BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments
arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 · Peer-reviewed
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- Baseline: Select perturbations for a defined cellular response: Baseline Random selection (tgtval-20261009-source-roohani2025: Table 2 (Random baseline by round) and baselines description)
- Baseline: Select therapeutic targets for validation: Baseline Random and pathway-based selection (tgtval-20261009-source-roohani2025: Appendix (human pathway baseline) and Table 6 (pathways), Table 2 (Random); tgtval-20261009-source-gupta2025: baselines description and Table 3 (Random))
- Claude 3 Haiku: description: Description Large multimodal model with vision capabilities, the fastest and least expensive of Anthropic's Claude 3 family. (qa-descriptions-20261011-b-source-claude3: model card abstract, p.1 ('Claude 3 Haiku, our fastest and least expensive model'))
- Claude 3 Opus: description: Description Large multimodal model with vision capabilities, the most capable of Anthropic's Claude 3 family. (qa-descriptions-20261011-b-source-claude3: model card abstract, p.1 ('Claude 3 Opus, our most capable offering'; 'All new models have vision capabilities'))
- Claude 3 Sonnet: description: Description Large multimodal model with vision capabilities in Anthropic's Claude 3 family, positioned between Opus and Haiku in skills and speed. (qa-descriptions-20261011-b-source-claude3: model card abstract, p.1 ('Claude 3 Sonnet, which provides a combination of skills and speed'))
- Claude 3.5 Sonnet: description: Description Large multimodal model from Anthropic, an evolution of the Claude 3 family with improved coding and visual processing. (qa-descriptions-20261011-b-source-claude3: Claude 3.5 Sonnet Model Card Addendum, section 1 Introduction ('Claude 3.5 Sonnet offers improved capabilities, including better coding and visual processing. Since it is an evolution of the Claude 3 model family'))
- cross_source_consistency: tgtval-20261009-protocol-gupta2025-cumulative-hits-round5: Cross source consistency The 'BDA (Reported Numbers)' row divided by the printed ground-truth hit counts reproduces the all-gene hit ratios of Roohani et al. 2025 Table 1 for Claude 3.5 Sonnet to the printed rounding: IL2 68.01/654 = 0.104 against 0.104, IFNG 87.4/920 = 0.095 against 0.095, Carnevale 39.6/943 = 0.042 against 0.042 and Sanchez 60.72/924 = 0.0657 against 0.066. This indicates that both sources score against the same screens and the same hit sets, and that the row converts the original results rather than reporting a new run. The conversion used values more precise than Roohani Table 1 prints: 0.066 x 924 = 60.98, while the row prints 60.72. Checked during extraction; no value was altered. (Gupta et al. 2025 Tables 1 and 2 against Roohani et al. 2025 Table 1)
- Evidence summary: therapeutic target validation: Summary Three sources compare target-nomination methods against measured CRISPR screen outcomes, and all three are retrospective replays of published screens: a method picks genes and the screen's existing measurement is looked up. Non-hits are genes the screen assayed that did not meet its criterion; genes a screen never assayed are outside the candidate pool or, in AssayBench's headline metric, removed before scoring, so these results say nothing about an untested target. Roohani et al. 2025 (ICLR) were run by the developers of the agent they test, two of whom are authors of two of the screens, and they state that patent applications have been filed on the findings. They report the fraction of each screen's hits found after five rounds of 128 genes. With Claude 3.5 Sonnet the agent reached 0.095 on the interferon-gamma screen, 0.104 on interleukin-2, 0.130 on CAR-T proliferation, 0.326 on lysosomal choline recycling, 0.042 on T-cell inhibition resistance and 0.066 on tau level, against random selection at 0.037, 0.031, 0.033, 0.160, 0.036 and 0.034. Conventional baselines were close on some screens: Coreset reached 0.102 on interleukin-2 and 0.047 on T-cell inhibition resistance, above the agent's 0.042 there. Gupta et al. 2025 (Findings of EMNLP), independent of the agent's authors, replayed five of the same screens and report cumulative hits. Their re-run of the Claude 