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01.
arXiv (CS.AI) 2026-06-11

READER: Robust Evidence-based Authorship Decoding via Extracted Representations

arXiv:2606.10794v2 Announce Type: replace Abstract: As agentic applications increasingly route user tasks through official and third-party LLM APIs, provenance becomes an operational question: which model generated a given black-box response? We study Dynamic Black-Box LLM Provenance: identifying the source LLM from generations elicited by query-varying, non-predefined prompts rather than a fixed input set or benchmark suite. This setting is difficult because prompt semantics dominate the text, while model-specific authorship traces are weak and inconsistent at the surface level. We introduce READER (Robust Evidence-based Authorship Decoding via Extracted Representations), a lightweight provenance framework that treats a frozen proxy LLM as a reader of hidden authorship evidence. READER maps black-box outputs into proxy activation space, temporally filters token states within each response, and performs Bayesian Evidence Accumulation by summing single-response log-posterior evidence across independently sampled prompts. This avoids fragile mean-pooling of prompt-specific representations while preserving the query-wise evidence needed for calibrated confidence. On Agent500, a 50-target dataset built from agent-style prompts, READER reaches $31.0$-$42.4\%$ top-1 accuracy from a single response and $70.0$-$84.0\%$ from 50 responses, substantially outperforming sentence-encoder fingerprints. Scaling across nine proxy readers further shows that stronger LLMs expose more linearly decodable authorship structure, suggesting that authorship perception is already present in frozen LLM representations and can be converted into reliable multi-query attribution.

02.
arXiv (quant-ph) 2026-06-11

Multipartite reference-frame-independent quantum cryptographic communication

arXiv:2606.12284v1 Announce Type: new Abstract: Reference frame mismatch among communication parties introduces errors in quantum cryptographic protocols. As the number of participants increases, aligning reference frames becomes increasingly difficult, complicating multipartite quantum cryptographic implementations. Here, we theoretically and experimentally investigate multipartite reference-frame-independent (RFI) quantum cryptographic communication using Greenberger-Horne-Zeilinger (GHZ) states. We generalize the bipartite RFI security parameter $C$ to an $N$-party parameter $C_N$ and derive the asymptotic secret key rate expressed solely in terms of experimentally accessible quantities. We analyze the key rate under global and local depolarizing noise models and find that increasing the number of parties $N$ enhances robustness against global depolarizing noise while increasing vulnerability to local channel noise. We also present a proof-of-principle experimental demonstration of four-party RFI quantum cryptographic communication using four-photon GHZ states, confirming the reference-frame invariance of both the $C_4$ parameter and the secret key rate under various reference frame rotations.

03.
arXiv (quant-ph) 2026-06-15

A new class of degenerate solutions to the massless Dirac equation and their potential applications in optical memories

arXiv:2606.14256v1 Announce Type: new Abstract: In this article, we present a novel class of degenerate solutions to the massless Dirac equation, corresponding to a wide variety of electromagnetic 4-potentials and fields, including both zero field and circularly polarized electromagnetic waves. An interesting property of these solutions is that the spin of the particles rotates in synchronization with the electric and magnetic fields of the electromagnetic waves. These results could be utilized for the development of optical memories based on materials supporting massless Dirac fermions, such as graphene.

04.
arXiv (CS.AI) 2026-06-16

Heteroskedastic Signals in Budgeted LLM Verification: Structural Heterogeneity Limits Optimization Gains

作者:

arXiv:2606.15841v1 Announce Type: new Abstract: Large language model (LLM) systems increasingly use uncertainty signals to allocate limited computation across verification, test-time scaling, tool execution, and other selective-compute decisions. Such policies rely on a global signal comparability assumption: equal scores should carry comparable decision value across inputs. Using budgeted verification as a controlled diagnostic setting, we identify a failure mode of this assumption: uncertainty quality is heteroskedastic across cost strata, with some regions exhibiting near-random discriminability despite concentrating many errors. Under an explicit local model, we characterize the resulting distortion of global allocation and show that its upper bound scales with cross-stratum signal-quality dispersion. We separate weak signals, optimization instability, and structural heterogeneity through a controlled intervention hierarchy: Threshold, MP-Adapt, MP-Strat, and a deliberately simple cost-stratified thresholding intervention (CST). Across MBPP and MATH using Qwen3-8B, LLaMA3-8B, and GPT-4o-mini, global online adaptation yields inconsistent gains over static thresholding; MP-Strat partially recovers performance, while CST improves hit rate by up to 17 percentage points in strongly heterogeneous settings without gradient updates. These results identify structural heterogeneity, rather than optimizer weakness alone, as the primary bottleneck in the observed settings. More broadly, misaligned feedback structure cannot always be repaired by stronger optimization.

05.
Nature (Science) 2026-06-23

Silicon Valley’s vision for global AI is flawed: each country needs its own blueprint

From energy grids to language performance, emerging economies are exposing the limits of today’s artificial-intelligence strategy as it expands globally. From energy grids to language performance, emerging economies are exposing the limits of today’s artificial-intelligence strategy as it expands globally.

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

Sensing Intelligence as a Trainable Metamaterial Property

arXiv:2605.23967v2 Announce Type: replace-cross Abstract: In biological systems, sensing is not performed by the brain alone: the body deforms, vibrates, and filters external stimuli before they are transduced into neural signals. In engineered systems, this processing burden is placed largely on electronics and computation, while the mechanical body is usually designed only for strength and stability. Here, we present sensing intelligence as a trainable property of the body. We show that the geometry of a metamaterial can be optimized to reshape external stimuli into internal signals that are easier for a neural network to interpret. Rather than hand-designing this physical preprocessing, we let the neural network train its own body for sensing by backpropagating the sensing loss to the body's design parameters through differentiable simulation. Across numerical and experimental sensing scenarios, the optimized body improves sensing accuracy by up to fivefold or reduces the number of required electronic sensors by nearly an order of magnitude.

07.
medRxiv (Medicine) 2026-06-24

INCREASED REMOVAL SIGNALS ON ERYTHROCYTES OF ANEMIC CANCER PATIENTS

BACKGROUND: Anemia is a negative factor in cancer, influencing the prognosis, quality of life and financial situation of cancer patients. Recent studies have shown that anemia in cancer is provoked by augmented erythrocyte removal. OBJECTIVE: In this study we sought to investigate the molecular bases for erythrocyte removal in cancer patients with anemia. In particular, we explored the levels of erythrocyte CD47, lactadherin, calreticulin and MCP1. METHODS: Thirty five anemic cancer patients (25 women, aged 66.4 +/-11.35 years old) and twelve healthy non-anemic controls (8 men, aged 61.1+/-9.98 years old) participated in our study. Red blood cells were isolated throug multiple centrifugations, and were lysed with the use of Triton-X 100. The levels of CD47, lactadherin, calreticulin and monocyte chemoattrractant protein 1 were determined by ELISA. RESULTS: Erythrocytes of anemic cancer patients display reduced CD47 (p

08.
arXiv (CS.AI) 2026-06-24

E-MRL: Cross-view Aligned Evidence-driven Multimodal Reinforcement Learning for Reliable 3D Tumor Analysis

arXiv:2606.23888v1 Announce Type: cross Abstract: While Vision-Language Models (VLMs) show great promise in volumetric medical report generation, they frequently suffer from visual hallucinations and a lack of grounding in 3D CT data. Current Supervised Fine-Tuning (SFT) and Reinforcement Learning (RL) strategies typically optimize text fidelity alone, essentially rewarding correct diagnoses derived from language priors rather than genuine visual perception. To address this, we propose cross-view aligned Evidence-driven Multimodal Reinforcement Learning (Evidence-MRL, noted as E-MRL), a reliable RL reasoning framework that formulates the generation process as a Markov Decision Process of "diagnosis-localization-verification". Unlike standard approaches, our model is explicitly trained to identify a "key evidence slice" alongside the global diagnostic report, grounding its findings in verifiable visual evidence. Crucially, we introduce a novel cross-view consistency reward, which validates the semantic alignment between the golden-standard report and a local visual re-query of the selected key slice, providing additional rewards for correctly-localized reasoning. Experiments on large-scale 3D CT tumor datasets demonstrate that E-MRL significantly reduces hallucinations and improves diagnostic accuracy compared to SFT and RL baselines, offering a clinically interpretable solution for visually-grounded and tumor analysis.

