DOI: 10.64898/2026.10.26.761864

30 Agents, 18 Pipelines, One Glass Box: Verifiable Agentic Science on Public Infrastructure

Scroll through six visual "one-bite" chapters from our new preprint (Baker et al., 2026)—showing why unguided local coding agents splinter into irreproducible chaos, and how grounding them in free public Galaxy and ACCESS-CI supercomputers turns AI agents into forensic auditors and discovery engines across 48 datasets.

30 → 18
Incompatible pipelines when 30 frontier agents reanalyze the same RNA-seq study locally
~2M Jobs/mo
Free public supercomputing via UseGalaxy.org & ACCESS-CI with full DAG provenance
82% Missing
Cells silently dropped by a Nature agent benchmark that ran a 1,000-cell demo file
48 Studies
Audited & scaled—from unifying 2,592 malaria antigens on GPUs to dating 42 epidemics
Step:
Bite 1 of 6 • The Local Reproducibility Crisis

Hand One Dataset to 30 Local Coding Agents—Get 18 Incompatible Pipelines

Autonomous coding agents can design and execute a complete multi-step study from a single prompt. But what happens when they improvise in isolated local terminals?

We handed a published bacterial RNA-seq study of Bacillus cereus enterotoxin regulation (Vyklická et al., 2025) to 30 independent frontier agents—10 Claude Opus, 10 OpenAI Codex, and 10 Google Gemini—and asked each for a replication plan.

Exposed to two routine ambiguities (a suppressed RefSeq assembly after taxonomic reclassification to B. pacificus, and whether DESeq2 pooled all 19 libraries or only 5 focal samples), 29 of the 30 agents diverged from the paper, splintering into 18 distinct pipelines.

Silent biological distortion: When executed locally, aligning to B. pacificus completely erased an actively transcribed toxin gene (cytK2, ~800 read pairs/library on ATCC 10987) and left behind 26 unversioned glue scripts (>1,200 lines of code).
Bite 2 of 6 • Public Infrastructure

Moving Agentic Science from Private Black Boxes onto the Galactic Plane

Today's vision of "agentic science" is largely being built behind closed doors—running on laptops or paid commercial clouds where intermediate files vanish when the session ends.

We took the opposite path. We connected CLI coding agents—and Orbit, our open-source desktop workbench built on Pi.dev—directly into UseGalaxy.org and free national ACCESS-CI supercomputers (Stampede3, Bridges-2, Expanse, Anvil, Jetstream2) via curated domain skills and a typed Galaxy Model Context Protocol (MCP) server.

Any researcher or student can drive multi-core CPUs, terabyte-RAM nodes, and NVIDIA GPUs at zero cost under one rule: the agent cannot hide its tracks.

Permanent provenance by design: Instead of throwaway local scripts, bespoke code is packaged into containerized User-Defined Tools (UDTs), and every input, parameter, and output is locked into an inspectable Directed Acyclic Graph (DAG) and living research notebook.
Bite 3 of 6 • Forensic Audit I

When an Agent Benchmark Silently Runs a Demo File: The 82% Missing-Data Trap

What if a landmark Nature paper about reproducible agentic science itself fell prey to an unverified agentic shortcut—and our public provenance harness caught it?

In Paper2Agent (Miao et al., 2026), an agent wrapped the spatial transcriptomics tool TISSUE and cited a 5,613-cell mouse somatosensory cortex atlas (Dataset 15). Yet when we audited the result on Galaxy, we discovered that the benchmark had actually been run on a 1,000-cell unit-test demo file (tests/data/scRNA_count.txt) bundled inside the GitHub repo—silently discarding 82% of the reference cells!

On the 1,000-cell demo subset, predicted Acta2 expression was nearly uncorrelated with ground truth ($r = 0.0861$). Running TISSUE on UseGalaxy.org reproduced their 1,000-cell tutorial output to floating-point precision ($r = 1.0000$) and scaled to all 5,613 cells—tripling prediction accuracy to $r = 0.2553$.

