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5 papers in the last four weeks, down 17% on the four weeks before. 0.1% of all new papers.

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Latest papers 63

Oct 1, 2026cs.LG

Auditable Algebraic Counting Field for Cryptic-Pocket Detection from Apo Structures

Cryptic ligand-binding pockets are not apparent in experimentally determined apo structures, making them difficult to identify from unbound receptor geometry. A complementary challenge is to make the structural measurements and learned evidence behind each prediction directly inspectable. We introduce a supervised algebraic counting field (ACF) for predicting cryptic-pocket residues from apo structures. ACF compiles explicit geometric, physicochemical, and topological features into compact, integer-weighted lookup tables. Each prediction score can be reconstructed from feature values, training counts, table weights, and spatial aggregation, without sequence search, structural-template transfer, or a protein language model at inference. We evaluate ACF on CryptoBench and two locked external collections, separating ranking performance from the effects of residue-calling budgets. On an external set of 57 post-CryptoBench apo-holo units, ACF exceeded P2Rank by +0.044 in mean paired ROC-AUC (multiplicity-adjusted 95% CI [+0.010, +0.079]). The advantage was dataset-dependent: official-fold ROC-AUC and matched-budget F1 differences against P2Rank remained unresolved, and a second external evaluation did not confirm gains from added structural features. ACF thus provides a compact predictor with externally validated signal and an inspectable path from structural measurements and training counts to residue scores.

Shan Yu, Xuening Wu

Pfizer, Shanghai, China

Molecular Property Prediction Roc-Auc Captcha Cells Language Modeling

Sep 30, 2026cs.LG

scTrilemma: Balancing Identity, Invariance, and Fidelity in Single-Cell Representation Learning

Single-cell RNA-seq representation learning is fundamentally label-free: cell identities, states, and contexts are not fixed training targets, so what constitutes signal or nuisance is analysis-dependent. A single representation must therefore preserve biological identity and state, remain robust to nuisance context, and retain the gene-level variation needed for expression analysis, three demands we call the representation trilemma. To tackle this problem, we introduce scTrilemma, a latent-bottleneck VAE that routes expression-derived variation to the embedding, the decoder, or the prior rather than forcing all of it through one embedding. It gates gene tokens by expression, routes the cell representation through the decoder, and conditions the prior on unlabeled pseudo-bulk context, under a single reconstruction objective and without target annotations or auxiliary representation losses. In release-based zero-shot evaluation on successive CZ CELLxGENE Census releases, scTrilemma leads all three demands at once and preserves biological-state, differential-expression, and pathway structure across multiple disease settings. Latent interventions further show that context can be removed at almost no cost to the other demands, leaving identity against fidelity as the remaining tension. Code is publicly available at https://github.com/yunhak0/scTrilemma.

Yunhak Oh, Yoonho Lee, Junseok Lee +9

KAIST · Work done during an internship at HITS · HITS

Cells Molecular Representation Learning Conditional Variational Autoencoder

Sep 29, 2026cs.CV

Towards Scalable Context-Aware Single-Cell Spatial Transcriptomics Prediction from Histology Images

Predicting gene expression from H&E-stained histology images offers a scalable alternative to costly spatial transcriptomics, yet most existing methods operate at the spot level, where signals from multiple cells are aggregated and critical cellular heterogeneity is obscured. Extending this paradigm to single-cell resolution is non-trivial. Naively applying pathology foundation models faces a scale mismatch: their patch-level representations mix multiple cells, whereas per-cell cropping or resizing distorts morphology and removes local context. Conversely, segmentation-based models without strong pretrained visual encoders often lack the morphological representation capacity needed for accurate molecular prediction and inherit errors from imperfect cell boundary masks. Here, we present CELLO, an efficient end-to-end framework that performs a single pathology foundation model forward pass per image and uses grid sampling to extract location-specific features for all cells simultaneously. We further introduce a distance-decay cross-attention module that refines each cell representation using spatially biased local morphological context. Using 52 public Xenium-H&E pairs from HEST-1k that span 12 organs and approximately 10 million cells, CELLO improves the average predictive accuracy over the evaluated baselines while reducing the mean whole-slide inference time compared to DeepSpot2Cell, a 14.0x speed-up on average that excludes upstream cell segmentation. Our work establishes a scalable foundation for single-cell gene expression prediction from H&E images.

Zijun Gao, Chunbin Gu, Jinxi Xiang +2

The Chinese University of Hong Kong · Stanford University School of Medicine

Spatial Transcriptomics Digital Pathology Single-Cell Rna Cells

Sep 29, 2026cs.AI

From Retrieval to Reasoning: Agentic Mechanism Prediction from Cell Painting Profiles

Cell Painting is a high-content morphological profiling assay widely used for phenotype-based biological inference, with mechanism of action (MOA) prediction as a central application. Existing approaches largely formulate Cell Painting-based inference as representation matching, assigning predictions from nearby reference perturbations in morphological feature space. However, retrieved neighbors are often noisy and partially misleading evidence due to batch effects, non-specific cytotoxicity, phenotypic convergence, and source-dependent variability. We reformulate Cell Painting-based MOA prediction as a calibrated evidence reasoning problem, where retrieved neighbors are treated as uncertain observations that must be evaluated, compared, and sometimes rejected before supporting a mechanistic conclusion. We propose PhenoAIR, a reliability-aware multi-agent framework that maintains a candidate-centric evidence memory and performs controller-guided refinement over phenotype- and mechanism-side evidence. PhenoAIR uses offline reference-set calibration to weight evidence by source reliability, phenotype stability, and mechanism-level confusion. We evaluate PhenoAIR on a benchmark constructed from JUMP Cell Painting profiles and annotations, covering controlled, realistic, and discovery-oriented open-world MOA prediction settings. PhenoAIR outperforms representation-matching and LLM-based baselines across all settings.

Jiayuan Chen, Botao Yu, Tianyu Liu +3

Department of Computer Science and Engineering, The Ohio State University · Department of Biomedical Informatics, The Ohio State University · Department of Biostatistics, Yale University +1

Phenotypes Cells Mechanistic Interpretability Clinical Prediction Art

Sep 28, 2026cs.LG

DRIFT: Disentangled Responsive-Invariant Flow Transport for Single-Cell Perturbation Prediction

Predicting cellular responses to perturbations is a central problem in cellular biology, with broad applications in systems biology and drug discovery. This task is challenging because cellular responses can be complex and cell-state dependent, intrinsic cell-to-cell variability can be confounded with perturbation effects, and destructive single-cell RNA sequencing precludes paired measurements of the same cell before and after treatment. Flow matching transports control cells to perturbed states flexibly, but acting on the full cell state can confound perturbation effects with pre-existing cell-to-cell variability. Disentangled approaches separate responsive from invariant components, but model perturbations through prescribed mechanisms, such as latent shifts or graph edits, limiting their flexibility. We address both limitations in a unified framework. A variational encoder disentangles each cell into an invariant block, capturing state unaffected by the perturbation, and a responsive block, capturing state it changes, through conditional priors and an information-theoretic invariance constraint. Conditional flow matching transports only the responsive block, conditioned on the perturbation and invariant state, yielding a flexible, data-driven model of perturbation effects without confounding pre-existing variability. Across several benchmarks, our method outperforms the strongest published method in settings involving combinatorial and unseen perturbation prediction.

Mustapha Bounoua, Giulio Franzese, Pietro Michiardi

Department of Data Science EURECOM, France

Single-Cell Perturbation Prediction Cells Conditional Flow Matching Conditional Variational Autoencoder

Sep 28, 2026cs.ET

P2P: Cross-View Population Denoising for Unpaired Single-Cell Perturbation Response Prediction

AIVC (AI Virtual Cell) is a learned simulator of cellular behavior across conditions. Predicting how a cell population responds transcriptionally to a genetic perturbation is a core task. Perturb-seq records that response by destructive sequencing, so a control cell and a perturbed cell are never observed as a pair, and cells under one condition remain heterogeneous and noisy. Regression on individual cells absorbs sampling variation into the estimated effect, whereas interpretation requires the reproducible population effect. P2P (Perturbation-to-Perturbation) takes a stochastic cell-set view as its supervision unit. Two views drawn from the same condition share a reproducible population effect and differ by view-specific variation. A permutation-invariant set encoder summarizes the control population, a structured encoder represents perturbation tokens, cellular context, dose, and combination interactions, and a gate blends empirical condition-effect memory with a neural residual. A heteroscedastic head predicts the population mean and gene-wise response variance. Under one protocol and five seeds, P2P attains the lowest expression RMSE and the highest Effect Pearson, DEG F1, and DEG average precision on each of Adamson, Norman, Replogle K562, and Replogle RPE1 relative to GenePert, LinearPert, SLIM, Scouter, and scPILOT. On Replogle K562, Effect Pearson rises from 0.643 to 0.702 and DEG F1 rises from 0.067 to 0.178 relative to Scouter, the strongest baseline on both metrics.

Haojie Yang, Ran Su

College of Intelligence and Computing Tianjin University, Tianjin, China

Single-Cell Perturbation Prediction Cells Populations Cross-View Responses

Sep 28, 2026cs.CV

See, Measure, and Reason: Learning Visually Grounded Reasoning in Pathology

Pathological assessment relies on recognizing fine-grained visual details in histological images. Vision-language models (VLMs) increasingly support pathology interpretation, yet their ability to perceive these details remains inadequate. This weakness leads to inaccurate cellular observations that can persist even when final answers are correct. In this paper, we propose ASPECT to improve visually grounded reasoning through explicit supervision of cellular appearance and abundance. ASPECT trains intermediate visual tokens through pathology feature reconstruction, cell feature alignment, and count supervision. Three-stage supervised fine-tuning teaches the model to perceive, generate visual tokens, and reason, followed by reinforcement learning that rewards answer correctness and consistency with reported measurements. We also introduce PathoVernier, a benchmark of 759 expert-reviewed questions from five pathology datasets covering four cellular composition tasks. It evaluates both final answers and intermediate measurements to expose errors hidden by answer accuracy. On PathoVernier, ASPECT achieves relative accuracy gains of approximately 19.2% over the strongest baseline, Gemini-3.1-Pro, and 99.3% over its Qwen3-VL-8B backbone, while reducing RAWR, which measures counting errors within correct responses, by 28.1% and 42.7%, respectively. ASPECT also improves over its backbone on three external pathology benchmarks covering classification and question answering beyond cellular composition tasks.