09.
arXiv (CS.AI) 2026-06-25

Reliability-Asymmetric Spacecraft Autonomy: Co-Designing a Capable Learned GNC Stack with a Verified, Adaptation-Aware Runtime Shield

arXiv:2606.25366v1 Announce Type: cross Abstract: Deep-space missions need onboard autonomy that is both capable and certifiable. Rule-based autonomy is certifiable but brittle, while learned autonomy is capable but hard to verify. We present AMPLE-GNC, a three-tier guidance, navigation, and control stack. Its capability path combines a small foundation-model commander that maps natural language to PDDL+, a constraint-screening verifier, and a fault-adaptive controller. All three are bounded by a runtime shield with nine linear-temporal-logic invariants whose predictor soundness is machine-checked by the Kind 2 model checker. On a 6-DOF Basilisk testbed, we make three contributions. First, we deploy an edge commander. Fine-tuning a pretrained 360M model with grammar-constrained decoding gives a hard output-validity guarantee and 84% planner-executable actions. On a de-leaked test, novel-phrasing generalization is 38% exact and 51% action, rising to 48% exact after phrasing-diversity re-finetuning; we separate syntactic validity from semantic accuracy. Second, we introduce a fault-adaptive controller. Rapid Motor Adaptation infers latent actuator faults online and recovers 97.8% of actuator-sign faults and 94.4% of continuous-gain faults within the training randomization envelope. Fault-unaware PD and from-scratch end-to-end RL both score 0%, while the strongest classical-adaptive baseline reaches 55% on continuous gain. Beyond the envelope, a split-conformant retrain scores 57-67%, and adding 4x more in-regime data worsens performance, showing that randomization breadth, not data volume, drives generalization. Robustness is flat under star-tracker noise to 0.005. Third, we show that a latching safe-hold shield can suppress even a capable controller. A split-conformal recovery-deadline certificate with adaptation-aware engagement reconciles safety and recovery, keeping the controller 94.5% autonomous while still catching non-recovery.

10.
arXiv (CS.CL) 2026-06-11

Cross-Layer Discrete Concept Discovery for Interpreting Language Models

Interpreting language models remains challenging due to the existence of residual stream, which linearly mixes and duplicates features across adjacent layers, causing single-layer analyses to miss this cross-layer structure. Cross-layer sparse autoencoders (SAEs) address layer mixing but operate in continuous space, where concepts split across many neurons without clear boundaries. We introduce Cross-Layer Vector Quantized-Variational Autoencoder (CLVQ-VAE), a novel framework which maps representations from a lower layer to a higher layer through a discrete vector-quantization bottleneck, collapsing duplicated residual-stream features into compact, interpretable concept vectors. Our approach combines top-k temperature-based sampling with exponential moving average (EMA) codebook updates, providing controlled exploration of the discrete latent space while maintaining codebook diversity. Across both encoder- and decoder-based models on ERASER-Movie, Jigsaw, and AGNews, CLVQ-VAE outperforms clustering, single-layer vector quantized-variational autoencoder (VQ-VAE), and sparse autoencoder (SAE) baselines across three evaluation axes: removing identified concepts drops model accuracy by up to 93%, LLM judges rank our concepts first in 66.7% of comparisons, and human annotators recover model predictions from our visualizations with 78% accuracy versus 54% for clustering.