Why provenance matters: Without an auditable trail of input file digests and dimensions, an agent substituting a 1,000-cell unit test for a 5,613-cell atlas looks like a successful run.
Bite 4 of 6 • Forensic Audit II

Exposing Unstated Pooling, Unmerged Replicates, and Annotation Traps

Across 48 biological analyses, keeping every intermediate table in the open turned our agents into automated forensic auditors of peer-reviewed papers:

• Aspergillus fumigatus (30-library azole time-course): Pairwise DESeq2 missed 39% of published DEGs until our agent spotted identical baseMean values across all 5 timepoints—proving the authors had fitted one pooled 30-sample model (25 residual d.f.). Switching to the pooled design matched published counts within 0.3–1.3% ($r \ge 0.9996$).
• Anopheles gambiae (infection ATAC-seq): Reproduced 90.7–93.2% of chromatin peaks while proving headline region counts came from unmerged replicate rows.
• Aedes aegypti (midgut scRNA-seq, 6,707 cells): Fixed a non-model AAEL mitochondrial prefix that caused standard Scanpy QC to report 0% mitochondrial reads.

Hover any row in the scorecard → to inspect the exact discrepancy uncovered and how the Galaxy workflow resolved it.
Bite 5 of 6 • Discovery at Scale I

Unifying 2,592 Malaria Surface Antigens Across Three Continents on Public GPUs

Moving from auditing past studies to new discovery, we directed Orbit to resolve the hypervariable VIR surface protein repertoire across three Plasmodium vivax genomes from Indonesia, Thailand, and Peru (2,592 proteins).

Because VIR proteins diverge into the sequence twilight zone ($\le 30\%$ amino acid identity), sequence clustering fractures them into 146–203 fragmented groups, obscuring whether parasites on different continents use distinct immune-evasion scaffolds.

By registering 10 unprivileged UDTs on UseGalaxy.org to orchestrate ProstT5 (3Di protein language model), Foldseek, FoldMason, and IQ-TREE 3 on national ACCESS-CI GPUs, Orbit collapsed the entire repertoire into 73–76 structural classes—showing that over 97% of all VIR proteins belong to 21 conserved ancestral folds shared across all three continents ($p = 0.55$).

Zero local GPU required: Any researcher can orchestrate heavyweight protein language models and structural phylogenetics on national GPU allocations directly through Galaxy.
Bite 6 of 6 • Discovery at Scale II

Dating 42 Pathogen Epidemics in Seconds Instead of Days of MCMC

Finally, we wrapped ChronAeon as Galaxy User-Defined Tools and tasked Orbit with dating 42 published viral and bacterial BEAST benchmark alignments (41 unique cohorts across 37 studies, including Ebola, SARS-CoV-2, Zika, Dengue, Mpox, H1N1, Rabies, and Yersinia pestis).

Traditional Bayesian molecular clock inference (`BEAST`) requires hours to days of Markov chain Monte Carlo (MCMC) sampling per dataset. On UseGalaxy.org, Orbit executed all 42 cohorts in seconds per alignment, matching reference Bayesian emergence ($t_{\text{MRCA}}$) intervals across 61.5–64.1% of scored outbreaks with a median error of just 0.40 years for post-1980 epidemics.