Chengyang Zhang, Wenchuan Zhang, Bo Li +8

College of Computer Science, Sichuan University · Department of Pathology and Institute of Clinical Pathology, West China Hospital, Sichuan University · Department of Computer Science, School of Computing, National University of Singapore +1

Pathology Foundation Models Cells Reasoning Skills Measures

Sep 14, 2026cs.CV

End-to-End Cell Detection via Instance-aware Graph Modeling

Accurate cell detection and classification are crucial for pathological analysis, directly affecting diagnostic accuracy and treatment planning. To capture complex cellular interactions beyond visual appearance within the tumor microenvironment, several approaches have employed graph neural networks to model spatial and relational patterns among cell nuclei, yielding promising results. However, these methods typically adopt a two-stage paradigm of visual extraction followed by relational modeling, which necessitates separate tuning for each stage, thereby increasing pipeline complexity and hindering end-to-end joint optimization. In this paper, we propose an end-to-end framework for cell detection and classification that jointly models patch-level visual representations and instance-level interactions, which incorporates a dynamic graph construction module and an instance-aware graph network. Specifically, the graph construction module dynamically builds the graph structure using learnable queries derived from patch-level features as cell instance representations, with adjacency defined by integrating feature similarity and spatial distances. The instance-aware graph network performs adaptive instance filtering and feature reorganization, aggregating them over the cell graph into a topological latent state for a selective state-space transition driven by visual cues, fusing appearance and relational evidence. When evaluated on multiple datasets with different staining protocols for cell and nucleus detection, our method significantly outperforms existing approaches in both detection and classification performance. The code will be released at https://github.com/RuochenLiu23/IGM.

Ruochen Liu, Yalin Zheng, Jingxin Liu +5

Faculty of Science and Engineering, University of Liverpool, Liverpool, L69 3GJ, U.K. · Department of Eye and Vision Sciences, University of Liverpool, Liverpool, L7 8TX, U.K. · School of AI and Advanced Computing, Xi’an Jiaotong-Liverpool University, Suzhou, 215400, China +3

Cells Graph Representation Learning Graph Neural Networks Biomarker

Sep 14, 2026cs.CV

Beyond Accuracy: Uncertainty-Guided Boundary Refinement for Reliable Biomedical Image Segmentation

Accurate biomedical image segmentation requires not only high global overlap but also reliable delineation of clinically meaningful boundaries. In blood-smear microscopy, cytoplasm and nucleus contours provide the structural basis for downstream morphology analysis; however, deep segmentation models may remain uncertain or overconfident near ambiguous boundary regions even when achieving strong Dice scores. This work proposes a Reliability-Aware Boundary Refinement Network (RABR-Net), a two-stage framework for trustworthy image segmentation. A strong UNet++ EfficientNet-B4 base segmenter first produces initial class probabilities and logits. Predictive entropy, test-time augmentation variance, margin uncertainty, probability gradients, and soft boundary cues are then combined into a boundary-aware reliability representation. This representation guides a gated residual refiner that selectively corrects uncertain boundary pixels while preserving confident regions of the base prediction. The framework is evaluated using overlap accuracy, class-wise Dice, Boundary Dice, HD95/ASSD, calibration, risk--coverage analysis, robustness under image perturbations, qualitative correction maps, and paired statistical testing. On the held-out test set, the proposed method improves Dice from 0.9602 to 0.9614, Boundary Dice from 0.3448 to 0.3611, and HD95 from 3.0354 to 2.8274 compared with the cached base prediction. Statistical analysis confirms significant improvements in Dice, Boundary Dice, and HD95. Qualitative results show that the learned gate concentrates around uncertain cytoplasm and nucleus boundaries, and correction maps confirm localized boundary refinement. Although calibration does not automatically improve after refinement, the proposed framework provides an interpretable and reliability-focused strategy for boundary-sensitive biomedical image segmentation.

Anima Kujur

Interdisciplinary Centre for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany

Semi-Supervised Medical Image Segmentation Delineation U-Net Boundaries Cells

Sep 9, 2026q-bio.QM

scDEFT: A deep learning framework for drug-effect prediction and counterfactual reasoning

Longitudinal single cell atlases now capture matched pre treatment and post treatment states from responders and non responders, presenting an opportunity to mechanistically explain why two patients on the same drug diverge. We introduce scDEFT (single cell Drug EFfect Transducer), which treats a drug as a conditioning operator on cell representations, enabling prediction and explanation. In scDEFT, feature wise linear modulation produces drug conditioned cell latents, learned under abundant per cell supervision and then frozen. Two independent heads aggregate those latents over shared transcriptional neighborhoods to predict drug induced state change and responder status. A backward stage ranks the latent dimensions by how strongly they separate responders from non responders and maps them to genes under a cell composition control. On a harmonized inflammatory bowel disease atlas of 1.16 million cells, three cohorts and two drug classes, scDEFT predicts state change at 45% of the baseline to reproducibility ceiling headroom and stratifies responders before treatment at AUROC 0.70, where standard predictors remain at chance. These predictions and the drivers behind them support target and co target nomination, patient stratification, and counterfactual prediction of unseen drug cohort effects.

Murthy Devarakonda

Causal Data AI (causaldata.ai)

Single-Cell Perturbation Prediction Cells Clinical Prediction Deep Learning Framework

Sep 7, 2026cs.CV

Multi-label versus multi-class classification of blood cells and their aggregates in microfluidic channels

Deformability cytometry (DC) is a type of imaging flow cytometry, which uses a camera-equipped device to measure cellular stiffness in addition to other cellular properties at high throughput. Cellular properties such as area and elongation can identify cell types, but this requires prior knowledge of distinguishing properties and cannot be applied to clinically important cell aggregates. Using DC data, we evaluated conventional multi-class (MC) classification and introduced a multi-label (ML) approach for identifying blood cells and their aggregates. In particular, an ML classifier can simultaneously assign multiple cell-type labels to a single imaged event. We show that, unlike MC classification, ML classification can identify cell aggregates not represented in the training data. It also avoids the need for exhaustive, strictly defined aggregate labels, thereby simplifying and speeding up annotation. Since automated blood analyzers do not reliably analyze cell aggregates, our approach may help address this clinical gap.

Igor Zingman, Shada Abuhattum, Sara Kaliman +8

Max Planck Institute for the Science of Light, Erlangen, Germany · Max-Planck-Zentrum für Physik und Medizin · Friedrich-Alexander Universiät Erlangen-Nürnberg, Erlangen, Germany

Acute Myeloid Leukemia Cells Multi-Label Classification Multiclass Classification Fluid Controls

Sep 1, 2026cs.CV

Semantic-Guided Multimodal Preprocessing for Vision Transformer-Based Clear Cell Renal Cell Carcinoma Grading

Clear cell renal cell carcinoma (CCRCC) grading is essential for treatment planning, yet existing approaches either analyze patch-level images directly or focus solely on nuclei-level classification, without linking to final tumor grading. We propose a semantic-guided multimodal preprocessing method that integrates nuclei classification maps from existing pre-trained models with RGB histopathology images for Vision Transformer (ViT)-based CCRCC grading. Our approach employs classification map channel concatenation and multiplicative modulation, with optimized overlays to leverage nuclei grading information, while preserving RGB textural features. Evaluation of multiple preprocessing strategies demonstrates that semantic-guided enhancement achieves 0.916 balanced accuracy, outperforming RGB-only baseline (0.707) and max-voting aggregation from prior studies (0.427). Sensitivity analysis reveals that this 21 percentage point improvement over baseline persists even under simulated perturbation at rates matching current state-of-the-art nuclei classification model error thresholds, suggesting both effective semantic utilization and practical robustness. These findings show that preprocessing-based multimodal fusion can leverage the diagnostic potential of existing imperfect nuclei classifiers, effectively bridging previously isolated fine-grained nuclear-level analysis with coarse-grained ViT-based patch classification. Per-class recall was consistent across grades (0.93, 0.91, 0.91), indicating that gains are not concentrated in the majority class. Because the sensitivity analysis perturbs ground-truth maps rather than predictions from an actual nuclei model, this result characterizes robustness under simulated error rather than deployment with a real upstream model, which remains for future work.

Fatemeh Javadian, Zhu Chen, Zahra Aminparast +1

Institute of Imaging and Computer Vision, RWTH Aachen University, Aachen, Germany · Machine Learning for Medical Data, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Düsseldorf, Germany · Institute of Medical Sciences, Kermanshah University, Medical School,Sep Kermanshah, Iran

Cancer Detection Digital Pathology Multimodal Pretraining Cells

Aug 7, 2026eess.SY

Topology Inference for Immune System Networks by Using Cell Amount Data

Recent years have witnessed the advanced development of topology inference research, which helps elucidate the interaction relationships of components in many biological networks. This paper focuses on inferring the topology of a group of immune cells, based on the collected data from cell-depletion based experiments. The problem is very challenging due to i) the lack of standard analytical models for the cell interactions, and ii) the restrictive data availability determined by the huge experiment and time costs. To address these issues, we first leverage certain common knowledge and observations on the experiments to characterize three properties on the cell amounts during the interaction process: state non-negativity, ratio-based convergence, and triple signs of topology weights. Then, we construct a new model with simple structure and analytical convenience, and obtain sufficient conditions for the model to accommodate all three properties. Finally, based on the constructed model, we propose a constrained quadratic programming method to infer the topology from limited number of data pairs. Validation on experiment data demonstrate the effectiveness of the proposed method.

Yushan Li, Rikard Forlin, Dimos V. Dimarogonas +1

Department of Decision and Control Systems, KTH Royal Institute of Technology, Sweden · Department of Women’s and Children’s Health, Karolinska Institutet, Sweden

Cells Topology Quadratic Programs Financial Question Answering

Aug 7, 2026q-bio.QM

JUMP-lite: Compact, reproducible benchmarking of cell representations

Image-based profiling captures rich phenotypic signatures for drug discovery and functional genomics. Large public datasets like JUMP Cell Painting now provide millions of images for systematic study. However, JUMP alone occupies 115 TB, and fragmented evaluation practices make systematic comparisons of representation methods impractical for many researchers. Here we present Nahual, an open-source framework for reproducible model deployment, and JUMP-lite, a 92.0 GB subset of JUMP that is approximately 1,250-fold smaller, selected to cover genetic modalities and compound annotations and reduced via lossy JPEG XL compression. Using these resources, we benchmark five representation methods, including classical features (CellProfiler) and deep learning models (MorphEM, OpenPhenom, SubCell, DINOv2). Moderate compression broadly retains signal relative to uncompressed images. Standardized phenotypic activity and consistency metrics reveal meaningful performance differences across methods. Together, JUMP-lite and Nahual provide a foundation for accessible, reproducible benchmarking of image-based cell representations.

Alán F. Muñoz, Johan Fredin Haslum, Runxi Shen +2

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA

Cells Phenotypes Benchmark Datasets Reproducibility Art

Aug 7, 2026cs.AI

CellWorld: From Gene-Level Reconstruction to Latent Cell Prediction in Spatial Transcriptomics Foundation Models

This paper shows that latent-space predictive pretraining can provide a scalable route to foundation models for spatial transcriptomics. Existing spatial transcriptomics foundation models primarily reconstruct masked gene identities or expression values, potentially encouraging the reproduction of assay-specific technical variation and limiting representation transferability. To avoid directly reconstructing such variation, we shift the prediction target from observed gene measurements to latent cell representations and introduce CellWorld, which predicts the latent representations of masked cells from visible spatial context and a limited partial-expression hint. We pretrain four CellWorld variants, spanning 5.74M to 94.56M trainable parameters, on a corpus of 46 million human cells. Our controlled scaling experiments show that performance improves with model capacity, particularly on spatial tasks, while spatial transfer depends more on sufficient optimization and broad biological source diversity than on cell count alone. Across four held-out datasets, even CellWorld-Small, with 5.74M trainable parameters, outperforms every baseline on all 11 linear-probe benchmarks and all seven fine-tuned spatial benchmarks. Most notably, a frozen CellWorld-Large pretrained on only 5% of the corpus with broad biological source coverage outperforms every fully fine-tuned baseline across all seven spatial benchmarks. Code is available at https://github.com/UoM-HealthAI/CellWorld.

