Agentic biomedical machine learning (ML) draws on complementary advances in biomedical evidence acquisition and executable program search. Existing systems connect aspects of these capabilities, but coordinating them throughout program search remains challenging. New evidence must guide candidate construction, execution outcomes must inform subsequent discovery and reuse, and validation demands must fit the search budget. We introduce BioDyad, which couples biomedical discovery and ML engineering through two hierarchies within Monte Carlo graph search. Its scientific hierarchy combines prior biomedical guidance with iterative discovery, then links biomedical plans to execution outcomes in memory for reuse across candidates. Its engineering hierarchy moves candidate programs from smoke execution, through train/validation evaluation, to full-data retraining. We evaluate BioDyad on the 76-task BioXArena benchmark under a two-hour per-task budget with three matched LLM backends. It achieves the highest penalized all-task score and task success rate among four agent methods and a one-shot baseline under each backend. These results support coordinating biomedical discovery and ML engineering to integrate external knowledge into executable programs across heterogeneous biomedical tasks.
Figures & tables
Type
Method
Scientific hierarchy
Search and engineering
Bio. discovery
Bio. memory
Program search
Staged eval.
Budget adapt.
Harness
BioXArena harness ( Li et al., 2026 )
✗
✗
✗
✗
✗
Bio. agents
Biomni ( Huang et al., 2025 )
✓
✗
✗
✗
✗
STELLA ( Jin et al., 2025 )
✓
✗
✗
✗
✗
VCHarness ∗ ( Cheng et al., 2026 )
△
△
✓
✗
✗
MLE agents
MLEvolve ( Du et al., 2026 )
✗
✗
✓
✗
✓
Table 1: Capabilities of representative agentic systems for biomedical ML program discovery.
Figure 1: BioDyad couples biomedical discovery and ML engineering within MCGS. The scientific hierarchy combines prior guidance, node-level discovery, and biomedical memory; the engineering hierarchy advances programs through smoke execution, train/validation evaluation, and full-data runs. Biomedical evidence guides candidate expansion, while execution feedback updates the search graph and memory within the wall-clock budget. The hERG Binding Affinity task from BioXArena ( Li et al., 2026 ) provides an illustrative example.
Figure 2: ReAct-based prior biomedical guidance. A plan-only agent alternates reasoning with read-only probes to compile verified data findings and biomedical insights.
Figure 3: Success rate (x-axis) and penalized all-task score (y-axis) under three LLM backends. Each panel compares four agent methods with a two-hour per-task budget and a one-shot baseline retaining only the first attempt, evaluated on the same 76 tasks.
LLM backend
Method
Seq
SC
Str
Net
Chem
Pert
Phen
Img
Text
Avg.
GPT-5.6-sol
One-shot
0.416
0.288
0.727
0.458
0.576
0.291
0.508
0.500
0.546
0.472
BioXArena Harness
0.663
0.786
0.834
0.458
0.928
0.517
0.606
0.714
0.637
0.685
Biomni
0.773
0.652
0.591
0.490
0.690
0.404
0.431
0.702
0.656
0.605
MLEvolve
0.790
0.798
0.794
0.527
0.922
0.597
0.575
0.673
0.720
0.715
BioDyad (ours)
0.776
0.861
0.815
0.521
0.926
0.776
0.594
0.666
0.671
0.738
GLM-5.1
One-shot
0.187
0.102
0.236
0.062
0.556
0.121
0.374
0.139
0.030
0.198
Table 2: Domain breakdowns of four agent methods and a one-shot baseline under three matched LLM backends on the 76 BioXArena tasks. Scores are penalized average scores; higher is better. Avg. is weighted by task count across all 76 tasks. Bold and underlining indicate the highest and second-highest distinct displayed scores, respectively, within each backend and column.
Method
Penalized score
Success rate
BioXArena Harn.
