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Oct 15

Virtual Cells: Predict, Explain, Discover

Drug discovery is fundamentally a process of inferring the effects of treatments on patients, and would therefore benefit immensely from computational models that can reliably simulate patient responses, enabling researchers to generate and test large numbers of therapeutic hypotheses safely and economically before initiating costly clinical trials. Even a more specific model that predicts the functional response of cells to a wide range of perturbations would be tremendously valuable for discovering safe and effective treatments that successfully translate to the clinic. Creating such virtual cells has long been a goal of the computational research community that unfortunately remains unachieved given the daunting complexity and scale of cellular biology. Nevertheless, recent advances in AI, computing power, lab automation, and high-throughput cellular profiling provide new opportunities for reaching this goal. In this perspective, we present a vision for developing and evaluating virtual cells that builds on our experience at Recursion. We argue that in order to be a useful tool to discover novel biology, virtual cells must accurately predict the functional response of a cell to perturbations and explain how the predicted response is a consequence of modifications to key biomolecular interactions. We then introduce key principles for designing therapeutically-relevant virtual cells, describe a lab-in-the-loop approach for generating novel insights with them, and advocate for biologically-grounded benchmarks to guide virtual cell development. Finally, we make the case that our approach to virtual cells provides a useful framework for building other models at higher levels of organization, including virtual patients. We hope that these directions prove useful to the research community in developing virtual models optimized for positive impact on drug discovery outcomes.

  • 15 authors
·
Jun 3, 2025

Artificial Intelligence Virtual Cells: From Measurements to Decisions across Modality, Scale, Dynamics, and Evaluation

Artificial Intelligence Virtual Cells (AIVCs) aim to learn executable, decision-relevant models of cell state from multimodal, multiscale measurements. Recent studies have introduced single-cell and spatial foundation models, improved cross-modality alignment, scaled perturbation atlases, and explored pathway-level readouts. Nevertheless, although held-out validation is standard practice, evaluations remain predominantly within single datasets and settings; evidence indicates that transport across laboratories and platforms is often limited, that some data splits are vulnerable to leakage and coverage bias, and that dose, time and combination effects are not yet systematically handled. Cross-scale coupling also remains constrained, as anchors linking molecular, cellular and tissue levels are sparse, and alignment to scientific or clinical readouts varies across studies. We propose a model-agnostic Cell-State Latent (CSL) perspective that organizes learning via an operator grammar: measurement, lift/project for cross-scale coupling, and intervention for dosing and scheduling. This view motivates a decision-aligned evaluation blueprint across modality, scale, context and intervention, and emphasizes function-space readouts such as pathway activity, spatial neighborhoods and clinically relevant endpoints. We recommend operator-aware data design, leakage-resistant partitions, and transparent calibration and reporting to enable reproducible, like-for-like comparisons.

  • 2 authors
·
Dec 1, 2025

OmniVCBench: Benchmarking Evidence-Grounded Multimodal Reasoning Towards AI Virtual Cells

Artificial Intelligence Virtual Cells (AIVCs) are envisioned as scientific agents that simulate cellular responses, explain underlying mechanisms, and support hypothesis-driven discovery. Existing AIVC benchmarks, however, operate primarily at the simulation layer, motivating complementary evaluation of how models interpret experimental evidence and formulate biological hypotheses. We introduce OmniVCBench, a figure-centric, source-traceable benchmark for the interpretation component of an AIVC. It contains 6,077 curated single- and multi-subfigure question--answer pairs derived from figures and experimental contexts in the scientific literature. Guided by Bloom's taxonomy, we instantiate interpretation-layer counterparts of the AIVC Predict--Explain--Discover agenda through three scientific reasoning tasks. We further introduce AIVC-Judge, a task-conditioned MLLM-as-a-judge framework with category-specific, reference-aware rubrics for evaluating open-ended responses. A complementary Model-Derived Hard-Negative Mining (MDHNM) strategy converts plausible errors observed during model inference into MCQ distractors for lower-cost evaluation. Within the evaluated heterogeneous model pool, MCQ accuracy correlates positively with AIVC-Judge scores, providing a complementary view of performance alongside open-response evaluation. Code and data demo are available at https://anonymous.4open.science/r/OmniVCBench.

  • 6 authors
·
Sep 28

Lingshu-Cell: A generative cellular world model for transcriptome modeling toward virtual cells

Modeling cellular states and predicting their responses to perturbations are central challenges in computational biology and the development of virtual cells. Existing foundation models for single-cell transcriptomics provide powerful static representations, but they do not explicitly model the distribution of cellular states for generative simulation. Here, we introduce Lingshu-Cell, a masked discrete diffusion model that learns transcriptomic state distributions and supports conditional simulation under perturbation. By operating directly in a discrete token space that is compatible with the sparse, non-sequential nature of single-cell transcriptomic data, Lingshu-Cell captures complex transcriptome-wide expression dependencies across approximately 18,000 genes without relying on prior gene selection, such as filtering by high variability or ranking by expression level. Across diverse tissues and species, Lingshu-Cell accurately reproduces transcriptomic distributions, marker-gene expression patterns and cell-subtype proportions, demonstrating its ability to capture complex cellular heterogeneity. Moreover, by jointly embedding cell type or donor identity with perturbation, Lingshu-Cell can predict whole-transcriptome expression changes for novel combinations of identity and perturbation. It achieves leading performance on the Virtual Cell Challenge H1 genetic perturbation benchmark and in predicting cytokine-induced responses in human PBMCs. Together, these results establish Lingshu-Cell as a flexible cellular world model for in silico simulation of cell states and perturbation responses, laying the foundation for a new paradigm in biological discovery and perturbation screening.

Alibaba-DAMO-Academy DAMO Academy
·
Mar 26 8

CellPrism: A Visual Analytics System for Exploring AI-Driven Virtual Cells in Drug Discovery

Gene perturbation analysis plays a critical role in drug discovery by enabling researchers to investigate how interventions on specific genes influence global gene expression patterns within cells. Recent advances in artificial intelligence-driven virtual cell models have made it possible to predict gene expression outcomes for a wide range of perturbation strategies in silico, substantially reducing reliance on costly and time-consuming biological experiments. However, effectively exploring and interpreting the high-dimensional perturbation spaces produced by these models remains challenging because of the combinatorial nature of perturbations and the complex cell-specific gene expression responses they generate. In this work, we present CellPrism, a visual analytics system designed to support the systematic exploration of gene perturbation strategies for drug discovery. Specifically, CellPrism integrates clustering-based overviews to summarize perturbation outcomes, a glyph-based representation to compactly encode gene expression patterns across cell types, and coordinated views that enable fine-grained comparison and interpretation of perturbation effects. We demonstrate the effectiveness of CellPrism through a real-world case study and expert interviews. This work highlights the value of visual analytics in bridging virtual cell modeling with expert-driven decision making in drug discovery.

  • 6 authors
·
Aug 3

How to Build the Virtual Cell with Artificial Intelligence: Priorities and Opportunities

The cell is arguably the most fundamental unit of life and is central to understanding biology. Accurate modeling of cells is important for this understanding as well as for determining the root causes of disease. Recent advances in artificial intelligence (AI), combined with the ability to generate large-scale experimental data, present novel opportunities to model cells. Here we propose a vision of leveraging advances in AI to construct virtual cells, high-fidelity simulations of cells and cellular systems under different conditions that are directly learned from biological data across measurements and scales. We discuss desired capabilities of such AI Virtual Cells, including generating universal representations of biological entities across scales, and facilitating interpretable in silico experiments to predict and understand their behavior using virtual instruments. We further address the challenges, opportunities and requirements to realize this vision including data needs, evaluation strategies, and community standards and engagement to ensure biological accuracy and broad utility. We envision a future where AI Virtual Cells help identify new drug targets, predict cellular responses to perturbations, as well as scale hypothesis exploration. With open science collaborations across the biomedical ecosystem that includes academia, philanthropy, and the biopharma and AI industries, a comprehensive predictive understanding of cell mechanisms and interactions has come into reach.

  • 42 authors
·
Oct 13, 2024

VCLMU: Mechanism-Centric Virtual Cell World Modeling for Perturbation Response

Predicting cellular responses to genetic perturbations is a central capability for virtual cells and a key step toward computational modeling of biological interventions. Most existing models directly map an unperturbed molecular profile and perturba- tion to the resulting observation without explicitly representing the latent cellular transition induced by the intervention. We introduce a mechanism-centric virtual cell world model that represents cellular state as a set of Latent Mechanism Units (LMUs) and treats genetic perturbations as actions on these latent states. Each LMU combines a reusable identity grounded in multimodal biological evidence with an observation-specific state, allowing a perturbation to induce mechanism- specific stochastic transitions before decoding the resulting transcriptional response. We train VCLMU through two-stage pretraining, first on around 200K pseudo-bulk perturbation profiles and then on gene-aligned single-cell perturbation data. Across six perturbation-disjoint benchmarks, VCLMU consistently improves perturbation- specific response recovery over strong baselines while maintaining competitive global response accuracy. We further analyze learned LMUs through enrichment between perturbation responses and LMU gene sets and show that they capture structured biological response programs. These results support mechanism-level latent state transition as a useful formulation for virtual cell models that aim to predict and interpret cellular responses to biological interventions.

  • 6 authors
·
Oct 2

CellForge: Agentic Design of Virtual Cell Models

Virtual cell modeling represents an emerging frontier at the intersection of artificial intelligence and biology, aiming to predict quantities such as responses to diverse perturbations quantitatively. However, autonomously building computational models for virtual cells is challenging due to the complexity of biological systems, the heterogeneity of data modalities, and the need for domain-specific expertise across multiple disciplines. Here, we introduce CellForge, an agentic system that leverages a multi-agent framework that transforms presented biological datasets and research objectives directly into optimized computational models for virtual cells. More specifically, given only raw single-cell multi-omics data and task descriptions as input, CellForge outputs both an optimized model architecture and executable code for training virtual cell models and inference. The framework integrates three core modules: Task Analysis for presented dataset characterization and relevant literature retrieval, Method Design, where specialized agents collaboratively develop optimized modeling strategies, and Experiment Execution for automated generation of code. The agents in the Design module are separated into experts with differing perspectives and a central moderator, and have to collaboratively exchange solutions until they achieve a reasonable consensus. We demonstrate CellForge's capabilities in single-cell perturbation prediction, using six diverse datasets that encompass gene knockouts, drug treatments, and cytokine stimulations across multiple modalities. CellForge consistently outperforms task-specific state-of-the-art methods. Overall, CellForge demonstrates how iterative interaction between LLM agents with differing perspectives provides better solutions than directly addressing a modeling challenge. Our code is publicly available at https://github.com/gersteinlab/CellForge.