Haiping Liu, Qian Zhao, Lijing Lin +2

University of Manchester

Spatial Transcriptomics Cells Latent Prediction Swarms

Aug 6, 2026cs.LG

CohortHijack: Robustness of Single Cell Annotation to Companion Cell Removal

Many single-cell annotation tools refine an initial cell label using nearby cells or cluster-level voting. We study whether this refinement can be manipulated without changing the target cell. We introduce CohortHijack, a robustness audit that removes selected non-target cells from the query cohort while preserving the target expression profile, base prediction, and trained model. We evaluate random and structured removal methods, together with greedy, multi-start, and beam search, on PBMC3K and Paul15 using logistic regression and calibrated linear SVM classifiers. Structured removal was consistently stronger than random removal on Paul15. Multi-start search changed 24.33% of linear-SVM targets and 19.67% of logistic-regression targets while removing a small fraction of the cohort and keeping mean collateral changes below 0.4%. Ablations confirmed that the effect disappeared when neighborhood refinement was disabled. We also evaluated CellTypist majority voting, where independent predictions remained unchanged across all evaluations, but refined labels changed after small companion-cell removals. These findings identify query cohort composition as a target-preserving attack surface in single-cell annotation.

Arash Vashagh, Yasmin Vashagh

Faculty of Computer Science, University of New Brunswick, Fredericton, New Brunswick E3B 5A3, Canada · Farzanegan Amin 2 High School, Isfahan, Iran

Cells Cohort Biomarker Hijacking

Aug 3, 2026cs.LG

Learning Molecular Representations from Cellular Phenotypes with Structure Preservation

Phenotypic drug discovery enables the discovery of functional relationships between molecular structures and cellular responses. However, existing multimodal representation learning methods often optimize cross-modal alignment without considering the intrinsic organization of chemical space, resulting in distorted molecular representations and loss of structural information. We propose \textbf{PhenMol}, a structure-preserving framework for phenotype-aware molecular representation learning. PhenMol disentangles molecular and cellular representations into shared and private components, enabling phenotype-guided alignment while preserving chemical structures through a dedicated molecular branch. This design integrates cellular phenotype information without disrupting molecular neighborhood organization. Experiments on approximately

3.04 \times 10^{4}

molecule--cell morphology pairs demonstrate that PhenMol improves molecular property prediction across 270 bioactivity tasks, molecule--phenotype retrieval, and clinical trial outcome prediction. Moreover, ECFP4-based structural analysis shows that PhenMol better preserves molecular neighborhoods and reduces embedding distortion compared with existing multimodal alignment methods. These results highlight the importance of structure-aware constraints in multimodal molecular representation learning and provide an effective approach for integrating cellular phenotypes with chemical knowledge for drug discovery.

Xuan Lin, Jingyu Sheng, Tengfei Ma +2

School of Computer Science, Xiangtan University, Xiangtan, Hunan, China · College of Computer Science and Electronic Engineering, Hunan University, Changsha, Hunan, China · School of Computer Science, Beijing University of Posts and Telecommunications, Beijing, China +1

Molecular Representation Learning Chemical Structures Cells Cross-Modal Alignment Preservation

Aug 3, 2026cs.LG

LLM-Guided Retrieval for Prediction of Molecular Perturbation Responses

Predicting transcriptomic responses to small-molecule perturbations across cell lines is central to drug discovery, but exhaustive profiling of drug-cell combinations is infeasible. We frame molecular perturbation prediction as retrieve-and-aggregate: approximate an unmeasured drug's response in a cell line by aggregating measured responses of a small set of biologically related compounds. We propose LLM-Guided Retrieval (LGR), where a large language model (LLM) ranks candidate neighbor drugs (restricted to those profiled in the target cell line); after which a fixed mean aggregator combines their observed expression deltas to form the prediction. We evaluate on the Tahoe-100M single-cell perturbation atlas under unseen-drug, unseen-cell-line, and open-world regimes. LGR consistently improves over drug mean, ChemCPA, and chemistry-based kNN baselines, with the strongest gains for unseen cell-line generalization, where it achieves higher correlation and lower error than mean baselines. Across settings, LGR improves directional (sign) accuracy of gene regulation, indicating better recovery of biologically meaningful perturbation effects even when magnitude-based metrics are similar. These results suggest that retrieval quality, rather than predictor complexity, is a key driver of zero-shot molecular perturbation prediction, and that LLMs can provide a useful biological prior when used as constrained retrieval modules.

Betty Xiong, Jan-Christian Huetter, Gabriele Scalia +2

Department of Biomedical Data Science Stanford University Stanford, CA 94305, USA · Biology Research & AI Development, Genentech DNA Way, South San Francisco, CA 94080, USA

Single-Cell Perturbation Prediction Transcriptomics Drug Discovery Molecular Property Prediction Cells Responses

Aug 2, 2026cs.LG

Beyond Gene Reconstruction: Learning Cell Representations through Complementary Transcriptomic Views

The rapid growth of single-cell transcriptomic data has enabled the development of foundation models pretrained primarily by reconstructing masked expression values. This objective encourages these models to learn gene dependencies but does not directly optimize whole-cell representations, which are essential for many downstream tasks. To bridge this gap, we propose a contrastive pretraining framework that learns cell representations through complementary transcriptomic views. Since standard contrastive learning is not readily applicable to single-cell pretraining, we introduce specific adaptations along three dimensions --- co-expression-guided gene partitioning, expression-aware contrast-set construction, and competence-gated contrastive onset. Specifically, we first construct two complementary views of each cell by partitioning its genes according to their co-expression structure. Then, to prevent the model from using gene-set identity as a shortcut, we construct hard negatives by permuting expression values while keeping gene identities unchanged. Finally, we introduce a competence-aware controller to determine how the contrastive objective is applied. Experiments on cell-type annotation and gene regulatory network inference demonstrate competitive transfer under the evaluated protocols. In the six-network GRN evaluation, our method records the highest mean AUROC and AUPRC point estimates among the compared variants, while the highest-scoring variant differs across individual networks. These results establish complementary-view contrastive learning as an effective direction for single-cell pretraining beyond gene reconstruction.

Jiaqi Xiong, Yuntao hu, Yu Zheng +3

University of Oxford, Oxford, United Kingdom · Tongji University, Shanghai, China · Hunan University, Changsha, China +2

Single-Cell Rna Transcriptomics Cells Contrastive Learning Single-Cell Foundation Models Representation Learning+1

Jul 30, 2026cs.AI

PerturbMap: Cross-Context Transfer of Single-Cell Perturbation Responses

Single-cell perturbation atlases rarely measure every intervention in every cellular context: a query perturbation is often observed in one or more source contexts but missing in the recipient context where its effect is needed. Ignoring those measured responses discards query-specific experimental evidence, whereas copying or weakly calibrating them across contexts risks transferring the wrong signal. We propose PerturbMap, which predicts a missing recipient-context effect by combining a recipient-local low-rank base with accepted proposals that transport the same perturbation's measured source responses through source-to-recipient ridge experts fit on paired training perturbations, with proposal weights determined by route reliability estimated on validation anchors. On the Perturb-CITE-seq melanoma cohort, PerturbMap improves full-effect MSE by 4.1% over a recipient-local low-rank base and achieves lower MSE than FedAvg, zero-response, raw-copy, calibrated-copy, and identity-shuffled affine controls. It remains within

2.82\times10^{-6}

MSE of our centralized token-matched pooled reference, which uses a stronger training interface. A condition-mean specificity diagnostic shows the same direction: same-recipient top-10 counterpart retrieval by cosine increases from 74.5% for the low-rank base to 80.5% for PerturbMap.

Panpan Cui, Yiqi Liu, Wenhao Sun

School of Advanced Interdisciplinary Sciences, University of Chinese Academy of Sciences · Institute of Computing Technology, CAS; University of Chinese Academy of Sciences · 3Hong Kong University of Science and Technology

Single-Cell Perturbation Prediction Cells Responses

Jul 27, 2026cs.CL

Neural Circuit Function Inference with LLMs

The success of connectome mapping now shifts the challenge of understanding the nervous system to the interpretation of neural circuits. Here, we devise a new automated method, LLantia (LLM automated neural circuit inference and analysis), to systematically infer neural circuit function and the role of its component neural cell types. Our approach distills descriptions of cell type function from the literature and, in combination with the connectome, then infers the function for all other cell types, which serves as a basis for subsequent neural circuit function inference. Results are structured hierarchically, with different possible circuit functions organised under multiple possible behavioural and physiological contexts, and each circuit function composed of subcircuit descriptions alongside relevant cell types to facilitate both backtracking to known, published information and support further experimental research. We illustrate our method by inferring cell type function for all cell types of the adult fruit fly brain and for select broader circuits within, and validate our findings, including by cross-checking with literature published after the release date of our analysis.

Yijie Yin, Albert Cardona

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK · MRC Laboratory of Molecular Biology, Cambridge, UK

Neural Circuits Connectome Circuits Cells

Jul 17, 2026q-bio.QM

Auditing Retrieval-Augmented LLM Hypotheses for Longitudinal Cell Painting Morphology

High-content morphological profiling (Cell Painting) yields sensitive, high-dimensional signatures of cellular state, but translating longitudinal morphology trajectories into interpretable biology remains difficult, especially for weak, chronic perturbations such as low-dose-rate ionizing radiation. Large language models (LLMs) can synthesize heterogeneous evidence into biological narratives, yet their scientific use requires quantitative auditing. We present an evaluation-first, retrieval-augmented interpretation framework for longitudinal Cell Painting morphology, applied to a 9-week RPE-1 time course across five dose rates (0.003--6.0 mGy/hr). Week-matched treated-control morphology deltas are combined with retrieved perturbation neighbors, pathway context, and literature evidence through stable evidence identifiers, enabling an LLM to generate structured, evidence-linked hypotheses that are hierarchically summarized while preserving provenance. We introduce two quantitative auditing tests: V1 citation validity, which verifies that cited evidence identifiers exist in the prompt, and V2 proxy-based morphology compatibility, which evaluates consistency between predicted biological processes and the most altered morphology features. In our experiments, V1 detected no invalid evidence references, while V2 showed meaningful morphology compatibility that increased with perturbation strength and was positively associated with an independent morphology drift summary. The framework produces auditable, falsifiable biological hypotheses, including an adaptive phenotype involving metabolic reprogramming and proteostatic stress at lower dose rates (0.003--0.3 mGy/hr). Current limitations include proxy-based evaluation and the lack of ground-truth mechanism labels.

