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01.
arXiv (CS.CV) 2026-06-16

VisualClaw: A Real-Time, Personalized Agent for the Physical World

Vision language models are serving as general-purpose interfaces for complex multimodal tasks. However, deployment still faces three gaps: VLMs typically incur high latency and cost when processing dense video frames and long prompts, the agent scaffold remains static after deployment, and standard video-QA benchmarks do not test whether agents can use visual evidence inside tool-using workspaces. We present VisualClaw, a self-evolving multimodal agent built around two principles. First, hybrid encoding reduces deployment cost by filtering less informative streaming frames with a cascaded gate and compressing the text skill bank through hot/cold top-k injection. Second, skill evolution lets the agent learn from failures: retrieved memories condition an evolver as direct concatenated context or as guided evidence, producing skill-bank updates that help future questions. Across 4 video-QA benchmarks with 2 VLMs, VisualClaw cuts per-question API cost by an average -98% versus full-frame upload and by -25.9% over the offline uniform 8 frame baseline, while boosting accuracy in most settings, e.g., an average +3.85% and a peak +15.80% on EgoSchema with Gemini 3 Flash. To address the gap, we curate VisualClawArena, a 200-scenario multimodal agentic benchmark built through a strict five-stage pipeline; models must use video evidence, documents, dynamic updates, and executable checks inside a workspace. On VisualClawArena, the same framework with computer-use agent backends improves macro accuracy by +2.9% for Codex (GPT-5.5) and +3.2% for Claude Code (Sonnet 4.6) over no-evolution baselines, with a -9.5% cost reduction compared to the uniform-sampled baseline. These properties make VisualClaw a natural fit for edge applications, where the cascade reduces a 1-hour streaming session from ~3,600 API uploads down to only 5-20 calls and the self-evolution makes it a perfect personalized assistant.

02.
arXiv (CS.LG) 2026-06-11

Composing Linear Layers from Irreducibles

arXiv:2507.11688v4 Announce Type: replace Abstract: Contemporary large models often exhibit behaviors suggesting the presence of low-level primitives that compose into modules with richer functionality, but these fundamental building blocks remain poorly understood. We investigate this compositional structure in linear layers by asking: can we identify/synthesize linear transformations from a minimal set of geometric primitives? Using Clifford algebra, we show that linear layers can be expressed as compositions of bivectors – geometric objects encoding oriented planes – and introduce a differentiable algorithm that decomposes them into products of rotors. This construction uses only O(log^2 d) parameters, versus O(d^2) required by dense matrices. Applied to the key, query, and value projections in LLM attention layers, our rotor-based layers match the performance of strong baselines such as block-Hadamard and low-rank approximations. Our findings provide an algebraic perspective on how these geometric primitives can compose into higher-level functions within deep models.

03.
Nature (Science) 2026-06-17

Analysis of 173,303 exomes and genomes in the Pakistan Genome Resource

Naturally occurring loss-of-function variants in human genes enable drug target discovery because they mimic pharmacological inhibition of proteins. However, the study of these genetic variants is constrained by their rarity. Sequencing of diverse populations, particularly those enriched in familial relatedness, has been postulated to promote discovery of rare genetic variants1–3. Here we present the Pakistan Genome Resource, a South Asian biobank with high familial relatedness comprising 173,303 participants, who collectively carry naturally occurring homozygous loss-of-function variants in 6,476 genes. We describe the genetic architecture of this population, associations between genes and biomarkers, the distribution of loss-of-function variants across molecular pathways, and recall-by-genotype studies of therapeutically relevant genes. The Pakistan Genome Resource expands the catalogue of human genetic variants, provides a comprehensive genetic reference resource for the Pakistani population, and demonstrates the value of studying diverse cohorts to advance human health. The Pakistan Genome Resource compiles biobank data from 173,303 individuals with high familial relatedness, broadening the catalogue of human genetic variation and establishing a population-specific genomic reference for Pakistan.