3.5 Sonnet agent found fewer hits than the original numbers on three of four shared screens, for example 31.6 against 60.72 on tau level. Giving the agent randomly permuted feedback changed little: the permuted variant scored at least as high on three of five screens with each of the three backbones tested, for example 51 against 44 on interferon-gamma with Llama-3.1-8B, and the authors conclude that the models they tested do not perform in-context experimental design. Gaussian process optimisation over the same embeddings reached 147.8 hits on interleukin-2 against the agent's 39.4 with Llama-3.1-8B, from 654 ground-truth hits; the source prints identical Gaussian process values under both backbones. De Brouwer et al. 2026, a preprint that is not peer reviewed, asked 16 systems to rank 100 genes for each of 571 benchmark entries, each a described screen. On the 334 test entries the best system was an evolved ensemble of language models at 0.1631 adjusted NDCG@100 and the best single model, Gemini 3 Pro, 0.1570, against 0.1334 for a baseline ranking genes by how often they are hits in training screens of the same phenotype and 0.2918 for a retrieval upper bound that uses the answer. Most systems scored lower on the 19 entries published after the models' training cutoff, the ensemble falling to 0.1088, which that source reads as partly prior exposure to the literature. None of these sources tests a prospective validation batch, a target's usefulness, dependency, tractability or therapeutic window, or whether modulating a target benefits patients. (tgtval-20261009-source-roohani2025: Table 1, sections 2 and 4.1, conflicts of interest; tgtval-20261009-source-gupta2025: Tables 1 and 2, abstract, section 5; tgtval-20261009-source-debrouwer2026: Tables 2 and 3, sections 2 to 5)
- GPT-4o: description: Description Autoregressive omni model from OpenAI, trained end to end across text, vision and audio, that accepts text, audio, image and video input and generates text, audio and image output. (qa-descriptions-20261011-b-source-gpt-4o: abstract)
- metric_definition: tgtval-20261009-protocol-roohani2025-hitratio-round5: Metric definition A hit is a gene whose perturbation produces a phenotypic response above a threshold tau, f(g) > tau. The hit ratio after T rounds is the fraction of all such genes that the method selected, which the source describes as similar to recall. (Section 2 (problem setting), equations for hit ratio)
- o1-mini: description: Description Model in OpenAI's o1 series, trained with large-scale reinforcement learning to reason using a chain of thought before answering. (qa-descriptions-20261011-b-source-o1: abstract ('The o1 model series is trained with large-scale reinforcement learning to reason using chain of thought'))
- o1-preview: description: Description Model in OpenAI's o1 series, trained with large-scale reinforcement learning to reason using a chain of thought before answering. (qa-descriptions-20261011-b-source-o1: abstract ('The o1 model series is trained with large-scale reinforcement learning to reason using chain of thought'))
- Relevance of tgtval-20261009-protocol-roohani2025-hitratio-round5 to "Which targets should I test to change a defined disease-relevant phenotype?": Assessed by BioDiscoveryAgent 1-gene perturbation design: hit ratio after 5 rounds of 128 genes (tgtval-20261009-source-roohani2025: Sections 2 and 4.1; Table 1; appendix Table 7)
- scoring_population: tgtval-20261009-protocol-roohani2025-hitratio-round5: Scoring population The 'N/E' columns count only non-essential genes among the hits. The source argues essential genes are likely to be detected as hits under many phenotypes, so the non-essential subset is the harder and more biologically useful task. The source does not print which gene list defines essentiality. (Section 5 (results, non-essential genes) and Table 1 caption)
Models, benchmarks and other records
Models (9)
Methods (11)
- Badge acquisition function (MLP surrogate)
- BioDiscoveryAgent
- Coreset acquisition function (MLP surrogate)
- DiscoBAX
- Human pathway-based selection
- K-Means (D) acquisition function (MLP surrogate)
- K-Means (E) acquisition function (MLP surrogate)
- Margin Sample acquisition function (MLP surrogate)
- Random selection
- Soft Uncertain acquisition function (MLP surrogate)