Gilchan Park, Guang Zhao, Byung-Jun Yoon +1

Brookhaven National Laboratory Upton, New York, USA

Cells Model Auditing Art Rapid Adaptation

Jul 17, 2026cs.NE

Transient State Reorganization and Cell Differentiation in the Developmental Dynamics of Growing Neural Cellular Automata

Growing Neural Cellular Automata (GNCA) develop complex morphologies from a single seed cell through shared local rules, yet the internal dynamics of this process remain poorly understood. To investigate how GNCA grows, the full developmental trajectory of trained GNCA models was traced. The trajectory of cell state development revealed that morphological convergence often proceeds non-monotonically through transient intermediate configurations. In addition, channel-wise analysis showed that the hidden channels self-organize into modular groups in parallel with the visible form. Furthermore, geometric analysis of the cell state space indicated that cell states diversify within a low-dimensional, smooth manifold. To examine cell development in more detail, community detection on an

ε

-neighbour network of cells was conducted. This analysis successfully extracted discrete cell types from this continuous space, and identified transient cell-type communities during early development and stable, finer-grained types corresponding to spatially coherent regions of the mature morphology. The temporal coordination of these phenomena across multiple independent measures indicates that the developmental process of GNCA is a reorganization of transient states rather than incremental refinement.

Hiroki Sato, Atsushi Masumori, Takashi Ikegami

1The University of Tokyo, Japan · 2Alternative Machine Inc., Japan · 3Atomi University, Japan

Neural Cellular Automata Cells Developmental Trajectories Morphology

Jul 14, 2026cs.CV

Virtual Chromoendscopy with Tunable Visibility Enhancement

Chromoendoscopy (CE) is a common clinical practice that sprays indigo carmine blue dye onto the gastric surface to improve the visibility of gastric lesions, such as an early cancer. While CE is effective in detecting the lesions, preparing and spraying the dye needs additional cost and time, which is undesirable both for patients and medical practitioners. To overcome this issue, virtual chromoendoscopy (V-CE) was recently proposed, which applies a learned image translation model to virtually generate a CE image from a standard endoscopy (SE) image. In this paper, we propose virtual enhanced chromoendoscopy (V-ECE) that combines V-CE with image enhancement techniques to further improve the visibility of gastric lesions. Because a desired enhancement level depends on the inspected lesion and the practitioner's preference, we introduce a novel image translation model that can generate V-ECE images using an enhancement level tunable by a user. Experimental results demonstrate that our proposed model can plausibly generate V-ECE images with various enhancement levels using a unified model.

Yuhi Kanno, Yusuke Monno, Sho Suzuki +2

Department of Systems and Control Engineering, School of Engineering, Institute of Science Tokyo, Meguro-ku, Tokyo 152-8550, Japan · Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa-shi, Chiba 272-0827, Japan · AI Medical Service Inc., Toshima-ku, Tokyo 170-0013, Japan

Colonoscopy Colorectal Cancer Coronary Angiography Enhancement Unpaired Image-To-Image Translation Visibility+1

Jul 13, 2026cs.CV

Higher-Order Cell Tracking Transformer

Reconstructing lineages from live-imaging microscopy requires linking cell detections across time, including through cell divisions. A common approach is to construct a candidate graph and associate cell segmentations (nodes) across frames. However, these and other existing methods overlook two structural obstacles in candidate tracking graphs: (i) cell divisions entangle distinct lineage paths in the node embedding space, and (ii) edges sharing a node have near-random label agreement, so the candidate-graph topology carries no useful information for graph neural networks to aggregate. We propose the \textbf{Higher-Order Cell Tracking Transformer} (HOCT), an edge-centric architecture in which candidate cell links attend to one another under a 3D geometric prior, resolving both issues. Evaluated on the Cell Tracking Challenge and a bacteria division benchmark, HOCT achieves state-of-the-art results without deep pre-trained image encoders. Moreover, the proposed approach is easier to fine-tune, quickly reducing tracking errors by 59% with 400 annotations in a human-in-the-loop setting, outperforming LoRA fine-tuning of competing transformer baselines (6.75% improvement).

Jordão Bragantini, Ilan Theodoro, Loïc A. Royer

Biohub San Francisco, CA

Cells Spatio-Temporal Transformers Multiplex Graph Transformers Transformer Architectures Lineages

Jul 6, 2026cs.LG

Data-Driven Soft Labeling Scales DNA Read Classification to Whole-Body Cell-Type Deconvolution

Revised following peer review. We expanded baseline comparisons, corrected evaluation leakage and read-boundary handling, clarified the confidence-weighted loss, and added sensitivity analyses for pooling and region selection. We also expanded TCS failure-mode and limitations analyses, added a discussion section, and provided code and data links for reproducibility.

Dmytro Rizdvanetskyi, Nathan Roos, Pavlo Lutsik

Department of Oncology KU Leuven Leuven, Belgium

Cells Multi-Label Classification Atlas

Jul 6, 2026cs.LG

Score Distributions, Not Cells: Evaluating Single-Cell Perturbations Under Class Overlap

Most classification problems assume the classes are roughly separable, so that an individual sample can usually be assigned to one class. Single-cell perturbation data violates this assumption: two perturbations can produce different populations of cells while overlapping so much that an individual cell could belong to either. Per-cell accuracy then measures this overlap rather than model quality. We see this on Tahoe-100M and the Virtual Cell Challenge, where a linear classifier, an MLP, and a Transformer all plateau near macro-F1 0.2-0.3 even though almost every pair of perturbations is statistically distinguishable. The fix is to score perturbations across the whole population rather than cell by cell. We average a classifier's per-cell probability vectors over all cells of a perturbation to form a population profile, then rank candidate perturbations by this profile; we call the resulting score the Classifier Discrimination Score (CDS). Taking the top-ranked class recovers the winning perturbation. It needs no retraining, costs linear time in the number of cells, and recovers near-perfect identification from the same weak models. CDS differs from the pseudobulk-based Perturbation Discrimination Score (PDS) used in recent benchmarks only in where the average is taken, raw gene expression for PDS versus a learned discriminative space for CDS, and identifies the true perturbation more reliably on both datasets, with the gap widening as cells grow scarce. Because a metric that misranks the ground truth will misrank the models scored against it, per-cell accuracy and raw-pseudobulk scores should be used with caution when comparing perturbation models.

Youssef Marrakchi, Davide D'Ascenzo, Sebastiano Cultrera di Montesano

Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA. · Department of Computer Science, University of Milan, Milan, Italy. · Department of Control and Computer Engineering, Politecnico di Torino, Torino, Italy. +1

Single-Cell Perturbation Prediction Cells Virtual Cell Classifier

Jul 1, 2026eess.IV

MalariAI: A Label-Resilient Decoupled Framework for Universal Cell Segmentation and Explainable Stage Classification in Dense Malaria Blood Smears

Automated malaria diagnosis from blood smear microscopy is a critical challenge in global health AI; in resource-limited settings, the scarcity of expert microscopists remains the primary bottleneck to timely and accurate diagnosis. Three compounding failure modes prevent reliable clinical deployment of existing deep learning systems. First, end-to-end detectors treat unannotated cells as background during training, producing recall figures that are strongly influenced by annotation completeness rather than reflecting true cell recovery. Second, Non-Maximum Suppression tends to suppress valid detections in dense smear regions where infection counts matter most. Third, existing whole-slide detection pipelines lack per-cell spatial evidence for clinical audit, despite image-level explainability methods such as Grad-CAM having been applied to malaria image classification tasks. We present MalariAI, a two-stage decoupled framework that addresses all three failure modes in a unified pipeline. Stage 1 applies an annotation-agnostic distance-transform guided watershed algorithm to isolate every cell in a full 1600x1200 blood smear image, recovering 75.95% of ground-truth cells by centroid localisation across the 120-image NIH BBBC041 test set without any ground-truth input. Stage 2 fine-tunes EfficientNet-B0 with Focal Loss (gamma = 2.0, per-class inverse-frequency weights) on 64x64 crops, achieving 98.36% overall classification accuracy with 87.5% and 75.0% per-class accuracy on the rare schizont and gametocyte stages, compared to only 24.57% and 25.95% AP for a Faster R-CNN baseline on the same classes. Grad-CAM++ heatmaps generated per detected cell provide instance-level spatial evidence for clinical audit, enabling microscopists to verify model predictions at the individual parasite level without sacrificing classification performance.

Kaysarul Anas Apurba, Md Hasibul Hasan, Mohammed Ali +1

Department of Electrical and Computer Engineering, North South University, Dhaka 1229, Bangladesh · Department of Computer Science and Engineering, International University of Business Agriculture and Technology (IUBAT), Dhaka 1230, Bangladesh

Acute Myeloid Leukemia Multiple Instance Learning Cells Loss Function Resilience

Jun 28, 2026cs.CV

CellDETR: A Detection-Guided Framework for Scalable Cell Representation Learning from Histopathology Images

Recent advances in pathology foundation models have substantially improved patch and slide level representation learning from whole-slide images (WSIs).However, cell-level representations learning remain underexplored, limiting cell resolved interpretability, biological discovery, and clinical translation. We propose CellDETR, a detection-guided framework built on Deformable DETR for scalable cell representation learning from WSIs. By introducing location feature decoupling and box-constrained attention mechanism, CellDETR enables automated extraction of cell-level embeddings, and outperform existing state-of-the-art methods in supervised cell classification on PanNuke data. In addition, by incorporating contrastive learning design, we build a CellDETR-based pretraining model for scalable cell representation learning from unlabeled WSIs, which improves downstream cell classification performance. Furthermore, we show that after pretraining with Xenium spatial transcriptomics-derived cell annotations, CellDETR achieves accurate cross-dataset cell classification, demonstrating the transferability and biological relevance of the learned cell embeddings. Together, CellDETR provides a scalable route toward general cell-level representation learning framework for interpretable computational patholog

Shikang Zhang, Guojun Li, Yicong Mao +1

Zhejiang University of Technology · Tianjin University · Hangzhou Institute of Medicine, Chinese Academy of Sciences

Digital Pathology Whole-Slide Images Cells Virtual Cell

Jun 22, 2026cs.LG

3D Masked Autoencoders are Robust Learners of Volumetric and Multimodal Cellular Representations for Microscopy

Self-supervised learning in fluorescence microscopy often relies on 2D projections, despite the inherently three-dimensional nature of cells. We present a systematic comparison of 2D and 3D masked autoencoders (MAE-2D vs. MAE-3D) on volumetric microscopy data. Under matched architectures and training protocols, MAE-3D consistently outperforms 2D max-projection and slice-based variants on downstream single-cell tasks. We further align visual representations with a pretrained protein language model (ESM2) and show that cross-modal supervision yields larger gains for volumetric models. Channel cross-attention and frequency-domain regularization are critical for leveraging 3D spatial context. On protein--protein interaction prediction, our best model achieves a ROC--AUC of 0.86, while on protein localization it reaches an AUC

_{\text{micro}}

of 0.95 and an F1

_{\text{micro}}

of 0.74, demonstrating competitive performance on both tasks. Overall, our findings highlight the potential of volumetric modeling and multimodal alignment for representation learning in single-cell microscopy.