04.
arXiv (CS.AI) 2026-06-19

Before the Pull Request: Mining Multi-Agent Coordination

arXiv:2606.19616v1 Announce Type: cross Abstract: Autonomous coding agents now open millions of pull requests, yet large-scale studies find their PRs are produced faster but accepted less often - a coordination and trust gap that pull-request-level telemetry cannot explain. We argue the missing signal lives before the PR, in how concurrent agents claim, divide, and collide over shared work. We study this process through grite, our open-source coordination substrate that needs no central server and stores its records inside git itself, so its append-only, signed event log captures the coordination process directly. We show that (i) this shared substrate reduces duplicate and conflicting work at bounded overhead - the share of work that merely re-does a teammate's task falls from 78% to 0% while useful throughput more than triples; (ii) every agent's copy of the log converges to the same state with no write silently dropped, where a file-based tracker loses concurrent writes; and (iii) the log is a mineable artefact from which concrete failure modes - conflicting edits, lock starvation, redundant rediscovery, race-to-close - are automatically recoverable with provenance, several invisible in pull-request history. We release the dataset, harness, and mining toolkit.

05.
arXiv (CS.CV) 2026-06-19

HumanScale: Egocentric Human Video Can Outperform Real-Robot Data for Embodied Pretraining

Embodied foundation models are expected to benefit from data scaling like large language models, but face a much tighter data bottleneck. Teleoperated real-robot trajectories remain the dominant pretraining source due to their precise action supervision and embodiment alignment, yet their scalability is limited by high collection cost, acquisition difficulty, and low behavioral and environmental diversity. These limitations have sparked interest in egocentric human video as a scalable, substantially lower-cost, and more diverse alternative for embodied model pretraining. However, its effectiveness compared to teleoperated real-robot data remains underexplored. To address this question, we conduct a systematic study comparing egocentric human video and teleoperated real-robot trajectories as pretraining data sources for embodied foundation models, under fixed post-training and validation protocols. Surprisingly, we find that egocentric data, when processed through a carefully designed filtering and labeling pipeline, is not merely a viable substitute for model pretraining but can lead to superior performance. With the same amount of pretraining data, models pretrained on egocentric data achieve a 24% lower validation loss on real-robot action prediction, as well as 52.5% and 90% higher success rates on in-distribution and out-of-distribution real-robot task execution, respectively. This finding verifies a scalable paradigm for embodied foundation models: pretrain on egocentric human video to learn diverse world representations, then adapt with a small amount of labeled real-robot data for action-space alignment. We hope this study encourages broader exploration of egocentric data and offers guidance for data quality assessment before costly robot data collection.

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

Attention Alignment Between Humans and Vision-Language Models

Visual perception depends on top-down goals and bottom-up sensory mechanisms. Vision-language models implement both, allowing us to treat each component as a separable hypothesis about what drives where we look. We compared spatial attention maps from six vision-language models against human fixation heatmaps recorded on 200 images during two tasks (general description and social captioning). The six models spanned a 2$\times$2 factorial of CNN vs.\ ViT encoders crossed with LSTM vs.\ Transformer decoders, plus Molmo 7B-D and Qwen3.5 9B. We found that both decoder and encoder architecture shaped alignment, but decoder choice dominated. LSTM vs.\ Transformer decoders increased alignment by 40–50 percentage points (80–87\% vs.\ 40–59\% of the human noise ceiling). In contrast, CNN vs.\ ViT encoders contributed a secondary 5–20 point advantage depending on decoder family, with CNN-LSTM the most aligned model overall (85–87\%). Despite their alignment advantage, LSTM-decoder attention maps were spatially diffuse and minimally task-differentiated; ViT-Transformer, the weakest in alignment, showed the sharpest spatial concentration and strongest task differentiation. A hemispatial-neglect simulation confirmed that ablating attention impacted LSTM decoders more than Transformer decoders. In an exploratory extension using TRIBE-simulated synthetic neural responses, fixation alignment and neural relevance dissociate: CNN-Transformer attention maps better predicted synthetic brain activity despite lower fixation alignment, with attention maps best predicting early visual cortex. Together, top-down and bottom-up components trade off what they predict in behavioral and synthetic neural data.