  • 15 authors
·
Aug 4, 2025 2

PerturbDiff: Functional Diffusion for Single-Cell Perturbation Modeling

Building Virtual Cells that can accurately simulate cellular responses to perturbations is a long-standing goal in systems biology. A fundamental challenge is that high-throughput single-cell sequencing is destructive: the same cell cannot be observed both before and after a perturbation. Thus, perturbation prediction requires mapping unpaired control and perturbed populations. Existing models address this by learning maps between distributions, but typically assume a single fixed response distribution when conditioned on observed cellular context (e.g., cell type) and the perturbation type. In reality, responses vary systematically due to unobservable latent factors such as microenvironmental fluctuations and complex batch effects, forming a manifold of possible distributions for the same observed conditions. To account for this variability, we introduce PerturbDiff, which shifts modeling from individual cells to entire distributions. By embedding distributions as points in a Hilbert space, we define a diffusion-based generative process operating directly over probability distributions. This allows PerturbDiff to capture population-level response shifts across hidden factors. Benchmarks on established datasets show that PerturbDiff achieves state-of-the-art performance in single-cell response prediction and generalizes substantially better to unseen perturbations. See our project page (https://katarinayuan.github.io/PerturbDiff-ProjectPage/), where code and data will be made publicly available (https://github.com/DeepGraphLearning/PerturbDiff).

  • 6 authors
·
Feb 22

Discover, Falsify, Revise: Auditing Input-Use Claims from Source Code to Predictive Contribution in Agent-Discovered Cell Models

AI virtual cells aim to predict cellular responses to specified interventions, yet held-out predictive performance alone does not establish use of the supplied perturbation information. This prediction-claim gap matters in agentic model discovery, where language-model agents generate and revise predictors using score-based feedback. We introduce CELLAUDIT, which audits input-use claims by asking whether an input can enter the cited computation, whether fitted predictions depend on it, and whether that dependence improves prediction of observed response. On a paired morphology-transcriptomics perturbation benchmark (BBBC047), an agent-selected predictor attains a mean held-out Global Pearson correlation coefficient (PCC) of 0.3153 but remains invariant to compound replacement; a control-profile-only predictor reaches 0.3142. Source inspection identifies a compound-query pathway blocked by singleton key-value attention, and the invariance persists after refitting with disjoint control wells. In a stratified audit of 48 candidates across two linked tasks, 47 change predictions under compound replacement on both held-out folds, but only 20 show target-loss gains with intervals above zero on both folds. On BBBC047, falsification-guided revisions recover positive mean compound contributions while retaining gains over the control-profile-only baseline. In matched sci-Plex searches, audit-enriched feedback yields higher held-out performance and larger mean compound and dose contributions across five trajectories, although paired intervals span zero. Refitting fixed designs on an independently acquired cohort shows predictive generalization need not imply generalization of input-use claims: dose contribution persists, whereas support for compound identity does not. CELLAUDIT adds a falsification layer to agentic model discovery, moving from generate-score-revise toward discover-falsify-revise.

  • 6 authors
·
Sep 22

Benchmarking virtual cell models for in-the-wild perturbation response

Virtual cell (VC) models aim to predict cellular responses to any perturbations in silico and have emerged as a promising approach for drug discovery and precision medicine. Yet, a clear gap still remains: while models routinely reported impressive results on standard benchmarks, it is unclear whether their predictions are truly meaningful in practice. This is mainly due to limitations in current evaluation setups, which are often overly simplified or inconsistent, and do not reflect the complexity and variability of real biological systems. Here, we introduce a standardized and modular benchmarking framework for virtual cell prediction. Our framework evaluates diverse models under in-the-wild challenging scenarios, including unseen cell contexts, unseen perturbations, and cross-dataset generalization, which better reflect practical applications. Our analysis shows that model performance is highly context-dependent and shaped by task design and evaluation criteria. In commonly used setups, performance is often overestimated, and naive dataset aggregation can even reduce performance. When evaluated under more strict conditions, model performance drops markedly, indicating limited robustness to shifts across cellular contexts. In unseen perturbation settings, models including simple linear approaches capture global transcriptional trends but fail to recover fine-grained perturbation-specific effects. In addition, different evaluation metrics focus on different biological properties, leading to substantially different model rankings. Together, our framework provides a more reliable and biologically grounded evaluation, offering clearer guidance for applying virtual cell models in real scenarios.

  • 13 authors
·
Apr 29

Deep learning-based virtual perturbation reveals increasing heterogeneity of gene regulatory responses with aging

A central hypothesis in aging biology proposes that the gradual accumulation of stochastic molecular damage drives transcriptional deregulation (TD), ultimately leading to functional decline. However, existing single-cell analyses largely rely on static expression measurements and provide limited resolution of how regulatory responses change at the level of individual cells. Here, we leverage DKO, a deep learning framework that predicts cell-specific virtual gene perturbation effects from unperturbed transcriptomes, capturing cell-to-cell differences in regulatory context without requiring a reconstructed gene regulatory network or matched perturbation data. Applying DKO to single-cell transcriptomic datasets from humans, mice, Drosophila, and C. elegans revealed that the transcriptional consequences of perturbing the same gene became increasingly heterogeneous across cells with age, indicating that gene regulatory responses become less consistent and more dependent on cellular context. Furthermore, we find that cells with higher somatic mutation burdens have greater knockout-response variability, linking accumulated molecular damage to regulatory inconsistency. Within the same cellular populations, higher impact variability was also associated with higher senescence scores, linking transcriptional dysregulation to senescence-associated states. Our findings identify a progressive loss of regulatory robustness at both the gene and cell levels as a conserved feature of aging, linking stochastic molecular damage to increasing heterogeneity in cellular regulatory responses.

  • 4 authors
·
Oct 13

SWE-WebDevBench: Evaluating Coding Agent Application Platforms as Virtual Software Agencies

The emergence of "vibe coding" platforms, where users describe applications in natural language and AI agents autonomously generate full-stack software, has created a need for rigorous evaluation beyond code-level benchmarks. In order to assess them as virtual software development agencies on understanding business requirements, making architectural decisions, writing production code, handling iterative modifications, and maintaining business readiness, we introduce SWE-WebDev Bench, a 68-metric evaluation framework spanning 25 primary and 43 diagnostic metrics across seven groups, organized along three dimensions: Interaction Mode (App Creation Request (ACR) vs. App Modification Request (AMR)), Agency Angle (Product Manager (PM), Engineering, Ops), and Complexity Tier (T4 multi-role SaaS, T5 AI-native). Our evaluation (six platforms, three domains, 18 evaluation cells) reveals four recurring shortcomings in the current generation of AI app builders: (1) A specification bottleneck, where platforms compress rich business requirements into oversimplified technical plans, (2) A pervasive frontend-backend decoupling, where visually polished UIs mask absent or broken backend infrastructure, (3) A steep production-readiness cliff, where no platform scores above 60% on engineering quality and post-generation human effort varies substantially across platforms and (4) Widespread security and infrastructure failures, with no platform exceeding 65% Security Score against a 90% target and concurrency handling as low as 6%. These observations are descriptive of our sample and require larger-scale replication to establish generality. We release SWE-WebDev Bench as a community benchmark to enable such replication and help platform builders identify and address these gaps. Code and benchmark resources are available at: https://github.com/snowmountainAi/webdevbench and https://webdevbench.com/.

qwikbuild QwikBuild
·
May 5 2

AssayBench: An Assay-Level Virtual Cell Benchmark for LLMs and Agents

Recent advances in machine learning and large-scale biological data collections have revived the prospect of building a virtual cell, a computational model of cellular behavior that could accelerate biological discovery. One of the most compelling promises of this vision is the ability to perform in silico phenotypic screens, in which a model predicts the effects of cellular perturbations in unseen biological contexts. This task combines heterogeneous textual inputs with diverse phenotypic outputs, making it particularly well-suited to LLMs and agentic systems. Yet, no standard benchmark currently exists for this task, as existing efforts focus on narrower molecular readouts that are only indirectly aligned with the phenotypic endpoints driving many real-world drug discovery workflows. In this work, we present AssayBench, a benchmark for phenotypic screen prediction, built from 1,920 publicly available CRISPR screens spanning five broad classes of cellular phenotypes. We formulate the screen prediction task as a gene rank prediction for each screen and introduce the adjusted nDCG, a continuous metric for comparing performance across heterogeneous assays. Our extensive evaluation shows that existing methods remain far from empirically estimated performance ceilings and zero-shot generalist LLMs outperform biology-specific LLMs and trainable baselines. Optimization techniques such as fine-tuning, ensembling, and prompt optimization can further improve LLM performance on this task. Overall, AssayBench offers a practical testbed for measuring progress toward in silico phenotypic screening and, more broadly, virtual cell models.

  • 12 authors
·
May 10

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.

  • 2 authors
·
Sep 27

Intelligent Load Balancing in Cloud Computer Systems

Cloud computing is an established technology allowing users to share resources on a large scale, never before seen in IT history. A cloud system connects multiple individual servers in order to process related tasks in several environments at the same time. Clouds are typically more cost-effective than single computers of comparable computing performance. The sheer physical size of the system itself means that thousands of machines may be involved. The focus of this research was to design a strategy to dynamically allocate tasks without overloading Cloud nodes which would result in system stability being maintained at minimum cost. This research has added the following new contributions to the state of knowledge: (i) a novel taxonomy and categorisation of three classes of schedulers, namely OS-level, Cluster and Big Data, which highlight their unique evolution and underline their different objectives; (ii) an abstract model of cloud resources utilisation is specified, including multiple types of resources and consideration of task migration costs; (iii) a virtual machine live migration was experimented with in order to create a formula which estimates the network traffic generated by this process; (iv) a high-fidelity Cloud workload simulator, based on a month-long workload traces from Google's computing cells, was created; (v) two possible approaches to resource management were proposed and examined in the practical part of the manuscript: the centralised metaheuristic load balancer and the decentralised agent-based system. The project involved extensive experiments run on the University of Westminster HPC cluster, and the promising results are presented together with detailed discussions and a conclusion.

  • 1 authors
·
Sep 22, 2025

SC-Arena: A Natural Language Benchmark for Single-Cell Reasoning with Knowledge-Augmented Evaluation

Large language models (LLMs) are increasingly applied in scientific research, offering new capabilities for knowledge discovery and reasoning. In single-cell biology, however, evaluation practices for both general and specialized LLMs remain inadequate: existing benchmarks are fragmented across tasks, adopt formats such as multiple-choice classification that diverge from real-world usage, and rely on metrics lacking interpretability and biological grounding. We present SC-ARENA, a natural language evaluation framework tailored to single-cell foundation models. SC-ARENA formalizes a virtual cell abstraction that unifies evaluation targets by representing both intrinsic attributes and gene-level interactions. Within this paradigm, we define five natural language tasks (cell type annotation, captioning, generation, perturbation prediction, and scientific QA) that probe core reasoning capabilities in cellular biology. To overcome the limitations of brittle string-matching metrics, we introduce knowledge-augmented evaluation, which incorporates external ontologies, marker databases, and scientific literature to support biologically faithful and interpretable judgments. Experiments and analysis across both general-purpose and domain-specialized LLMs demonstrate that (i) under the Virtual Cell unified evaluation paradigm, current models achieve uneven performance on biologically complex tasks, particularly those demanding mechanistic or causal understanding; and (ii) our knowledge-augmented evaluation framework ensures biological correctness, provides interpretable, evidence-grounded rationales, and achieves high discriminative capacity, overcoming the brittleness and opacity of conventional metrics. SC-Arena thus provides a unified and interpretable framework for assessing LLMs in single-cell biology, pointing toward the development of biology-aligned, generalizable foundation models.