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

Focus, Align, and Sustain: Counteracting Gradient Dilution in Incremental Object Detection

Adapting Detection Transformers to Incremental Object Detection (IOD) poses a systemic challenge, as set-based optimization is inherently destabilized by sequential learning. In this work, we identify Gradient Dilution as the root cause of performance degradation, wherein optimization signals required to preserve old knowledge are progressively weakened. This phenomenon manifests as a cascading erosion of preservation gradients in magnitude, direction, and support coverage, driven by three tightly coupled factors: Signal Dispersion, where foreground gradients are overwhelmed by background noise; Assignment Drift, where stochastic query-target matching induces inconsistent gradient trajectories; and Support Attrition, where gradients from retained samples insufficiently cover the old-class feature space, weakening decision boundaries under interference from new classes. To counteract this, we propose FAS, a unified framework that Focuses, Aligns, and Sustains gradient flow throughout incremental learning. Specifically, we introduce prior-injected queries to focus discriminative signals by filtering background interference at the source. We further propose deterministic anchor distillation to align query-target assignments and enforce semantic consistency across stages under unstable matching. Finally, we devise manifold-support replay to sustain distributional support of old classes, counteracting representational erosion induced by continual updates. Extensive experiments show that FAS restores robust optimization dynamics and outperforms state-of-the-art methods, achieving over 5.0 AP improvement in the challenging 40+10x4 incremental setting.

12.
arXiv (CS.CL) 2026-06-17

Non-Autoregressive Minimum Bayes' Risk Decoding for Fast Speech Recognition

Non-autoregressive (NAR) decoding generates output tokens in parallel, making speech recognition faster than autoregressive decoding, which generates them sequentially from left to right. However, the recognition performance is degraded because NAR decoding cannot resolve uncertainty by conditioning on previously generated tokens. To address this issue, we propose a novel NAR decoding framework based on minimum Bayes' risk (MBR) decoding, termed NAR-MBR decoding, that maximizes the expected utility calculated from samples drawn from the output probability of an NAR model rather than maximizing the output probability. Notably, by leveraging the nature of NAR models, multiple samples are obtained efficiently with a single forward computation. Our experiments across LibriSpeech, Switchboard, AMI, and web presentation corpus demonstrated that our NAR-MBR decoding outperformed previous NAR decoding and ran faster than AR decoding.

13.
arXiv (CS.CV) 2026-06-15

A Multi-Domain Feature Fusion Framework for Generalizable Deepfake Detection Across Different Generators

Deepfakes are artificially generated images, audio, or videos that threaten privacy, security, and information integrity. Detecting such content is crucial for countering disinformation, as the latest models generate highly realistic content. While spatial- or frequency-based approaches achieve good detection rates on Generative Adversarial Networks (GANs)-based generated deepfakes, they often struggle with recent diffusion model-generated images. In particular, existing approaches rarely exploit complementary multi-domain representations or systematically evaluate cross-generator robustness. To address these challenges, we propose a multi-domain deepfake detection framework called SGFF-Net (Spatial-Gradient-Frequency Fusion Network) that integrates spatial, gradient, and DWT (Discrete Wavelet Transform)-based frequency representations within a dual residual learning architecture. Experimental results show that the SGFF-Net achieves 98.95\% accuracy in intra-dataset evaluation and improves performance in both cross-model (70.46\%) and cross-paradigm (69.94\%) settings. Incorporating multi-source training and data augmentation further enhances robustness, increasing accuracy from 70.46\% to 79.80\% in cross-model evaluation, from 69\% to 78\% in cross-paradigm evaluation, and from 61.50\% to 75.80\% on real-world data. Unlike single-domain detectors, the SGFF-Net learns complementary forensic cues across spatial, gradient, and wavelet-frequency domains, resulting in greater robustness under cross-generator and cross-paradigm evaluation. The results further show that combining multi-domain representations with data diversity and augmentation substantially improves generalization, providing practical insights for developing more reliable deepfake detection systems.

14.
arXiv (math.PR) 2026-06-16

Uniform integrability of the distance to the nearest leaf in random trees

arXiv:2606.15339v1 Announce Type: new Abstract: We study the distance from the root to the nearest leaf, the analogous quantity for a uniformly chosen vertex, and its protection number, in size-conditioned simply generated trees. We prove a uniform exponential tail bound for each of these quantities, valid for arbitrary offspring distributions. As a consequence, these random variables are uniformly integrable of every order. This yields convergence of all moments to those of the corresponding local limit. The argument is probabilistic and unified across the three quantities.

