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01.
arXiv (quant-ph) 2026-06-17

Optimal Calibration of Quantum Network Links

arXiv:2606.18167v1 Announce Type: new Abstract: The reliable distribution of entanglement is essential for the effective operation of quantum networks. Due to fundamental differences between quantum and classical communication systems, it is necessary to develop specialised algorithms and protocols that also account for quantum-specific constraints. In this work, we focus on the issue of recalibration. As suggested by recent experimental studies, the process of local entanglement generation in a quantum link degrades over time due to environmental changes that have to be estimated and compensated via a calibration operation, during which the link is not available. Therefore, in such a quantum network, every link alternates between an activation period, during which it operates normally, and a calibration period, during which it cannot participate in the end-to-end entanglement distribution, thereby creating a trade-off between link quality (the fidelity of generated pairs, which decays during activation) and availability (the fraction of time the link is usable, which calibration reduces). We develop analytically a protocol for optimally assigning activation periods to each link in linear quantum repeater chains, subject to any general end-to-end fidelity requirements and local initial fidelity thresholds. Building on this foundation, we extend to general quantum networks, where multiple paths may cross at common links, proposing a heuristic approach evaluated in simulations and compared with a benchmark, numerical approach, and theoretical bounds.

02.
arXiv (CS.LG) 2026-06-15

Provably Safe, Yet Scalable Reinforcement Learning

arXiv:2606.14536v1 Announce Type: new Abstract: Safe reinforcement learning (RL) aims to learn policies that optimize rewards while satisfying constraints. Predominant approaches rely on soft-constrained policy optimization, which has achieved empirical success but does not provide formal safety guarantees for the learned policy. In contrast, methods with strict guarantees typically rely on explicit certificate functions, whose construction requires the direct synthesis and verification of control-invariant sets, a process that scales poorly with state dimension and often yields overly conservative behavior. In this paper, we present the Provably Safe, yet Scalable RL (PS2-RL) framework, a novel two-phase architecture for learning provably safe policies in a scalable manner, designed to overcome the key bottlenecks of prior methods. Rather than explicitly computing invariant sets, PS2-RL leverages a learned backup policy to forward-integrate the system dynamics, generating an implicit control-invariant set online. In the first phase, the backup policy is trained with our proposed safe-arrival value function, which characterizes the optimal backup policy for invariant-set construction. In the second phase, an RL policy is trained end-to-end through a differentiable projection layer that strictly enforces the safety guarantees induced by the learned backup policy. By maximizing the volume of the implicit control-invariant set in the first phase, the resulting PS2 policy from the second phase is performant and scalable, while maintaining provable safety. Crucially, PS2-RL imposes no restrictions on the underlying RL algorithm and can be plugged into any existing training pipeline. We establish theoretical guarantees for the proposed framework and evaluate it on robotic control tasks with state dimensions up to 10, a regime in which prior provably safe RL methods struggle or become impractical.

04.
arXiv (CS.CV) 2026-06-15

ForceForget: Reinforcement Concept Removal for Enhancing Safety in Text-to-Image Models

With the advance of generative AI, the text-to-image (T2I) model has the ability to generate various contents. However, T2I models still can generate unsafe contents. To alleviate this issue, various concept erasing methods are proposed. However, existing methods tend to excessively erase unsafe concepts and suppress benign concepts contained in harmful prompts, which can negatively affect model utility. In this paper, we focus on eliminating unsafe content while maintaining model capability in safe semantic meaning interpretation by optimizing the concept erasing reward (CER) with reinforcement learning. To avoid overly content erasure, we introduce the Safe Adapter to project partial text embedding for efficient concept regulation in cross-attention layers. Extensive experiments conducted on different datasets demonstrate the effectiveness of the proposed method in alleviating unsafe content generation while preserving the high fidelity of benign images compared with existing state-of-the-art (SOTA) concept erasing methods. In terms of robustness, our method outperforms counterparts against red-teaming tools. Moreover, we showcase the proposed approach is more effective in emerging image-to-image (I2I) scenarios compared with others. Lastly, we extend our method to erase general concepts, such as artistic styles and objects. Disclaimer: This paper includes discussions of sexually explicit content that may be offensive to certain readers. All images used in this work are synthesized or from public datasets.