  • 8 authors
·
Feb 25

VirtualEnv: A Platform for Embodied AI Research

As large language models (LLMs) continue to improve in reasoning and decision-making, there is a growing need for realistic and interactive environments where their abilities can be rigorously evaluated. We present VirtualEnv, a next-generation simulation platform built on Unreal Engine 5 that enables fine-grained benchmarking of LLMs in embodied and interactive scenarios. VirtualEnv supports rich agent-environment interactions, including object manipulation, navigation, and adaptive multi-agent collaboration, as well as game-inspired mechanics like escape rooms and procedurally generated environments. We provide a user-friendly API built on top of Unreal Engine, allowing researchers to deploy and control LLM-driven agents using natural language instructions. We integrate large-scale LLMs and vision-language models (VLMs), such as GPT-based models, to generate novel environments and structured tasks from multimodal inputs. Our experiments benchmark the performance of several popular LLMs across tasks of increasing complexity, analyzing differences in adaptability, planning, and multi-agent coordination. We also describe our methodology for procedural task generation, task validation, and real-time environment control. VirtualEnv is released as an open-source platform, we aim to advance research at the intersection of AI and gaming, enable standardized evaluation of LLMs in embodied AI settings, and pave the way for future developments in immersive simulations and interactive entertainment.

  • 7 authors
·
Jan 12 1

AROMA: Augmented Reasoning Over a Multimodal Architecture for Virtual Cell Genetic Perturbation Modeling

Virtual cell modeling predicts molecular state changes under genetic perturbations in silico, which is essential for biological mechanism studies. However, existing approaches suffer from unconstrained reasoning, uninterpretable predictions, and retrieval signals that are weakly aligned with regulatory topology. To address these limitations, we propose AROMA, an Augmented Reasoning Over a Multimodal Architecture for virtual cell genetic perturbation modeling. AROMA integrates textual evidence, graph-topology information, and protein sequence features to model perturbation-target dependencies, and is trained with a two-stage optimization strategy to yield predictions that are both accurate and interpretable. We also construct two knowledge graphs and a perturbation reasoning dataset, PerturbReason, containing more than 498k samples, as reusable resources for the virtual cell domain. Experiments show that AROMA outperforms existing methods across multiple cell lines, and remains robust under zero-shot evaluation on an unseen cell line, as well as in knowledge-sparse, long-tail scenarios. Overall, AROMA demonstrates that combining knowledge-driven multimodal modeling with evidence retrieval provides a promising pathway toward more reliable and interpretable virtual cell perturbation prediction. Model weights are available at https://huggingface.co/blazerye/AROMA. Code is available at https://github.com/blazerye/AROMA.

  • 4 authors
·
Apr 21

OCOO-T : A Simple and Scalable Virtual Cell Model for Transcriptional Perturbation Response Prediction

Predicting single-cell transcriptional responses to genetic, chemical and cytokine perturbations is a fundamental challenge in computational biology and AI Virtual Cell (AIVC) modeling, with direct implications for drug discovery and the elucidation of gene regulatory networks. Existing approaches often rely on auxiliary cell-state encoders, hierarchical variational autoencoders, dedicated Transformer encoder-decoder modules, or gene-interaction priors to compress high-dimensional expression profiles into latent representations. While effective, these designs increase architectural complexity and may limit scalability and generalizability. This paper introduces OCOO-T, a minimalist flow-matching-based AIVC model for transcriptional perturbation response prediction. OCOO-T utilizes a vanilla Transformer stack that operates directly on continuous gene expression profiles and formulates perturbation response prediction as a continuous-time denoising process. Perturbation embeddings, dosage information, and cell-line/cell-type specificity are integrated through adaptive layer normalization and in-context tokens. Comprehensive evaluations on Tahoe100M, Replogle, and PBMC benchmarks demonstrate that OCOO-T achieves state-of-the-art performance across diverse perturbations and cell types while effectively scaling to long transcriptional profiles through patching and depatching of cellular contexts. By leveraging the simplicity of Transformer-based denoising for single-cell omics, OCOO-T provides an effective and scalable framework for in-silico cellular simulation.

  • 6 authors
·
Aug 13

Control-Anchored Residual Flow Matching Conditioned on Gene Geometry for Virtual Cell Perturbation Modeling

A central task in virtual cell modeling is predicting single-cell transcriptional responses to unseen genetic perturbations and drug combinations, and biological networks provide valuable priors on gene relationships. Existing graph-based models commonly use the same network to structure gene representations and mediate intergene interactions, thereby implicitly treating stable associations as perturbation-response pathways. Gene Ontology and control-derived coexpression networks encode relatively stable relationships rather than intervention-specific response directions or magnitudes. We therefore propose GeneGeoFlow, which conditions a control-anchored residual flow on gene-wise geometry derived from biological networks to learn intervention-specific transcriptional responses. GeneGeoFlow derives multi-scale spectral coordinates from Gene Ontology and control-derived coexpression networks. A perturbation-conditioned, gene-wise gating module selects relevant structural scales and network sources, yielding intervention-specific gene geometry. The resulting geometry conditions a control-anchored residual flow without explicitly propagating target-derived signals along the graph. Condition-wise optimal transport couples unpaired control and perturbed populations for training, while a Delta-correlation objective aligns the predicted and observed condition-level expression-shift directions. GeneGeoFlow achieves Pearson Delta scores of 0.8979 on the Norman additive benchmark and 0.9088 on five held-out drug combinations in the fixed ComboSciPlex test split. These results support perturbation-conditioned gene geometry as an effective structural prior for intervention-specific response prediction, without conflating stable gene relationships with response propagation.

  • 13 authors
·
Aug 6

PerturbBridge: Direct Phenotypic Supervision for Cellular Perturbation Generation

Virtual cell models should capture phenotypes induced by specific perturbations. However, image-based models are typically trained and evaluated to match real-image distributions, which alone does not explicitly prioritize perturbation-specific biological responses. Recent approaches add biological signals through reinforcement-learning post-training or inference-time steering, raising a central question: where should biological response information enter the generative pipeline? We introduce PerturbBridge, a stochastic data-to-data bridge model that directly supervises perturbation-specific phenotypes in predicted perturbed images during training. PerturbBridge jointly optimizes bridge regression and differentiable biological response losses, with biological gradients passing through a frozen image encoder. We further introduce perturbation-response evaluations based on downstream classification and retrieval. Across three microscopy benchmarks for perturbation profiling and subcellular imaging, PerturbBridge surpasses CellFlux in biological fidelity, image quality, and sampling efficiency. On BBBC021, mechanism-of-action classification improves by 5.66 and 7.5 percentage points with morphological and learned visual features, respectively. On JUMP and AllenCell, retrieval Hit@10 and Hit@1 improve by 1.77 and 7.15 percentage points, respectively. On BBBC021 and JUMP, PerturbBridge achieves lower FID with 80% fewer model evaluations than CellFlux. Overall, these results show that directly supervising perturbation responses during training improves phenotypic fidelity while enabling efficient cellular image generation. Code is available at https://github.com/yyc1215lll-creator/PerturbBridge.

  • 6 authors
·
Oct 11

Fast Registration of Photorealistic Avatars for VR Facial Animation

Virtual Reality (VR) bares promise of social interactions that can feel more immersive than other media. Key to this is the ability to accurately animate a photorealistic avatar of one's likeness while wearing a VR headset. Although high quality registration of person-specific avatars to headset-mounted camera (HMC) images is possible in an offline setting, the performance of generic realtime models are significantly degraded. Online registration is also challenging due to oblique camera views and differences in modality. In this work, we first show that the domain gap between the avatar and headset-camera images is one of the primary sources of difficulty, where a transformer-based architecture achieves high accuracy on domain-consistent data, but degrades when the domain-gap is re-introduced. Building on this finding, we develop a system design that decouples the problem into two parts: 1) an iterative refinement module that takes in-domain inputs, and 2) a generic avatar-guided image-to-image style transfer module that is conditioned on current estimation of expression and head pose. These two modules reinforce each other, as image style transfer becomes easier when close-to-ground-truth examples are shown, and better domain-gap removal helps registration. Our system produces high-quality results efficiently, obviating the need for costly offline registration to generate personalized labels. We validate the accuracy and efficiency of our approach through extensive experiments on a commodity headset, demonstrating significant improvements over direct regression methods as well as offline registration.

  • 5 authors
·
Jan 19, 2024 1

Can We Trust In-Distribution Success? Locked Evaluation Reveals Transfer Failure and Sampling-Depth Entanglement in CRISPRi Perturbation Prediction

AI evaluation can support the wrong inference when an in-domain benchmark success does not survive distribution shift, or when the benchmark endpoint is entangled with a design factor. We study this problem in CRISPRi perturbation-effect prediction, evaluating a frozen Geneformer representation under a locked, pre-registered protocol: heads and model selection were frozen before test evaluation; the protocol required external outcome labels to remain withheld until final unblinding; and analysis-governing decisions were fixed before the evaluations they govern. In-distribution on the Virtual Cell Challenge (VCC), the frozen representation carries measurable predictive information beyond a dimension-matched random-feature control (Delta R^2 = +0.1645, 95% CI [+0.1375, +0.1920]), satisfying the pre-registered informativeness gate required before interpreting transfer. It then fails zero-shot transfer on both external screens (Spearman rho = -0.139 and -0.267), lying below that control on each. Adding a predefined magnitude block improves the representation externally (Delta rho = +0.032 and +0.143) but, under the frozen primary head, does not rescue transfer: both remain negative. A pre-registered, count-adjusted max-response secondary is positively associated with the outcome on both screens; we report it as correlational and secondary, not as a recovered magnitude signal. Finally, the VCC endpoint is strongly sample-size associated: a count-only linear model reaches R^2 = +0.4325, versus +0.2589 for the four magnitude scalars; adding those scalars to cell count improves R^2 by only +0.0017, so much of the aggregate-magnitude signal overlaps with cell count. This case study shows how locking the evaluation, harmonizing the measured endpoint, and separating primary from secondary evidence can change the inference supported by an AI benchmark.

  • 2 authors
·
Aug 30

SimWorld Studio: Automatic Environment Generation with Evolving Coding Agent for Embodied Agent Learning

LLM/VLM-based digital agents have advanced rapidly thanks to scalable sandboxes for coding, web navigation, and computer use, which provide rich interactive training grounds. In contrast, embodied agents still lack abundant, diverse, and automatically generated 3D environments for interactive learning. Existing embodied simulators rely on manually crafted scenes or procedural templates, while recent LLM-based 3D generation systems mainly produce static scenes rather than deployable environments with verifiable tasks and standard learning interfaces. We introduce SimWorld Studio, an open-source platform built on Unreal Engine 5 for generating evolving embodied learning environments. At its core is SimCoder, a tool/skill-augmented coding agent that writes and executes engine-level code to construct physically grounded 3D worlds from language/image instructions. SimCoder self-evolves by using verifier feedback (e.g., compilation errors, physics checks, VLM critiques) to revise environments and autonomously add reusable tools and skills to its library. Generated worlds are exported as Gym-style environments for embodied agent learning. SimWorld Studio further enables co-evolution between environment generation and embodied learning: agent performance feedback guides SimCoder to generate adaptive curricula near the learner's capability frontier, so that environments become increasingly challenging as the embodied agent improves. Three case studies on embodied navigation show that self-evolution improves generation reliability, generated environments substantially improve embodied agent performance that generalizes to unseen benchmarks, and co-evolution yields an 18-point success-rate gain over fixed-environment learning and a 40-point gain over an untrained agent.