Amirhossein Kardoost, Lion Gleiter, Tingying Peng +1

Institute of AI for Health & Helmholtz AI, Computational Health Center, Helmholtz Munich – German Research Center for Environmental Health, Neuherberg, Germany · Munich Center for Machine Learning (MCML), Munich, Germany · Department of Medicine III, Ludwig-Maximilian-University Hospital, Munich, Germany +2

3D Masked Autoencoders Microscopy Autoencoder Architectures Volume Cells 3D Generation+2

Jun 19, 2026cs.LG

Chem2Gen-Bench: Benchmarking Chemical-to-Genetic Translation in Perturbation Response Space

Virtual-cell and perturbation models are increasingly used to predict cellular responses for biomedical discovery, but chemical and genetic perturbations are not automatically interchangeable. Existing evaluations often study chemical response prediction or genetic perturbation prediction separately, leaving target-matched chemical-to-genetic translation under-tested. We introduce Chem2Gen-Bench, a benchmark comprising 260,084 chemical and 1,099,045 genetic perturbation profiles organized into cell-target contexts, and evaluate pairwise alignment, retrieval, protocol covariate associations, feature spaces, and foundation-model embeddings. Across matched contexts, translation fidelity is measurable but heterogeneous; background adjustment increases the association between pairwise similarity and retrieval success, while paired tests show lower mean retrieval success after adjustment under the evaluated settings. In a target-matched K562 audit, the evaluated foundation-model embeddings did not consistently improve over gene-delta baselines. Chem2Gen-Bench provides an auditable framework for testing when chemical and genetic perturbations align around shared targets and when representation gains are supported by matched perturbation evidence.

Yuxiang Lin, Ying Chen

National Institute for Data Science in Health and Medicine, Xiamen University · School of Informatics, Xiamen University

Jun 16, 2026cs.CV

Revisiting Structural Dependency in Autoregressive Multi-Task Table Recognition via Order-Independent Cell-Level Representations

Multi-task table recognition jointly addresses table structure prediction, cell localization, and cell content recognition within a unified framework. Existing approaches often rely on autoregressive decoders to generate table structures and reuse their hidden states for cell localization and content recognition. This autoregressive generation process can make cell representations order-dependent, degrading global consistency across cells. This paper proposes a structural refinement module that produces order-independent cell features through non-causal attention. This design enables parallel inference of cell contents while conditioning each cell on global context encoded in the refined features. Experiments on two large datasets demonstrate consistent gains in cell localization and end-to-end recognition, while reducing overall inference time by around threefold.

Takaya Kawakatsu

Preferred Networks, Inc., 1-6-1 Otemachi, Chiyoda, Tokyo, Japan.

Tabular Learning Multi--Task Learning Representation Learning Cells Causal Attention Refinement

Jun 15, 2026q-bio.QM

Towards a Pseudo-Labeling Workflow for Celltype-Classification from Explanted Brain Slice Recordings

This paper proposes an unsupervised workflow to pseudo-label extracellular spikes from human brain slice MEA recordings into two putative cell types: pyramidal cells and interneurons. Here, the raw data from the data acquisition system is used and processed. The pipeline for pre-processing includes bandpass filtering, threshold--based spike detection, frame alignment and normalization. In the ML workflow, dimensionality reduction (PCA, t-SNE, UMAP), clustering (GMM, k-means). To achieve an online system, template matching and OSort under varying curation strictness is also considered. All pipelines are evaluated by different cluster quality with within-cluster Pearson correlation, Silhouette score, and Calinski-Harabasz index. Applying stricter curation improves separation at some cost to inclusivity.

Cora Jostock, Jonas Ort, Henner Koch +2

University of Duisburg-Essen, Intelligent Embedded Systems Lab, Duisburg, Germany · RWTH University Hospital, Department of Neurosurgery, Aachen, Germany · RWTH University Hospital, Department of Epileptology, Aachen, Germany

Neural Recordings Cells Pseudo-Label Quality Unsupervised Time-To-First-Spike Spearman Correlation+1

Jun 10, 2026q-bio.GN

CisTransCell: Single-Cell Perturbation Prediction via Gene Function, Regulatory Control, and Cellular Context

Predicting cellular transcriptional responses to genetic perturbations is a central problem in single-cell biology, especially in the zero-shot setting where the perturbed gene or gene combination is unseen during training. A major difficulty is that perturbation effects are not determined by expression state alone: they depend on how the perturbed gene product influences other genes and proteins, how those downstream factors act on cis-regulatory elements, and which regulatory programs are active in the current cell state. To better capture this biological complexity, we propose CisTransCell, a cell-conditioned multi-modal framework for single-cell perturbation prediction that augments each gene with two complementary priors: a regulatory-sequence prior that captures how the gene is controlled, and a coding-sequence prior that captures what the gene product does. By integrating these priors with cellular expression state, CisTransCell models perturbation response as a cascade from gene function to regulatory control to downstream transcriptional change. Experiments on benchmark single-cell perturbation datasets show that CisTransCell achieves strong performance in zero-shot perturbation prediction.

Wei Zhang, Xun Jiang, Yuesi Xi +1

1L3S Research Center, Leibniz Universität Hannover, Germany · School of Clinical Medicine & Laboratory Medicine, Jiangsu University, China · Institute for Information Processing (tnt), Leibniz Universität Hannover, Germany.

Single-Cell Perturbation Prediction Cells Regulation

Jun 10, 2026cs.CV

CellNet -- Localizing Cells using Sparse and Noisy Point Annotations

Counting living cells is an important step in many biological research workflows. Our collaborators at the Wellcome Sanger Institute study vital genes in humans via large scale saturation genome editing screening, which requires repeatedly counting cells a great number of times. Computer Vision based automation is crucial for high throughput and resource efficiency. In this work, we develop a regression-based deep learning computer vision algorithm to detect and count cells in phase-contrast microscopy images. To reduce annotation effort, which in practice often becomes a bottleneck, we focus on counting cells only using sparse point annotations, which are fast and easy to acquire. By comparison to state-of-the-art 0-shot methods, we show that regression-based counting is a promising alternative in low data regimes. Through developing methods to automatically count living cells in microscopy images, we contribute to valuable research on the human genome. The code is available at https://github.com/beijn/cellnet.

Benjamin Eckhardt, Dmytro Fishman, Stuart Fawke +3

University of Göttingen · University of Tartu · Wellcome Sanger Institute

Cells Microscopy Computer Vision

Jun 9, 2026cs.CL

Small Experiments, Cheaper Decisions: A Case Study in Staged Promotion for Micro-Pretraining

Short pretraining runs can reduce experimental cost, but they can also over-promote configurations that only look strong at tiny budgets. We study an auditable staged-promotion protocol for a fixed micro-pretraining runner on two heterogeneous host blocks: Windows A100 and Linux L40S. Starting from twelve prior-screened configurations, we use staged budgets of 2 minutes, 5 minutes, 10 minutes, 60 minutes, and 12 hours, with frozen promotion rules before expensive continuations. The early screens are intentionally treated as unstable: the 5- and 10-minute rankings are host-sensitive, and the eventual 12-hour top-ranked condition is not the mean-best condition at the replicated 10-minute gate. Because seed ranges differ across stages, these changes are operational promotion evidence, not within-seed curves. A replicated 60-minute gate keeps the Staged Factorial Screening bridge reference in the promoted set, where it ranks first in all four 60-minute host-seed cells. In the final 12-hour confirmation package, the bridge condition ranks first in all four host-seed cells across two seeds; the greedy comparator does not meet the frozen 0.010 val_bpb near-equivalence rule; and the cheaper d8/ar48 (depth-8, aspect-48) sentinel does not meet the frozen 0.020 mean-gap rule. The executed 12-hour branch spends 144 GPU-hours, and the full staged protocol records 169.2 training GPU-hours including screening stages. Continuing all four 60-minute candidates would spend 192 GPU-hours, while continuing all nine replicated 10-minute candidates would spend 432 GPU-hours. The latter numbers are accounting counterfactuals for unrun continuations, not evidence that skipped candidates could not have overtaken the reference. The result is a bounded cost-allocation finding, not a claim of global optimality, capacity-normalized superiority, or superiority over adaptive hyperparameter optimization methods.

Felipe Chavarro Polania

Hewlett Packard Enterprise

Token Budget Allocation Pretraining Gating Case Study Cells

Jun 2, 2026cs.DS

Incremental Sheaf Cohomology on Cellular Complexes: O(1)-in-n Lazy Edit Processing under Bounded Local Geometry

We present an algorithmic framework for incremental maintenance of first sheaf cohomology

H^1(X; \mathcal{F})

on dynamically evolving 1-dimensional cellular complexes equipped with finite-dimensional cellular sheaves. The classical computation of

H^1

via factorization of the coboundary matrix requires

O(n^3)

time; when the complex evolves with a stream of

m

edits, full recomputation after each edit costs

O(mn^3)

. Under a bounded local geometry assumption -- bounded cell size

v_{\max}

, bounded stalk dimension

d

, and bounded nerve degree

D

-- each edit (vertex insertion, edge insertion, restriction map update) affects only a bounded set of local coboundary blocks. The algorithm therefore processes lazy streaming edits in

O(1)

time with respect to the total complex size

n

(with cost polynomial in the local geometry parameters

v_{\max}

,

d

, and

D

, which are treated as constants independent of

n

), deferring local eigensolves and Mayer-Vietoris global assembly to synchronization points (Flush). At synchronization, the maintained state agrees with the corresponding batch assembly of the partitioned sheaf model; we observe zero measured drift in all batch-verified runs (through

V = 10^6

). We also give an amortized

O(|E|)

streaming construction for the cellular decomposition and discuss an adversarial algebraic-RAM barrier arguing that unpartitioned non-trivial sheaves (

d \geq 2

, non-identity restriction maps) do not admit the same locality. Experiments on Barabasi-Albert graphs with up to

5 \times 10^6

vertices and

1.7 \times 10^7

streaming edits show 35

μ

s median lazy per-edit update latency (excluding flush); query time (global assembly at synchronization) is

O(n)

per flush in the implemented full-traversal path. Exact synchronization costs are reported separately.

Jason L. Volk

Invariant Research

Sheaf Persistent Homology Cells Edit

Jun 2, 2026q-bio.CB

Quantifying the biophysical properties of stomatocytes in health and disease

Hereditary stomatocytosis (HS) comprises red blood cell (RBC) disorders characterized by cup-shaped erythrocytes that respond oppositely to splenectomy: curative in overhydrated HS (OHS) but potentially thrombogenic in dehydrated HS (DHS/xerocytosis). This paradox persists because RBC biomechanics is governed by partly independent parameters--shear modulus, bending rigidity, surface-to-volume ratio (S/V), and cytoplasmic viscosity--that existing assays capture only piecemeal. Here we combine dissipative particle dynamics (DPD) simulations with microfluidic imaging to construct a control discocyte and three stomatocyte models (ST-RBC1-3) at fixed membrane area and decreasing volume (109.7, 101.5, 89.8 fL), spanning the OHS-to-DHS range. Tracing this parameter set through five mechanically orthogonal assays, we find that interendothelial-slit (IES) traversal is geometry-dominated: overhydrated ST-RBC1 requires an order of magnitude higher critical pressure than healthy RBCs, whereas dehydrated ST-RBC3 passes freely. ST-RBC3 nonetheless suppresses membrane tank-treading and raises low-shear whole-blood viscosity by ~29% at physiological haematocrit, comparable to Gaucher-disease hyperviscosity. A funnel-obstacle chip amplifies these differences into a label-free centerline-offset signal predicted to separate all four RBC types (~4.5 standard deviations between extreme phenotypes). These results unite single-cell mechanics, splenic filtration, and hemorheology in one framework, resolve the splenectomy paradox, and point toward microfluidic pre-operative risk stratification in HS.

