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01.
arXiv (CS.AI) 2026-06-15

tap: A File-Based Protocol for Heterogeneous LLM Agent Collaboration

Authors:

arXiv:2606.14445v1 Announce Type: cross Abstract: Existing multi-agent software development systems have proposed many forms of agent collaboration, including role-based collaboration and automated code review. However, many systems assume a common runtime, a central conversation server, or the same API family. Under these assumptions, LLM agents from different vendors cannot easily exchange messages directly from their own execution environments while dividing development and review work on a shared codebase. This paper presents tap, a file-based collaboration protocol that allows Claude (Anthropic) and Codex (OpenAI) to collaborate on one codebase without shared memory or an identical runtime. The core of tap is a file-first design that preserves markdown files with metadata as original messages, combines a file inspection path (file communication, Tier 1) with real-time notification paths for Claude and Codex (real-time communication, Tier 2), and isolates work through separate git worktrees. Even if real-time notification fails or a receiver restarts, the message file remains available and the same content can be inspected again. In a 27-day, 37-generation self-applied operation where tap was used to develop and review itself, we collected 209 tap-related pull requests and 717 operational artifacts. An analysis of 375 review artifacts showed that the share of reviews recording at least one defect or requested change was 69.8% for heterogeneous model pairs and 53.1% for homogeneous model pairs. These results show that tap, which combines file-based message preservation with real-time notification, operates in a real production repository, and that combining heterogeneous models and execution environments can broaden review perspectives. tap is distributed as the open-source npm package @hua-labs/tap (v0.5.2).

02.
arXiv (CS.AI) 2026-06-17

Membership Inference Attacks against Large Audio Language Models

arXiv:2603.28378v2 Announce Type: replace-cross Abstract: We present the first systematic Membership Inference Attack (MIA) evaluation of LALMs. Using Multi-modal Blind Baselines based on textual, spectral and prosodic features, we demonstrate that common audio datasets exhibit near-perfect train/test separability (AUC ~ 1.0) even without model inference, thus MIA may primarily detect distribution shift. We therefore introduce a blind-baseline protocol to control for this confound. Under this protocol, we identify that the distribution-matched datasets enable reliable MIA evaluation without distribution-shift artifacts. We benchmark multiple MIA methods and conduct modality disentanglement experiments on these datasets. The results reveal that LALM memorization is cross-modal, arising only from binding a speaker's vocal identity with its text. These findings establish a principled standard for auditing LALMs beyond spurious correlations. Our codebase is available at https://github.com/snooow1029/ALM_MIA.

03.
arXiv (CS.CL) 2026-06-24

Progressive Alignment Objectives for Aligner-Encoder based ASR

Aligner-Encoders are recently proposed seq2seq end-to-end ASR models that replace decoder attention by predicting the uth token directly from the u-th encoder position, so the encoder must learn the alignment internally without cross-attention or a transducer lattice. In practice, this alignment often forms abruptly in the upper layers, making training sensitive and brittle on long utterances. We propose InterAligner, which adds an intermediate Aligner objective so alignment can form progressively across depth, together with an intermediate CTC loss (InterCTC) to stabilize optimization. On LibriSpeech with a 17-layer Conformer, a final-only Aligner reaches 5.0/7.8 WER (test-clean/other). InterCTC improves to 3.4/6.0, and InterAligner further reduces WER to 3.1/5.6 with the largest gains on long utterances.

04.
arXiv (CS.AI) 2026-06-24

Minimisation of Quasar-Convex Functions Using Random Zeroth-Order Oracles

arXiv:2505.02281v3 Announce Type: replace-cross Abstract: This paper explores the performance of a random Gaussian smoothing zeroth-order (ZO) scheme for minimising quasar-convex (QC) and strongly quasar-convex (SQC) functions in both unconstrained and constrained settings. For the unconstrained problem, we establish the ZO algorithm's convergence to a global minimum along with its complexity when applied to both QC and SQC functions. For the constrained problem, we introduce the new notion of proximal-quasar-convexity and prove analogous results to the unconstrained case. Specifically, we derive complexity bounds and prove convergence of the algorithm to a neighbourhood of a global minimum whose size can be controlled under a variance reduction scheme. Beyond the theoretical guarantees, we demonstrate the practical implications of our results on several machine learning problems where quasar-convexity naturally arises, including linear dynamical system identification and generalised linear models.