- Top Uncertain acquisition function (MLP surrogate)
Configurations (20)
- Badge acquisition function on an MLP surrogate (Roohani et al. 2025)
- BioDiscoveryAgent (Claude 3.5 Sonnet) combined with the Coreset acquisition function (Roohani et al. 2025)
- BioDiscoveryAgent (No-Tools), Claude 3 Haiku (Roohani et al. 2025)
- BioDiscoveryAgent (No-Tools), Claude 3 Opus (Roohani et al. 2025)
- BioDiscoveryAgent (No-Tools), Claude 3 Sonnet (Roohani et al. 2025)
- BioDiscoveryAgent (No-Tools), Claude 3.5 Sonnet (Roohani et al. 2025)
- BioDiscoveryAgent (No-Tools), Claude v1 (Roohani et al. 2025)
- BioDiscoveryAgent (No-Tools), GPT-3.5-Turbo (Roohani et al. 2025)
- BioDiscoveryAgent (No-Tools), GPT-4o (Roohani et al. 2025)
- BioDiscoveryAgent (No-Tools), o1-mini (Roohani et al. 2025)
- BioDiscoveryAgent (No-Tools), o1-preview (Roohani et al. 2025)
- Coreset acquisition function on an MLP surrogate (Roohani et al. 2025)
- DiscoBAX (Roohani et al. 2025)
- Human pathway-based selection (Roohani et al. 2025)
- K-Means (D) acquisition function on an MLP surrogate (Roohani et al. 2025)
- K-Means (E) acquisition function on an MLP surrogate (Roohani et al. 2025)
- Margin Sample acquisition function on an MLP surrogate (Roohani et al. 2025)
- Random selection (Roohani et al. 2025)
- Soft Uncertain acquisition function on an MLP surrogate (Roohani et al. 2025)
- Top Uncertain acquisition function on an MLP surrogate (Roohani et al. 2025)
Protocols (1)
Datasets (6)
- CAR-T proliferation screen (unpublished dataset used by Roohani et al. 2025)
- Carnevale et al. 2022 screen, T-cell resistance to tumour-microenvironment inhibitory signals
- Sanchez et al. 2021 screen, endogenous tau protein level in neurons
- Scharenberg et al. 2023 screen, lysosomal choline recycling in pancreatic cells
- Schmidt et al. 2022 screen, interferon-gamma production in primary human T cells
- Schmidt et al. 2022 screen, interleukin-2 production in primary human T cells
Evaluations (120)
- Badge on CAR-T (Roohani et al. 2025)
- Badge on Carnev. (Roohani et al. 2025)
- Badge on Sanchez (Roohani et al. 2025)
- Badge on Scharen. (Roohani et al. 2025)
- Badge on Schmidt1 (Roohani et al. 2025)
- Badge on Schmidt2 (Roohani et al. 2025)
- Claude 3 Haiku on CAR-T (Roohani et al. 2025)
- Claude 3 Haiku on Carnev. (Roohani et al. 2025)
- Claude 3 Haiku on Sanchez (Roohani et al. 2025)
- Claude 3 Haiku on Scharen. (Roohani et al. 2025)
- Claude 3 Haiku on Schmidt1 (Roohani et al. 2025)
- Claude 3 Haiku on Schmidt2 (Roohani et al. 2025)
- Claude 3 Opus on CAR-T (Roohani et al. 2025)
- Claude 3 Opus on Carnev. (Roohani et al. 2025)
- Claude 3 Opus on Sanchez (Roohani et al. 2025)
- Claude 3 Opus on Scharen. (Roohani et al. 2025)
- Claude 3 Opus on Schmidt1 (Roohani et al. 2025)
- Claude 3 Opus on Schmidt2 (Roohani et al. 2025)
- Claude 3 Sonnet on CAR-T (Roohani et al. 2025)
- Claude 3 Sonnet on Carnev. (Roohani et al. 2025)
- Claude 3 Sonnet on Sanchez (Roohani et al. 2025)
- Claude 3 Sonnet on Scharen. (Roohani et al. 2025)
- Claude 3 Sonnet on Schmidt1 (Roohani et al. 2025)
- Claude 3 Sonnet on Schmidt2 (Roohani et al. 2025)
- Claude 3.5 Sonnet on CAR-T (Roohani et al. 2025)
Use cases (1)
Evidence
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Evidence table
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21 evidence rows matching the loaded filters
| Property and statement | Original source and location | Review and provenance |
|---|---|---|
| Access and reuse CC-BY-4.0 permits redistribution of the article bytes. Source metadata | BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments No field-specific location recorded Version: arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 | catalogued No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: pdftotext -layout text layer, parsed by extract/extract_target_validation.py |
| Archive note Not archived in the batch although the licence permits it: the PDF is 3,953,768 bytes and the repository keeps releases small. The artifact_sha256 pins the bytes that were read. Source metadata | BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments No field-specific location recorded Version: arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 | catalogued No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: pdftotext -layout text layer, parsed by extract/extract_target_validation.py |