07.
arXiv (CS.AI) 2026-06-12

Interaction-Centered Intelligence: Toward an Interaction-Based Theory of Human-AI Co-Creation

arXiv:2606.00807v2 Announce Type: replace Abstract: Traditional artificial intelligence has largely conceptualized intelligence as isolated computation occurring within bounded agents. Across classical AI, machine learning, and many generative systems, the dominant unit of analysis remains the individual model or autonomous system evaluated through outputs, benchmarks, prediction accuracy, or optimization performance. While these approaches have produced major advances, they often under-theorize the role of interaction in the emergence of intelligence, creativity, meaning, and adaptive behavior. This paper proposes interaction as the primary unit of analysis for co-creative AI and interaction-centered intelligence more broadly. Drawing from distributed cognition, embodied cognition, enaction, participatory sense-making, human-computer interaction, and computational creativity, the paper traces a historical progression toward increasingly relational accounts of intelligence. Building upon prior work in Creative Sense-Making, quantified co-creation, and co-creative systems such as the Drawing Apprentice and AI Drawing Partner, it argues that intelligence emerges through evolving interaction dynamics among agents, environments, and socio-technical systems rather than solely through internal computation. The paper introduces Interaction-Centered Intelligence as a framework for understanding human-AI co-creation, collaborative emergence, adaptive participation, and interactional dynamics. Rather than evaluating intelligence solely through generated outputs, the framework emphasizes interaction trajectories, coordination patterns, participatory engagement, adaptive regulation, and interactional drift unfolding through time. Implications for explainable co-creative AI, hybrid intelligence, enactive AI, and future human-AI systems are discussed.

08.
arXiv (CS.LG) 2026-06-16

Federated Foundation Language Model Post-Training Should Focus on Open-Source Models

arXiv:2505.23593v4 Announce Type: replace Abstract: Post-training of foundation language models has emerged as a promising research domain in federated learning (FL) with the goal to enable privacy-preserving model improvements and adaptations to user's downstream tasks. Recent advances in this area adopt centralized post-training approaches that build upon black-box foundation language models where there is no access to model weights and architecture details. Although the use of black-box models has been successful in centralized post-training, their blind replication in FL raises several concerns. Our opinion is that using black-box models in FL contradicts the core principles of federation such as data privacy and autonomy. In this paper, we critically analyze the usage of black-box models in federated post-training, and provide a detailed account of various aspects of openness and their implications for FL.

09.
arXiv (CS.CL) 2026-06-12

AI SciBrief as a Gateway to Research: A Framework for Onboarding Students into New Research Areas

Students at all levels of higher education face a significant barrier in the form of information overload, which often paralyzes the initial stages of the research process and suppresses motivation. In response, this article introduces a pedagogical framework that leverages AI SciBrief, a platform powered by a Large Language Model (LLM) designed to automatically generate digests of scientific trends. We describe how this multidisciplinary tool - with initial coverage in finance, medicine, and education - can be integrated into the curriculum to overcome this "entry barrier." The framework provides concrete methodologies for utilizing these digests to facilitate topic selection for term papers, accelerate literature reviews for dissertations, and enable postgraduate students to continuously monitor emerging trends. We conclude that AI SciBrief functions as a "gateway to research" effectively reducing students' cognitive load and empowering them to transition more rapidly from information searching to knowledge creation.