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

ChartFI: Benchmarking Faithfulness and Insightfulness of Chart Descriptions from Multimodal Large Language Models

Chart descriptions are essential for accessibility, cross-modal retrieval, and assisting readers in extracting insights from complex visualizations. As multimodal large language models (MLLMs) are increasingly adopted for automated chart description generation, a critical question arises: how faithfully and insightfully do these models actually describe charts? Current benchmarks fall short on two fronts: existing datasets consist of simple, homogeneous charts paired with shallow, fact-enumerating descriptions; and prevailing metrics fail to capture the multi-faceted nature of description quality. To address these gaps, we present the Chart Faithfulness and Insightfulness Benchmark (ChartFI-Bench). We first summarize four dimensions that characterize high-quality chart descriptions: factual accuracy, salient feature emphasis, domain-informed guidance, and chart-text complementarity. Guided by these dimensions, we construct a high-quality benchmark comprising 896 chart-description pairs, which feature visually complex charts and semantically rich descriptions. Furthermore, we design four aligned evaluation metrics – Faithfulness, Coverage, Informativeness, and Acuity – to systematically assess the quality of descriptions across these dimensions. Experiments conducted on mainstream MLLMs demonstrate the effectiveness of the proposed framework and reveal common weaknesses among existing models.

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

Decomposing one-class support vector machine into an ensemble of one-data support vector machines

arXiv:2606.16002v1 Announce Type: new Abstract: One-class classification (OCC) is a classification problem in which the training data contains only one class. The one-class support vector machine (OCSVM) is one of the most competitive OCC algorithms. However, OCSVM has scalability issues with large-scale datasets. This paper proposes the acceleration strategy of OCSVM. The idea is to decompose the dataset into samples and train OCSVM models for single data points. Subsequently, ensemble learning is applied to combine all models to compute the OCSVM model for the dataset. In addition, further acceleration is achieved through a data-reduction strategy with an OCSVM model trained on the average of the training samples. The experiment compared the proposal and traditional OCSVM using the Python package. The proposed strategy is faster than traditional OCSVM, while achieving similar classification results. Moreover, the proposed strategy can create one-to-one correspondence between samples and models. Source code is uploaded at https://github.com/ToshiHayashi/ODSVM

17.
arXiv (CS.AI) 2026-06-16

Integrating Multi-Label Classification and Generative AI for Scalable Analysis of User Feedback

arXiv:2601.23018v1 Announce Type: cross Abstract: In highly competitive software markets, user experience (UX) evaluation is crucial for ensuring software quality and fostering long-term product success. Such UX evaluations typically combine quantitative metrics from standardized questionnaires with qualitative feedback collected through open-ended questions. While open-ended feedback offers valuable insights for improvement and helps explain quantitative results, analyzing large volumes of user comments is challenging and time-consuming. In this paper, we present techniques developed during a long-term UX measurement project at a major software company to efficiently process and interpret extensive volumes of user comments. To provide a high-level overview of the collected comments, we employ a supervised machine learning approach that assigns meaningful, pre-defined topic labels to each comment. Additionally, we demonstrate how generative AI (GenAI) can be leveraged to create concise and informative summaries of user feedback, facilitating effective communication of findings to the organization and especially upper management. Finally, we investigate whether the sentiment expressed in user comments can serve as an indicator for overall product satisfaction. Our results show that sentiment analysis alone does not reliably reflect user satisfaction. Instead, product satisfaction needs to be assessed explicitly in surveys to measure the user's perception of the product.