0.699±0.005
0.944±0.000
Biomni
0.647±0.012
0.889±0.000
MLEvolve
0.688±0.019
0.907±0.032
BioDyad
0.711±0.002
0.944±0.000
Table 3: Repeated-run robustness on the fixed 18-task subset with GPT-5.6-sol. Values are mean ± sample standard deviation (SD) across three independent runs.
Hierarchy
Mechanism
MLEvolve
MLEvolve
BioDyad
BioDyad
BioDyad
BioDyad
w/ discovery
w/o memory
w/o Sci.
w/o Eng.
(full)
Sci. hierarchy
Bio. discovery
✗
✓
✓
✗
✓
✓
Bio. memory
✗
✗
✗
✗
✓
✓
Eng. hierarchy
Staged evaluation
✗
✗
✓
✓
✗
✓
Performance ↑
Chemical biology
0.898
0.795
0.913
0.861
0.896
0.919
Phenotype-disease
0.538
0.599
0.560
0.468
0.570
0.606
Table 4: Component ablations with the GPT-5.4 backend. Scores are penalized task averages. Avg. is the task-weighted mean across all 16 tasks in the two domains; higher is better.
Figure 4: Biomedical feature integration in BioDyad: (a) predictive gain, (b) smoke-guided execution repair, and (c) no predictive gain despite successful execution. Scores are task-specific validation metrics; full execution denotes candidate train/validation evaluation.
Domain
Best-so-far test score
Score gain
2 h
4 h
6 h
8 h
10 h
12 h
2-4 h
4-12 h
2-12 h
Chemical biology
0.927
0.932
0.936
0.936
0.936
0.937
+0.006
+0.004
+0.010
Phenotype-disease
0.640
0.663
0.688
0.690
0.690
0.690
+0.022
+0.027
+0.050
Table 5: Retrospective best-so-far normalized test scores during 12-hour BioDyad runs with GPT-5.6-sol. Each checkpoint averages task-level maxima over all eight tasks in a domain, using the same runs as Appdx. D . Gain columns report absolute differences computed before rounding.
Figure 5: Candidate test scores during 12-hour searches: (a) BACE1 binding affinity, (b) CYP inhibition, (c) Alzheimer’s disease staging, (d) breast-cancer subtype. Gray points show candidate scores; blue lines show retrospective maxima; orange dashed lines show linear fits against time.
Appendix figures & tables7 assets
Supplementary material from the paper’s appendix.
Appendix
Agent
Seq
SC
Str
Net
Chem
Pert
Phen
Img
Text
Avg.
BioDyad (GPT-5.6-sol)
0.776
0.861
0.815
0.521
0.926
0.776
0.594
0.666
0.671
0.738
BioDyad (GLM-5.1)
0.776
0.771
0.729
0.509
0.932
0.737
0.600
0.700
0.552
0.705
BioDyad (DeepSeek-V4)
0.717
0.791
0.789
0.510
0.909
0.717
0.600
0.646
0.608
0.701
MLEvolve ( Du et al., 2026 )
0.765
0.798
0.750
0.510
0.869
0.601
0.502
0.606
0.534
0.666
STELLA ( Jin et al., 2025 )
0.677
0.559
0.481
0.497
0.878
0.555
0.574
0.651
0.641
0.613
Biomni ( Huang et al., 2025 )
0.526
0.646
0.569
0.497
0.723
0.628
0.547
0.659
0.415
0.579
Appendix
Table 6: Comparison with the penalized score presented on BioXArena’s leaderboard across all 76 tasks. Avg. is task-weighted across all tasks. Baseline scores are reported by BioXArena ( Li et al., 2026 ) ; BioDyad scores use the same evaluation protocol. Bold marks the highest score in each column. Backends differ across systems (Appdx. E.2 ).
Hierarchy
Mechanism
MLEvolve
MLEvolve
BioDyad
BioDyad
BioDyad
BioDyad
w/ discovery
w/o memory
w/o Sci.
w/o Eng.