10.
arXiv (CS.CV) 2026-06-19

QG-MIL: A Gated Transformer Aggregator for Domain-Agnostic Multiple Instance Learning in Medical Imaging

Attention-based Multiple Instance Learning aggregators in medical imaging are prone to attention concentration, producing overconfident and unstable predictions. We introduce QG-MIL, a gated transformer aggregator that addresses this through four synergistic architectural components: RMSNorm-based pre-normalization, per-head QK normalization, fine-grained attention output gating, and SwiGLU-style feed-forward modules. Together, these design choices stabilize training and distribute attention more uniformly across instances without auxiliary losses, masking, or multi-stage regularization. We evaluate QG-MIL across six benchmarks spanning whole-slide pathology and cell-level hematology, covering two fundamentally different MIL scales. The best-performing QG-MIL variants outperform leading baselines on all six benchmarks, with an average improvement of +6.1 mean macro F1 points. Attention overlays and attention mass analysis confirm more distributed instance weighting. Ablation studies show that while individual components can match the full model on specific datasets, the QG-MIL design provides the most consistent cross-domain performance and tightest variance when compared to selected baselines. We release a configurable implementation to support reproducibility at: https://github.com/unica-visual-intelligence-lab/QG-MIL

11.
arXiv (CS.CL) 2026-06-12

SafeLLM: Extraction as a Hallucination-Resistant Alternative to Rewriting in Safety-Critical Settings

Large language models (LLMs) are increasingly used to access organisational documentation, including standard operating procedures (SOPs), HR policies and institutional guidelines. However, retrieval-augmented generation (RAG) systems that rely on free-form rewriting can introduce hallucinations and unstable trade-offs between completeness and conciseness, particularly in safety- and compliance-critical settings. Objectives: To evaluate extraction as a hallucination-resistant alternative to rewriting-based RAG and compare strategies that balance precision, recall and safety across document types and model scales. Methods: We compare multiple prompting strategies, including line-number-based source selection, extraction of relevant guideline sentences with explicit safety annotations, and a multi-stage pipeline that refines draft answers using supporting evidence from source guidelines. Experiments are conducted on documents of varying length and structure, including local NHS acute care and oncology guidelines and UK-wide NICE guidelines, using both frontier-scale and locally deployable models. Performance is assessed using automatic metrics and human expert evaluation of relevance and completeness. Results: Line-number selection achieves the strongest results, outperforming direct copying and safety-focused strategies across both large and small models while maintaining high term recall (up to 95%) and close alignment with source text. Safety-oriented approaches improve precision but introduce systematic omissions, while multi-stage filtering further amplifies this trade-off. Performance varies with document structure: line-based extraction excels in protocol-like content, whereas alternative strategies perform better on more verbose documents (up to 97% term recall).

12.
arXiv (CS.CV) 2026-06-16

MMLongEmbed: Benchmarking Multimodal Embedding Models in Long-Context Scenarios

Recent advancements have significantly expanded the theoretical context windows of Multimodal Embedding Models (MEMs). However, larger context windows do not necessarily translate into effective comprehension and representation of long-context multimodal inputs, which remains a critical bottleneck for real-world deployment. To address the lack of systematic evaluation in this setting, we introduce MMLongEmbed, the first comprehensive benchmark for evaluating MEMs in long-context scenarios. MMLongEmbed comprises four retrieval tasks spanning multiple context-length ranges, covering text, document, and video modalities. Through extensive evaluation of state-of-the-art models, we find that current architectures rely heavily on superficial feature matching and struggle to capture deep semantic and structural dependencies. We further observe that performance degradation varies systematically with context length and key information placement. Moreover, models exhibit substantially different robustness to redundant contextual information across modalities. For reproducibility, the benchmark and code are publicly available.

13.
arXiv (quant-ph) 2026-06-12

Approximate quantum error correction theory of non-isometric codes

arXiv:2606.13559v1 Announce Type: new Abstract: Non-isometric encoding arises in various important contexts in quantum error correction, most notably in the finite-energy, non-ideal codewords inevitable in experimental realizations of continuous-variable codes, and holographic quantum gravity. In this work, we present a general and systematic theory of non-isometric quantum error-correcting codes. In particular, we employ the approximate quantum error correction framework to quantitatively study the fundamental limitations imposed by non-isometric encodings on the accuracy of quantum error correction and implementation of logical operations. We apply our theory to analyze GKP and tiger codes under energy constraints, and discuss the implications to holography.