  • 8 authors
·
May 9 1

SimWorld: An Open-ended Realistic Simulator for Autonomous Agents in Physical and Social Worlds

While LLM/VLM-powered AI agents have advanced rapidly in math, coding, and computer use, their applications in complex physical and social environments remain challenging. Building agents that can survive and thrive in the real world (for example, by autonomously earning income or running a business) requires massive-scale interaction, reasoning, training, and evaluation across diverse embodied scenarios. However, existing world simulators for such development fall short: they often rely on limited hand-crafted environments, simulate simplified game-like physics and social rules, and lack native support for LLM/VLM agents. We introduce SimWorld, a new simulator built on Unreal Engine 5, designed for developing and evaluating LLM/VLM agents in rich, real-world-like settings. SimWorld offers three core capabilities: (1) realistic, open-ended world simulation, including accurate physical and social dynamics and language-driven procedural environment generation; (2) a rich interface for LLM/VLM agents, with multimodal world inputs and open-vocabulary actions at varying levels of abstraction; and (3) diverse and extensible physical and social reasoning scenarios that are easily customizable by users. We demonstrate SimWorld by deploying frontier LLM agents (e.g., GPT-4o, Gemini-2.5-Flash, Claude-3.5, and DeepSeek-Prover-V2) on long-horizon multi-agent delivery tasks involving strategic cooperation and competition. The results reveal distinct reasoning patterns and limitations across models. We open-source SimWorld and hope it becomes a foundational platform for advancing real-world agent intelligence across disciplines: https://simworld.org.

SimWorld-AI SimWorld
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Nov 30, 2025 3

Measuring Asset and Scene Reconstruction Effects in Real-to-Sim Robot Evaluation

Simulated evaluation is increasingly used alongside real-world evaluation of robot policies because it is cheaper and easier to repeat; however, its value depends on how closely its outcomes track the real robot's. We test whether our reconstruction pipeline, combining metrically scaled object geometry, authored physical parameters and scene reconstruction, reduces disagreement between simulated and real robot scores relative to a default open-source recipe. We constructed two simulated versions of one bimanual robot cell: an authored reconstruction, using object geometry at estimated metric scale, projected textures, authored physics and our own scene splat; and a baseline, referred to as the default reconstruction, using the open-source recipe of a generative single-image mesh, engine-default physics and a Gaussian-splat scene. Both reconstructions use the same object photographs and scene video. Two policies ran five tasks each, giving ten task-policy pairs, which we call cells; each cell was run twenty times in each reconstruction with all other settings held fixed. Both reconstructions were scored against the same real trials, graded by a third-party evaluator. Pearson correlation between the ten simulated and real cell means is r = 0.90 for the authored reconstruction and 0.51 for the default. Mean score error is 6.97 percentage points for the authored reconstruction and 17.54 for the default, a reduction of 10.56 percentage points. These results show that improving the quality of the environment reconstruction through higher visual fidelity, authored physics and metric scale makes the simulation more faithful to the real world and narrows the sim-to-real gap. We release the harness, the per-trial scores, every reported run's configuration, and the assets and scenes of both reconstructions.

  • 3 authors
·
Sep 29

μ-Bench: A Vision-Language Benchmark for Microscopy Understanding

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.

  • 7 authors
·
Jul 1, 2024 1

LatticeWorld: A Multimodal Large Language Model-Empowered Framework for Interactive Complex World Generation

Recent research has been increasingly focusing on developing 3D world models that simulate complex real-world scenarios. World models have found broad applications across various domains, including embodied AI, autonomous driving, entertainment, etc. A more realistic simulation with accurate physics will effectively narrow the sim-to-real gap and allow us to gather rich information about the real world conveniently. While traditional manual modeling has enabled the creation of virtual 3D scenes, modern approaches have leveraged advanced machine learning algorithms for 3D world generation, with most recent advances focusing on generative methods that can create virtual worlds based on user instructions. This work explores such a research direction by proposing LatticeWorld, a simple yet effective 3D world generation framework that streamlines the industrial production pipeline of 3D environments. LatticeWorld leverages lightweight LLMs (LLaMA-2-7B) alongside the industry-grade rendering engine (e.g., Unreal Engine 5) to generate a dynamic environment. Our proposed framework accepts textual descriptions and visual instructions as multimodal inputs and creates large-scale 3D interactive worlds with dynamic agents, featuring competitive multi-agent interaction, high-fidelity physics simulation, and real-time rendering. We conduct comprehensive experiments to evaluate LatticeWorld, showing that it achieves superior accuracy in scene layout generation and visual fidelity. Moreover, LatticeWorld achieves over a 90times increase in industrial production efficiency while maintaining high creative quality compared with traditional manual production methods. Our demo video is available at https://youtu.be/8VWZXpERR18

  • 10 authors
·
Sep 5, 2025 3

CytoSyn: a Foundation Diffusion Model for Histopathology -- Tech Report

Computational pathology has made significant progress in recent years, fueling advances in both fundamental disease understanding and clinically ready tools. This evolution is driven by the availability of large amounts of digitized slides and specialized deep learning methods and models. Multiple self-supervised foundation feature extractors have been developed, enabling downstream predictive applications from cell segmentation to tumor sub-typing and survival analysis. In contrast, generative foundation models designed specifically for histopathology remain scarce. Such models could address tasks that are beyond the capabilities of feature extractors, such as virtual staining. In this paper, we introduce CytoSyn, a state-of-the-art foundation latent diffusion model that enables the guided generation of highly realistic and diverse histopathology H&E-stained images, as shown in an extensive benchmark. We explored methodological improvements, training set scaling, sampling strategies and slide-level overfitting, culminating in the improved CytoSyn-v2, and compared our work to PixCell, a state-of-the-art model, in an in-depth manner. This comparison highlighted the strong sensitivity of both diffusion models and performance metrics to preprocessing-specific details such as JPEG compression. Our model has been trained on a dataset obtained from more than 10,000 TCGA diagnostic whole-slide images of 32 different cancer types. Despite being trained only on oncology slides, it maintains state-of-the-art performance generating inflammatory bowel disease images. To support the research community, we publicly release CytoSyn's weights, its training and validation datasets, and a sample of synthetic images in this repository: https://huggingface.co/Owkin-Bioptimus/CytoSyn.

  • 10 authors
·
Mar 18

Text-Guided Generation and Editing of Compositional 3D Avatars

Our goal is to create a realistic 3D facial avatar with hair and accessories using only a text description. While this challenge has attracted significant recent interest, existing methods either lack realism, produce unrealistic shapes, or do not support editing, such as modifications to the hairstyle. We argue that existing methods are limited because they employ a monolithic modeling approach, using a single representation for the head, face, hair, and accessories. Our observation is that the hair and face, for example, have very different structural qualities that benefit from different representations. Building on this insight, we generate avatars with a compositional model, in which the head, face, and upper body are represented with traditional 3D meshes, and the hair, clothing, and accessories with neural radiance fields (NeRF). The model-based mesh representation provides a strong geometric prior for the face region, improving realism while enabling editing of the person's appearance. By using NeRFs to represent the remaining components, our method is able to model and synthesize parts with complex geometry and appearance, such as curly hair and fluffy scarves. Our novel system synthesizes these high-quality compositional avatars from text descriptions. The experimental results demonstrate that our method, Text-guided generation and Editing of Compositional Avatars (TECA), produces avatars that are more realistic than those of recent methods while being editable because of their compositional nature. For example, our TECA enables the seamless transfer of compositional features like hairstyles, scarves, and other accessories between avatars. This capability supports applications such as virtual try-on.

  • 6 authors
·
Sep 13, 2023 1

De novo protein design using geometric vector field networks

Innovations like protein diffusion have enabled significant progress in de novo protein design, which is a vital topic in life science. These methods typically depend on protein structure encoders to model residue backbone frames, where atoms do not exist. Most prior encoders rely on atom-wise features, such as angles and distances between atoms, which are not available in this context. Thus far, only several simple encoders, such as IPA, have been proposed for this scenario, exposing the frame modeling as a bottleneck. In this work, we proffer the Vector Field Network (VFN), which enables network layers to perform learnable vector computations between coordinates of frame-anchored virtual atoms, thus achieving a higher capability for modeling frames. The vector computation operates in a manner similar to a linear layer, with each input channel receiving 3D virtual atom coordinates instead of scalar values. The multiple feature vectors output by the vector computation are then used to update the residue representations and virtual atom coordinates via attention aggregation. Remarkably, VFN also excels in modeling both frames and atoms, as the real atoms can be treated as the virtual atoms for modeling, positioning VFN as a potential universal encoder. In protein diffusion (frame modeling), VFN exhibits an impressive performance advantage over IPA, excelling in terms of both designability (67.04% vs. 53.58%) and diversity (66.54% vs. 51.98%). In inverse folding (frame and atom modeling), VFN outperforms the previous SoTA model, PiFold (54.7% vs. 51.66%), on sequence recovery rate. We also propose a method of equipping VFN with the ESM model, which significantly surpasses the previous ESM-based SoTA (62.67% vs. 55.65%), LM-Design, by a substantial margin.

  • 7 authors
·
Oct 18, 2023

Habitat: A Platform for Embodied AI Research

We present Habitat, a platform for research in embodied artificial intelligence (AI). Habitat enables training embodied agents (virtual robots) in highly efficient photorealistic 3D simulation. Specifically, Habitat consists of: (i) Habitat-Sim: a flexible, high-performance 3D simulator with configurable agents, sensors, and generic 3D dataset handling. Habitat-Sim is fast -- when rendering a scene from Matterport3D, it achieves several thousand frames per second (fps) running single-threaded, and can reach over 10,000 fps multi-process on a single GPU. (ii) Habitat-API: a modular high-level library for end-to-end development of embodied AI algorithms -- defining tasks (e.g., navigation, instruction following, question answering), configuring, training, and benchmarking embodied agents. These large-scale engineering contributions enable us to answer scientific questions requiring experiments that were till now impracticable or 'merely' impractical. Specifically, in the context of point-goal navigation: (1) we revisit the comparison between learning and SLAM approaches from two recent works and find evidence for the opposite conclusion -- that learning outperforms SLAM if scaled to an order of magnitude more experience than previous investigations, and (2) we conduct the first cross-dataset generalization experiments {train, test} x {Matterport3D, Gibson} for multiple sensors {blind, RGB, RGBD, D} and find that only agents with depth (D) sensors generalize across datasets. We hope that our open-source platform and these findings will advance research in embodied AI.