05.
arXiv (quant-ph) 2026-06-24

On the Berry-Keating Operator

arXiv:2606.24405v1 Announce Type: cross Abstract: We review here two different viewpoints on the Berry-Keating operator $H_{BK}$, whose connection to the Riemann hypothesis remains an intriguing and not yet fully understood question, despite considerable attention in the recent literature. In particular, we propose two somehow complementary views to $H_{BK}$: the first is based on a purely Hilbertian point of view, on dilation operators and on the Mellin transform. The second is a distributional approach, with a specific view to ladder operators, generalized eigenstates of $H_{BK}$, and generalized coherent states.

06.
arXiv (CS.LG) 2026-06-19

A graph neural network surrogate model for mesh-based crashworthiness prediction of vehicle panel components

arXiv:2503.17386v2 Announce Type: replace-cross Abstract: Crashworthiness is a key performance measure in the design of safety-critical vehicle panel components such as B-pillars. Finite element (FE) simulations are widely used to evaluate crash responses but remain computationally expensive for large-scale, nonlinear impact scenarios, particularly when integrated into iterative design and optimisation processes. Although machine learning-based surrogate models have been developed for rapid crashworthiness analysis, they exhibit limitations in detailed representation of complex 3-dimensional components. Graph Neural Networks (GNNs) have emerged as a promising solution for processing data with complex structures. However, existing GNN models often lack sufficient accuracy and computational efficiency to meet industrial demands. This paper proposes Recurrent Graph U-Net (ReGUNet), a graph-based surrogate model for crashworthiness analysis of vehicle panel components. By representing FE meshes in graph form, the model naturally accommodates complex irregular structural geometries. Its hierarchical architecture improves computational efficiency and accuracy, while the introduction of recurrence enhances stability of temporal predictions over multiple time steps. A side-impact case study of hot-stamped steel B-pillars with varying geometries is used to generate training dataset. The trained model demonstrates high accuracy in predicting the dynamic deformation behaviour and crashworthiness indicators of previously unseen component designs. ReGUNet achieves over a 52% reduction in the average deformation prediction error relative to baseline methods, together with markedly improved computational efficiency. ReGUNet provides rapid and reliable crashworthiness assessments, which in turn accelerates the design cycle of vehicle panel components.

08.
arXiv (CS.AI) 2026-06-11

Using Explainability as a Training-Time Reliability Signal for Efficient ECG Classification

arXiv:2606.12252v1 Announce Type: cross Abstract: Training deep neural networks for clinical time-series analysis is computationally demanding, yet many healthcare settings lack the resources required for repeated model development and deployment. This challenge is particularly evident in electrocardiogram classification, where large datasets and long training schedules make efficiency practically important. Progressive Data Dropout reduces training cost by excluding samples from gradient updates once they are learned, but it relies on model confidence and may retain samples that are difficult due to noise or ambiguity rather than useful signal. In this work, we introduce ERTS, an explainability-based reliability training signal for efficient ECG classification. ERTS uses explanation quality during training to distinguish between informative and unreliable uncertainty. Building on progressive data selection, we compute Grad-CAM attention maps for candidate samples and derive a focus score that measures whether model predictions are supported by coherent and localised patterns. Samples with low focus are filtered out, while those with meaningful attention are prioritised for gradient updates. We evaluate ERTS across three ECG datasets and multiple backbone architectures, showing consistent improvements in macro-F1 alongside reduced effective training cost. These results suggest that explanation quality can serve as a practical signal for improving both efficiency and reliability in clinical time-series learning. Code will be released.