14.
arXiv (CS.AI) 2026-06-15

YeasierAgent: Agentic Social Sandbox as a Canvas for Intent-Driven Creation of Platform-Agnostic Symbiotic Agent-Native Applications

作者:

arXiv:2606.13722v1 Announce Type: new Abstract: This paper introduces YeasierAgent, an application-building paradigm based on symbiotic agents, narrative worlds, and scene-aware interaction. It challenges the conventional device-coupled model of software by redefining applications as collaborative spaces among users, agents, and worlds. We present a system architecture that achieves two primary contributions: (1) enabling the rapid, cross-platform construction of agent-native applications by utilizing platform-agnostic interactive units (agents, scenes, dialogue) rather than fixed graphical layouts; and (2) unifying the emotional companionship and practical tool execution attributes of intelligent agents within a single experiential sandbox. By integrating automated generation, user-created worlds, and spatial multi-agent collaboration, YeasierAgent formalizes the category of Symbiotic Agent-Native Applications, demonstrating a shift from isolated, tool-specific chatbots toward cohesive, socially embedded computational environments.

15.
arXiv (quant-ph) 2026-06-16

Flux magnetism in a strongly interacting dipolar lattice supersolid under tunable gauge fields

arXiv:2509.05058v2 Announce Type: replace-cross Abstract: Supersolidity and magnetism are fundamental phenomena characterizing strongly correlated matter. Here we unveil a mechanism that directly connects these two regimes and can be experimentally accessed in ultracold atomic systems. Specifically, we exploit the distinctive properties of magnetic lanthanide atoms trapped in a one-dimensional anti-magic wavelength optical lattice. This platform enables a realistic implementation of a triangular Bose-Hubbard ladder featuring two key ingredients: strong long-range interactions and tunable gauge fields. Owing to these properties, our numerical analysis reveals a robust lattice supersolid regime with finite fluxes in each triangular plaquette. Remarkably, we show that the density modulation of the supersolid phase and a finite gauge field induce magnetic ordering of the fluxes, forming ferromagnetic and ferrimagnetic patterns. Our results thus reveal a fascinating quantum effect that bridges supersolidity and magnetism.

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

On a class of reflected McKean-Vlasov Stochastic Differential Equations with jumps

arXiv:2606.18433v1 Announce Type: new Abstract: This paper investigates a class of reflected McKean-Vlasov Stochastic Differential Equations driven by both Brownian motion and a compensated Poisson random measure. We establish the existence and uniqueness of solutions and provide moments estimates for the state processes.

18.
arXiv (CS.AI) 2026-06-11

When Researchers Say Mental Model/Theory of Mind of AI, What Are They Really Talking About?

arXiv:2510.02660v2 Announce Type: replace-cross Abstract: When researchers claim AI systems possess ToM or mental models, they are fundamentally discussing behavioral predictions and bias corrections rather than genuine mental states. This position paper argues that the current discourse conflates sophisticated pattern matching with authentic cognition, missing a crucial distinction between simulation and experience. While recent studies show LLMs achieving human-level performance on ToM laboratory tasks, these results are based only on behavioral mimicry. More importantly, the entire testing paradigm may be flawed in applying individual human cognitive tests to AI systems, but assessing human cognition directly in the moment of human-AI interaction. I suggest shifting focus toward mutual ToM frameworks that acknowledge the simultaneous contributions of human cognition and AI algorithms, emphasizing the interaction dynamics, instead of testing AI in isolation.