Zhaojie Chai, Jianlu Zheng, He Li +2

Division of Applied Mathematics, Brown University, Providence, Rhode Island, United States · Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts · College of Engineering, University of Georgia, Athens, Georgia, United States

Acute Myeloid Leukemia Cells Disease

Jun 2, 2026cs.AI

Toward Pre-Deployment Assurance for Enterprise AI Agents: Ontology-Grounded Simulation and Trust Certification

Pre-deployment verification of enterprise artificial intelligence (AI) agents remains a critical gap between large language model (LLM) capability benchmarking and production deployment. Post-deployment monitoring, human-in-the-loop controls, and prompt-level guardrails offer limited assurance once an agent is operating in production. We present an ontology-grounded verification framework -- to our knowledge the first to combine three components: an Agent Operational Envelope formalizing the certification space across permissions, domain constraints, safety properties, governance rules, and autonomy levels; an ontology-to-scenario generation pipeline that derives regulatory, operational, and adversarial test scenarios automatically; and a machine-verifiable Trust Certificate with graduated deployment verdicts. A controlled pilot across four regulated industries (Fintech, Banking, Insurance, Healthcare), instantiated as five industry-by-regulatory-regime cells across the United States and Vietnam (where Vietnam's 2025 AI Law makes such verification legally mandated for financial services), generated 1,800 scenarios evaluated against 125 primary-source regulatory requirements and 25 injected faults. Ontology-grounded generation significantly outperformed the dominant persona-based baseline on regulatory coverage (48.3% versus 33.1%; corrected p_c = .0006) and attained the highest domain specificity (4.77/5.0; p = 2e-6); transparently, its advantage over plain and retrieval-augmented prompting did not survive Bonferroni correction. Cross-validation across three LLM families (Claude Sonnet 4, Qwen 2.5 72B, Gemma 4 26B; 5,400 total scenarios) replicated the persona-versus-ontology pattern. The framework offers a reproducible, regulation-grounded route to pre-deployment assurance for enterprise AI agents, complementing runtime governance with an auditable deployment gate.

Thanh Luong Tuan, Abhijit Sanyal

Golden Gate University, San Francisco, CA, USA · Data, Digital & IT, Novartis Healthcare Pvt. Ltd., Hyderabad, India

Agentic Deployments Pre-Deployment Safety Assessments Artificial Intelligence Agents AI Trustworthiness Adversarial Robustness Cells

Jun 1, 2026cs.CV

GC-MoE: Genomics-Guided Cell-Type-Specific Mixture of Experts for Histology-Based Single-Cell Spatial Transcriptomics

Histology-based single-cell spatial transcriptomics (ST) estimation aims to predict gene expression for individual cells from histopathological images and cell locations, reducing the need for costly single-cell ST measurements. Unlike existing histology-to-ST methods that mainly predict spot-level profiles for local regions containing multiple cells, this task requires modeling cell-to-cell expression variability, which is strongly structured by cell type. We propose Genomics-Guided Cell-Type-Specific Mixture-of-Experts (GC-MoE), which estimates cell-type probabilities with a routing network and softly combines cell-type-specific experts for gene expression prediction. To further encode cell-type-dependent gene programs, we introduce the Cell-Type-Specific Co-Expression-Aware Predictor (CAP), together with a lightweight Cell-to-Cell Interaction Attention (C2CA) module for neighboring-cell context. Experiments and ablations on public single-cell ST datasets show consistent improvements over existing single-cell and adapted spot-level baselines.

Kaito Shiku, Ahtisham Fazeel Abbasi, Ryoma Bise +4

Kyushu University, Japan · German Research Center for Artificial Intelligence (DFKI GmbH), Germany · RPTU University Kaiserslautern-Landau, Germany +3

Spatial Transcriptomics Cells Experts

May 30, 2026cs.CV

CodeCytos: AI-assisted spatial molecular imaging analysis via code-augmented agent action space

Conventional tissue image analysis software provides foundational capabilities for cellular analysis, including segmentation, basic morphological feature extraction, and spatial organization analysis. However, these tools often require manual intervention and are not well integrated with code-driven automation, limiting efficiency and scalability for complex spatial tissue studies. In addition, they offer limited flexibility for custom analyses, as they typically support only a fixed set of pre-implemented spatial cellular features. To address these limitations, we propose CodeCytos, a coding-based reasoning agent framework that enables dynamic, programmable interaction with spatial molecular imaging data to improve automation and customization. CodeCytos is designed to streamline the exploration of custom spatial cellular features and adapt to diverse research needs. We demonstrate its utility through case studies on four expert-curated datasets from distinct tissue types: frontal cortex, non-small-cell lung cancer, pancreas, and tonsil. We evaluate CodeCytos under a realistic minimal prompt setting, where bioscientists pose simple questions without task-specific instructions or contextual information about spatial cellular analysis, and benchmark multiple LLM backbones with strong coding capabilities. We further show that incorporating tailored, domain-agnostic few-shot in-context coding-reasoning examples (randomly sampled demonstrations outside the spatial analysis domain) can substantially improve performance without requiring costly, expert-crafted in-domain demonstrations. Overall, CodeCytos outperforms baseline approaches, highlighting the potential of code-action agents to assist with custom feature exploration in spatial molecular imaging and to accelerate biomarker discovery.

Hung Q. Vo, Huy Q. Vo, Son T. Ly +6

University of Houston, Department of Electrical and Computer Engineering, Houston, Texas, 77004, USA · Houston Methodist Hospital, Department of Systems Medicine and Biomedical Engineering, Houston, Texas, 77030, USA

Microscopy Cells Action Space

May 29, 2026cs.LG

AI-Guided Design and Optimization of Graphite-Based Anodes via Iterative Experimental Feedback

This study presents an iterative AI-guided workflow that accelerates graphite-based anode development by improving both formulation feasibility and process robustness. Sequential learning via AI/ML-guided multiobjective inverse design for anode optimization was implemented using the Citrine Platform. Starting from a noisy, incomplete dataset, the Citrine Platform was used to generate early surrogate models, which despite low predictive certainty highlighted missing process constraints. By iteratively adding feasibility labels and boundary condition failures, the workflow rapidly converged toward manufacturable, higher-performing formulations. Fabrication reliability improved from frequent process failures to 100% successful cell production, while the fraction of cells delivering

\geq

350 mAh g

^{-1}

increased from 28.4% to 84.8%, with capacity retention rising from 42.1% to 97.3%. These results demonstrate that structured, feedback-driven AI workflows can transform imperfect industrial data into actionable guidance, enabling faster, more reproducible optimization of battery electrode manufacturing.

Qian Du, Mark M. Sullivan, James E. Saal +1

hte GmbH, Kurpfalzring 104, 69123 Heidelberg, Germany · Citrine Informatics, 2629 Broadway St., Redwood City, CA 94063, USA

Lithium-Ion Batteries Generative Inverse Design Iterative Cells

May 28, 2026cs.CV

One Click per Cell Type Suffices: Training-free Group Interaction for Cell Instance Segmentation

Cell instance segmentation models trained on cell-specific datasets suffer severe performance drops on out-of-distribution cell types, while interactive foundation models overcome this through per-instance prompting at a cost that is prohibitively expensive for histopathology images containing hundreds to thousands of densely packed instances. We introduce \textbf{Group Prompting}, a new paradigm that shifts interactive segmentation from per-instance

O(N)

to per-type

O(T)

, where a single click per cell type suffices to segment all instances of that type. Our key observation is that the frozen image encoder of the Segment Anything Model (SAM) already clusters same-type cells in its feature space before any prompt is given, and that this clustering holds across staining modalities without any training. Exploiting this property, we propose \textbf{Chain-of-Prompts (CoP)}, a training-free framework that recursively expands a single user click by (1) identifying reliable same-type locations through non-parametric gating of multi-scale encoder features, and (2) selecting the most spatially distant reliable point as the next prompt to maximize coverage. On eleven benchmarks, CoP generalizes to both unseen cell types and unseen imaging modalities without any adaptation: with one click per type it retains over 90% of per-instance performance on three cell-type-annotated datasets while surpassing fully-supervised methods, and with one click per image it retains over 95% on eight datasets spanning both H&E and non-H&E imaging. Project Page: https://shjo-april.github.io/Chain-of-Prompts/

Sanghyun Jo, Seo Jin Lee, Seohyung Hong +4

1OGQ, Korea · 2Seoul National University, Korea · 3LG CNS, Korea

Cells Multiple Instance Learning Multiple Prompt Learning Frameworks Digital Pathology Prompt Engineering

May 27, 2026cs.LG

Chreode: A Cell World Model for One-Step Temporal Dynamics and Perturbation Prediction

Predicting how a cell will change its transcriptional state under a developmental signal or a genetic perturbation is the computational core of in-silico biology and the AI Virtual Cell program. Existing approaches either fit static control-to-treated maps that discard time, or solve multi-step ODE / Schrödinger-bridge problems on each dataset independently. We introduce Chreode, a one-step cell world model that predicts action-conditioned cell-state transitions through a structured residual transition operator. It shifts distributional evolution from inference time to training time, enabling single-pass generation while preserving a Waddington-inspired decomposition into downhill landscape flow, rotational in-tangent dynamics, and stochastic spread. The model is pretrained with a shared scVI encoder and a DiT-based dynamics backbone on a 2.4M-cell mouse embryonic atlas spanning 7 datasets. As a fine-tuning initialization, Chreode improves per-target Sinkhorn distance on Weinreb hematopoiesis and Veres islet differentiation over matched scratch models, PI-SDE, and PRESCIENT. As a transferable gene-state embedding for GEARS, the pretrained dynamics representation reduces shared-vocabulary DE20 mean squared error on Norman Perturb-seq from 0.2121 to 0.1858, a 12.4% relative improvement, without changing the GEARS training procedure. We interpret this transfer to perturbation prediction as evidence that pretrained developmental-trajectory dynamics encode differentiation primitives transferable to CRISPR-induced state shifts, since both involve cell-state transitions in a shared latent geometry. The pretrained backbone additionally produces zero-shot clonal fate scores on Weinreb that are competitive with strong dynamic-OT baselines.

Mufan Qiu, Genhui Zheng, Yinuo Xu +4

University of North Carolina at Chapel Hill · The University of Texas at Austin · University of Pennsylvania

Cells Developmental Trajectories Sequence Modeling Temporal Dynamics World Models Learning Dynamics

May 21, 2026cs.CV

Cell Phantom Video Generation in Elliptical Fourier Descriptor Domain

Training Deep Neural Networks for tracking individual cells in biomedical videos requires a large amount of annotated data. The annotation of videos for cell tracking is very time consuming and often requires domain expertise; this explains the limited availability of public annotated data to address important medical problems like tissue repair or cancer treatment. Generating synthetic videos along with their Ground Truth annotations is a promising solution that relies, as a foundational first step, on the synthesis of single cell annotations (or phantoms). Phantoms need to be time consistent, as they have to replicate biological processes that are specific to the cell types. In this work, we propose a novel framework for generating videos of cell phantoms in the Elliptical Fourier Descriptors (EFDs) domain, a compact and geometrically interpretable representation for 2D closed contours. We represent the cell phantom evolution as a multivariate time series of EFD coefficients, introducing a strong prior for cell morphology and enabling the efficient generation of sequences that evolve coherently in time. Our experimental validation proves that modelling the temporal evolution in EFD space enables the generation of biologically plausible phantom videos. Our method can be used in generative pipelines for synthesizing annotated data for cell tracking, thus strongly mitigating the annotation effort for creating new datasets. Our code is available for download here: https://github.com/FrancescoBenedetto99/efd-cell-video-gen.