  • 12 authors
·
Nov 24, 2019

Ghost on the Shell: An Expressive Representation of General 3D Shapes

The creation of photorealistic virtual worlds requires the accurate modeling of 3D surface geometry for a wide range of objects. For this, meshes are appealing since they 1) enable fast physics-based rendering with realistic material and lighting, 2) support physical simulation, and 3) are memory-efficient for modern graphics pipelines. Recent work on reconstructing and statistically modeling 3D shape, however, has critiqued meshes as being topologically inflexible. To capture a wide range of object shapes, any 3D representation must be able to model solid, watertight, shapes as well as thin, open, surfaces. Recent work has focused on the former, and methods for reconstructing open surfaces do not support fast reconstruction with material and lighting or unconditional generative modelling. Inspired by the observation that open surfaces can be seen as islands floating on watertight surfaces, we parameterize open surfaces by defining a manifold signed distance field on watertight templates. With this parameterization, we further develop a grid-based and differentiable representation that parameterizes both watertight and non-watertight meshes of arbitrary topology. Our new representation, called Ghost-on-the-Shell (G-Shell), enables two important applications: differentiable rasterization-based reconstruction from multiview images and generative modelling of non-watertight meshes. We empirically demonstrate that G-Shell achieves state-of-the-art performance on non-watertight mesh reconstruction and generation tasks, while also performing effectively for watertight meshes.

  • 7 authors
·
Oct 23, 2023

STP-BENCH: A Unified Systematic Benchmark for Virtual Spatial Transcriptomics from Histopathology Images

Spatial transcriptomics (ST) provides unprecedented insights into tumor heterogeneity by capturing spatially resolved gene expression, yet its high experimental cost hinders large-scale adoption. Consequently, computational approaches that predict spatial gene expression directly from hematoxylin and eosin slides, termed virtual ST, have rapidly emerged. Despite this progress, assessing advances in the field remains difficult due to insufficient benchmarking: prior studies rely on small, heterogeneous datasets, inconsistent training and inference pipelines, and limited evaluation of biological interpretability and model robustness. To address these gaps, we present STP-BENCH, a standardized benchmark for virtual ST models. STP-BENCH comprises six cancer types spanning two ST platforms (Visium and Xenium), with each training dataset containing more than 30,000 spots and at least 15 slides to ensure statistical reliability. We evaluate 21 predictive approaches, re-implemented with a unified pathology foundation model as the morphological encoder when architecturally applicable. Beyond conventional benchmarks that report average predictive accuracy on highly variable genes, we systematically examine which genes and gene sets are recoverable from histomorphology. We further evaluate the downstream biological utility of predicted profiles through cell-type deconvolution and spatial domain identification, and assess model reliability under domain shifts and data scaling. Notably, unified morphological encoding substantially re-orders model rankings established in prior studies, indicating that architectural innovations and image encoding have been conflated in previous evaluations. We publicly release STP-BENCH to support reproducibility and serve as a community benchmark at https://github.com/NEXGEM/STP-Bench.

  • 11 authors
·
Sep 4

$D^{2}R^{2}$: Discrete Diffusion with Regulation Reinforcement for Single-Cell Perturbation Prediction

Predicting single-cell transcriptomic responses to genetic perturbations is central to functional genomics and virtual-cell modeling. Existing approaches, however, typically predict an entire expression profile as a whole, leaving the order in which individual gene responses are generated unmodeled. To address this problem, we introduce D^{2R^{2}} (Discrete Diffusion with Regulation Reinforcement), which reformulates perturbation prediction as regulation-guided gene-wise progressive generation. A Masked Discrete Diffusion Model represents expression as ordinal tokens and reconstructs a fully masked profile step by step, allowing generated gene responses to condition those that remain masked. A Regulatory Policy Module initializes the generation policy from a gene regulatory network inferred from control cells and adapts it to the perturbation and current partially generated state. Then, group-relative policy optimization refines only the ordering policy using final perturbation-effect agreement as reward. Across Norman19 and VCC-H1, D^{2}R^{2} achieves the best performance on all five metrics on Norman19 and remains competitive on H1. Controlled ablations holding the generator and generation budget fixed show that biological-prior ordering improves over random ordering and is more reliable than uncertainty-based heuristics, whereas reversing the biological-prior ordering degrades every metric. Biological analyses further show that the refined policy prioritizes regulatory genes early while promoting perturbation-specific transcription factors and responsive genes. These results establish gene generation order as an effective, controllable, and biologically interpretable dimension of single-cell perturbation prediction.

  • 12 authors
·
Aug 14

CellVTA: Enhancing Vision Foundation Models for Accurate Cell Segmentation and Classification

Cell instance segmentation is a fundamental task in digital pathology with broad clinical applications. Recently, vision foundation models, which are predominantly based on Vision Transformers (ViTs), have achieved remarkable success in pathology image analysis. However, their improvements in cell instance segmentation remain limited. A key challenge arises from the tokenization process in ViTs, which substantially reduces the spatial resolution of input images, leading to suboptimal segmentation quality, especially for small and densely packed cells. To address this problem, we propose CellVTA (Cell Vision Transformer with Adapter), a novel method that improves the performance of vision foundation models for cell instance segmentation by incorporating a CNN-based adapter module. This adapter extracts high-resolution spatial information from input images and injects it into the ViT through a cross-attention mechanism. Our method preserves the core architecture of ViT, ensuring seamless integration with pretrained foundation models. Extensive experiments show that CellVTA achieves 0.538 mPQ on the CoNIC dataset and 0.506 mPQ on the PanNuke dataset, which significantly outperforms the state-of-the-art cell segmentation methods. Ablation studies confirm the superiority of our approach over other fine-tuning strategies, including decoder-only fine-tuning and full fine-tuning. Our code and models are publicly available at https://github.com/JieZheng-ShanghaiTech/CellVTA.

  • 4 authors
·
Apr 1, 2025

AutoBio: A Simulation and Benchmark for Robotic Automation in Digital Biology Laboratory

Vision-language-action (VLA) models have shown promise as generalist robotic policies by jointly leveraging visual, linguistic, and proprioceptive modalities to generate action trajectories. While recent benchmarks have advanced VLA research in domestic tasks, professional science-oriented domains remain underexplored. We introduce AutoBio, a simulation framework and benchmark designed to evaluate robotic automation in biology laboratory environments--an application domain that combines structured protocols with demanding precision and multimodal interaction. AutoBio extends existing simulation capabilities through a pipeline for digitizing real-world laboratory instruments, specialized physics plugins for mechanisms ubiquitous in laboratory workflows, and a rendering stack that support dynamic instrument interfaces and transparent materials through physically based rendering. Our benchmark comprises biologically grounded tasks spanning three difficulty levels, enabling standardized evaluation of language-guided robotic manipulation in experimental protocols. We provide infrastructure for demonstration generation and seamless integration with VLA models. Baseline evaluations with two SOTA VLA models reveal significant gaps in precision manipulation, visual reasoning, and instruction following in scientific workflows. By releasing AutoBio, we aim to catalyze research on generalist robotic systems for complex, high-precision, and multimodal professional environments. The simulator and benchmark are publicly available to facilitate reproducible research.

  • 15 authors
·
May 28, 2025

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.

  • 7 authors
·
May 26

Open World Knowledge Aided Single-Cell Foundation Model with Robust Cross-Modal Cell-Language Pre-training

Recent advancements in single-cell multi-omics, particularly RNA-seq, have provided profound insights into cellular heterogeneity and gene regulation. While pre-trained language model (PLM) paradigm based single-cell foundation models have shown promise, they remain constrained by insufficient integration of in-depth individual profiles and neglecting the influence of noise within multi-modal data. To address both issues, we propose an Open-world Language Knowledge-Aided Robust Single-Cell Foundation Model (OKR-CELL). It is built based on a cross-modal Cell-Language pre-training framework, which comprises two key innovations: (1) leveraging Large Language Models (LLMs) based workflow with retrieval-augmented generation (RAG) enriches cell textual descriptions using open-world knowledge; (2) devising a Cross-modal Robust Alignment (CRA) objective that incorporates sample reliability assessment, curriculum learning, and coupled momentum contrastive learning to strengthen the model's resistance to noisy data. After pretraining on 32M cell-text pairs, OKR-CELL obtains cutting-edge results across 6 evaluation tasks. Beyond standard benchmarks such as cell clustering, cell-type annotation, batch-effect correction, and few-shot annotation, the model also demonstrates superior performance in broader multi-modal applications, including zero-shot cell-type annotation and bidirectional cell-text retrieval.

  • 8 authors
·
Jan 8

SEEAvatar: Photorealistic Text-to-3D Avatar Generation with Constrained Geometry and Appearance

Powered by large-scale text-to-image generation models, text-to-3D avatar generation has made promising progress. However, most methods fail to produce photorealistic results, limited by imprecise geometry and low-quality appearance. Towards more practical avatar generation, we present SEEAvatar, a method for generating photorealistic 3D avatars from text with SElf-Evolving constraints for decoupled geometry and appearance. For geometry, we propose to constrain the optimized avatar in a decent global shape with a template avatar. The template avatar is initialized with human prior and can be updated by the optimized avatar periodically as an evolving template, which enables more flexible shape generation. Besides, the geometry is also constrained by the static human prior in local parts like face and hands to maintain the delicate structures. For appearance generation, we use diffusion model enhanced by prompt engineering to guide a physically based rendering pipeline to generate realistic textures. The lightness constraint is applied on the albedo texture to suppress incorrect lighting effect. Experiments show that our method outperforms previous methods on both global and local geometry and appearance quality by a large margin. Since our method can produce high-quality meshes and textures, such assets can be directly applied in classic graphics pipeline for realistic rendering under any lighting condition. Project page at: https://seeavatar3d.github.io.

  • 3 authors
·
Dec 13, 2023 1

Central Dogma Transformer: Towards Mechanism-Oriented AI for Cellular Understanding

Understanding cellular mechanisms requires integrating information across DNA, RNA, and protein - the three molecular systems linked by the Central Dogma of molecular biology. While domain-specific foundation models have achieved success for each modality individually, they remain isolated, limiting our ability to model integrated cellular processes. Here we present the Central Dogma Transformer (CDT), an architecture that integrates pre-trained language models for DNA, RNA, and protein following the directional logic of the Central Dogma. CDT employs directional cross-attention mechanisms - DNA-to-RNA attention models transcriptional regulation, while RNA-to-Protein attention models translational relationships - producing a unified Virtual Cell Embedding that integrates all three modalities. We validate CDT v1 - a proof-of-concept implementation using fixed (non-cell-specific) RNA and protein embeddings - on CRISPRi enhancer perturbation data from K562 cells, achieving a Pearson correlation of 0.503, representing 63% of the theoretical ceiling set by cross-experiment variability (r = 0.797). Attention and gradient analyses provide complementary interpretive windows: in detailed case studies, these approaches highlight largely distinct genomic regions, with gradient analysis identifying a CTCF binding site that Hi-C data showed as physically contacting both enhancer and target gene. These results suggest that AI architectures aligned with biological information flow can achieve both predictive accuracy and mechanistic interpretability.