19.
arXiv (quant-ph) 2026-06-17

Creating squeezed and non-classical collective motional many-body states through stroboscopic Rydberg dressing

arXiv:2606.17849v1 Announce Type: cross Abstract: Realizing conditional quantum operations, e.g., quantum gates, for quantum computing and simulation requires controlled interactions between particles. Often, these interactions depend on the interparticle distance, and accordingly, an uncertainty of the relative particle position may translate into gate infidelities. We consider here a quantum computing platform based on an array of neutral atoms and present a method that allows to reduce the uncertainty of all interatomic distances. Our approach exploits the coupling between atomic motion and stroboscopically excited atomic Rydberg states. It allows to collectively squeeze the modes corresponding to interatomic displacements, thereby reducing distance fluctuations down to a fraction of the motional vacuum state. Furthermore, the method permits the creation of non-classical states with substantial Wigner negativity. These correlated states may allow reducing motional decoherence, increasing gate fidelity, and potentially yield a resource for quantum-enhanced metrology.

20.
bioRxiv (Bioinfo) 2026-06-10

HOMED enables hierarchical and multimodal optimization of DNA methylation deconvolution across tissues

Cellular heterogeneity is a major confounder in bulk DNA methylation data for epigenome-wide association studies. Existing reference-based DNAm deconvolution methods often ignore hierarchies among related cell types and may generalize poorly across datasets due to limited variability in reference profiles. We developed HOMED (Hierarchically Optimized Methylation Deconvolution), a framework that integrates cell-lineage hierarchies, single-cell RNA sequencing-guided deconvolution, and paired bulk RNA-seq/DNAm data for CpG signature optimization. Across simulated and real peripheral blood mononuclear cell, lung, and placental datasets, HOMED consistently yielded the highest PCCs and lowest RMSEs, outperforming existing scRNA-seq-guided DNAm deconvolution methods, improving accuracy, resolution, and cross-tissue generalizability.

21.
arXiv (CS.CL) 2026-06-18

PEC-Home: Interpretation of Progressively Elliptical Commands in Smart Homes

Recent advancements in Large Language Models (LLMs) have empowered home assistants with natural language interaction capabilities. However, current assistants overlook the progressive omission that occurs in human dialogue as shared context accumulates, leading to more elliptical expressions for efficient communication. Thus, current assistants still struggle to interpret such elliptical expressions accurately, which limits their effectiveness in real-world applications. In practical smart home scenarios, assistants face two major challenges caused by elliptical commands: (1) referential ambiguity caused by different environmental expectations among multiple users; and (2) intention ambiguity resulting from user preferences that evolve over time or change with the environment. To address these challenges, we introduce PEC-Home, the first simulated home dataset specifically designed for interpreting progressively elliptical commands in smart homes. Extensive experiments on various LLMs, including GPT-4o, show that existing home assistants struggle to execute user-intended operations based solely on elliptical commands. Even when equipped with tools for storing and retrieving user dialogue history, execution accuracy remains below that achieved with complete commands.}.

22.
medRxiv (Medicine) 2026-06-15

Multidimensional nutritional assessment in Crohns disease: cross-sectional comparison of active disease and remission

Malnutrition is common in Crohns disease (CD), and its assessment requires multiple tools. Comprehensive evaluation of nutritional status in a population with CD, predominantly characterized by metabolic phenotype, was inadequately reported. This study evaluated the nutritional status of CD patients using anthropometric, clinical, and biochemical measures and compared patients with active disease with those in remission. This cross-sectional study included 127 adults with CD: 63 with active disease and 64 in remission. Disease activity was classified using the Crohns Disease Activity Index, the Simple Endoscopic Score for Crohns Disease, and magnetic resonance enterography. Nutritional assessment included body mass index (BMI), mid-upper arm circumference, calf circumference, triceps skinfold thickness, mid-arm muscle circumference, Mini Nutritional Assessment-Short Form (MNA-SF), and biochemical markers including hemoglobin, serum iron, folate, vitamin B12, albumin, and zinc. Malnutrition was defined using the Global Leadership Initiative on Malnutrition criteria. Overall, 47.2% of participants were malnourished. Malnutrition was significantly more frequent in active disease than in remission (81.0% vs. 14.1%, P