06.
arXiv (CS.LG) 2026-06-25

What's in an Earth Embedding? An Explainability Analysis of Location Encoders

arXiv:2606.24997v1 Announce Type: new Abstract: Geographic implicit neural representations (INRs) learn to map any coordinate on Earth to a location embedding, implicitly encoding geospatial data into the weights of a neural network. Location embeddings are widely used off the shelf as general-purpose geospatial representations, yet users lack principled tools to audit what geographic or semantic information these embeddings capture. In this work, we analyze the information content of geographic INRs through their location embeddings. We decompose these embeddings into human-interpretable features$\unicode{x2014}$namely, (i) sparse latent concepts, (ii) natural language concepts, and (iii) visual features. The latent concept embeddings are learned using sparse autoencoders. To recover natural language concepts, we apply sparse linear concept embeddings (SpLiCE) over a predefined geospatial dictionary. Finally, visual features are extracted using saliency maps derived from CLIP Surgery. We show that location embeddings can be decomposed into human-interpretable representations while retaining high reconstruction capability, revealing interpretable geographic structures such as forests, deserts, and urban features. Across methods, sparse decompositions expose systematic differences in encoded information, ranging from urban structures to broader biome and climate signals, and pretraining-space saliency maps further highlight complementary features such as roads and landmarks. We hope this work provides a first step toward interpretable geospatial representations.

07.
arXiv (quant-ph) 2026-06-24

Two-Electron Effects Extend High-Harmonic Generation into the keV Regime

arXiv:2606.24765v1 Announce Type: cross Abstract: Two-electron processes can generate high harmonics beyond the conventional single-active-electron cutoff. Motivated by recent experimental evidence of an extended secondary plateau in the helium high-harmonic spectrum [S. Wang et al, Optica, (2023); S. Wang et al, In Print in Nature Photon., (2026)], we present a two-electron generalisation of the strong-field approximation. We analyse the resulting expressions using the saddle-point method and determine the extended cutoff. We find good agreement with classical predictions of cutoff scalings of $4.7$ and $5.5$ times the ponderomotive energy, which significantly exceed the established single-electron scaling of 3.17. We calculate high-harmonic spectra generated via a two-electron process in helium atoms driven by an intense few-cycle infrared laser pulse. Our results demonstrate that the harmonic spectrum extends far beyond the water window, reaching photon energies up to $\approx 1.2\,\mathrm{keV}$ in the soft x-ray region. The large spectral bandwidth can support the generation of sub-attosecond soft x-ray pulses, which are of particular interest for probing ultrafast dynamics across matter, including applications in core-level spectroscopy and biological imaging.

08.
bioRxiv (Bioinfo) 2026-06-24

InVitroGap: an open-source tool for automated quantification of wound closure in the in vitro scratch assay

Abstract Background and Objective: Scratch assays are widely used to study wound closure in vitro, but quantitative image analysis remains constrained by manual variability, proprietary workflows, and tools requiring programming expertise. We developed InVitroGap, a Python-based application with a browser-accessible interface for automated quantification of scratch assay closure from sequential microscopy images. Methods: RCC-ER and Renca cells were seeded in 96-well ImageLock plates and scratched using a WoundMaker device for uniform linear wounds or a 200 uL pipette tip for crisscross wounds. Phase-contrast time-lapse images acquired at 0, 24, and 48 h with an IncuCyte SX5 system were independently analyzed using IncuCyte 2023A Rev2 and InVitroGap. The InVitroGap pipeline combines Gaussian smoothing, gradient-based texture mapping, adaptive percentile thresholding, and morphological post-processing to quantify wound confluence and relative wound density (RWD). Agreement was evaluated using paired comparisons, Pearson and Spearman correlations, Bland-Altman analysis, and mean absolute error (MAE). Results: InVitroGap measurements closely tracked IncuCyte outputs across both cell lines, with no significant between-method differences (p > 0.05), strong pooled correlations (R square = 0.964 for RWD; R square = 0.983 for wound confluence), and small mean biases (absolute bias [≤] 1.64%). The tool successfully processed crisscross wounds from brightfield image series, and a complete four-timepoint series was analyzed in approximately 10 seconds, with robust performance across distinct cell morphologies and wound geometries. Conclusions: InVitroGap provides a transparent, computationally efficient, and platform-independent alternative for scratch assay analysis, delivering performance comparable to commercial systems while remaining freely accessible at https://invitrogap.vercel.app/.