18.
arXiv (math.PR) 2026-06-16

Risk-averse mean field games: exploitability and non-asymptotic analysis

arXiv:2301.06930v5 Announce Type: replace-cross Abstract: In this paper, we use mean field games (MFGs) to investigate approximations of $N$-player games ($N$pGs) with uniformly symmetrically continuous heterogeneous closed-loop actions. To incorporate agents' risk aversion (beyond the classical expected utility of total costs), we use an abstract evaluation functional for their performance criteria. Centered around the notion of exploitability, we conduct non-asymptotic analysis on the approximation capability of MFGs from the perspective of state-action distributions without requiring the uniqueness of equilibria. Under suitable assumptions, we first show that scenarios in the $N$pGs with large $N$ and small average exploitabilities can be well approximated by approximate solutions of MFGs with relatively small exploitabilities. We then show that $\delta$-mean field equilibria can be used to construct $\varepsilon$-equilibria in $N$pGs. Furthermore, in this general setting, we prove the existence of mean field equilibria. This proof reveals a possible avenue for incorporating penalization for randomized action into MFGs.

19.
arXiv (CS.CL) 2026-06-25

Story Operators: Decomposing the Original $\to$ Sequel Transformation in Embedding Space

I treat a book as a point in a sentence-embedding space and a literary transformation as an operation on points. Given an original novel and its sequel, I ask what it takes, geometrically, to turn the first into the second. Using all-mpnet-base-v2 paragraph embeddings drawn from a precomputed index of the PG19 corpus, I form the displacement $d=\bar{x}_seq-\bar{x}_orig$ and greedily decompose it along a content basis obtained by PCA over the two books' own paragraphs. Each component is an interpretable axis anchored by real passages at its poles. Across thirteen verified author pairs from Project Gutenberg, the decomposition reveals a small taxonomy of sequels: formulaic (a tiny, low-rank change: Doyle's Holmes collections, $\|d\|=0.12$), concentrated (one dominant axis: Alcott's Little Women $\to$ Little Men, 75% on a single move), and compositional (many small axes: Twain, Burroughs's Barsoom, Nesbit). For the canonical case, Tom Sawyer $\to$ Huckleberry Finn, the dominant recovered axis is structural – the collapse of sheltering domesticity into a picaresque road – rather than the famous surface themes of vernacular voice or slavery, which ride later, smaller axes; and the transformation routes through adventure-journey space rather than diluting toward generic realism. I corroborate the recovered geometry against Twain's documented authorial intent (his 1875–76 letters to Howells), which names the first-person picaresque move years in advance, and I quantify, with an explicit representation caveat, how much of the realized transformation his stated intentions span. All computations are reproducible from the released scripts and data.

20.
arXiv (math.PR) 2026-06-18

Rigidity of infinite exchangeable sequences with Gaussian marginals

arXiv:2606.18654v1 Announce Type: new Abstract: We study infinite exchangeable sequences with Gaussian one-dimensional marginals. We formulate the conjecture that joint Gaussianity of a single pair of coordinates forces the entire sequence to be a Gaussian process. Although this conjecture remains open, we prove that joint Gaussianity of the first four coordinates is sufficient. We also establish the corresponding two-point criterion under the additional assumption that the directing measure is almost surely infinitely divisible.

21.
arXiv (CS.CV) 2026-06-12

Visual Place Recognition in Forests with Depth-Aware Distillation

Visual place recognition in natural forest environments remains challenging due to repetitive vegetation, weak structural cues, and significant appearance variation across traversals. To address this limitation, this paper proposes a lightweight depth-aware distillation framework that injects geometric cues into a DINOv2-based place recognition model, while maintaining its pre-trained descriptor space. Evaluated on the recent WildCross benchmark, the proposed approach yields gains over an appearance-only counterpart, providing robustness to appearance variations. These results demonstrate the importance of depth as a strong complementary modality for place recognition in natural environments and identify depth-aware distillation as a promising direction for more robust forest perception.

22.
arXiv (math.PR) 2026-06-24

Exact Evaluation of Probabilistic Programs with Cylindrical Algebraic Decomposition

arXiv:2606.24514v1 Announce Type: cross Abstract: We present a method for computing the exact output distribution of small programs with random inputs. Specifically, we are interested in inline programs manipulating sensor data such as \eg GPS or inertial measurement sensors whose inputs have a known or well-modelled distribution. These programs typically only include relatively few variables, arithmetic operations, square roots and if-else statements. This small syntax allows us to recast the problem of computing the exact output distribution as a cylindrical algebraic decomposition problem followed by symbolic and/or numerical integration. We present this method in detail and show with two prototypes that it can successfully be applied to benchmarks from the literature on floating-point arithmetic and small programs from open-source sensor libraries.