| Artifact SHA-256 dd94d80ec75c9bb84ec3989c910a313ef1a7aec57c772d3dd35ecadd250132a7 Source metadata | BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments No field-specific location recorded Version: arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 | catalogued No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: pdftotext -layout text layer, parsed by extract/extract_target_validation.py |
| Artifact url https://arxiv.org/pdf/2405.17631v3 Source metadata | BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments No field-specific location recorded Version: arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 | catalogued No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: pdftotext -layout text layer, parsed by extract/extract_target_validation.py |
| Doi 10.48550/arXiv.2405.17631 Source metadata | BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments No field-specific location recorded Version: arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 | catalogued No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: pdftotext -layout text layer, parsed by extract/extract_target_validation.py |
| Extraction method pdftotext -layout text layer, parsed by extract/extract_target_validation.py Source metadata | BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments No field-specific location recorded Version: arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 | catalogued No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: pdftotext -layout text layer, parsed by extract/extract_target_validation.py |
| Licence CC-BY-4.0 Source metadata | BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments No field-specific location recorded Version: arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 | catalogued No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: pdftotext -layout text layer, parsed by extract/extract_target_validation.py |
| Media type application/pdf Source metadata | BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments No field-specific location recorded Version: arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 | catalogued No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: pdftotext -layout text layer, parsed by extract/extract_target_validation.py |
| Publication status peer_reviewed Source metadata | BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments No field-specific location recorded Version: arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 | catalogued No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: pdftotext -layout text layer, parsed by extract/extract_target_validation.py |
| Retrieved at 2026-10-09T20:51:27Z Source metadata | BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments No field-specific location recorded Version: arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025 | catalogued No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: pdftotext -layout text layer, parsed by extract/extract_target_validation.py |
Sources and history
Release 2026-11-02-a7f03c9e55a5 · Record review: source checked
Primary source retrieved and hashed for the therapeutic target validation use-case pass.
Technical metadata and extraction receipts
Stable ID: tgtval-20261009-source-roohani2025
- areas
- cells-tissues
- contexts
- research
- url
- https://arxiv.org/abs/2405.17631v3
- artifact url
- https://arxiv.org/pdf/2405.17631v3
- version
- arXiv:2405.17631 version 3, updated 2025-03-09; published as a conference paper at ICLR 2025
- retrieved at
- 2026-10-09T20:51:27Z
- artifact sha256
- dd94d80ec75c9bb84ec3989c910a313ef1a7aec57c772d3dd35ecadd250132a7
- publication status
- peer_reviewed
- licence
- CC-BY-4.0
- media type
- application/pdf
- doi
- 10.48550/arXiv.2405.17631
- source locator
- Full artifact bytes; per-record locators on each record
- access and reuse
- CC-BY-4.0 permits redistribution of the article bytes.
- archive note
- Not archived in the batch although the licence permits it: the PDF is 3,953,768 bytes and the repository keeps releases small. The artifact_sha256 pins the bytes that were read.
- extraction method
- pdftotext -layout text layer, parsed by extract/extract_target_validation.py