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

Pantheon360: Taming Digital Twin Generation via 3D-Aware 360{\deg} Video Diffusion

Generating complete digital twins from videos requires precise camera control, global scene coverage, and strict spatial-temporal consistency constraints that remain challenging for perspective video generators due to their limited field of view (FoV). Their narrow FoV forces long or multi-view trajectories, amplifying cross-view inconsistency and temporal drift. We argue that 360{\deg} video generation offers a natural solution: panoramic coverage simplifies trajectory design and provides a strong global context for maintaining coherence. We introduce Pantheon360: Taming Digital Twin Generation via 3D-Aware 360{\deg} Video Diffusion, a controllable 360{\deg} video generation framework that synthesizes high-fidelity videos from sparse 360{\deg} inputs. The key idea is an explicit 3D Cache, reconstructed from the input, which serves as a geometric scaffold for any user-defined camera path. This allows the diffusion model to focus on photorealistic texture refinement while the 3D Cache enforces global geometric consistency. Experiments show that Pantheon360 achieves superior visual quality and unmatched geometric coherence, enabling reliable and flexible 360{\deg} scene generation for downstream simulation and digital-twin applications.

10.
arXiv (quant-ph) 2026-06-11

Implementing Hamiltonian Renormalization Group Flow on Quantum Computers with VAPOR

arXiv:2606.11306v1 Announce Type: cross Abstract: While Hamiltonian Lattice Gauge Theory is gaining traction, today's limited numerical capacity leaves simulations affected by discretization errors. This motivates the implementation of renormalization group (RG) techniques to find discretization-error-free operators. To this end, we introduce VAPOR, a variational quantum algorithm that decomposes operators into Pauli strings, identifies RG flow orbits, and determines fixed points of a naively discretized operator. We illustrate this using a toy model of a kinematic operator in a symmetry-restricted SU(2) Yang-Mills theory.

11.
arXiv (CS.AI) 2026-06-15

HierSVA: A Data Synthesis Pipeline, Dataset, and Benchmark for LLM-Driven Hierarchical Hardware Formal Verification

arXiv:2606.13706v1 Announce Type: cross Abstract: We present HierSVA, an integrated suite that combines a pipeline, dataset, and benchmark for LLM-driven hierarchical hardware formal verification. HierSVA-SP pairs an RTL preprocessing toolchain with an LLM-in-the-loop formal verification flow to produce reference SystemVerilog Assertions (SVA) on hierarchical RTL. Applying it to BaseJump STL yields HierSVA-DS, a dataset of 342 modules, with hierarchy metadata and depths 0–9, accompanied by a deep subset of 28 module-bug pairs with natural-language specifications and bug variants. HierSVA-B decomposes assertion quality into six metric axes: syntax correctness, assertion proof success rate, vacuity, specification faithfulness, mutation coverage, and formal core coverage. Applying HierSVA-B to twelve recent LLMs reveals three findings. First, the module-level compile rate is 67.1\%; among generated assertions in evaluable runs, 82.1\% prove non-vacuously, but the corresponding assertion sets detect only 70.2\% of eligible injected faults and cover 36.2\% of the formal core. Second, on 211 evaluable model–module entries in the deep subset, assertion sets flag buggy RTL with 0.87 recall, but 40\% of predicted-buggy outcomes are false positives on correct RTL, limiting precision to 0.60. Third, agentic mode improves S1-style provability and strength metrics, but gains plateau and oscillate. Codes and artifacts are available at \href{https://github.com/HierSVAAnon/HierSVACodeAndArtifacts}{https://github.com/HierSVAAnon/HierSVACodeAndArtifacts}. Dataset is available at \href{https://huggingface.co/datasets/AnonymousHierSVA/HierSVA}{https://huggingface.co/datasets/AnonymousHierSVA/HierSVA}.

