting human values by optimizing multiple objectives simultaneously. Existing methods predominantly rely on static preference weight construction strategies. However, rigidly aligning to fixed targets discards valuable intermediate information, as training responses inherently embody valid preference trade-offs even when deviating from the target. To address this limitation, we propose Meal, i.e., MEta ALigner, a bi-level meta-learning framework enabling bidirectional optimization between preferences and policy responses, generating instructive dynamic preferences for steadier training. Specifically, we introduce a preference-weight-net as a meta-learner to generate adaptive preference weights based on input prompts and update the preference weights as learnable parameters, while the LLM policy acts as a base-learner optimizing response generation conditioned on these preferences with rejection sampling strategy. Extensive empirical results demonstrate that our method achieves superior performance on several multi-objective benchmarks, validating the effectiveness of the dynamic bidirectional preference-policy optimization framework.

The wide deployment of LLMs has made model alignment necessary to make newly trained models safely and effectively respond to user instructions. Among different methods, inference-time alignment is often cheaper as it intervenes (i.e., offers guidances) only during output generation. Existing proposals apply guidances extracted from certain aligned models without properly assessing their reliability. Nonetheless, our systematic evaluation reveals that guidance effectiveness varies drastically across models; since ineffective guidances lead to further confusion and thus further interventions, the resulting excessive interventions typically indicate poor performance. To make interventions more effective and thus more efficient, we introduce BlendIn, an inference-time alignment framework that shifts from binary decisions to creating hybrid distributions integrating both models' knowledge. BlendIn stabilizes inference-time alignment by performing quality-aware alignment and proportionally weighting each model's contribution based on reliability. Compared with existing works, it preserves beneficial guidance while downweighting unreliable suggestions. BlendIn provides both diagnostic signals and mitigation strategies for misaligned guidance, achieving consistent and up to 50% performance improvement on challenging model pairs. Our code is available at: https://github.com/DecayingSeart/BlendIn.

The inverse Potts problem for estimating evolutionary single-site fields and pairwise couplings in homologous protein sequences from their single-site and pairwise amino acid frequencies observed in their multiple sequence alignment would be still one of useful methods in the studies of protein structure and evolution. Since the reproducibility of fields and couplings are the most important, the Boltzmann machine method is employed here, although it is computationally intensive. In order to reduce computational time required for the Boltzmann machine, parallel, persistent Markov chain Monte Carlo method is employed to estimate the single-site and pairwise marginal distributions in each learning step. Also, stochastic gradient descent methods are used to reduce computational time for each learning. Another problem is how to adjust the values of hyperparameters; there are two regularization parameters for evolutionary fields and couplings. The precision of contact residue pair prediction is often used to adjust the hyperparameters. However, it is not sensitive to these regularization parameters. Here, they are adjusted for the fields and couplings to satisfy a specific condition that is appropriate for protein conformations. This method has been applied to eight protein families.

Iterative alignment methods based on purely greedy updates are remarkably effective in practice, yet existing theoretical guarantees of $O(\log T)$ KL-regularized regret can seem pessimistic relative to their empirical performance. In this paper, we argue that this mismatch arises from the regret criterion itself: KL-regularized regret conflates the statistical cost of learning with the exploratory randomization induced by the softened training policy. To separate these effects, we study the traditional temperature-zero regret criterion, which evaluates only the top-ranked response at inference time. Under this decision-centric notion of performance, we prove that standard greedy online alignment methods, including online RLHF and online DPO, achieve constant $(O(1))$ cumulative regret. By isolating the cost of identifying the best response from the stochasticity induced by regularization, our results provide a sharper theoretical explanation for the practical superb efficiency of greedy alignment.

Generating novel protein sequences that respect a family's statistical constraints typically requires training deep generative models on thousands to millions of examples. Yet most protein families are small: the median Pfam seed alignment contains only 22 sequences, a regime where learned models overfit or collapse. We propose \emph{stochastic attention} (SA), a training-free sampler that treats the modern Hopfield energy over stored sequences as a Boltzmann distribution and draws samples via Langevin dynamics. The score function is the residual of a single softmax attention operation, eliminating the need for a trained score network, pretraining data, or graphics processing units (GPUs). Across eight Pfam families spanning 37 to 420 sequences and 23 to 262 residues, SA generates sequences with low composition divergence, novelty, and structural plausibility supported by ESMFold and AlphaFold2. Compared with profile hidden Markov models (HMMs), EvoDiff, and the multiple sequence alignment (MSA) Transformer, SA is the only tested method to simultaneously achieve low composition divergence, genuine novelty, and sequence identity within each family's nearest-neighbor identity range; the others drift outside this range or produce near-copies. The critical inverse temperature is predicted from principal component analysis (PCA) dimensionality alone, enabling fully automatic operation from a seed alignment. In two domains with deep mutational scanning data, SA-generated substitutions are enriched for experimentally tolerated mutations beyond a position-matched null, and an independent language model (ESM2-650M) scores them within the natural range. Stochastic attention thus opens training-free sequence generation to the long tail of protein families too small for deep learning.

How do protein structure prediction models fold proteins? We investigate this question through causal interventions on the folding trunks of ESMFold, OpenFold, and Boltz-1. Across all three models, we find a shared two-stage computational structure. In the first stage, early blocks initialize pairwise biochemical signals: features like charge propagate from sequence into pairwise representations through architecture-specific pathways. In the second stage, late blocks develop pairwise spatial features: distance and contact information accumulate in the pairwise representation. We verify these mechanisms causally by showing that steering charge and distance features induces predictable structural changes. Furthermore, these representations are functionally interchangeable: pairwise states can be linearly aligned and substituted across models. Together, these results suggest that folding trunks with different architectures, inputs, and training procedures converge on a shared representational organization for mapping sequence chemistry into spatial geometry.