09.
arXiv (CS.CL) 2026-06-16

Context Compression Is Not One Thing: Readable Symbolic Re-expression vs. Coherent Summary at Matched Budget

We study context compression for multi-hop question answering with small language models. We propose Telegraph English, a readable symbolic format that rewrites retrieved passages into structured entity-relation statements, preserving reasoning evidence at lower token cost. In controlled experiments on MuSiQue, TwoWiki, and HotpotQA, Telegraph English outperforms three matched-budget compression baselines (character-level deletion, truncation, and random sub-sampling) on every dataset, with gains of 13 to 20 F1 percentage point. It also outperforms a coherent prose summary produced by the same encoder on the hardest dataset. A pre-registered depth-interaction hypothesis is null: the advantage does not grow with reasoning depth within datasets. We interpret these results as evidence that readable symbolic re-expression preserves entity content more densely than either natural language or coherent summarization at matched token budget.

10.
arXiv (quant-ph) 2026-06-17

Singular Vector Finite Element Basis Functions for Tetrahedra in Complex Electromagnetic Geometries

arXiv:2606.18140v1 Announce Type: cross Abstract: Electromagnetic finite element method (FEM) implementations using traditional basis functions struggle to accurately represent field behavior near singular features such as conducting wedges. To combat this, specialized singular basis functions have been introduced to directly model the singular fields in these regions, leading to substantially improved performance. While these efforts have been pursued extensively in 2D, few functions have been developed for 3D elements. In this work, we develop basis functions for this in tetrahedra. Unlike prior functions, these basis functions are additive, meaning they are included alongside the standard vector basis functions to achieve more robust performance. Further, these functions are designed to be adaptable to tetrahedra touching several unique singular features by using combinations of basis functions singular with respect to each node and edge in the element, making them applicable to highly complex geometries. Higher-order interpolatory versions of the basis functions for modeling singular behavior with greater accuracy are also provided. These basis functions lead to substantial improvements in accuracy relative to the standard basis functions, and allow otherwise expensive simulations to be performed at far lower costs. As an application example, we perform simulations to extract critical quantities for designing superconducting qubits that significantly depend on the behavior of singular fields. In Ansys HFSS, this took 21.27 hours and a peak memory usage of 6.23 TB with 800 processors available, while using our singular basis functions achieved comparable results in 196 seconds while using 27.24 GB of memory and only 16 processors. Due to these benefits, our singular basis functions could be applied to enable design optimization of electromagnetic geometries with dominantly singular behavior, such as superconducting qubits.

11.
arXiv (CS.CL) 2026-06-17

Do Large Language Models Always Tell The Same Stories?

Recent advances in large language models (LLMs) have enabled the generation of high-quality prose, yet the question of whether these models are capable of generating diverse outputs remains contested. In this work, we investigate the diversity of LLM-generated stories through the framework of narrative similarity. Using a contrastive framework and a dataset of human-written stories and prompts from r/WritingPrompts, we collect narrative similarity judgments across 10 representative LLMs, utilizing both human evaluations and three different automatic annotation methods. Our findings reveal a consistent trend: LLM-generated narratives are consistently more similar to each other than human-written stories are. We demonstrate that frontier models in particular converge on a ``mean'' generic narrative that approximates individual human stories but lacks the collective diversity of human authors. Finally, we show that common mitigation strategies, including negative prompting and temperature scaling, fail to meaningfully address this homogeneity.

12.
arXiv (CS.LG) 2026-06-12

Positional Encoding in the Context of Memristor-Based Analog Computation for Automatic Speech Recognition

arXiv:2606.13379v1 Announce Type: new Abstract: Memristors provide a new chance for resource-efficient computation of neural models for natural language processing by enabling analog execution of vector-matrix-multiplication. Yet, computations on these devices are currently subject to larger distortion, both in weight programming and execution. In this work, we identify large output values of transformed positional encodings to cause major degradation within analog-to-digital conversion (ADC) as part of memristor-based computation. By adjusting the proportion of weight and precision bits of the ADC of specific memristor layers, we reduce the degradation of the execution by ~50% relative, while keeping the estimated energy consumption stable. Additionally, we investigate scenarios where the ADC cannot be modified. In that case the degradation can be reduced by ~30% relative after removing encoding-related linear transformations.