13.
arXiv (CS.AI) 2026-06-11

Rule Taxonomy and Evolution in AI IDEs: A Mining and Survey Study

arXiv:2606.12231v1 Announce Type: cross Abstract: The adoption of AI-powered Integrated Development Environments (AI IDEs) has introduced "Rules" as a novel software artifact, allowing developers to persistently inject project-specific constraints and architectural guidelines into the context of Large Language Models (LLMs). Despite their role in aligning AI behavior with developer intent, the taxonomy, evolution, and practical impact of these rules remain largely unexplored. To bridge this gap, we conducted a mixed-methods empirical study on AI IDE rules. By mining 83 open-source projects and extracting 7,310 rules, we established a comprehensive taxonomy comprising 5 primary and 25 secondary categories. We then triangulated these artifacts with survey responses from 99 practitioners. Our analysis identified a contrast between developer priorities and actual configurations: while practitioners rate architectural constraints as highly important, rule files in repositories primarily consist of low-level workflow and code formatting constraints. Furthermore, our analysis of 1,540 rule evolution events revealed that rules are updated frequently. Repository data further indicate that rule evolution is primarily driven by constructive context expansions (29.17%) and enrichments (26.59%). In contrast, surveyed developers reported modifying rules primarily to correct AI errors (77.78%), typically by adding new negative constraints rather than editing existing ones. Finally, an artifact compliance assessment of 160 rule evolution events revealed that updating rules significantly improves the adherence of software artifacts, with the average artifact compliance rate increasing by 22.99% (from 49.14% to 72.13%) following an update. Our study provides empirical insights that can help developers optimize prompting strategies and guide tool builders in designing automated conflict-detection and context-management mechanisms for AI IDEs.

14.
arXiv (quant-ph) 2026-06-15

Experimental violation of a Bell-like inequality for causal order

arXiv:2506.20516v2 Announce Type: replace Abstract: Quantum mechanics is compatible with scenarios where physical processes happen in an indefinite order. In theory, this feature could be detected through violations of inequalities on the observed correlations, analogous to Bell inequalities. However, experimental demonstrations of such violations have been missing until recently due to the complexity of the required setup. Here we report an experimental violation of a Bell-like inequality involving the correlations of four parties, one of which is spacelike separated from the others. Our demonstration employs 3 km fiber spools to simulate spacelike separation, and achieves high-speed operations in photonic time-bin encoding, nanosecond synchronization, and accurate temperature stabilization. These experimental advances enable a violation by 5.7 standard deviations and open a path towards a certification of indefinite order in conditions that guarantee spacelike separation with existing state-of-the-art devices. However, the certification is not device-independent, as it relies on knowledge about the setup to exclude bidirectional signaling–a loophole inherent to implementations in classical acyclic spacetimes, which may be resolved in future quantum-spacetime tests.

15.
arXiv (CS.AI) 2026-06-19

AI-enhanced tuning of quantum dot Hamiltonians toward Majorana modes

arXiv:2601.02149v4 Announce Type: replace-cross Abstract: We propose a neural network-based model capable of learning the broad landscape of working regimes in quantum dot simulators, and using this knowledge to autotune these devices - based on transport measurements - toward obtaining Majorana modes in the structure. The model is trained in an unsupervised manner on synthetic data in the form of conductance maps, using a physics-informed loss that incorporates key properties of Majorana zero modes. We show that, with appropriate training, a deep vision-transformer network can efficiently memorize relation between Hamiltonian parameters and structures on conductance maps and use it to propose parameters update for a quantum dot chain that drive the system toward topological phase. Starting from a broad range of initial detunings in parameter space, a single update step is sufficient to generate nontrivial zero modes. Moreover, by enabling an iterative tuning procedure - where the system acquires updated conductance maps at each step - we demonstrate that the method can address a much larger region of the parameter space.