(full)
Sci. hierarchy
Bio. discovery
✗
✓
✓
✗
✓
✓
Bio. memory
✗
✗
✗
✗
✓
✓
Eng. hierarchy
Staged evaluation
✗
✗
✓
✓
✗
✓
Outcomes
Full runs
552
672
639
446
668
566
Valid
304 (55.1%)
314 (46.7%)
425 (66.5%)
319 (71.5%)
411 (61.5%)
458 (80.9%)
Appendix
Table 7: Candidate outcomes in the component ablations. Each entry gives a count and its percentage of that configuration’s full-execution runs.
Domain
Task
Test 2 h
Test 4 h
Test 12 h
Δ 2-4 h
Δ 4-12 h
CB
BACE1 Binding Affinity
0.934
0.936
0.939
+0.002
+0.003
CB
Cell Painting Perturbation
0.982
1.000
1.000
+0.018
+0.000
CB
CYP Inhibition (Multi-label)
0.940
0.941
0.944
+0.001
+0.003
CB
EGFR Binding Affinity
0.925
0.927
0.927
+0.003
+0.000
CB
GPCR Binding (Multi-class)
0.948
0.953
0.970
+0.005
+0.017
CB
hERG Binding Affinity
0.898
0.908
0.909
+0.010
+0.001
Appendix
Table 8: Normalized test-score checkpoints and gains in the 12-hour traces. CB denotes chemical biology and PD denotes phenotype-disease. Each checkpoint is a retrospective maximum over completed candidates. Gains are absolute differences computed before rounding.
Figure 6: Cumulative best normalized test scores for all 16 tasks, using the same runs as Table 8 . The upper two rows show chemical-biology tasks and the lower two show phenotype-disease tasks. Each task has its own vertical scale. Steps occur at logged candidate completion; dashed guides mark 2 and 4 hours. No score is shown before the first completed candidate, and the last observed best is carried forward to 12 hours.
Domain
First task
Second task
Sequence
gene-tissue-expression
isoform-expression
Single-cell
batch-integration
cell-type-from-expression
Structure
complex-structure-evaluation
enzyme-commission-prediction
Network biology
gene-disease-association
go-function-multi-label
Chemical biology
bace1-binding-affinity
cell-painting-perturbation
Perturbation dynamics
cancer-drug-sensitivity
crispr-perturbation-prediction
Appendix
Table 9: Fixed repeated-run subset: the first two tasks per domain in BioXArena Table A4, preserving its within-domain order.
Method
Metric
Run 1
Run 2
Run 3
Mean ± SD
BioXArena Harness
Score
0.695
0.705
0.699
0.699±0.005
Success rate
0.944
0.944
0.944
0.944±0.000
Biomni
Score
0.637
0.660
0.644
0.647±0.012
Success rate
0.889
0.889
0.889
0.889±0.000
MLEvolve
Score
0.709
0.683
0.672
0.688±0.019
Success rate
0.944
0.889
0.889
0.907±0.032
Appendix
Table 10: Per-run results on the fixed 18-task subset with GPT-5.6-sol. Score is the penalized mean over all 18 tasks; success rate is the successful task count divided by 18. Summary entries report mean ± sample standard deviation (SD) across three independent runs.
Method
LLM backend
Biomni
Claude Sonnet 4 ( Anthropic, 2025 )
STELLA
Dev/Tool-Creation: Claude Sonnet 4.6 ( Anthropic, 2026b ) ;
Manager/Critic: Gemini 3.1 Pro ( The Gemini Team, 2026 )
MLEvolve
Gemini 3.1 Pro ( The Gemini Team, 2026 )
ML-Master 2.0
DeepSeek-V4-Pro ( Xu et al., 2026 )
Appendix
Table 11: Original backends of BioXArena’s reported agent systems, retained for the overall reference experiment.