Francesco Benedetto, Roberto Basla, Luca Magri +1

Department of Electronics Information and Bioengineering, Politecnico di Milano, Italy

Long Video Generation Cells Fourier

May 20, 2026cs.LG

Training distribution determines the ceiling of drug-blind cancer sensitivity prediction

Precision oncology requires predicting which drugs will suppress a specific tumor from its molecular profile, but drug-blind sensitivity prediction has plateaued despite increasingly complex drug representations. Here we show that this stagnation reflects a metric artifact rather than a representational bottleneck. The standard benchmark, global Pearson r, is dominated by between-drug potency differences that a trivial drug-mean predictor captures without any cell-specific learning. Per-drug Pearson r, which isolates within-drug cell ranking, reveals that no drug encoding improves over cell-only features across four independent datasets. A controlled experiment channeling mechanism-of-action identity as either a drug feature or a training-distribution constraint identifies the cause. Supplying MoA as a feature yields negligible benefit, whereas using it to stratify training raises per-drug r substantially for targeted kinase inhibitors, because pan-cancer co-training suppresses pathway-specific sensitivity signals. Mechanism-stratified training and response matching from pilot observations provide two deployable strategies that together recover the principal sources of predictive gain in drug-blind sensitivity prediction.

Taekyung Heo

Pharmacokinetics Cells Spearman Correlation Ceiling

May 19, 2026cs.CV

WBCAtt+: Fine-Grained Pixel-Level Morphological Annotations for White Blood Cell Images

The microscopic examination of white blood cells (WBCs) plays a fundamental role in pathology and is essential for diagnosing blood disorders such as leukemia and anemia. To support further research on WBC images, multiple datasets have been proposed. However, they mainly annotate cell categories, and lack detailed morphological characteristics that pathologists use to explain their interpretations of cells. To address this gap, we introduce WBCAtt+, a novel dataset of WBC images densely annotated with 11 morphological attributes and five pixel-level cell components. With 113k image-level labels and 10k segmentation maps, WBCAtt+ is the first to provide comprehensive annotations for WBC images. Leveraging this dataset, we provide baseline models for attribute recognition and semantic segmentation. We also design an attribute recognition model to incorporate compositional structure of cells, further improving the recognition performance. Lastly, we showcase various applications enabled by our dataset, such as explainable AI models, including counterfactual example generation. \revision{The dataset and code are publicly available\footnote{https://doi.org/10.57967/hf/8143}}.

Satoshi Tsutsui, Winnie Pang, Shuting He +1

Rapid-Rich Object Search (ROSE) Lab, School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore · Shanghai University of Finance and Economics, Shanghai, China

Acute Myeloid Leukemia Pixel-Level Annotation Medical Imaging Datasets Cells Morphology Semantic Segmentation

May 14, 2026cs.LG

Reading the Cell, Designing the Cure: Perturbation-Conditioned Molecular Diffusion for Function-Oriented Drug Design

When reliable target structures are unavailable at scale or phenotypes arise from dysregulated pathways, transcriptomic perturbations provide a system-level functional readout for drug action. In this work, we formalize \emph{Transcriptome-based Drug Design (TBDD)} as a generative inverse problem: designing drug molecules conditioned on desired transcriptomic state transitions. We analyze the inherently ill-posed nature of this task, which is further complicated by the profound domain gap between biology and chemistry and by the sparsity of transcriptomic signals. To address these challenges, we propose \textbf{\themodel{}} (A \textbf{C}ell\textbf{U}lar \textbf{R}esponse \textbf{E}ngine), a multi-resolution transcriptome-guided diffusion framework. \themodel{} features a specialized \textbf{Transcriptome Perturbation Functional Feature Extractor (TFE)} that (1) distills function-oriented perturbation embeddings from pre/post states, (2) aligns these signatures to dual chemical views to bridge the cross-modal gap, and (3) performs heterogeneity-aware aggregation to extract robust state-specific signals from noisy transcriptomic data. Extensive evaluations on both standard benchmarks and rigorous out-of-distribution protocols demonstrate that \themodel{} consistently outperforms strong baselines in structural quality and functional consistency. Furthermore, we validate its practical utility via a zero-shot gene-inhibitor design task, highlighting the potential of phenotype-driven generative discovery.

Ziyu Xu, Zijian Zhang, Liang Wang +4

NLPR, MAIS, Institute of Automation, Chinese Academy of Sciences, Beijing, China · School of Advanced Interdisciplinary Sciences, University of Chinese Academy of Sciences, Beijing, China · School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China +1

Drug Design Transcriptomics Cells Diffusion Dynamics Diffusion Models

May 14, 2026cs.AI

From Table to Cell: Attention for Better Reasoning with TABALIGN

Multi-step LLM reasoning over structured tables fails because planning and execution share no explicit cell-grounding contract. Existing methods constrain the planner to a left-to-right factorization at odds with table permutation invariance, and score intermediate states by generated content alone, overlooking cell grounding. We conduct a pilot study showing that diffusion language models (DLMs) produce more human-aligned and permutation-stable cell attention on tables than autoregressive models, with a 40.2% median reduction in attention-AUROC variability under row reordering. Motivated by this, we propose TABALIGN, a planned table reasoning framework that operationalizes the contract. TABALIGN pairs a masked DLM planner, whose bidirectional denoising emits plan steps as binary cell masks, with TABATTN, a lightweight verifier trained on 1,600 human-verified attention standards to score each step by its attention overlap with the plan-designated mask. Across eight benchmarks covering table question answering and fact verification, TABALIGN improves average accuracy by 15.76 percentage points over the strongest open-source baseline at comparable 8B-class scale, with a matched-backbone ablation attributing 2.87 percentage points of this gain to the DLM planner over an AR planner on a fixed reasoner. Cleaner DLM plans also accelerate downstream reasoning execution by 44.64%.

Tung Sum Thomas Kwok, Zeyong Zhang, Xinyu Wang +6

University of California, Los Angeles · SimpleWay · New Jersey Institute of Technology +4

Tabular Data LLM Reasoning Strategies Reasoning Skills Large Language Model Planning Cells

May 8, 2026cs.LG

Neurally-plausible radial basis kernels using distributed Fourier embeddings

Coherent, continuous spatial representations are critical for synthesizing physical and perceptual phenomena into a single representational space. Radial basis kernels provide a path forward for this type of distributed representation. In this work, we aim to characterize and analyze common radial basis kernels realizable in the neurally-plausible framework of spatial semantic pointers. Further, we analyze previous radial basis kernel work based on grid cell-like representations and demonstrate that such representations are both capable of and optimal for realizing radial basis kernels.

Jakeb Chouinard

Department of Systems Design Engineering, University of Waterloo · Centre for Theoretical Neuroscience, University of Waterloo

Radial Basis Function Semantic Geometry Spherical Latent Space Fourier Spatiotemporal Representations Neuro-Symbolic Framework+1

May 8, 2026q-bio.MN

Inference of Qualitative Models from Steady-State Data via Weighted MaxSMT

Qualitative models provide crucial instruments for modelling complex biological systems. While advances in automated reasoning and symbolic encodings have enabled rigorous inference of these models from data, the process remains highly fragile. First, biological measurement errors inevitably propagate into formal model specifications. Second, when a specification becomes unsatisfiable, distinguishing between fundamental design flaws and minor technical errors is notoriously difficult. This uncertainty often leads to under-specification, as it is unclear which observations are still ``safe'' to incorporate. To overcome these challenges, we introduce a robust inference method based on weighted MaxSMT. By encoding uncertain biological observations as weighted soft constraints, our approach enables the solver to identify a model best reflecting the observations, even with some conflicting constraints. Our method allows for Boolean and multi-valued variable domains, alongside observations derived from discretisation (level constraints) and differential expression (ordering constraints). We show our approach can be used to successfully infer neural cell differentiation models from prior-knowledge networks with 200--1300 genes using ordering constraints on all included genes.

Ondřej Huvar, Nikola Beneš, Martin Jonáš +2

Masaryk University, Brno, Czechia

Cells Structural Constraints

May 5, 2026q-bio.QM

Donor-Aware scRNA-seq Benchmarks for IBD Classification

Donor-level disease classification from single-cell RNA sequencing (scRNA-seq) requires strict donor-aware cross-validation: naive pipelines that split cells randomly conflate training and test donors, inflating reported performance through pseudoreplication. We present a donor-aware benchmark evaluating three feature representations across two independent IBD cohorts: centered log-ratio (CLR) transformed cell-type composition, GatedStructuralCFN dependency embeddings, and scVI variational autoencoder latent embeddings. The cohorts are the SCP259 ulcerative colitis atlas (UC vs. Healthy, n=30 donors, 51 cell types) and the Kong 2023 Crohn's disease atlas (CD vs. Healthy, n=71 donors, 55-68 cell types across three intestinal regions). Compartment-stratified CLR composition achieves AUROC 0.956 +/- 0.061 on SCP259; GatedStructuralCFN on the same features achieves 0.978 +/- 0.050. In the Kong cohort, CFN achieves its best performance in the colon region (0.960 +/- 0.055 after feature filtering), exceeding linear CLR (0.900 +/- 0.100), while terminal ileum classification is dominated by linear models (CatBoost CLR 0.967 +/- 0.075 vs. CFN 0.811 +/- 0.164). Cross-dataset transfer (CD->UC, four shared cell types) achieves AUC 0.833 with XGBoost CLR; the reverse direction performs at chance. CFN edge stability analysis shows that compartment-wise composition eliminates spurious unit-sum-induced instability present in global composition (Jaccard 0.026 vs. top-20 recurrence 1.0). CFN shows a consistent numerical advantage over linear models in the colon region of CD (AUROC 0.960 vs. 0.900), though no inter-method comparison reached statistical significance at n<=34 donors per region. Compartment-aware feature construction is critical for both classification performance and structural interpretability. Code: https://github.com/Jonathan-321/sfn-scrna-study

Jonathan Muhire

Department of Computer Science, Oklahoma Christian University

Single-Cell Rna Cells Cancer Detection Cross Validation

May 4, 2026cs.CV

Approaching human parity in the quality of automated organoid image segmentation

Organoids are complex, three dimensional, self-organizing cell cultures which manifest organ-like features and represent a powerful platform for studying human disease and developing treatment options. Organoid development is characterized by dynamic morphological and cellular organization, which mimic some aspects of organ development. To study these rapid changes over the course of organoid development, advanced imaging and analytical tools are critical to accurately monitor the trajectory of organoid growth and investigate disease processes. In this work, we focus on computer vision and machine learning techniques to automatically measure the size and shape of developing spheroids derived from pluripotent stem cells (iPSCs), which are typically the starting material for generating organoid cultures. To facilitate this task, we introduce a composite method that combines the Segment Anything Model (SAM), a general-purpose foundation model, with an existing domain-specific tool. This composite method is evaluated together with several existing tools by testing them on organoid image data and comparing with the results of manual image segmentation. We find that no single existing tool is able to segment the test images with sufficient accuracy across all test conditions, but the newly introduced composite method produces consistent and accurate results for all but a very small fraction of the most challenging images. Finally, we compare the accuracy of this method to the variability between manual segmentations by independent annotators (inter-observer variability) and find that by one measure it performs at the level of inter-observer variability and by others it performs very close to it.