  • 1 authors
·
Jan 9

MicroVerse: A Preliminary Exploration Toward a Micro-World Simulation

Recent advances in video generation have opened new avenues for macroscopic simulation of complex dynamic systems, but their application to microscopic phenomena remains largely unexplored. Microscale simulation holds great promise for biomedical applications such as drug discovery, organ-on-chip systems, and disease mechanism studies, while also showing potential in education and interactive visualization. In this work, we introduce MicroWorldBench, a multi-level rubric-based benchmark for microscale simulation tasks. MicroWorldBench enables systematic, rubric-based evaluation through 459 unique expert-annotated criteria spanning multiple microscale simulation task (e.g., organ-level processes, cellular dynamics, and subcellular molecular interactions) and evaluation dimensions (e.g., scientific fidelity, visual quality, instruction following). MicroWorldBench reveals that current SOTA video generation models fail in microscale simulation, showing violations of physical laws, temporal inconsistency, and misalignment with expert criteria. To address these limitations, we construct MicroSim-10K, a high-quality, expert-verified simulation dataset. Leveraging this dataset, we train MicroVerse, a video generation model tailored for microscale simulation. MicroVerse can accurately reproduce complex microscale mechanism. Our work first introduce the concept of Micro-World Simulation and present a proof of concept, paving the way for applications in biology, education, and scientific visualization. Our work demonstrates the potential of educational microscale simulations of biological mechanisms. Our data and code are publicly available at https://github.com/FreedomIntelligence/MicroVerse

FreedomIntelligence FreedomAI
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Feb 28 2

GPU-accelerated single-cell analysis at scale with rapids-singlecell

Single-cell sequencing technologies reveal cellular heterogeneity at high resolution, advancing our understanding of biological complexity. As datasets start to scale to tens of millions of cells, computational workflows face substantial bottlenecks, with CPU-based analytical pipelines requiring hours or days for routine processing steps like filtering, normalization, and clustering. These scalability limitations fundamentally restrict common interactive data exploration and iterative hypothesis testing. Here we introduce rapids-singlecell, a GPU-accelerated framework that integrates natively with the scverse ecosystem and operates directly on the AnnData data structure, which delivers orders-of-magnitude speedups for single-cell workflows. Built on CuPy arrays and the NVIDIA CUDA-X Data Science (RAPIDS) ecosystem, rapids-singlecell provides near drop-in GPU replacements for core scanpy-based analysis steps. Across standard single-cell workflows such as preprocessing, dimensionality reduction, neighborhood graph construction, clustering, and batch correction, rapids-singlecell achieves speedups of up to several hundred-fold compared to optimized CPU baselines. This reduces analysis time from hours to minutes on standard hardware, while maintaining consistent biological interpretations. These performance improvements make it possible to analyze large data sets in close to real time, without the need for data splitting. Together with real-time parameter tuning and iterative workflows, rapids-singlecell makes interactive large-scale single-cell analysis possible.

  • 13 authors
·
Mar 1

ViSA: 3D-Aware Video Shading for Real-Time Upper-Body Avatar Creation

Generating high-fidelity upper-body 3D avatars from one-shot input image remains a significant challenge. Current 3D avatar generation methods, which rely on large reconstruction models, are fast and capable of producing stable body structures, but they often suffer from artifacts such as blurry textures and stiff, unnatural motion. In contrast, generative video models show promising performance by synthesizing photorealistic and dynamic results, but they frequently struggle with unstable behavior, including body structural errors and identity drift. To address these limitations, we propose a novel approach that combines the strengths of both paradigms. Our framework employs a 3D reconstruction model to provide robust structural and appearance priors, which in turn guides a real-time autoregressive video diffusion model for rendering. This process enables the model to synthesize high-frequency, photorealistic details and fluid dynamics in real time, effectively reducing texture blur and motion stiffness while preventing the structural inconsistencies common in video generation methods. By uniting the geometric stability of 3D reconstruction with the generative capabilities of video models, our method produces high-fidelity digital avatars with realistic appearance and dynamic, temporally coherent motion. Experiments demonstrate that our approach significantly reduces artifacts and achieves substantial improvements in visual quality over leading methods, providing a robust and efficient solution for real-time applications such as gaming and virtual reality. Project page: https://lhyfst.github.io/visa

  • 12 authors
·
Dec 8, 2025

ML-SIM: A deep neural network for reconstruction of structured illumination microscopy images

Structured illumination microscopy (SIM) has become an important technique for optical super-resolution imaging because it allows a doubling of image resolution at speeds compatible for live-cell imaging. However, the reconstruction of SIM images is often slow and prone to artefacts. Here we propose a versatile reconstruction method, ML-SIM, which makes use of machine learning. The model is an end-to-end deep residual neural network that is trained on a simulated data set to be free of common SIM artefacts. ML-SIM is thus robust to noise and irregularities in the illumination patterns of the raw SIM input frames. The reconstruction method is widely applicable and does not require the acquisition of experimental training data. Since the training data are generated from simulations of the SIM process on images from generic libraries the method can be efficiently adapted to specific experimental SIM implementations. The reconstruction quality enabled by our method is compared with traditional SIM reconstruction methods, and we demonstrate advantages in terms of noise, reconstruction fidelity and contrast for both simulated and experimental inputs. In addition, reconstruction of one SIM frame typically only takes ~100ms to perform on PCs with modern Nvidia graphics cards, making the technique compatible with real-time imaging. The full implementation and the trained networks are available at http://ML-SIM.com.

  • 4 authors
·
Mar 24, 2020

GraspLook: a VR-based Telemanipulation System with R-CNN-driven Augmentation of Virtual Environment

The teleoperation of robotic systems in medical applications requires stable and convenient visual feedback for the operator. The most accessible approach to delivering visual information from the remote area is using cameras to transmit a video stream from the environment. However, such systems are sensitive to the camera resolution, limited viewpoints, and cluttered environment bringing additional mental demands to the human operator. The paper proposes a novel system of teleoperation based on an augmented virtual environment (VE). The region-based convolutional neural network (R-CNN) is applied to detect the laboratory instrument and estimate its position in the remote environment to display further its digital twin in the VE, which is necessary for dexterous telemanipulation. The experimental results revealed that the developed system allows users to operate the robot smoother, which leads to a decrease in task execution time when manipulating test tubes. In addition, the participants evaluated the developed system as less mentally demanding (by 11%) and requiring less effort (by 16%) to accomplish the task than the camera-based teleoperation approach and highly assessed their performance in the augmented VE. The proposed technology can be potentially applied for conducting laboratory tests in remote areas when operating with infectious and poisonous reagents.

  • 5 authors
·
Oct 24, 2021

The TYC Dataset for Understanding Instance-Level Semantics and Motions of Cells in Microstructures

Segmenting cells and tracking their motion over time is a common task in biomedical applications. However, predicting accurate instance-wise segmentation and cell motions from microscopy imagery remains a challenging task. Using microstructured environments for analyzing single cells in a constant flow of media adds additional complexity. While large-scale labeled microscopy datasets are available, we are not aware of any large-scale dataset, including both cells and microstructures. In this paper, we introduce the trapped yeast cell (TYC) dataset, a novel dataset for understanding instance-level semantics and motions of cells in microstructures. We release 105 dense annotated high-resolution brightfield microscopy images, including about 19k instance masks. We also release 261 curated video clips composed of 1293 high-resolution microscopy images to facilitate unsupervised understanding of cell motions and morphology. TYC offers ten times more instance annotations than the previously largest dataset, including cells and microstructures. Our effort also exceeds previous attempts in terms of microstructure variability, resolution, complexity, and capturing device (microscopy) variability. We facilitate a unified comparison on our novel dataset by introducing a standardized evaluation strategy. TYC and evaluation code are publicly available under CC BY 4.0 license.

  • 3 authors
·
Aug 23, 2023

Scaffold Splits Overestimate Virtual Screening Performance

Virtual Screening (VS) of vast compound libraries guided by Artificial Intelligence (AI) models is a highly productive approach to early drug discovery. Data splitting is crucial for better benchmarking of such AI models. Traditional random data splits produce similar molecules between training and test sets, conflicting with the reality of VS libraries which mostly contain structurally distinct compounds. Scaffold split, grouping molecules by shared core structure, is widely considered to reflect this real-world scenario. However, here we show that the scaffold split also overestimates VS performance. The reason is that molecules with different chemical scaffolds are often similar, which hence introduces unrealistically high similarities between training molecules and test molecules following a scaffold split. Our study examined three representative AI models on 60 NCI-60 datasets, each with approximately 30,000 to 50,000 molecules tested on a different cancer cell line. Each dataset was split with three methods: scaffold, Butina clustering and the more accurate Uniform Manifold Approximation and Projection (UMAP) clustering. Regardless of the model, model performance is much worse with UMAP splits from the results of the 2100 models trained and evaluated for each algorithm and split. These robust results demonstrate the need for more realistic data splits to tune, compare, and select models for VS. For the same reason, avoiding the scaffold split is also recommended for other molecular property prediction problems. The code to reproduce these results is available at https://github.com/ScaffoldSplitsOverestimateVS

  • 3 authors
·
Jun 29, 2024

GenCA: A Text-conditioned Generative Model for Realistic and Drivable Codec Avatars

Photo-realistic and controllable 3D avatars are crucial for various applications such as virtual and mixed reality (VR/MR), telepresence, gaming, and film production. Traditional methods for avatar creation often involve time-consuming scanning and reconstruction processes for each avatar, which limits their scalability. Furthermore, these methods do not offer the flexibility to sample new identities or modify existing ones. On the other hand, by learning a strong prior from data, generative models provide a promising alternative to traditional reconstruction methods, easing the time constraints for both data capture and processing. Additionally, generative methods enable downstream applications beyond reconstruction, such as editing and stylization. Nonetheless, the research on generative 3D avatars is still in its infancy, and therefore current methods still have limitations such as creating static avatars, lacking photo-realism, having incomplete facial details, or having limited drivability. To address this, we propose a text-conditioned generative model that can generate photo-realistic facial avatars of diverse identities, with more complete details like hair, eyes and mouth interior, and which can be driven through a powerful non-parametric latent expression space. Specifically, we integrate the generative and editing capabilities of latent diffusion models with a strong prior model for avatar expression driving. Our model can generate and control high-fidelity avatars, even those out-of-distribution. We also highlight its potential for downstream applications, including avatar editing and single-shot avatar reconstruction.

  • 12 authors
·
Aug 24, 2024 3

ImmerseGen: Agent-Guided Immersive World Generation with Alpha-Textured Proxies

Automatic creation of 3D scenes for immersive VR presence has been a significant research focus for decades. However, existing methods often rely on either high-poly mesh modeling with post-hoc simplification or massive 3D Gaussians, resulting in a complex pipeline or limited visual realism. In this paper, we demonstrate that such exhaustive modeling is unnecessary for achieving compelling immersive experience. We introduce ImmerseGen, a novel agent-guided framework for compact and photorealistic world modeling. ImmerseGen represents scenes as hierarchical compositions of lightweight geometric proxies, i.e., simplified terrain and billboard meshes, and generates photorealistic appearance by synthesizing RGBA textures onto these proxies. Specifically, we propose terrain-conditioned texturing for user-centric base world synthesis, and RGBA asset texturing for midground and foreground scenery. This reformulation offers several advantages: (i) it simplifies modeling by enabling agents to guide generative models in producing coherent textures that integrate seamlessly with the scene; (ii) it bypasses complex geometry creation and decimation by directly synthesizing photorealistic textures on proxies, preserving visual quality without degradation; (iii) it enables compact representations suitable for real-time rendering on mobile VR headsets. To automate scene creation from text prompts, we introduce VLM-based modeling agents enhanced with semantic grid-based analysis for improved spatial reasoning and accurate asset placement. ImmerseGen further enriches scenes with dynamic effects and ambient audio to support multisensory immersion. Experiments on scene generation and live VR showcases demonstrate that ImmerseGen achieves superior photorealism, spatial coherence and rendering efficiency compared to prior methods. Project webpage: https://immersegen.github.io.