23.
arXiv (quant-ph) 2026-06-17

Impulse Decoding of Quantum LDPC Codes: Equivalence of Degeneracy and Code-Shortening

arXiv:2606.18240v1 Announce Type: new Abstract: Quantum error correction is essential for building scalable quantum computers. Within the stabilizer formalism, the Calderbank-Shor-Steane framework constructs quantum codes from pairs of classical linear codes. A distinctive feature in this setting is degeneracy, where multiple equivalent error estimates exist-a phenomenon that has no classical counterpart, and the lack of a meaningful classical coding-theoretic interpretation of which has remained a gap in the literature. In this paper, we demonstrate that degeneracy is closely related to the classical operation of shortening of a linear block code. Interestingly, the shortening here takes place at the decoder rather than at the encoder. Leveraging this insight, we present a parallel decoding scheme for quantum low-density parity-check codes, which we term impulse decoding, that significantly outperforms belief propagation with ordered statistics decoding, as well as several other existing techniques, under both code-capacity and circuit-level noise, with significantly lesser complexity. We then present another algorithm based on decoding of residual errors, which when combined with impulse decoding achieves further performance improvement under circuit-level noise.

24.
arXiv (CS.LG) 2026-06-16

Rethinking Structural Anomaly Detection: From Decision Boundaries to Projection Operators

arXiv:2606.15280v1 Announce Type: new Abstract: Most existing anomaly detection methods rely on estimating a probability density or learning an enclosing decision boundary, implicitly assuming that normal data occupies a region of non-zero volume in the ambient space. In contrast, structural anomaly detection considers data that lies near a low-dimensional manifold, creating a mismatch between the inductive bias of existing methods and the structure of the data, often resulting in degraded performance. To address this mismatch, we introduce a geometric perspective. Specifically, we learn a projection operator onto the manifold of normal samples and define a sample as anomalous if it is altered by this projection. This formulation naturally integrates the inductive bias of manifold-supported data and reframes anomaly detection in terms of a projection residual, thereby resolving issues arising from modeling degenerate distributions. Notably, it provides a unifying interpretation of reconstruction-based methods by explaining their success and failure in terms of projection quality. In particular, it explains the strong generalization ability of projection-aligned models as a consequence of contraction behavior toward the manifold. Moreover, by decoupling anomaly detection from probabilistic modeling, it reduces the tendency to misclassify rare but normal samples, a widely recognized limitation of existing approaches. Empirically, we demonstrate that projection-aligned methods achieve strong performance, outperforming boundary-based methods while improving upon existing reconstruction-based approaches.

25.
bioRxiv (Bioinfo) 2026-06-12

Evaluating cell type annotations in single-cell omics in the absence of ground truth

Accurate cell type annotation is essential for single-cell transcriptomics, directly shaping downstream analyses and biological interpretations. Yet, objective evaluation of annotation quality remains a major challenge. Here, we argue that a cell type or cell state label has practical utility only if it captures a molecular pattern that is reproducible across biological replicates. Based on this principle, we introduce inter-sample consistency (ISC), a quantitative framework to assess annotation quality in single-cell RNA-seq datasets. Unlike existing cluster validation approaches, ISC distinguishes annotations that generalize across samples and individuals from those driven by technical or unwanted variation, thereby providing principled criteria for annotation quality and transferability. When applied to published single-cell atlases, ISC reveals widespread reproducibility gaps and provides actionable guidance for repairing inconsistent annotations. Notably, ISC enables benchmarking of automated cell type annotation tools even when ground-truth labels are unavailable, providing interpretable metrics to guide their development and evaluation. Implemented as the scTypeEval Bioconductor package, this framework offers a broadly applicable resource for evaluating and improving cell type annotations in single-cell RNA-seq experiments.