16.
arXiv (CS.CV) 2026-06-19

Distill Once, Adapt Life-Long: Exploring Dataset Distillation for Continual Test-Time Adaptation

Continual Test-Time Adaptation (CTTA) aims to maintain model performance under evolving target domains by adapting online without labeled data. However, practical deployments often cannot retain the source dataset due to privacy or licensing constraints, and purely source-free CTTA methods tend to become unstable under long-term distribution shift, suffering from compounding self-training errors and catastrophic forgetting. We introduce DO-ALL (Distill Once, Adapt Life-Long), a plug-and-play framework that revisits source information in a compact and privacy-conscious form via Dataset Distillation (DD). Before deployment, DO-ALL performs DD to produce a small set of synthetic distilled anchors that summarize the source distribution. During adaptation, each target sample is matched with its most semantically aligned anchor, which provides a stable reference for various CTTA via source replay, representation alignment, and manifold-smoothing regularization. DO-ALL can be seamlessly integrated into existing CTTA algorithms, consistently improving long-term robustness across CIFAR100-C, ImageNet-C, and the CCC benchmark. This demonstrates the potential of leveraging DD to enable stable and continuous adaptation without retaining raw source data. The code is available at https://github.com/blue-531/DOALL.

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

nD-RoPE: A Generalized RoPE for n-Dimensional Position Embedding

arXiv:2606.12146v1 Announce Type: cross Abstract: Rotary Position Embedding (RoPE) is widely adopted in Transformer models, yet its extension to high-dimensional domains lacks a unified theoretical formulation. Most existing approaches either apply rotations independently along each axis or empirically mix frequencies, which limits cross-dimensional interactions and yields direction-dependent representations. To address these limitations, we propose nD-RoPE, a decomposition-free generalization of RoPE to arbitrary dimensions. From a translation-invariant formulation in continuous Hilbert space, we derive a spectral condition for isotropy that requires treating positions and frequencies as coupled \(n\)-dimensional vectors. We instantiate this formulation with a multi-scale regular-simplex wave-vector design, which provides non-degenerate spatial coverage and a symmetric, directionally balanced second-order response. Experiments across images, videos, and point clouds demonstrate consistent performance gains and improved generalization in high-dimensional settings.

18.
Nature Medicine 2026-06-24

Automated reanalysis of genomic data for rare disease diagnostics at scale

Reanalysis of genomic data in rare disease is highly effective in increasing diagnostic yields but remains limited by manual approaches. Automation and optimization for high specificity will be necessary to ensure scalability, adoption and sustainability of iterative reanalysis. We developed Talos, an open-source tool that automates variant prioritization by integrating dynamically updated gene−disease and variant-level evidence with inheritance-aware filtering and validated its performance using data from 1,089 individuals with rare disease. Trio-based analysis identified 90% of known diagnoses, returning 1.3 variants per case on average. Variant burden reduced to one variant per 200 cases on iterative monthly reanalysis. Application to an unselected cohort of 4,735 undiagnosed individuals identified 241 diagnoses (5.1% yield): 78 (32%) due to new gene−disease relationships, 54 (22%) due to new variant-level evidence and 109 (45%) due to improved analysis strategies. Our automated, iterative reanalysis model demonstrates the feasibility of delivering frequent, systematic reanalysis at scale. Talos, a new tool for the automated analysis of genomic data, demonstrates the feasibility and diagnostic utility of systematic reanalyses of data in rare diseases.

19.
arXiv (CS.LG) 2026-06-16

Constraining the outputs of ReLU neural networks

arXiv:2508.03867v2 Announce Type: replace-cross Abstract: We introduce a class of algebraic varieties naturally associated with ReLU neural networks, arising from the piecewise linear structure of their outputs across activation regions in input space, and the piecewise multilinear structure in parameter space. By analyzing the rank constraints on the network outputs within each activation region, we derive polynomial equations that characterize the functions representable by the network. We further investigate conditions under which these varieties attain their expected dimension, providing insight into the expressive and structural properties of ReLU networks.

