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199 recordsLinked to original sources
arXiv2026

Large-scale spatial variable gene atlas for spatial transcriptomics

Spatial variable genes (SVGs) reveal critical information about tissue architecture, cellular interactions, and disease microenvironments. As spatial transcriptomics (ST) technologies proliferate, accurately identifying SVGs across diverse platforms, tissue types, and disease contexts has become both a major opportunity and a significant computational challenge. Here, we present a comprehensive benchmarking study of 20 state-of-the-art SVG detection methods using human slides from STimage-1K4M, a large-scale resource of ST data comprising 662 slides from more than 18 tissue types. We evaluate each method across a range of biologically and technically meaningful criteria, including recovery of pathologist-annotated domain-specific markers, cross-slide reproducibility, scalability to high-resolution data, and robustness to technical variation. Our results reveal marked differences in performance depending on tissue type, spatial resolution, and study design. Beyond benchmarking, we construct the first cross-tissue atlas of SVGs, enabling comparative analysis of spatial gene programs across cancer and normal tissues. We observe similarities between pairs of tissues that reflect developmental and functional relationships, such as high overlap between thymus and lymph node, and uncover spatial gene programs associated with metastasis, immune infiltration, and tissue-of-origin identity in cancer. Together, our work defines a framework for evaluating and interpreting spatial gene expression and establishes a reference resource for the ST community.

stat.AP↗
arXiv2026

Storage-Centric System Designs for Enabling Fast, Efficient, and Low-Cost Genomic and Metagenomic Analyses

Genomic and metagenomic analyses play critical roles in many fields, such as precision medicine, urgent clinical settings, discovering early warnings of communicable diseases, ensuring food safety through pathogen monitoring, agriculture, and scientific discovery. Due to the challenges of analyzing and storing massive volumes of genomic and metagenomic sequence data, significant efforts have been made to accelerate (meta)genomic analyses and store sequence data compressed. Despite the benefits of these techniques, we identify two major outstanding problems in accessing stored sequence data and supplying it to the analysis units: (i) the data movement bottleneck due to moving large amounts of low-reuse data from storage and the unnecessary burden on the rest of the system, and (ii) the data preparation bottleneck, where compressed sequence data needs to be first decompressed and formatted before analysis. In this dissertation, we present customized storage-centric systems, which efficiently (i) analyze (meta)genomic data inside the storage system, and (ii) enable highly-compressed storage and high-performance access of large-scale sequence data, thereby alleviating the overheads of data movement, computation, and data preparation. We demonstrate that the proposed systems significantly improve system performance, energy efficiency, and system cost-efficiency of (meta)genomic analysis. We hope that the storage-centric systems proposed in this dissertation facilitate the broader adoption of (meta)genomic analyses and inspire future research to fundamentally improve the performance, energy efficiency, and cost-effectiveness of other data-intensive application domains related to health and life sciences.

cs.AR↗
arXiv2026

Scaling an Autoregressive Transformer for Single-Cell Generation

We study a self-supervised generation task for single-cell gene expression vectors: given a set of vectors from a cell type, we aim to generate additional gene expression vectors of that cell type. For this task we characterize both the biological fidelity of the generated gene expression vectors and the scaling behavior of the pretraining loss. The model is a causal transformer paired with a learned quantized VAE tokenizer, trained with a cross-entropy loss. To evaluate the model, we condition it on held-out gene expression vectors of a cell type and generate vectors of gene expression, comparing the resulting distribution over gene expression vectors to the ground truth distribution of that cell type. We study the scaling properties of the proposed architecture by varying the number of trained parameters and the amount of training data. To our knowledge, we find the first jointly-fit two-exponent scaling law and compute-optimal frontier for a single-cell foundation model. Finally, we discuss how this pretrained model could be finetuned for perturbation response prediction.

cs.LG↗
arXiv2026

Subcellularly Resolved Single-Cell Embedding Learning with Transcriptomic data, Protein Structure and Localization Information