13.
arXiv (CS.CV) 2026-06-17

DiffAttn: Diffusion-Based Drivers' Visual Attention Prediction with LLM-Enhanced Semantic Reasoning

Drivers' visual attention provides critical cues for anticipating latent hazards and directly shapes decision-making and control maneuvers, where its absence can compromise traffic safety. To emulate drivers' perception patterns and advance visual attention prediction for intelligent vehicles, we propose DiffAttn, a diffusion-based framework that formulates this task as a conditional diffusion-denoising process, enabling more accurate modeling of drivers' attention. To capture both local and global scene features, we adopt Swin Transformer as encoder and design a decoder that combines a Feature Fusion Pyramid for cross-layer interaction with dense, multi-scale conditional diffusion to jointly enhance denoising learning and model fine-grained local and global scene contexts. Additionally, a large language model (LLM) layer is incorporated to enhance top-down semantic reasoning and improve sensitivity to safety-critical cues. Extensive experiments on four public datasets demonstrate that DiffAttn achieves state-of-the-art (SoTA) performance, surpassing most video-based, top-down-feature-driven, and LLM-enhanced baselines. Our framework further supports interpretable driver-centric scene understanding and has the potential to improve in-cabin human-machine interaction, risk perception, and drivers' state measurement in intelligent vehicles.

14.
medRxiv (Medicine) 2026-06-22

Exploring the association of Obesity on Cold and Warm Autoimmune Hemolytic Anemia in San Joaquin Valley: A Retrospective Cross-Sectional Study

The relationship between obesity and specific autoimmune diseases haas been well-established, specifically due to obesity's role in promoting pro-inflammatory states. Although not much literature has been documented regarding obesity association with AIHA. As such, this study aims to assess any correlations in patients with elevated body mass index (BMI) and autoimmune hemolytic anemia (AIHA). Here we present a retrospective cross-sectional study conducted over a four-year period, across four medical centers during which a new electronic medical record was implemented. The study included 25 patients who had a previously documented history of AIHA from another facility, DAT positive with indicators of hemolysis, or DAT positive with monomer specific antisera. The patients BMI was recorded at the time of presentation to the hospital. However, for patients with a prior history of AIHA or those transferred from another facility, the BMI that was closest to the time period of when the patient was diagnosed with AIHA was used as an adjunct. Our results show that there is an association of patients with elevated BMI (>25) and AIHA; however, various other confounding variables should be taken into consideration, and further research should be done to establish a causal relationship.

15.
arXiv (CS.LG) 2026-06-16

How Post-Training Shapes Biological Reasoning Models

arXiv:2606.16517v1 Announce Type: new Abstract: Scientific reasoning models for biology combine language models with foundation models trained on multimodal biological data, including DNA, RNA, and proteins. These models are built through post-training, yet how each stage shapes reasoning and generalization remains poorly understood. We study when post-training improves performance and when it induces over-specialization. Across genomics, transcriptomics, and proteins, we train and evaluate more than 100 biological reasoning models under controlled variation in backbone, continued pre-training (CPT), supervised fine-tuning (SFT), and reinforcement learning (RL), measuring both in-domain (ID) and out-of-domain (OOD) performance. We find that each post-training stage reshapes generalization in a distinct way rather than contributing uniform gains. CPT improves downstream performance by aligning models with biological language. SFT consistently increases ID performance but causes OOD performance to peak early and decline as models fit the training distribution. RL, when applied to strong SFT checkpoints with aligned rewards, improves OOD performance and partially recovers generalization. These results show that biological reasoning does not improve monotonically with additional supervision or compute. Instead, performance depends on how training stages are composed. Under fixed post-training budgets, the strongest ID-OOD trade-off comes from brief SFT, larger RL allocations, and asymmetric adaptation capacity across stages.