Translational medicine turns underspecified development goals into evidence synthesis that must combine literature, trials, patents, and quantitative multi-omics analysis while preserving identifiers, uncertainty, and retrievable provenance. General-purpose foundation models and off-the-shelf tool-augmented or multi-agent systems are not built for this: they tend to produce single-shot answers or run open-endedly, and fall short on the auditable, scenario-specific workflows that heterogeneous biomedical sources demand. This paper introduces Ingenix BioResearcher, a scenario-guided multi-agent system that maps queries to versioned research playbooks, delegates to specialized subagents over 30+ tools and machine-learning endpoints, mixes structured database access with sandboxed code for genome-scale analyses, and applies claim-level multi-model reconciliation before editorial assembly. We evaluate BioResearcher across unit-level capabilities, open-ended biomedical reasoning, and end-to-end clinical discovery. It leads evaluated baselines on 109 single-step tests (83.49% pass rate; 0.892 average score), achieves strong biomedical benchmark performance (89.33% on BixBench-Verified-50 and the top 0.758 mean score on BaisBench Scientific Discovery), and leads on a 30-query clinical end-to-end benchmark with the highest positive hit rate (74.7% ± 3.3%) and negative clear rate (96.8% ± 0.2%). These results show broad, competitive performance across unit-level, open-ended, and end-to-end clinical evaluations.
Biomedical agents promise to automate complex biological workflows, yet current systems face two fundamental bottlenecks: bioinformatics tools are highly heterogeneous in interfaces and execution environments, while agent planning still relies on flat prompt-retrieved tool descriptions. As biomedical software ecosystems grow, this coupling between tool coverage and context size leads to tool confusion, unstable planning, and inefficient execution. We introduce BioManus, an MCP-native biomedical agent built on graph-scaffolded planning over structured biological capabilities. BioManus first introduces the BioinfoMCP Compiler, which converts heterogeneous bioinformatics software into standardized MCP servers, yielding a large executable MCP ecosystem. It then organizes this ecosystem as a typed heterogeneous MCP graph over tools, operations, datatypes, and workflow stages. At inference time, BioManus retrieves compact task-specific subgraphs, synthesizes operation-level workflow scaffolds. This design decouples planning complexity from raw tool inventory size, achieving a context compression ratio of Theta(N / (h * m_bar)) under high-recall retrieval, where N is the total tool count, h is the workflow horizon, and m_bar (much smaller than N) is the average number of candidate tools per operation. Experiments on BioAgentBench and LAB-Bench show that BioManus improves execution accuracy, workflow validity, and context efficiency over advanced biomedical agent baselines. This work suggests a paradigm shift: scalable biomedical reasoning requires structured executable capability graphs rather than increasingly larger prompt-level tool retrieval.
Reproducing and comparing deep research agents today is hard: the same backbone evaluated on the same benchmark can report different accuracies across papers because the harness and tool registry differ, and integrating a new model into a comparable evaluation surface costs weeks of model-specific engineering. These are symptoms of a broader reproducibility problem in deep research agent research. Here, we introduce BioMedArena, an open-source toolkit that addresses this reproducibility gap and provides an arena for comparing deep research agents under a shared evaluation environment. BioMedArena decouples six layers of biomedical agent evaluation -- benchmark loading, tool exposure, tool selection, harness mode, context management, and scoring -- and exposes 166 biomedical benchmarks and 75 biomedical tools across 9 functional families. Adding a new model, benchmark, or tool can be accomplished with a few-line provider adapter. Beyond evaluation infrastructure, BioMedArena ships a library of high-quality reference components: 6 agent harnesses (including our proposed Mutual-Evolve) and 6 context-management strategies, any of which can be equipped on any backbone. Equipping these components substantially improves all 12 backbones; on each of 8 representative biomedical benchmarks, the best equipped backbone surpasses prior state-of-the-art (SOTA), by 15.01 percentage points on average. The toolkit, configurations, and per-task traces are available at https://github.com/AI-in-Health/BioMedArena.
Jinge Wu, Hongjian Zhou, Mingde Zeng +8
University of Oxford · University College London · Technical University of Munich +1