20.
arXiv (CS.CL) 2026-06-12

LLM-based Embeddings: Attention Values Encode Sentence Semantics Better Than Hidden States

Sentence representations are foundational to many Natural Language Processing (NLP) applications. While recent methods leverage Large Language Models (LLMs) to derive sentence representations, most rely on final-layer hidden states, which are optimized for next-token prediction and thus often fail to capture global, sentence-level semantics. This paper introduces a novel perspective, demonstrating that attention value vectors capture sentence semantics more effectively than hidden states. We propose Value Aggregation (VA), a simple method that pools token values across multiple layers and token indices. In a training-free setting, VA outperforms other LLM-based embeddings, even matches or surpasses the ensemble-based MetaEOL. Furthermore, we demonstrate that when paired with suitable prompts, the layer attention outputs can be interpreted as aligned weighted value vectors. Specifically, the attention scores of the last token function as the weights, while the output projection matrix ($W_O$) aligns these weighted value vectors with the common space of the LLM residual stream. This refined method, termed Aligned Weighted VA (AlignedWVA), achieves state-of-the-art performance among training-free LLM-based embeddings, outperforming the high-cost MetaEOL by a substantial margin. Finally, we highlight the potential of obtaining strong LLM embedding models through fine-tuning Value Aggregation.

21.
arXiv (CS.CV) 2026-06-11

Multimodal Brain Tumour Classification Using Feature Fusion

Clinicians diagnose brain tumors by synthesizing patient symptoms, medical history, and quantitative imaging data from modalities such as MRI and CT scans into a unified clinical judgement. However, most deep learning models rely on MRI/CT images alone, failing to replicate the clinicians multimodal reasoning. We explore a two-branch multimodal network combining raw MRI scans with 91 extracted radiomic features (intensity, texture, shape, and boundary descriptors) to classify brain tumors into glioma, meningioma, pituitary, and no-tumor. A pre-trained CNN backbone encodes the image stream, whereas a dedicated MLP encodes the radiomic stream. Both streams are fused via concatenation, gated, or bidirectional cross-modal attention strategies. Across nine experimental runs on a balanced 7,200 image dataset, all multimodal configurations outperform unimodal baselines with gated fusion achieving the best accuracy of 96.13%.

22.
arXiv (CS.CL) 2026-06-16

TokenPilot: Cache-Efficient Context Management for LLM Agents

As LLM agents are deployed in long-horizon sessions, context accumulation drives up inference costs. Existing approaches utilize text pruning or dynamic memory eviction to minimize token footprints; however, their unconstrained sequence mutations alter layouts, introducing prefix mismatches and cache invalidation. This reveals a critical trade-off between text sparsity and prompt cache continuity. To address this, we present TokenPilot, a dual-granularity context management framework. Globally, Ingestion-Aware Compaction acts as a framework harness to stabilize prompt prefixes and eliminate open-world environmental noise at the ingestion gate. Locally, Lifecycle-Aware Eviction monitors the ongoing residual utility of context segments, enforcing a conservative batch-turn schedule to offload content segments only when task relevance expires. Experiments on PinchBench and Claw-Eval under both isolated and continuous modes demonstrate that TokenPilot reduces costs by 61% and 56% in isolated mode, and 61% and 87% in continuous mode, while maintaining competitive performance compared to prior systems. TokenPilot has been integrated into LightMem2 at https://github.com/zjunlp/LightMem2.