16.
arXiv (CS.LG) 2026-06-11

SPADE: Split-and-Delay Embeddings for Autoregressive High-Granularity Calorimeter Simulation

arXiv:2606.11304v1 Announce Type: cross Abstract: We introduce SPADE (SPlit And Delay Embeddings), an autoregressive transformer for sequences whose tokens carry multiple features. Rather than embedding these features jointly, SPADE embeds them independently. Delaying each feature stream relative to the previous one allows intra-token correlations to be learned by the standard self-attention mechanism. Applied to point-cloud calorimeter shower generation in the highly granular ILD detector, SPADE is competitive with the state of the art AllShowers model on photon showers, and substantially outperforms its VQ-VAE-based predecessor OmniJet-$\alpha_C$. The mechanism is applicable to any generative task with multi-feature tokens, enabling LLM-style pretraining workflows for higher-dimensional data.

17.
medRxiv (Medicine) 2026-06-11

Allostatic Load in Endometrial Cancer Disparities

Background: Endometrial cancer incidence and mortality are increasing, particularly among Black women and for aggressive subtypes. Allostatic load (AL), a composite measure of physiologic dysregulation across metabolic, cardiovascular, and immune systems, varies by racial category and tumor subtype in other cancers. Endometrial cancer is strongly associated with obesity, and it is unknown whether AL scores maintain sufficient heterogeneity to evaluate differences across subgroups or with clinical outcomes. Objective: To describe the performance of AL scoring in endometrial cancer patients and examine associations with tumor characteristics (grade/histology) and survival outcomes. Methods: We evaluated AL among 398 participants newly diagnosed with endometrial cancer. AL score was calculated by assigning 1 point for each ''high-risk'' value (by clinical reference range or distribution-based) for 15 biologic variables for vital signs, anthropometrics, blood-based biomarkers, and medical comorbidities. Results: Distribution-based thresholds for variables were used to preserve heterogeneity in this obesity-dominant context. Overall, 68.7% of Black women had high AL compared to White (56.7%), Hispanic (56.7%), and other race (32.3%) women. Decision tree analyses revealed grade-dependent associations between AL and survival. For women with low-grade tumors, higher AL was associated with poorer overall survival. For high-grade tumors, intermediate AL ([≥]4,

18.
bioRxiv (Bioinfo) 2026-06-12

The Geometry of Allostery: A Laplacian Minor Hierarchy for Many-Body Protein Communication

Quantifying how cooperative, many-body relationships drive allostery in protein networks remains a major challenge. To address this, we develop the Laplacian minor hierarchy, a mathematical framework that characterizes the geometric invariants of a protein network. Lower-order minors yield standard metrics including the partition function and effective distances, whereas higher-order minors define novel topological measures: cooperation indices, each bounded between zero and one, that characterize pathway correlations at increasing levels of complexity, the third-order minor determines whether allosteric pathways are correlated or uncorrelated, and the fourth-order minor quantifies how distinct pathways communicate through intermediary residues. We apply this framework to analyze the evolutionary adaptation of the PSD95pdz3 domain from Class I to Class II ligand specificity via mutations G330T and H372A. The cooperation index demonstrates a distinct evolutionary hierarchy: the G330T mutation establishes distributed pathway couplings that the H372A mutation subsequently exploits, whereas H372A alone produces minimal global changes. Furthermore, the fourth-order analysis identifies His317 as a critical intermediary node bridging the class-switching (330-372) and class-bridging (330-400) allosteric pathways. These results demonstrate that allosteric dependencies emerge only when mutations accumulate in specific combinations, with a hierarchical organization of pathways structured around position 330 and intermediary nodes His317 and Phe400. Rather than predicting allosteric mechanisms, this framework provides a mechanistic explanation for why and how allostery emerges during protein evolution.

19.
arXiv (CS.CL) 2026-06-24

Function-Vector Heads Are Two Populations: Writers and Cancellers in In-Context Learning

Authors:

Function-vector (FV) heads are identified by the magnitude of their causal contribution to in-context rule tasks, and the resulting top set is treated as a single functional class. We show this hides a sign structure. Under a sign-preserving criterion (refined direct logit attribution, validated head by head with path patching) the FV population splits into two opposing groups: writers push the rule-correct logit up, cancellers push it down, and ablating both together moves the readout less than the sum of the two. The split is causal and reproducible. It holds in all but two of the fifteen (model, task) cells we test, spanning three architectures and six Pythia scales, and a sign-shuffle null rejects the single-class account in all but one of the six main cells. It is also invisible to magnitude-only ranking, which surfaces whichever group locally dominates and misses the other, so any function vector or ablation built that way silently averages a promoting and a suppressing mechanism. Cancellers are not attention sinks, induction heads, or copy-suppression heads, and their causal effect is larger than that of magnitude-matched non-FV controls. Zero-ablating them recovers $+0.13$ to $+0.29$ nats on the correct label in every main cell, and shifts accuracy by $+2$ to $+7$ pp in the same direction.