Existing cell embedding methods predominantly rely on transcriptomic or proteomic measurements and represent each cell as a holistic entity, thereby overlooking the subcellular localization of individual molecules. Moreover, they rarely incorporate protein structural information, despite its fundamental role in determining molecular interactions and functions. In this work, we propose a multimodal framework for learning subcellularly resolved cell embeddings by jointly leveraging RNA expression profiles, protein sequence representations, and protein structural information. Specifically, we employ a cross-attention architecture to integrate transcriptomic, sequence, and structural modalities and model their interactions within distinct subcellular compartments. The resulting embeddings represent each cell through its fine-grained subcellular organization, capturing both molecular expression patterns and the functional properties of the associated proteins. By learning cell representations at subcellular resolution, our framework preserves spatially organized biological information while integrating complementary signals across multiple molecular levels. To the best of our knowledge, this is the first framework that produces subcellularly resolved cell embeddings by jointly incorporating transcriptomic information, protein sequence representations, and protein structural knowledge within a unified cross-modal learning paradigm.

q-bio.GN↗
arXiv2026

PopPert: Population-level Joint-Distribution Modeling for Single-Cell Perturbation Prediction

Predicting transcriptional responses to specific perturbations is critical for understanding cellular regulatory mechanisms and accelerating drug discovery. Single-cell RNA sequencing destroys each measured cell, yielding only unpaired populations of control and perturbed cells. However, existing methods typically model perturbation prediction at the single-cell level and assume cell-to-cell correspondence, which conflicts with the unpaired nature of the observed data. To address this challenge, we propose PopPert, a framework that explicitly parameterizes population-level joint gene expression distributions for collective transcriptional state modeling. Given a control population distribution and a perturbation condition, PopPert predicts perturbation-induced changes in distribution parameters, eliminating the need for cell-level correspondence and reducing sensitivity to single-cell noise. To effectively capture gene co-expression patterns, PopPert leverages a low-rank Gaussian Copula to model cross-gene statistical dependencies and construct the joint gene expression distribution, additionally allowing sampling of synthetic perturbed single-cell profiles. Across multiple single-cell benchmarks spanning both genetic and chemical perturbations, PopPert achieves superior overall performance in differential expression recovery, perturbation effect estimation, and population-level distribution matching. These results establish population-level joint distribution learning as an effective paradigm for predicting transcriptional responses from unpaired single-cell populations. Code for PopPert is publicly available at https://github.com/whd1125/PopPert.

q-bio.GN↗
arXiv2026

RIBOSPAN: A Long-Context RNA Foundation Model for Versatile RNA Modeling

Full-length RNAs, particularly messenger RNAs, often exceed the context lengths used to pretrain existing RNA foundation models, limiting complete-transcript modeling at single-nucleotide resolution. We present RIBOSPAN, a 1.61-billion-parameter bidirectional RNA foundation model natively pretrained with context lengths up to 10,240 nt. RIBOSPAN combines dense bidirectional self-attention, single-nucleotide tokenization, and attention-isolated sequence packing to enable high-resolution modeling of complete long RNAs. Native 10K pretraining preserves strong reconstruction at 10,240 tokens and, in a controlled long-context benchmark, maintains strong contextual responsiveness and context-specific representation separation while keeping perturbation-induced changes highly localized. Inference-time YaRN scaling recovers much of the contextual organization lost by direct short-context extrapolation, but induces substantially greater distal representation diffusion. Frozen RNA-type evaluations show that RIBOSPAN learns state-of-the-art RNA representations, with a particularly clear advantage on long RNAs. Across downstream biological benchmarks, RIBOSPAN emerges as the strongest encoder-only RNA foundation model, achieving state-of-the-art performance in both full-transcript biological property prediction and zero-shot mutation-fitness modeling. Building on the same backbone, we develop a multidimensionally conditioned discrete-diffusion framework for full-length mRNA generation and redesign, including synonymous-codon diffusion for protein-preserving CDS optimization. Together, RIBOSPAN establishes a powerful long-context foundation for transferable RNA representation learning, biological prediction, and full-transcript mRNA design.