23.
arXiv (CS.AI) 2026-06-25

Multi-Agent Goal Recognition with Team- and Goal-Conditioned Reinforcement Learning and Factorized Branch-and-Bound

arXiv:2606.25978v1 Announce Type: cross Abstract: Multi-agent goal recognition asks an observer to jointly infer which agents act together and what each team is trying to achieve, so the hypothesis space grows combinatorially with the number of team partitions and goals per team. Real applications such as drone surveillance and collaborative robotics expose only the agents' trajectory, which forces the observer to rank team-goal hypotheses from behavior alone. Multi-Agent Goal Recognition with Branch-and-Bound (MAGR-BB) addresses this setting with a shared team- and goal-conditioned policy used as the scoring model inside a factorized branch-and-bound search. On a controlled multi-agent Blocksworld benchmark, MAGR-BB returns the same top-ranked hypothesis as exhaustive search throughout the trajectory while cutting hypothesis materialization by orders of magnitude and reducing cumulative recognition runtime substantially.

24.
bioRxiv (Bioinfo) 2026-06-11

HoloCell: A Generative Foundation Model for Holistic Cellular Modeling

Single-cell multi-omics technologies have recently advanced to enable the profiling of epigenomic, transcriptomic, and proteomic layers within individual cells, offering new opportunities to characterize cellular states as integrated biological systems. However, developing a unified framework that can seamlessly integrate diverse omics modalities and remain robust to heterogeneous modality missingness remains challenging. Here we present HoloCell, to our knowledge the first generative foundation model for joint representation learning and generative modeling across all three major single-cell omics modalities, i.e., epigenomics, transcriptomics, and proteomics. HoloCell contains over 860 million parameters and is pretrained on the Human-Multi-Omics-Corpus, which comprises approximately 468 million single-cell profiles across these three omics layers, corresponding to over 425 billion tokens. HoloCell introduces a simple yet biologically grounded hierarchical tokenization strategy that encodes cis-regulatory elements, genes, and proteins as structured tokens within a shared modeling framework. We evaluated HoloCell across single-omics representation learning, paired multi-omics integration, unpaired multi-omics alignment, and cross-modal generation via iterative diffusion and remasking, demonstrating its superior performance and flexibility across diverse omics tasks. From a representation perspective, HoloCell provides a unified digital mapping of cellular states across multiple omics layers, capturing cell heterogeneity as an integrated system. From a generation perspective, its iterative diffusion and remasking framework accounts for the inherently unordered nature of biological features, enabling in silico simulation of multi-omics information flow. Together, these capabilities position HoloCell as a versatile foundation model toward the emerging concept of a virtual cell, offering both systematic characterization and generative simulation of cellular systems within a unified framework.

25.
bioRxiv (Bioinfo) 2026-06-14

Prediction of parsimonious and temporally sensitive sets of cell fate engineering transcription factors with IMCell

Transcription factor (TF) cocktails used in cell identity reprogramming protocols have largely been developed from experimental approaches. A handful of computational approaches have been reported, though have not been widely adopted by the scientific community. To standardize their use and assess their performance, we built CompForce, a platform that integrates these tools. Using CompForce, we found that existing computational methods offer modest improvements over differential expression on both synthetic and literature-curated data, and that their lackluster and inconsistent performance could be attributed to a reliance on local centrality metrics. To improve upon these methods, we developed IMCell, a prediction method that is inspired by the influence maximization problem. Unlike existing tools, IMCell returns optimized TF sets rather than ranked TF lists. We demonstrate that IMCell vastly out-performs existing tools, and further extend it to dynamic, stepwise contexts. The tools presented here are available in the R packages CompForce and IMCell.