DuaDeep-SeqAffinity is a sequence-only deep learning framework that predicts antibody--antigen binding affinity directly from primary amino acid sequences, avoiding the cost and scarcity of resolved three-dimensional structures. The antigen and the antibody heavy and light chains are processed as three independent streams, each embedded with a frozen ESM-2 protein language model and passed through parallel Transformer and convolutional neural network (CNN) branches before late fusion, a decoupled design intended to preserve local complementarity-determining region (CDR) signal that monolithic encoders can dilute. On a sequence-disjoint split of the AbRank benchmark, the model achieves a Pearson correlation of 0.683, an R^2 of 0.460, and a pairwise ranking AUC of 0.895, significantly outperforming single-branch ablations (paired t-test, p < 0.05). Attention-map and gradient-based saliency analyses further show that the model preferentially attends to CDR loops and candidate epitope residues, supporting its use as a scalable, structure-free tool for high-throughput antibody screening.

Online alignment of large language models (LLMs) is dominated by reinforcement learning from human feedback (RLHF) with gradient-based optimizers such as PPO or GRPO. While effective, these pipelines require backpropagation through long rollouts, gradient synchronization across devices, and careful hyperparameter tuning, all of which become increasingly costly at scale. We present ESSA (Evolutionary Strategies for Scalable Alignment), a gradient-free online alignment stage that follows supervised fine-tuning (SFT) and replaces the gradient loop with inference-only black-box search. ESSA optimizes only the singular values of low-rank adaptation (LoRA) factors after a short SFT warm-start, restricting the search to a compact, task-aligned subspace where evolutionary search is practical even for 72B-parameter models. Because the loop is inference-only, ESSA is compatible with INT4/INT8 weight quantization and reduces inter-GPU communication to a few bytes per iteration. Across instruction following (IFEval), preference-based assistant tuning (HelpSteer2, HH-RLHF), and mathematical reasoning (GSM8K, MATH500), ESSA matches or exceeds LoRA-GRPO in the reported LoRA comparisons; on GSM8K it also outperforms Online DPO and PPO, while remaining competitive with both methods on IFEval. At scale, ESSA reaches a fixed MATH500 accuracy on Qwen2.5-32B/PRM800K up to 7.8x faster than LoRA-GRPO on 128 GPUs.

We propose a novel benchmarking methodology for graph neural networks (GNNs) based on the graph alignment problem, a combinatorial optimization task that generalizes graph isomorphism by aligning two unlabeled graphs to maximize overlapping edges. We frame this problem as a self-supervised learning task and present several methods to generate graph alignment datasets using synthetic random graphs and real-world graph datasets from multiple domains. For a given graph dataset, we generate a family of graph alignment datasets with increasing difficulty, allowing us to rank the performance of various architectures. Our experiments prove that there is an optimal task difficulty for having a statistically relevant ranking of different models and that, even on a structure-only task, anisotropic models perform better compared to isotropic ones. To further prove that our synthetic task capture meaningful information, we show its effectiveness for self-supervised GNN pre-training: the learned node embeddings can be leveraged as positional encodings by transformers for graph regression or can be used to reconstruct the full structure of the graph with $98\%$ accuracy. To support reproducibility and further research, we provide an open-source Python package to generate graph alignment datasets and benchmark new GNN architectures. The source code is available at https://github.com/adrien-lagesse/graph-alignment-benchmark.

Due to the dynamics of the Semantic Web, version control is necessary to manage changes in widely used ontologies. Despite the long-standing recognition of ontology versioning (OV) as a crucial component of efficient ontology management, many approaches treat OV as similar to ontology matching (OM) and directly reuse OM systems for OV tasks. In this study, we systematically analyse similarities and differences between OM and OV and formalise an OM4OV framework to offer more advanced OV support. The framework is implemented and evaluated in the state-of-the-art OM system Agent-OM. The experimental results indicate that OM systems can be effectively reused for OV tasks, but without the necessary extensions, can produce skewed measurements, poor performance in detecting update entities, and limited explanations of false mappings. To tackle these issues, we propose an optimisation method called the cross-reference (CR) mechanism, which builds on existing OM alignments to reduce the number of matching candidates and to improve overall OV performance.

In this study, we identify depth-dependent prefix redundancy in final-readout LLM embedding models, notably across representative backbones including Qwen3-Embedding and Qwen3-VL-Embedding. We find that removing prefix states is substantially more damaging in shallow layers than at greater depth, showing that prefix states become increasingly compressible as the prefix and readout states propagate through the network. To this end, we introduce FastE, a training-free, plug-and-play method. FastE uses a shared fixed threshold on batch-mean readout-prefix alignment as a lightweight online heuristic for selecting when compression occurs, and ranks prefix states by the attention scores they receive from the readout position to determine which states are retained in subsequent layers. Our evaluations demonstrate FastE's ability to substantially reduce computational costs: on NarrativeQA with Qwen3-Embedding-0.6B, it reduces decoder-backbone FLOPs by 40.11% while retaining 99.53% of Full Forward nDCG@10. Across five text embedding benchmarks, two backbone scales, and three cross-modal retrieval tasks, the quality-efficiency trade-off is directly customizable through the maximum removal ratio without retraining. We believe FastE offers practical value for scalable embedding generation in retrieval, indexing, clustering, and multimodal representation systems.