cs.LG↗
arXiv2026

EvoLen: Evolution-Guided Tokenization for DNA Language Model

Tokens serve as the basic units of representation in DNA language models (DNALMs), yet their design remains underexplored. Unlike natural language, DNA lacks inherent token boundaries or predefined compositional rules, making tokenization a fundamental modeling decision rather than a naturally specified one. While existing approaches like byte-pair encoding (BPE) excel at capturing token structures that reflect human-generated linguistic regularities, DNA is organized by biological function and evolutionary constraint rather than linguistic convention. We argue that DNA tokenization should prioritize functional sequence patterns like regulatory motifs-short, recurring segments under evolutionary constraint and typically preserved across species. We incorporate evolutionary information directly into the tokenization process through EvoLen, a tokenizer that combines evolutionary stratification with length-aware decoding to better preserve motif-scale functional sequence units. EvoLen uses cross-species evolutionary signals to group DNA sequences, trains separate BPE tokenizers on each group, merges the resulting vocabularies via a rule prioritizing preserved patterns, and applies length-aware decoding with dynamic programming. Through controlled experiments, EvoLen improves the preservation of functional sequence patterns, differentiation across genomic contexts, and alignment with evolutionary constraint, while matching or outperforming standard BPE across diverse DNALM benchmarks. These results demonstrate that tokenization introduces a critical inductive bias and that incorporating evolutionary information yields more biologically meaningful and interpretable sequence representations. Code, pretrained and fine-tuned checkpoints, and tokenizer files are available at https://github.com/HN020719/EvoLen and https://huggingface.co/EvoLenTokenizer.

cs.LG↗
arXiv2026

Algorithmic Collusion by Large Language Models

We conduct experiments with algorithmic pricing agents based on Large Language Models (LLMs). In oligopoly settings, LLM-based pricing agents quickly and autonomously reach supracompetitive prices and profits. Variation in seemingly innocuous phrases in LLM instructions ("prompts") substantially influence the degree of supracompetitive pricing. We develop novel techniques for behavioral analysis of LLMs and use them to uncover price-war concerns as a contributing factor. Our results extend to auction settings. Our findings uncover unique challenges to any future regulation of LLM-based pricing agents, and AI-based pricing agents more broadly.

econ.GN↗
arXiv2026

Individualized Algorithmic Advice as a Strategic Signal on Competitive Markets

As algorithms increasingly mediate competitive decision-making, their influence extends beyond individual outcomes to shaping strategic market dynamics. In our experiment, we examined how algorithmic advice affects human behavior in a classic economic game with a unique, non-collusive, and analytically traceable equilibrium. Participants (N = 129) played a Cournot quantity competition with equilibrium-aligned or strategically biased algorithmic recommendations. While individualized equilibrium advice supported stable convergence, collusively downward-biased advice led to sustained underproduction and supracompetitive profits - hallmarks of tacit collusion. Participants' quantities converged faster and more consistently toward individualized than collective equilibrium advice, potentially due to an objective quality advantage or greater perceived ownership of the former. These findings demonstrate that algorithmic advice can function as a strategic signal, shaping coordination even without explicit communication. The results echo real-world concerns about algorithmic collusion and underscore the need for careful design and oversight of algorithmic decision-support systems in competitive environments.