20.
arXiv (CS.CL) 2026-06-24

Poster: Exploring the Limits of Audio-Based Detection of Turkish Phone Call Scams

Scam phone calls exploit vulnerable communities worldwide, yet research on detection has focused almost exclusively on English and other high-resource languages. In low-resource settings such as Turkish, detection is especially difficult, as annotated data is scarce and technological defenses remain limited. This research investigates how large language models (LLMs) can support scam detection in Turkish by introducing the first public multi-modal dataset of 100 aligned audio-transcript pairs of scam and benign conversations. We evaluate seven LLMs spanning three model families: Gemini 2.5 (Flash, Flash-Lite, Pro), GPT-4o, and Qwen (Max, Plus, Turbo), under three input conditions: raw audio, automatic speech-to-text transcripts, and transcripts refined by a native speaker. Our results suggest that transcript-based inputs consistently outperform direct audio processing, while human-corrected and uncorrected transcripts perform comparably. By centering a low-resource language and real world threat, this work highlights the urgent need for culturally and linguistically inclusive AI safety research and more robust multi-modal systems for fraud prevention.

22.
arXiv (CS.AI) 2026-06-11

CredibleDFGO: Differentiable Factor Graph Optimization with Credibility Supervision

arXiv:2605.06100v2 Announce Type: replace-cross Abstract: Global navigation satellite system (GNSS) positioning is widely used for urban navigation, but the covariance reported by the GNSS solver is often unreliable in urban canyons. Existing differentiable factor graph optimization (DFGO) methods learn measurement weighting through the solver, but they still use position-only objectives. As a result, the position estimate may improve while the reported covariance remains too small, too large, or incorrectly oriented. We propose CredibleDFGO (CDFGO), a differentiable GNSS factor graph framework that makes covariance credibility an explicit training target. A Weighting Generation Network (WGN) predicts per-satellite reliability weights, and a differentiable Gauss-Newton solver maps these weights to a position estimate and a Hessian-derived posterior covariance. We use proper scoring rules to supervise the East-North predictive distribution end to end. We study negative log-likelihood (NLL), the energy score (ES), and their combination. Results on three UrbanNav test scenes show consistent gains in covariance credibility. Positioning accuracy also improves on the medium-urban and harsh-urban scenes; on the deep-urban scene, both the mean horizontal error and the 95th-percentile error improve. On the harsh-urban Mong Kok (MK) scene, CDFGO-Combined reduces the mean horizontal error from 13.77 m to 11.68 m, reduces NLL from 40.63 to 6.59, and reduces ES from 12.31 to 9.05 relative to DFGO (MAE). Case studies link the MK improvement to better axis-wise consistency, more credible local covariance ellipses, and satellite-level reweighting.

23.
arXiv (CS.LG) 2026-06-19

Train, Retrieve, or Both? A Four-Arm Head-to-Head for Correct Statutory Citation on the Ontario Residential Tenancies Act

