# CellForge: Agentic Design of Virtual Cell Models

arXiv: https://arxiv.org/abs/2508.02276 · HTML: https://mlsanity.com/paper/2508.02276/

## Key facts

- Cited by 13 papers in the map (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 37 of its 121 references that are in the map.
- First posted on arXiv 4 Aug 2025.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 30 of 37)

- [A Survey on LLM-as-a-Judge](https://mlsanity.com/paper/2411.15594/) (2024)
- [PubMedQA: A Dataset for Biomedical Research Question Answering](https://mlsanity.com/paper/1909.06146/) (2019)
- [The AI Scientist: Towards Fully Automated Open-Ended Scientific Discovery](https://mlsanity.com/paper/2408.06292/) (2024)
- [Large Language Model based Multi-Agents: A Survey of Progress and Challenges](https://mlsanity.com/paper/2402.01680/) (2024)
- [LLMs-as-Judges: A Comprehensive Survey on LLM-based Evaluation Methods](https://mlsanity.com/paper/2412.05579/) (2024)
- [Can LLMs Generate Novel Research Ideas? A Large-Scale Human Study with 100+ NLP Researchers](https://mlsanity.com/paper/2409.04109/) (2024)
- [ScienceAgentBench: Toward Rigorous Assessment of Language Agents for Data-Driven Scientific Discovery](https://mlsanity.com/paper/2410.05080/) (2024)
- [ResearchAgent: Iterative Research Idea Generation over Scientific Literature with Large Language Models](https://mlsanity.com/paper/2404.07738/) (2024)
- [Language agents achieve superhuman synthesis of scientific knowledge](https://mlsanity.com/paper/2409.13740/) (2024)
- [DSBench: How Far Are Data Science Agents from Becoming Data Science Experts?](https://mlsanity.com/paper/2409.07703/) (2024)
- [RAGBench: Explainable Benchmark for Retrieval-Augmented Generation Systems](https://mlsanity.com/paper/2407.11005/) (2024)
- [DiscoveryBench: Towards Data-Driven Discovery with Large Language Models](https://mlsanity.com/paper/2407.01725/) (2024)
- [Towards Scientific Intelligence: A Survey of LLM-based Scientific Agents](https://mlsanity.com/paper/2503.24047/) (2025)
- [AgentRxiv: Towards Collaborative Autonomous Research](https://mlsanity.com/paper/2503.18102/) (2025)
- [MLR-Copilot: Autonomous Machine Learning Research based on Large Language Models Agents](https://mlsanity.com/paper/2408.14033/) (2024)
- [Nova: An Iterative Planning and Search Approach to Enhance Novelty and Diversity of LLM Generated Ideas](https://mlsanity.com/paper/2410.14255/) (2024)
- [xTrimoPGLM: Unified 100B-Scale Pre-trained Transformer for Deciphering the Language of Protein](https://mlsanity.com/paper/2401.06199/) (2024)
- [Automated Hypothesis Validation with Agentic Sequential Falsifications](https://mlsanity.com/paper/2502.09858/) (2025)
- [IdeaSynth: Iterative Research Idea Development Through Evolving and Composing Idea Facets with Literature-Grounded Feedback](https://mlsanity.com/paper/2410.04025/) (2024)
- [Transforming Science with Large Language Models: A Survey on AI-assisted Scientific Discovery, Experimentation, Content Generation, and Evaluation](https://mlsanity.com/paper/2502.05151/) (2025)
- [Human-LLM Compound System for Scientific Ideation through Facet Recombination and Novelty Evaluation](https://mlsanity.com/paper/2409.14634/) (2024)
- [AI Idea Bench 2025: AI Research Idea Generation Benchmark](https://mlsanity.com/paper/2504.14191/) (2025)
- [BioReason: Incentivizing Multimodal Biological Reasoning within a DNA-LLM Model](https://mlsanity.com/paper/2505.23579/) (2025)
- [AtomAgents: Alloy design and discovery through physics-aware multi-modal multi-agent artificial intelligence](https://mlsanity.com/paper/2407.10022/) (2024)
- [Curie: Toward Rigorous and Automated Scientific Experimentation with AI Agents](https://mlsanity.com/paper/2502.16069/) (2025)
- [Evaluating Sakana's AI Scientist: Bold Claims, Mixed Results, and a Promising Future?](https://mlsanity.com/paper/2502.14297/) (2025)
- [Evaluating LLMs' Divergent Thinking Capabilities for Scientific Idea Generation with Minimal Context](https://mlsanity.com/paper/2412.17596/) (2024)
- [Literature Meets Data: A Synergistic Approach to Hypothesis Generation](https://mlsanity.com/paper/2410.17309/) (2024)
- [Benchmarking Transcriptomics Foundation Models for Perturbation Analysis : one PCA still rules them all](https://mlsanity.com/paper/2410.13956/) (2024)
- [IRIS: Interactive Research Ideation System for Accelerating Scientific Discovery](https://mlsanity.com/paper/2504.16728/) (2025)