cs.HC↗
arXiv2026

Performance Manipulation: Labor Market Implications in AI-assisted Era

Performance manipulation arises when agents exploit easily measurable, routine tasks to inflate observable outcomes without contributing genuine innovation or expert judgment. We formalize this phenomenon in a game-theoretic model in which agents allocate effort along two margins. Creative effort is non-routine cognitive labor whose return is complementary to the agent's private expertise; it is the scarce input that principals seek. Mechanistic effort is the execution of well-defined, rule-based tasks that raise performance independently of expertise, a commoditized input that AI heavily augments. We establish the existence of a symmetric, monotone pure-strategy equilibrium and show that performance-based screening remains viable so long as evaluations retain a sufficient creative component, but collapses into an uninformative pooling equilibrium once AI capability grows large enough to crowd out creative effort. Comparing contest allocations against a single-agent baseline isolates performance manipulation as the competition-induced over-investment in mechanistic effort, which we show is undertaken systematically by low-type agents but not high-type ones. We further prove that more sharply skewed reward structures mitigate this friction by eliciting greater creative effort across the participant pool. Finally, using a novel, language-model-based methodology to measure both effort types from nearly 1,500 Kaggle competition scripts, we provide robust empirical support for the model's predictions.

econ.GN↗
arXiv2026

Forecasting Weather-Driven Price Dynamics Across Sri Lankan Tea Market Catalogues

The Colombo Tea Auction (CTA) plays a vital role in determining global tea prices, yet the relationship between local weather conditions and price behavior across different tea catalogues has not been thoroughly explored. In this study, we develop a novel, structured dataset by extracting information from 105 weekly broker reports spanning late 2023 to 2026, and combined with region-specific weather data. Our analysis focuses on four main tea catalogues of Sri Lankan tea: High Grown, Low Grown, Off-Grade, and Dust. To better understand the factors influencing tea prices, we apply Granger causality analysis alongside tree-based machine learning models: Random Forest, XGBoost, LightGBM, and Gradient Boosting. Our results show that while market dynamics are primary drivers, weather conditions also have significant effects. Notably, Low Grown tea shows strong sensitivity to precipitation and sunshine duration (p<0.05) across 1-3-week lags. Off-Grade and Dust catalogues also exhibit significant responses to temperature variations. Catalogue-specific modelling outperformed unified approaches, with LightGBM emerging as the superior model for three out of four catalogues. Overall, this study highlights the importance of considering both localized weather patterns and catalogue-level differences when forecasting tea prices, offering a more precise and practical framework for the tea industry.

econ.GN↗
arXiv2026

Tastes without distinction: silicon samples and the synthetic construction of tastes

Large-language models have proven to be remarkable if inconsistent parrots of public attitudes and opinions. The extent to which LLMs are able to produce reasonable approximations of cultural taste remains an open empirical question that becomes more urgent by the day, with market research companies already offering provisional 'synthetic' survey panels and the contamination of standard survey data from LLM-generated responses. In this study, we build on past work on silicon sampling by extending considerations of their ecological, relational, and positional fidelity in the doomain of cultural tastes. We use large-language models from OpenAI, Anthropic, and DeepSeek to produce 554,940 silicon surrogates of survey respondents from the Survey of Public Participation in the Arts (SPPA). We find these silicon surrogates' tastes to be highly stylized facsimiles of human tastes. First, silicon samples are super-omnivorous with a systematic postive-bias for liking. These individual-level bias of silicon samples are not well-explained by the WEIRD-bias often discussed in the literature. Second, the complex relationality in real taste structures is completely distorted among silicon samples. Third, very little of the known cultural alignment between tastes and social space are preserved. Silicon samples juvenilize age-taste associations, resurrect anachronistic class-taste associations, and caricaturize gender- and race-taste associations. Key words: AI, taste, consumption, culture, silicon sampling, meta-analysis.