arXiv:2606.20359v1 Announce Type: new Abstract: Self-represented tenants, landlords, and help-desk staff need to be pointed at the provision of law that actually governs a question, with a correct statutory citation. We study this task on the Ontario Residential Tenancies Act, 2006 (RTA) and its core regulation, asking the operator's question empirically: is fine-tuning enough, or is hybrid retrieval needed? We run a four-arm head-to-head on Qwen2.5-7B-Instruct (base zero-shot, LoRA SFT-only, RAG-only, and an SFT+RAG hybrid), scored on citation exact-match (section+subsection) over a small, human-verification-pending real eval set. The base model cannot cite the RTA and SFT-only mis-recalls sections; retrieval is essential and drives hallucination to zero by construction; and the SFT+RAG hybrid scores highest at 0.481 exact-match with zero hallucinated citations. Its edge comes from SFT making provision selection more robust to the higher-recall candidate sets that hurt zero-shot RAG. Notably, this cheap bge-small hybrid matches or beats a pipeline built on bigger, specialized retrieval models (a larger embedder and a cross-encoder reranker), and a larger/improved training set does not help either: strong statutory-citation performance here does not require specialized retrieval models or more data. The artifact zeroes hallucination and clears the lift-over-base bar but does not reach the aspirational 0.70 exact-match target. All results are on a small, human-verification-pending real eval set and are reported as preliminary.

24.
medRxiv (Medicine) 2026-06-11

Population-scale detection of methylation outliers from long-read genome sequencing

Background: Aberrant DNA methylation can mediate the functional effects of rare genetic variation and contribute to imprinting disorders, repeat expansion diseases, and other pathogenic regulatory mechanisms. Long-read sequencing technologies now enable genome-wide detection of CpG methylation alongside genetic variation from a single assay. However, methods for systematic identification and interpretation of methylation outliers from long-read sequencing data remain limited. Methods: We developed METAFORA, a computational workflow for detecting methylation outlier regions from PacBio and Oxford Nanopore long-read sequencing data. METAFORA constructs population-level methylation references, segments the genome into correlated CpG blocks, infers technical and biological sources of variation through hidden factor estimation, models uncertainty due to variable depth sequencing, and computes covariate-adjusted methylation outlier scores for individual samples. We applied METAFORA across large long-read sequencing cohorts and integrated methylation outliers with multi-omic data. METAFORA is implemented as a snakemake workflow available at https://github.com/tjense25/METAFORA. Results: METAFORA identified methylation outlier regions associated with rare structural variants, tandem repeat expansions, and imprinting abnormalities. We found outlier regions were enriched for molecular outliers across transcriptomic and chromatin accessibility datasets, supporting their functional relevance in gene regulation. In a representative case, METAFORA identified an imprinting defect affecting the GNAS locus associated with an STX16 deletion. Conclusions: METAFORA enables scalable detection and interpretation of methylation outliers from long-read sequencing data and provides a framework for integrating epigenetic outliers with genomic and multi-omic analyses. These approaches may improve interpretation of rare regulatory variation and support discovery of clinically relevant epigenetic abnormalities in genomic medicine.

25.
bioRxiv (Bioinfo) 2026-06-13

MoE-Bind: Guiding De Novo Protein Binder Generation with Sparse Experts

Authors:

De novo protein binder design has been dominated by structure-based pipelines that require known three-dimensional target conformations and consume substantial compute and generation time per design, limiting their throughput and accessibility for routine large-scale binder exploration. Sequence-only generative models promise a faster and lighter alternative, yet existing systems remain uniformly dense and frequently reintroduce structural computation at inference, undermining the core advantages they were intended to deliver. Across the broader language modelling community, transformers have meanwhile transitioned from fully dense designs to sparse Mixture-of-Experts architectures that decouple capacity from per-token compute, a shift that has yet to reach sequence-only protein binder generation. We present MoE-Bind, an autoregressive protein binder generator that, for the first time in this domain, combines Multi-head Latent Attention with a sparse Mixture-of-Experts feed-forward network and is evaluated under two independent structure predictors, Boltz-2 and AlphaFold2-Multimer. Despite activating less than half the per-token parameters of compute-matched dense baselines, MoE-Bind matches or exceeds them on full-length receptor-conditioned binder generation on a leakage-free Docking Benchmark 5.0 evaluation, transfers without peptide-specific training to short-peptide design, and reduces training and inference compute by a large margin. Routing analysis on generated binders reveals interpretable expert specialization at both the individual amino acid and biochemical group level, a structured expert-token alignment not previously reported for natural-language MoE models. These results show that sparse architectural design, rather than scale, can deliver fast, structure-free, and interpretable protein binder generation.