## Built on by (most cited first, 13 of 13)

- [MIRA: Multimodal Iterative Reasoning Agent for Image Editing](https://mlsanity.com/paper/2511.21087/) (2025)
- [Benchmarking AI Agents for Addressing Scientific Challenges Across Scales](https://mlsanity.com/paper/2606.12736/) (2026)
- [MementoGUI: Learning Agentic Multimodal Memory Control for Long-Horizon GUI Agents](https://mlsanity.com/paper/2605.18652/) (2026)
- [LatentChem: From Textual CoT to Latent Thinking in Chemical Reasoning](https://mlsanity.com/paper/2602.07075/) (2026)
- [VCWorld: A Biological World Model for Virtual Cell Simulation](https://mlsanity.com/paper/2512.00306/) (2025)
- [TusoAI: Agentic Optimization for Scientific Methods](https://mlsanity.com/paper/2509.23986/) (2025)
- [HarmonyCell: Automating Single-Cell Perturbation Modeling under Semantic and Distribution Shifts](https://mlsanity.com/paper/2603.01396/) (2026)
- [SciMDR: Advancing Scientific Multimodal Document Reasoning](https://mlsanity.com/paper/2603.12249/) (2026)
- [CellScientist: From Execution Feedback to Auditable Model-Revision Trajectories for Cellular Perturbation Prediction](https://mlsanity.com/paper/2605.07335/) (2026)
- [AgentFold: Closed-Loop Agentic Search for Protein Folding Model Design](https://mlsanity.com/paper/2608.26747/) (2026)
- [AblateCell: A Reproduce-then-Ablate Agent for Virtual Cell Repositories](https://mlsanity.com/paper/2604.19606/) (2026)
- [Knowledge Graphs and Reasoning LLMs for Finding Simple Yet Effective Transcriptomic Perturbation Predictors](https://mlsanity.com/paper/2606.08816/) (2026)
- [Discover, Falsify, Revise: Auditing Input-Use Claims from Source Code to Predictive Contribution in Agent-Discovered Cell Models](https://mlsanity.com/paper/2609.27234/) (2026)

## Abstract (arXiv)

Autonomous agents, from virtual laboratories to biological data-analysis agents and co-scientists, have begun to turn scientific goals into hypotheses. Whether they can go further and convert real, noisy and complex biological data into executable model hypotheses and architectures that encode testable assumptions remains unclear. Predicting how cells respond to genetic and chemical perturbations is a natural test of this ability: it is central to decoding disease mechanisms and therapeutic discovery, yet it demands cross-disciplinary expertise rarely concentrated in a single research group. Here, we introduce CellForge, an organized team of autonomous agents for single-cell perturbation modeling. Given a dataset and a task, it surveys the literature, parses the data, identifies relevant baselines, and formulates a model hypothesis through critic-mediated discussion among agents specialized in data modeling, single-cell biology, and deep learning. It then writes the training code, runs the experiments, and returns a trained predictor including architecture, code, and validation results. The architecture itself is the hypothesis: CellForge produces it end-to-end, with no human specifying the design, loss, or training protocol. Across six perturbation datasets spanning transcriptomic, epigenomic, and proteomic contexts, CellForge yields models that are competitive with hand-crafted state-of-the-art results on established tasks and extends the same workflow to paired multi-omic readouts. Blinded human evaluators rate CellForge's research plans as more scientifically sound and innovative than those from single LLMs or deep-research systems. In summary, we show autonomous agents can complete the full hypothesis-to-validation cycle in single-cell biology, with an AI effectively building another AI, in a complex setting that currently requires a team of human experts.