cs.CL↗
arXiv2026

The Price of Intelligence: A Quality-Adjusted Price Index for AI Services

Posted prices for AI inference have fallen steadily since 2024, yet the measured speed of that fall depends almost entirely on the method of measurement. This paper constructs quality-adjusted price indices for the AI inference market from public data. The panel assembles 21,024 posted-price observations across 3,208 models and 86 providers and joins them to 4,605 benchmark scores through a latent quality index estimated from benchmark response patterns, so the quality ladder of the hedonic tradition is built here from evaluations in place of product characteristics. Measured by the matched-model methods that statistical agencies apply to software, inference prices fell at 0.10 log points a year. The quality-adjusted index fell at 0.73, so 87% of the decline is invisible to current methods, with direct consequences for measured competition, concentration and productivity in this market. Counted per completed task, moreover, the buyer's price stopped falling. Reasoning models raised token consumption faster than token prices fell, and the seller's and buyer's prices accordingly diverged. A pre-registered validity audit disciplines the quality measure and yields the sharpest result. Excluding contamination-flagged benchmarks leaves model rankings intact at 0.998 yet moves the index by 0.49 log points a year, so the leaderboard-stability arguments standard in AI evaluation offer no defence of economic statistics built on benchmarks. Prices, quality and the audit are fully reproducible from public sources at zero cost.

econ.GN↗
arXiv2026

Measuring Computer Science Enthusiasm: A Questionnaire-Based Analysis of Age and Gender Effects on Students' Interest

This study examines how age and gender independently shape adolescents' interest in computer science (CS) education. Building on the Person-Object Theory of Interest (POI), we define enthusiasm as a short-term, activating response that combines positive affect, perceived relevance, and intention to re-engage. Because such enthusiasm can shift CS attitudes and engagement intentions even briefly, it offers a useful measure for short outreach activities. We developed a 28-item pre-post questionnaire to assess whether CS interventions raise enthusiasm, then applied it to more than 400 students (244 female, 187 male, aged 10-18) in CS courses. Contrary to the common assumption that early exposure secures lasting interest, we found a marked decline during early adolescence, especially among girls, along with wide variation in interest trajectories across ages. Exploratory factor analysis and ANOVA show that age predicts interest development more strongly than gender, and reveal specific developmental breakpoints. Although older students began with lower baseline attitudes, they showed the largest gains after the intervention, indicating that well-designed short activities can re-engage interest even later in adolescence. These results point to the need for CS education strategies that adapt to developmental stage rather than assuming a single early window matters most. Our validated questionnaire offers a way to measure immediate affective and motivational responses, giving researchers and practitioners a tool to evaluate whether specific interventions succeed in raising enthusiasm.

cs.SE↗
arXiv2026

Digital Engagement, Income Disparities, and Job Seeking in the United States since 2010

Surveys often record how frequently people use the internet without measuring the infrastructures, skills, and support systems that make digital participation possible. Using the U.S. National Longitudinal Survey of Youth 1997 cohort, we study how internet-use frequency relates to labor income, employment attachment, and job seeking after 2010. The main digital-engagement analysis uses the comparable 2011, 2013, and 2015 waves, with 2017 retained as later labor-market context. Across repeated cross sections, daily internet use consistently marks higher income and stronger employment attachment. Relative to daily use, less-than-daily use is associated with roughly 11 to 20 percent lower income, while nonuse is associated with about 18 to 21 percent lower income in 2011 and 2013. Respondents reporting no internet use are also 13 to 23 percentage points less likely to report full-year work. Job-search estimates reveal a distinct mechanism: active search is governed by employment status, search intensity, and application support, so a frequency item sorts respondents more sharply on durable labor-market attachment than on short-window search. Education accounts for a substantial share of the raw digital gradient, and pooled lagged-outcome and doubly robust transition estimates separate durable stratification from positive adoption margins. The results establish internet-use frequency as an informative behavioral marker of digitally mediated labor-market stratification and clarify why routine use should not be treated as a simple measure of digital access.

cs.CY↗
arXiv2026

Authority-Inference Separation in Agentic Finance: First-Line Control, Blockchain Enforcement, and Replayable Assurance