  • 9 authors
·
Jun 17, 2025 2

VoluMe -- Authentic 3D Video Calls from Live Gaussian Splat Prediction

Virtual 3D meetings offer the potential to enhance copresence, increase engagement and thus improve effectiveness of remote meetings compared to standard 2D video calls. However, representing people in 3D meetings remains a challenge; existing solutions achieve high quality by using complex hardware, making use of fixed appearance via enrolment, or by inverting a pre-trained generative model. These approaches lead to constraints that are unwelcome and ill-fitting for videoconferencing applications. We present the first method to predict 3D Gaussian reconstructions in real time from a single 2D webcam feed, where the 3D representation is not only live and realistic, but also authentic to the input video. By conditioning the 3D representation on each video frame independently, our reconstruction faithfully recreates the input video from the captured viewpoint (a property we call authenticity), while generalizing realistically to novel viewpoints. Additionally, we introduce a stability loss to obtain reconstructions that are temporally stable on video sequences. We show that our method delivers state-of-the-art accuracy in visual quality and stability metrics compared to existing methods, and demonstrate our approach in live one-to-one 3D meetings using only a standard 2D camera and display. This demonstrates that our approach can allow anyone to communicate volumetrically, via a method for 3D videoconferencing that is not only highly accessible, but also realistic and authentic.

  • 9 authors
·
Jul 28, 2025

Star-convex Polyhedra for 3D Object Detection and Segmentation in Microscopy

Accurate detection and segmentation of cell nuclei in volumetric (3D) fluorescence microscopy datasets is an important step in many biomedical research projects. Although many automated methods for these tasks exist, they often struggle for images with low signal-to-noise ratios and/or dense packing of nuclei. It was recently shown for 2D microscopy images that these issues can be alleviated by training a neural network to directly predict a suitable shape representation (star-convex polygon) for cell nuclei. In this paper, we adopt and extend this approach to 3D volumes by using star-convex polyhedra to represent cell nuclei and similar shapes. To that end, we overcome the challenges of 1) finding parameter-efficient star-convex polyhedra representations that can faithfully describe cell nuclei shapes, 2) adapting to anisotropic voxel sizes often found in fluorescence microscopy datasets, and 3) efficiently computing intersections between pairs of star-convex polyhedra (required for non-maximum suppression). Although our approach is quite general, since star-convex polyhedra include common shapes like bounding boxes and spheres as special cases, our focus is on accurate detection and segmentation of cell nuclei. Finally, we demonstrate on two challenging datasets that our approach (StarDist-3D) leads to superior results when compared to classical and deep learning based methods.

  • 5 authors
·
Aug 9, 2019

SimuWoB: Simulating Real-World Mobile Apps for Fast and Faithful GUI Agent Benchmarking

Mobile GUI agents powered by large language models have progressed rapidly, creating urgent needs for realistic and comprehensive evaluation. Existing benchmarks prioritize reproducibility but are often limited to open-source apps or file-operation tasks for the difficulty of constructing rewards on real applications, leaving a gap between benchmark settings and real-world usage. Moreover, most benchmarks focus on basic grounding and navigation, with limited coverage of complex, long-horizon interactions. To address these limitations, we introduce SimuWoB, a fully synthetic benchmark for mobile GUI agents with 120 challenging tasks spanning diverse types and difficulty levels. We build a robust virtual environment generation framework that synthesizes high-fidelity tasks and environments, and automatically provides valid rewards for each task. Each environment is deployed as a backend-free webpage accessible via URL, enabling efficient and reproducible evaluation. We conduct comprehensive experiments on several state-of-the-art mobile GUI agents. The average success rate is only 27.92%, dropping to 17.82% on long-horizon tasks, which reveals substantial weaknesses in current agents under complex scenarios. Evaluation result comparison with real-world sample tasks demonstrate that agent assessments based on our synthetic environment generalize well. We further provide diagnostic insights across key capability dimensions and discuss implications for future mobile GUI agent development.

Using Vision Language Foundation Models to Generate Plant Simulation Configurations via In-Context Learning

This paper introduces a synthetic benchmark to evaluate the performance of vision language models (VLMs) in generating plant simulation configurations for digital twins. While functional-structural plant models (FSPMs) are useful tools for simulating biophysical processes in agricultural environments, their high complexity and low throughput create bottlenecks for deployment at scale. We propose a novel approach that leverages state-of-the-art open-source VLMs -- Gemma 3 and Qwen3-VL -- to directly generate simulation parameters in JSON format from drone-based remote sensing images. Using a synthetic cowpea plot dataset generated via the Helios 3D procedural plant generation library, we tested five in-context learning methods and evaluated the models across three categories: JSON integrity, geometric evaluations, and biophysical evaluations. Our results show that while VLMs can interpret structural metadata and estimate parameters like plant count and sun azimuth, they often exhibit performance degradation due to contextual bias or rely on dataset means when visual cues are insufficient. Validation on a real-world drone orthophoto dataset and an ablation study using a blind baseline further characterize the models' reasoning capabilities versus their reliance on contextual priors. To the best of our knowledge, this is the first study to utilize VLMs to generate structural JSON configurations for plant simulations, providing a scalable framework for reconstruction 3D plots for digital twin in agriculture.

  • 7 authors
·
Mar 9

PixCell: A generative foundation model for digital histopathology images

The digitization of histology slides has revolutionized pathology, providing massive datasets for cancer diagnosis and research. Contrastive self-supervised and vision-language models have been shown to effectively mine large pathology datasets to learn discriminative representations. On the other hand, generative models, capable of synthesizing realistic and diverse images, present a compelling solution to address unique problems in pathology that involve synthesizing images; overcoming annotated data scarcity, enabling privacy-preserving data sharing, and performing inherently generative tasks, such as virtual staining. We introduce PixCell, the first diffusion-based generative foundation model for histopathology. We train PixCell on PanCan-30M, a vast, diverse dataset derived from 69,184 H\&E-stained whole slide images covering various cancer types. We employ a progressive training strategy and a self-supervision-based conditioning that allows us to scale up training without any annotated data. PixCell generates diverse and high-quality images across multiple cancer types, which we find can be used in place of real data to train a self-supervised discriminative model. Synthetic images shared between institutions are subject to fewer regulatory barriers than would be the case with real clinical images. Furthermore, we showcase the ability to precisely control image generation using a small set of annotated images, which can be used for both data augmentation and educational purposes. Testing on a cell segmentation task, a mask-guided PixCell enables targeted data augmentation, improving downstream performance. Finally, we demonstrate PixCell's ability to use H\&E structural staining to infer results from molecular marker studies; we use this capability to infer IHC staining from H\&E images. Our trained models are publicly released to accelerate research in computational pathology.

ShineOn: Illuminating Design Choices for Practical Video-based Virtual Clothing Try-on

Virtual try-on has garnered interest as a neural rendering benchmark task to evaluate complex object transfer and scene composition. Recent works in virtual clothing try-on feature a plethora of possible architectural and data representation choices. However, they present little clarity on quantifying the isolated visual effect of each choice, nor do they specify the hyperparameter details that are key to experimental reproduction. Our work, ShineOn, approaches the try-on task from a bottom-up approach and aims to shine light on the visual and quantitative effects of each experiment. We build a series of scientific experiments to isolate effective design choices in video synthesis for virtual clothing try-on. Specifically, we investigate the effect of different pose annotations, self-attention layer placement, and activation functions on the quantitative and qualitative performance of video virtual try-on. We find that DensePose annotations not only enhance face details but also decrease memory usage and training time. Next, we find that attention layers improve face and neck quality. Finally, we show that GELU and ReLU activation functions are the most effective in our experiments despite the appeal of newer activations such as Swish and Sine. We will release a well-organized code base, hyperparameters, and model checkpoints to support the reproducibility of our results. We expect our extensive experiments and code to greatly inform future design choices in video virtual try-on. Our code may be accessed at https://github.com/andrewjong/ShineOn-Virtual-Tryon.

  • 5 authors
·
Dec 18, 2020

Avat3r: Large Animatable Gaussian Reconstruction Model for High-fidelity 3D Head Avatars

Traditionally, creating photo-realistic 3D head avatars requires a studio-level multi-view capture setup and expensive optimization during test-time, limiting the use of digital human doubles to the VFX industry or offline renderings. To address this shortcoming, we present Avat3r, which regresses a high-quality and animatable 3D head avatar from just a few input images, vastly reducing compute requirements during inference. More specifically, we make Large Reconstruction Models animatable and learn a powerful prior over 3D human heads from a large multi-view video dataset. For better 3D head reconstructions, we employ position maps from DUSt3R and generalized feature maps from the human foundation model Sapiens. To animate the 3D head, our key discovery is that simple cross-attention to an expression code is already sufficient. Finally, we increase robustness by feeding input images with different expressions to our model during training, enabling the reconstruction of 3D head avatars from inconsistent inputs, e.g., an imperfect phone capture with accidental movement, or frames from a monocular video. We compare Avat3r with current state-of-the-art methods for few-input and single-input scenarios, and find that our method has a competitive advantage in both tasks. Finally, we demonstrate the wide applicability of our proposed model, creating 3D head avatars from images of different sources, smartphone captures, single images, and even out-of-domain inputs like antique busts. Project website: https://tobias-kirschstein.github.io/avat3r/

  • 5 authors
·
Feb 27, 2025

HDTree: Generative Modeling of Cellular Hierarchies for Robust Lineage Inference

In single-cell research, tracing and analyzing high-throughput single-cell differentiation trajectories is crucial for understanding biological processes. Key to this is the robust modeling of hierarchical structures that govern cellular development. Traditional methods face limitations in computational cost, performance, and stability. VAE-based approaches have made strides but still require branch-specific network modules, limiting their scalability and stability, while often suffering from posterior collapse. To overcome these challenges, we introduce HDTree, a generative modeling framework designed for robust lineage inference. HDTree captures tree relationships within a hierarchical latent space using a unified hierarchical codebook and employs a quantized diffusion process to model continuous cell state transitions. By aligning the generative process with the Waddington landscape, this method not only improves stability and scalability but also enhances the biological plausibility of inferred lineages. HDTree's effectiveness is demonstrated through comparisons on both general-purpose and single-cell datasets, where it outperforms existing methods in lineage inference accuracy, reconstruction quality, and hierarchical consistency. These contributions enable accurate and efficient modeling of cellular differentiation paths, offering reliable insights for biological discovery.\footnote{Code is available at https://github.com/zangzelin/code\_HDTree\_icml.