23.
arXiv (CS.AI) 2026-06-11

SPEA2$^+$: Improved Density Estimation in SPEA2 with Provable Runtime Guarantees

arXiv:2606.12382v1 Announce Type: cross Abstract: The Strength Pareto Evolutionary Algorithm 2 (SPEA2) is a popular and prominent evolutionary algorithm for solving multi-objective optimisation problems. Despite its popularity, theoretical analyses of SPEA2 have only appeared recently. Moreover, these analyses focus exclusively on how SPEA2 handles non-dominated solutions and disregard the algorithmic components responsible for handling dominated solutions. We conduct a first runtime analysis of SPEA2 for which these components are analysed. We prove that, unlike other prominent algorithms, including NSGA-II, NSGA-III and SMS-EMOA under the same setting of constant population size and duplicate elimination, SPEA2 is unable to cover the Pareto front of the OneTrapZeroTrap benchmark efficiently. Our results indicate that using k-th nearest-neighbour distance in the fitness assignment provides an insufficient signal to maintain diversity among dominated individuals. To address this issue, we propose an improved variant, SPEA2$^+$, that considers all pairwise distances. The new algorithm achieves the same performance guarantees as the other prominent algorithms on OneTrapZeroTrap, while matching the performance of the original SPEA2 on simpler problems. Experimental results complement our theoretical findings.

24.
bioRxiv (Bioinfo) 2026-06-08

DDI_single: Single-Sequence-Based Protein Domain Assembly

Authors:

Domains are the basic units of protein structure and function. Appropriate inter-domain organization is critical to enable cooperative execution of multiple related functions. It is thus a crucial step to determine the full-length structure of multi-domain proteins for the purpose of elucidating their functions and designing new drugs to regulate these functions. Existing structure prediction algorithms are generally better at solving the internal conformation of domains, rather than modeling the relative positions between domains. To address the challenge of accurately determining multi-domain protein conformations, we develop a single-sequence-based domain assembly algorithm called DDI_single. DDI_single directly extracts features from the amino acid sequence using the protein language model ESM-1b, and accurately predicts the interactions between residue pairs of structural domains through a novel gated cross-attention module, thus achieving the correct assembly of structural domains. With the knowledge of domain definition, DDI_single achieves more than 20% higher accuracy in the task of predicting the relative distances of residue pairs between domains than that of the single-sequence-based structure prediction algorithm trRosettaX_single. When assembling domains with known spatial conformations, DDI_single correctly assembles 74.4% of the samples in the test set (TM-score>0.5). When assembling domains with unknown spatial conformations, in cases where the internal spatial conformations of domains are correctly modeled, DDI_single correctly assembles 73.9% of the samples.

25.
bioRxiv (Bioinfo) 2026-06-23

VCBench: A Multi-Dimensional Benchmark for Single-Cell Foundation Models

Single-cell foundation models are increasingly positioned as virtual cells, yet their capabilities are assessed by fragmented, largely single-task benchmarks that obscure where these models improve on simple baselines. VCBench addresses this by synthesizing four independent virtual-cell frameworks into seven capability dimensions: perturbation response prediction, cross-species universality, gene regulatory network (GRN) inference, modality integration, temporal dynamics, multi-scale integration, and in silico experimentation. Each dimension is assessed for operational testability under current architectures and datasets: five admit direct or proxy evaluation, while multi-scale integration and in silico experimentation are structurally untestable as end-to-end tasks. We evaluate five foundation models (Geneformer, scGPT, UCE, TranscriptFormer, Arc State) against pre-registered linear and nearest-neighbor baselines across the five testable dimensions, and report three findings. First, the baselines match or exceed every foundation model on four of the five scored dimensions, replicating the reported competitiveness of linear baselines on perturbation prediction and extending it to cross-species transfer, GRN inference, and temporal ordering. Second, TranscriptFormer alone exceeds the strongest baseline on cross-modal RNA-to-protein prediction (53% Pearson improvement, with a documented contamination caveat) and is the only model to reach Level 2 in the pre-registered Virtual Cell (VC) Level rubric; the architectural choice behind this advantage simultaneously causes a spectral collapse that destroys its temporal-ordering performance, a tradeoff invisible to single-task benchmarks. Third, no foundation model publishes a complete cell-level training manifest, leaving data contamination undetectable to users. Alongside the benchmark, VCBench releases a Contamination Reporting Schema and contributes two further methodological tools: a common-label-set protocol that controls for class-count confounds in cross-species transfer, and a spread-error correlation probe for epistemic calibration.