AI agents can select tools, counterparties, and transaction parameters, yet inference should not itself confer authority to execute a financial action. This study develops and evaluates Authority-Inference Separation (AIS), an intent-centered architecture for bounded agentic finance. AIS treats a financial action intent as the control object: a machine-generated proposal can receive temporary executable authority only after an independent deterministic control plane validates registered agent identity, accountable ownership, mandate and risk-appetite lineage, policy version, state, approvals, and exact economic semantics. Blockchain can then enforce the operational representation of granted authority and record portable settlement evidence, while institutional legitimacy, service delivery, accounting classification, and human accountability remain off-chain obligations. Evaluation combines four-domain instantiation, official BIS and MAS cases, a 48-fixture executable prototype, and a public-ledger observability test. Across 36 synthetic authorization attacks, a direct-agent baseline accepted 36 attack effects, a prompt-policy baseline accepted 20, and AIS accepted none; all three accepted 8/8 admissible fixtures. AIS also rejected 4/4 token replays and 8/8 recipient or rail substitutions, withheld completion in 4/4 service-delivery failures, and populated all 13 defined evidence fields. A test of 1,700 recent Base transactions associated with public x402 facilitator addresses shows that public ledgers can evidence settlement and selected authorization parameters but cannot establish institutional mandate, legal accountability, service delivery, or accounting treatment. AIS and blockchain are therefore complementary: AIS decides whether a specific intent may act, while blockchain can make granted authority bounded, executable, and independently observable.

q-fin.GN↗
arXiv2026

Propensity Straight-Through Gradients for Discrete Stochastic Systems

Continuous-time Markov chains (CTMCs) provide the backbone for modeling discrete stochastic dynamics across applied, physical, and biological sciences. Their integration with modern gradient-based machine learning, however, is limited by the hard categorical event selection intrinsic to Gillespie-type simulation algorithms. We exploit the affine state update to obtain the exact one-step conditional-mean sensitivity by differentiating normalized reaction propensities. We pair this backward rule with exact forward trajectories to define the propensity straight-through (PST) estimator. At the trajectory level, we show that one-step sensitivities composed across events can depart from the exact multistep sensitivity. We derive the resulting per-step discrepancy in closed form and prove that it vanishes identically for affine downstream dependence. PST matches the accuracy of Gumbel-Softmax straight-through across all benchmarks: reversible dimerization (0.06% error), a genetic oscillator (1.7% error), a 50-task repressilator suite (0.17% median error), and patch-clamp ion-channel recordings ($R^2$ = 0.988). Under matched settings, PST converges 3.0-fold faster on the oscillator and 2.1-fold faster on the ion channel. At deep-learning scale, PST trains a 203,796-parameter stochastic reaction network with hard sampling, reaching 98.22% MNIST digit classification accuracy. By differentiating an exact conditional mean rather than a relaxed sample, PST offers a temperature- and Gumbel-free path to scalable gradient-based learning through exact stochastic trajectories.

q-bio.QM↗
arXiv2025

Intelligent Software System for Low-Cost, Brightfield Segmentation: Algorithmic Implementation for Cytometric Auto-Analysis

Bright-field microscopy, a cost-effective solution for live-cell culture, is often the only resource available, along with standard CPUs, for many low-budget labs. The inherent challenges of bright-field images -- their noisiness, low contrast, and dynamic morphology -- coupled with a lack of GPU resources and complex software interfaces, hinder the desired research output. This article presents a novel microscopy image analysis framework designed for low-budget labs equipped with a standard CPU desktop. The Python-based program enables cytometric analysis of live, unstained cells in culture through an advanced computer vision and machine learning pipeline. Crucially, the framework operates on label-free data, requiring no manually annotated training data or training phase. It is accessible via a user-friendly, cross-platform GUI that requires no programming skills, while also providing a scripting interface for programmatic control and integration by developers. The end-to-end workflow performs semantic and instance segmentation, feature extraction, analysis, evaluation, and automated report generation. Its modular architecture supports easy maintenance and flexible integration while supporting both single-image and batch processing. Validated on several unstained cell types from the public dataset of livecells, the framework demonstrates superior accuracy and reproducibility compared to contemporary tools like Cellpose and StarDist. Its competitive segmentation speed on a CPU-based platform highlights its significant potential for basic research and clinical applications -- particularly in cell transplantation for personalised medicine and muscle regeneration therapies. The access to the application is available for reproducibility

q-bio.QM↗