  • 8 authors
·
May 17

MagicTryOn: Harnessing Diffusion Transformer for Garment-Preserving Video Virtual Try-on

Video Virtual Try-On (VVT) aims to simulate the natural appearance of garments across consecutive video frames, capturing their dynamic variations and interactions with human body motion. However, current VVT methods still face challenges in terms of spatiotemporal consistency and garment content preservation. First, they use diffusion models based on the U-Net, which are limited in their expressive capability and struggle to reconstruct complex details. Second, they adopt a separative modeling approach for spatial and temporal attention, which hinders the effective capture of structural relationships and dynamic consistency across frames. Third, their expression of garment details remains insufficient, affecting the realism and stability of the overall synthesized results, especially during human motion. To address the above challenges, we propose MagicTryOn, a video virtual try-on framework built upon the large-scale video diffusion Transformer. We replace the U-Net architecture with a diffusion Transformer and combine full self-attention to jointly model the spatiotemporal consistency of videos. We design a coarse-to-fine garment preservation strategy. The coarse strategy integrates garment tokens during the embedding stage, while the fine strategy incorporates multiple garment-based conditions, such as semantics, textures, and contour lines during the denoising stage. Moreover, we introduce a mask-aware loss to further optimize garment region fidelity. Extensive experiments on both image and video try-on datasets demonstrate that our method outperforms existing SOTA methods in comprehensive evaluations and generalizes to in-the-wild scenarios.

  • 9 authors
·
May 27, 2025

Fold-CP: A Context Parallelism Framework for Biomolecular Modeling

Understanding cellular machinery requires atomic-scale reconstruction of large biomolecular assemblies. However, predicting the structures of these systems has been constrained by hardware memory requirements of models like AlphaFold 3, imposing a practical ceiling of a few thousand residues that can be processed on a single GPU. Here we present NVIDIA BioNeMo Fold-CP, a context parallelism framework that overcomes this barrier by distributing the inference and training pipelines of co-folding models across multiple GPUs. We use the Boltz models as open source reference architectures and implement custom multidimensional primitives that efficiently parallelize both the dense triangular updates and the irregular, data-dependent pattern of window-batched local attention. Our approach achieves efficient memory scaling; for an N-token input distributed across P GPUs, per-device memory scales as O(N^2/P), enabling the structure prediction of assemblies exceeding 30,000 residues on 64 NVIDIA B300 GPUs. We demonstrate the scientific utility of this approach through successful developer use cases: Fold-CP enabled the scoring of over 90% of Comprehensive Resource of Mammalian protein complexes (CORUM) database, as well as folding of disease-relevant PI4KA lipid kinase complex bound to an intrinsically disordered region without cropping. By providing a scalable pathway for modeling massive systems with full global context, Fold-CP represents a significant step toward the realization of a virtual cell.

  • 38 authors
·
Mar 15

The Geometry of Cortical Computation: Manifold Disentanglement and Predictive Dynamics in VCNet

Despite their success, modern convolutional neural networks (CNNs) exhibit fundamental limitations, including data inefficiency, poor out-of-distribution generalization, and vulnerability to adversarial perturbations. These shortcomings can be traced to a lack of inductive biases that reflect the inherent geometric structure of the visual world. The primate visual system, in contrast, demonstrates superior efficiency and robustness, suggesting that its architectural and computational principles,which evolved to internalize these structures,may offer a blueprint for more capable artificial vision. This paper introduces Visual Cortex Network (VCNet), a novel neural network architecture whose design is informed by the macro-scale organization of the primate visual cortex. VCNet is framed as a geometric framework that emulates key biological mechanisms, including hierarchical processing across distinct cortical areas, dual-stream information segregation for learning disentangled representations, and top-down predictive feedback for representation refinement. We interpret these mechanisms through the lens of geometry and dynamical systems, positing that they guide the learning of structured, low-dimensional neural manifolds. We evaluate VCNet on two specialized benchmarks: the Spots-10 animal pattern dataset, which probes sensitivity to natural textures, and a light field image classification task, which requires processing higher-dimensional visual data. Our results show that VCNet achieves state-of-the-art accuracy of 92.1\% on Spots-10 and 74.4\% on the light field dataset, surpassing contemporary models of comparable size. This work demonstrates that integrating high-level neuroscientific principles, viewed through a geometric lens, can lead to more efficient and robust models, providing a promising direction for addressing long-standing challenges in machine learning.

  • 3 authors
·
Aug 4, 2025

TryOnCrafter: Unleashing Camera Trajectories for Realistic Video Virtual Try-on via a Renderable 4D Try-on Proxy

While Video Virtual Try-on (VVT) has achieved remarkable progress in synthesizing realistic garment overlays on dynamic subjects, existing paradigms remains fundamentally constrained by a passive dependency on source camera trajectories, failing to accommodate the requisite interactive freedom for omnidirectional viewpoint exploration. To address this limitation, we define a pioneering research frontier: Camera-controllable Video Virtual Try-on (CaM-VVT). Unlike conventional VVT, CaM-VVT not only necessitates viewpoint-agnostic texture hallucination but also strict structural synchronization between non-rigid human dynamics and background contexts under arbitrary, unconstrained camera movements. To tackle these challenges, we present TryOnCrafter, the first unified DiT-based framework specifically architected for the CaM-VVT task. Departing from implicit pixel-space manipulation, we introduce a Renderable 4D Try-on Proxy that explicitly decouples the human subject from the environment. This is achieved by distilling high-fidelity 2D try-on priors into a clothed 3DGS-based avatar, which is subsequently animated via SMPL-X sequences and metric-aligned into a reconstructed background point cloud. This proxy establishes a robust structural foundation with superior texture density and motion integrity. Our Proxy-Anchored Video DiT leverages this robust structural foundation as a primary geometric anchor, ensuring that the synthesized photorealistic videos are strictly constrained by prescribed trajectories and physically plausible deformations. Benefiting from the inherent editability of the 4D proxy, TryOnCrafter facilitates diverse downstream applications, including human relocalization, ``bullet time'' effects, and 360-degree orbital viewing.

alibaba-inc Alibaba-Inc
·
Jun 23 1

SimVLA: Zero-Shot Sim-to-Real VLA Learning for Mobile Manipulation

Large-scale, diverse datasets have driven the success of LLMs and VLMs. But VLAs for robotics remain limited by the cost and complexity of real-world data collection. While simulation offers a scalable alternative, its potential for sim-to-real VLA learning in mobile manipulation remains largely underexplored. We introduce SimVLA, an end-to-end framework that trains VLAs entirely on synthetic simulation data without teleoperation for mobile manipulation. SimVLA is first pre-trained on two complementary simulation-derived datasets: SimAction, a large-scale robot action dataset spanning 35 diverse mobile manipulation tasks, generated by composing atomic skills, and SimVQA, which leverages privileged simulator state to provide spatial, geometric, and subtask-level visual-language supervision. We further post-train SimVLA on a mixture of SimAction and SimDeploy, a dataset collected from policy rollouts across diverse simulated environments. We evaluate SimVLA on tasks including restocking, pouring, and cleaning, and show zero-shot transfer to real-world mobile manipulation, including real home environments. SimVLA outperforms policies trained on 50 in-domain real-world demonstrations, suggesting that simulation can enable scalable sim-to-real mobile manipulation. We further demonstrate the value of multiple complementary forms of supervision for effectively leveraging simulation in VLA training.

  • 2 authors
·
Oct 7

DM-VTON: Distilled Mobile Real-time Virtual Try-On

The fashion e-commerce industry has witnessed significant growth in recent years, prompting exploring image-based virtual try-on techniques to incorporate Augmented Reality (AR) experiences into online shopping platforms. However, existing research has primarily overlooked a crucial aspect - the runtime of the underlying machine-learning model. While existing methods prioritize enhancing output quality, they often disregard the execution time, which restricts their applications on a limited range of devices. To address this gap, we propose Distilled Mobile Real-time Virtual Try-On (DM-VTON), a novel virtual try-on framework designed to achieve simplicity and efficiency. Our approach is based on a knowledge distillation scheme that leverages a strong Teacher network as supervision to guide a Student network without relying on human parsing. Notably, we introduce an efficient Mobile Generative Module within the Student network, significantly reducing the runtime while ensuring high-quality output. Additionally, we propose Virtual Try-on-guided Pose for Data Synthesis to address the limited pose variation observed in training images. Experimental results show that the proposed method can achieve 40 frames per second on a single Nvidia Tesla T4 GPU and only take up 37 MB of memory while producing almost the same output quality as other state-of-the-art methods. DM-VTON stands poised to facilitate the advancement of real-time AR applications, in addition to the generation of lifelike attired human figures tailored for diverse specialized training tasks. https://sites.google.com/view/ltnghia/research/DMVTON

  • 6 authors
·
Aug 26, 2023 1

En3D: An Enhanced Generative Model for Sculpting 3D Humans from 2D Synthetic Data

We present En3D, an enhanced generative scheme for sculpting high-quality 3D human avatars. Unlike previous works that rely on scarce 3D datasets or limited 2D collections with imbalanced viewing angles and imprecise pose priors, our approach aims to develop a zero-shot 3D generative scheme capable of producing visually realistic, geometrically accurate and content-wise diverse 3D humans without relying on pre-existing 3D or 2D assets. To address this challenge, we introduce a meticulously crafted workflow that implements accurate physical modeling to learn the enhanced 3D generative model from synthetic 2D data. During inference, we integrate optimization modules to bridge the gap between realistic appearances and coarse 3D shapes. Specifically, En3D comprises three modules: a 3D generator that accurately models generalizable 3D humans with realistic appearance from synthesized balanced, diverse, and structured human images; a geometry sculptor that enhances shape quality using multi-view normal constraints for intricate human anatomy; and a texturing module that disentangles explicit texture maps with fidelity and editability, leveraging semantical UV partitioning and a differentiable rasterizer. Experimental results show that our approach significantly outperforms prior works in terms of image quality, geometry accuracy and content diversity. We also showcase the applicability of our generated avatars for animation and editing, as well as the scalability of our approach for content-style free adaptation.

  • 6 authors
·
Jan 2, 2024 9

Label-free cell counting and viability prediction with brightfield imaging and deep learning

Cell viability assessment is a core requirement in cell culture systems, with critical applications in biopharmaceutical manufacturing and drug development. Conventionally, it is measured by adding membrane-impermeable dyes to a sample (a process called staining), which allows compromised cell membranes to be distinguished from intact ones. However, staining has several limitations: (a) chemical agents can perturb normal cellular processes of the cells being measured, (b) it is often ambiguous to assign viability to individual cells whose membrane integrity is only partially compromised. (c) photobleaching can undermine measurement accuracy over time when using fluorescent stains, and (d) staining cannot be performed in situ or in real time. Here, we show that (1) stained cells captured under brightfield imaging contain sufficient information to distinguish live and dead cells, and (2) cells captured under unstained brightfield imaging exhibit similar image features to their stained counterparts, enabling models trained on stained cells to generalize to unstained ones. We then report the development and validation of ViabiLens, an AI-assisted software for label-free cell viability analysis. The ViabiLens combines a cell detection model for localizing individual cells with a convolutional neural network (CNN) classifier for live/dead prediction, paired with an interactive UMAP-based viewer for visualizing and exploring individual cells across the sample. Evaluated on Chinese Hamster Ovary (CHO) cells spanning a wide range of viability conditions, ViabiLens achieves a mean absolute error of 2.68\% on unstained samples against fluorescence-based reference measurements. We also release a benchmark dataset for label-free cell viability analysis to facilitate future research, available at https://amirrezavazifeh.github.io/ViabiLens-Project-Page/.

  • 5 authors
·
Oct 6