Chase Cartwright, Gongbo Guo, Sai Teja Pusuluri +3

Department of Physics and Astronomy and Nanoscale and Quantum Phenomena Institute, Ohio University, Athens, Ohio 45701, USA · The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA. · Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. +1

Tissue Computer Vision Cells Sphere

May 2, 2026cs.AI

A Cellular Doctrine of Morality: Intrinsic Active Precision and the Mind-Reality Overload Dilemma

Current AI systems, grounded in oversimplified neuroscience, risk eroding the distinction between truth and falsehood. They maximize reward by amplifying attention to information without intrinsic precision mechanisms to assess whether it is valid or worth attending to. This increases both the volume of information and the inherent biases in what the system attends to, whether true, false, or irrelevant. If not corrected, this trend will accelerate, threatening to overload systems and individuals with biased and dubious information and increasing the risk of confusion, poor judgment, and irrational or harmful decisions and behaviour, a condition I term the mind-reality overload dilemma. I argue that this threat may be mitigated by providing the public with access to more advanced AI tools built on the biophysical dynamics of pyramidal neurons underlying awake thought and higher-order cognition. These neurons support an intrinsic active precision mechanism that, rather than merely maximizing reward, uses locally and globally coherent predictions to evaluate the validity and contextual adequacy of evidence before it is attended to or propagated through hierarchies, prioritizing coherence and adequacy before attention.~While this approach does not derive or prescribe moral rules from biology, it may give rise to AI with more "real understanding", helping restore epistemic conditions by reducing information overload and amplifying reliable information, thereby supporting the formation of better-informed beliefs and more coherent judgments that benefit society at large-though no guarantees exist.

Ahsan Adeel

Conscious Multisensory Integration (CMI) Lab, University of Stirling, UK

Moral Reasoning Neuroscience Cognitive Science Falsehood Cells

Apr 21, 2026cs.AI

AblateCell: A Reproduce-then-Ablate Agent for Virtual Cell Repositories

Systematic ablations are essential to attribute performance gains in AI Virtual Cells, yet they are rarely performed because biological repositories are under-standardized and tightly coupled to domain-specific data and formats. While recent coding agents can translate ideas into implementations, they typically stop at producing code and lack a verifier that can reproduce strong baselines and rigorously test which components truly matter. We introduce AblateCell, a reproduce-then-ablate agent for virtual cell repositories that closes this verification gap. AblateCell first reproduces reported baselines end-to-end by auto-configuring environments, resolving dependency and data issues, and rerunning official evaluations while emitting verifiable artifacts. It then conducts closed-loop ablation by generating a graph of isolated repository mutations and adaptively selecting experiments under a reward that trades off performance impact and execution cost. Evaluated on three single-cell perturbation prediction repositories (CPA, GEARS, BioLORD), AblateCell achieves 88.9% (+29.9% to human expert) end-to-end workflow success and 93.3% (+53.3% to heuristic) accuracy in recovering ground-truth critical components. These results enable scalable, repository-grounded verification and attribution directly on biological codebases.

Xue Xia, Chengkai Yao, Mingyu Tsoi +10

Shanghai Artificial Intelligence Laboratory · The Hong Kong University of Science and Technology (Guangzhou) · University of California San Diego +4

Virtual Cell Cells Single-Cell Perturbation Prediction Reproducibility

Apr 21, 2026cs.CL

Cell-Based Representation of Relational Binding in Language Models

Understanding a discourse requires tracking entities and the relations that hold between them. While Large Language Models (LLMs) perform well on relational reasoning, the mechanism by which they bind entities, relations, and attributes remains unclear. We study discourse-level relational binding and show that LLMs encode it via a Cell-based Binding Representation (CBR): a low-dimensional linear subspace in which each ``cell'' corresponds to an entity--relation index pair, and bound attributes are retrieved from the corresponding cell during inference. Using controlled multi-sentence data annotated with entity and relation indices, we identify the CBR subspace by decoding these indices from attribute-token activations with Partial Least Squares regression. Across domains and two model families, the indices are linearly decodable and form a grid-like geometry in the projected space. We further find that context-specific CBR representations are related by translation vectors in activation space, enabling cross-context transfer. Finally, activation patching shows that manipulating this subspace systematically changes relational predictions and that perturbing it disrupts performance, providing causal evidence that LLMs rely on CBR for relational binding.

Qin Dai, Benjamin Heinzerling, Kentaro Inui

1Tohoku University · 2RIKEN AIP · 3MBZUAI

Language Modeling Relational Discourse Cells

Apr 16, 2026cs.CV

Efficient Search of Implantable Adaptive Cells for Medical Image Segmentation

Purpose: Adaptive skip modules can improve medical image segmentation, but searching for them is computationally costly. Implantable Adaptive Cells (IACs) are compact NAS modules inserted into U-Net skip connections, reducing the search space compared with full-network NAS. However, the original IAC framework still requires a 200-epoch differentiable search for each backbone and dataset. Methods: We analyzed the temporal behavior of operations and edges within IAC cells during differentiable search on public medical image segmentation benchmarks. We found that operations selected in the final discrete cell typically emerge among the strongest candidates early in training, and their architecture parameters stabilize well before the final epoch. Based on this, we propose a Jensen--Shannon-divergence-based stability criterion that tracks per-edge operation-importance distributions and progressively prunes low-importance operations during search. The accelerated framework is called IAC-LTH. Results: Across four public benchmarks (ACDC, BraTS, KiTS, AMOS), several 2-D U-Net backbones, and a 2-D nnU-Net pipeline, IAC-LTH discovers IAC cells whose patient-level segmentation performance matches and sometimes slightly exceeds that of cells found by the original full-length search, while reducing wall-clock NAS cost by 3.7x to 16x across datasets and backbones. These results are consistent across architectures, benchmarks, and both non-augmented and augmented training settings, while preserving the gains of IAC-equipped U-Nets over strong attention-based and dense-skip baselines. Conclusion: Competitive IAC architectures can be identified from early-stabilizing operations without running the full search, making adaptive skip-module design more practical for medical image segmentation under realistic computational constraints.

Emil Benedykciuk, Marcin Denkowski, Grzegorz M. Wójcik

Institute of Computer Science and Mathematics, Maria Curie Sklodowska University, Akademicka 9, Lublin, 20-033,, Poland

Semi-Supervised Medical Image Segmentation U-Net Search Algorithms Cells Kullback-Leibler Divergence

Apr 16, 2026cs.AI

Intermediate Layers Encode Optimal Biological Representations in Single-Cell Foundation Models

Current single-cell foundation model benchmarks universally extract final layer embeddings, assuming these represent optimal feature spaces. We systematically evaluate layer-wise representations from scFoundation (100M parameters) and Tahoe-X1 (1.3B parameters) across trajectory inference and perturbation response prediction. Our analysis reveals that optimal layers are task-dependent (trajectory peaks at 60% depth, 31% above final layers) and context-dependent (perturbation optima shift 0-96% across T cell activation states). Notably, first-layer embeddings outperform all deeper layers in quiescent cells, challenging assumptions about hierarchical feature abstraction. These findings demonstrate that "where" to extract features matters as much as "what" the model learns, necessitating systematic layer evaluation tailored to biological task and cellular context rather than defaulting to final-layer embeddings.

Vincenzo Yuto Civale, Roberto Semeraro, Andrew David Bagdanov +1

University of Siena · University of di Firenze · University of Firenze

Cells Layer-Wise Biological Single-Cell Foundation Models Trajectory Generation

Mar 5, 2026cs.RO

Residual RL-MPC for Robust Microrobotic Cell Pushing Under Time-Varying Flow

Contact-rich micromanipulation in microfluidic flow is challenging because small disturbances can break pushing contact and induce large lateral drift. We study planar cell pushing with a magnetic rolling microrobot that tracks a waypoint-sampled reference curve under time-varying Poiseuille flow in simulation. We propose a hybrid controller that augments a nominal MPC with a learned residual policy trained by SAC. The policy outputs a bounded 2D velocity correction that is contact-gated, so residual actions are applied only during robot-cell contact, preserving reliable approach behavior and stabilizing learning. All methods share the same actuation interface and speed envelope for fair comparisons. Simulation results show improved robustness and tracking accuracy over pure MPC and PID under nonstationary flow, with generalization from a clover training curve to unseen circle and square trajectories. A residual-bound sweep identifies an intermediate correction limit as the best trade-off, which we use in all benchmarks.

Yanda Yang, Sambeeta Das

Department of Mechanical Engineering, University of Delaware, Newark, DE 19716, USA

Fluid Controls Model Predictive Control Residual Policy Cells

Jan 18, 2026cs.CV

CytoCLIP: Learning Cytoarchitectural Characteristics in Developing Human Brain Using Contrastive Language Image Pre-Training

The functions of different regions of the human brain are closely linked to their distinct cytoarchitecture, which is defined by the spatial arrangement and morphology of the cells. Identifying brain regions by their cytoarchitecture enables various scientific analyses of the brain. However, delineating these areas manually in brain histological sections is time-consuming and requires specialized knowledge. An automated approach is necessary to minimize the effort needed from human experts. To address this, we propose CytoCLIP, a suite of vision-language models derived from pre-trained Contrastive Language-Image Pre-Training (CLIP) frameworks to learn joint visual-text representations of brain cytoarchitecture. CytoCLIP comprises two model variants: one is trained using low-resolution whole-region images to understand the overall cytoarchitectural pattern of an area, and the other is trained on high-resolution image tiles for detailed cellular-level representation. The training dataset is created from NISSL-stained histological sections of developing fetal brains of different gestational weeks. It includes 86 distinct regions for low-resolution images and 379 brain regions for high-resolution tiles. We evaluate the model's understanding of the cytoarchitecture and generalization ability using region classification and cross-modal retrieval tasks. Multiple experiments are performed under various data setups, including data from samples of different ages and sectioning planes. Experimental results demonstrate that CytoCLIP outperforms existing methods. It achieves a weighted F1 score of 0.87 for whole-region classification and 0.91 for high-resolution image tile classification.

Pralaypati Ta, Sriram Venkatesaperumal, Keerthi Ram +1

Sudha Gopalakrishnan Brain Centre, Indian Institute of Technology, Madras, Chennai, India. · Department of Electrical Engineering, Indian Institute of Technology, Madras, Chennai, India.

Mitotic Figures Multimodal Neuroimaging Cells