The takeaway: Anchoring autonomous agents to open-source tools and free public supercomputing turns a looming reproducibility crisis into a permanent, verifiable engine for discovery.
BITE 1 • MULTI-AGENT DIVERGENCE BENCHMARK 1 / 6
30 Frontier Coding Agents Splinter Into 18 Incompatible Pipelines
Given the same Bacillus cereus RNA-seq study without infrastructure guardrails, 29 of 30 agents diverged from the published workflow.
30 INDEPENDENT AGENTS 10 Claude Opus Local shell planning 10 OpenAI Codex Local shell planning 10 Google Gemini Local shell planning OUTCOME ACROSS 8 DECISIONS 29 of 30 Diverged → 18 Pipelines Wrong genome (B. pacificus) or wrong DESeq2 matrix 11 Count-Altering Designs Split across Bowtie2, HISAT2, BWA-MEM, STAR, Subread Only 1 of 30 Matched the Paper ATCC 10987 reference + 5-sample focal contrast WHAT HAPPENED WHEN EXECUTED LOCALLY: cytK2 Toxin Gene Erased ~800 read pairs/lib → 0 reads Absent from B. pacificus reference 26 Disposable Glue Scripts >1,200 lines of unversioned code No container digest or audit trail
LAYER 1 • AGENT & WORKBENCH LAYER Orbit Desktop Workbench (Pi.dev) Execution guardrails + multi-model Generic CLI Agents + Skills Claude Code, Codex, Gemini CLI Galaxy MCP + Workflow Foundry LAYER 2 • PUBLIC CYBERINFRASTRUCTURE (UseGalaxy.org + ACCESS-CI) National HPC & GPUs TACC, PSC, SDSC, Anvil BioContainers & Tools ~2,000,000 jobs / month User-Defined Tools Unprivileged & versioned LAYER 3 • PERMANENT VERIFIABLE RECORD (THE GLASS BOX) Immutable Execution DAG + Container Digests + Shareable Research Notebook Every intermediate table, tool version, and parameter is inspectable and re-runnable by anyone.
1. REFERENCE CELLS USED Mouse somatosensory cortex (Dataset 15) Paper2Agent Benchmark Run: 1,000 cells (82% dropped!) Ran tests/data/scRNA_count.txt demo Orbit + UseGalaxy.org Full Run: All 5,613 Reference Cells Full cited archive + tutorial verified 2. SPATIAL ACCURACY (Acta2 r) Pearson correlation vs. ground truth 1,000-Cell Demo Subset: r = 0.0861 Reproduced on Galaxy at r = 1.0000 Full 5,613-Cell Atlas on Galaxy: r = 0.2553 (3.0× higher) Restores vascular smooth muscle signal HOW GALAXY PROVENANCE CAUGHT IT: Inspecting the exact input matrix dimensions and SHA-256 digests exposed the 1,000-cell test file immediately.
HOVER ANY STUDY TO INSPECT THE HIDDEN TRAP CAUGHT BY PROVENANCE: 1. Bacillus cereus RNA-seq (5 libraries, 5,472 loci) Trap: Spliced aligner on intronless bacterium + split CDS rows r = 0.9622 2. Aspergillus fumigatus Time-Course (30 libraries) Trap: Unstated 30-sample pooled DESeq2 dispersion model r ≥ 0.9996 3. Anopheles gambiae Chromatin ATAC-seq (4 libraries) Trap: Unmerged replicate rows & custom summit-window filter 93.2% Peaks 4. Aedes aegypti Single-Cell Atlas (6,707 post-QC cells) Trap: Non-model AAEL mitochondrial prefix → 0% MT reads 20 Clusters
Selected Audit: Aspergillus fumigatus (Hokken et al., 2019) • Identical baseMean across all 5 timepoints proved a single pooled 30-sample DESeq2 design.
STAGE 1 • SEQUENCE TWILIGHT ZONE (≤30% IDENTITY) 2,592 Hypervariable VIR Proteins Across 3 Genomes (Indonesia, Thailand, Peru) Sequence alignment fractures repertoire into 146–203 disconnected clusters 10 Galaxy UDTs on ACCESS-CI GPUs: ProstT5 3Di + Foldseek + FoldMason STAGE 2 • 3Di STRUCTURAL UNIFICATION (73–76 CLASSES) >97% in 21 Folds Conserved ancestral structural cores p = 0.55 Interleaving Shared across Asia & South America BIOLOGICAL INSIGHT (IQ-TREE 3 + FOLDMASON): Extreme sequence diversification operates on top of a globally conserved structural scaffold inherited prior to continental dispersal.
TRADITIONAL BAYESIAN MCMC Hours to Days Per pathogen alignment (BEAST chains) Bottlenecks real-time outbreak response CHRONAEON UDTs ON GALAXY Seconds / Cohort Across 42 viral & bacterial alignments 0.40 yr median error (post-1980 outbreaks) BENCHMARK CONCORDANCE ACROSS 42 EPIDEMIC ALIGNMENTS (37 STUDIES) Ebola (Gire 14) West Africa epidemic Zika (Faria 17) Americas introduction SARS-CoV-2 / H1N1 Pandemic emergence Mpox / Y. pestis Viral & ancient DNA 61.5%–64.1% Match Reference Bayesian 95% HPD Intervals: 25 / 39 Scored Cohorts Within Bayesian 95% HPD All 42 datasets, container digests, and ChronAeon UDTs permanently archived on UseGalaxy.org.

Summary of Empirical Validations & Discovery Analyses on the Galactic Plane

Across 48 biological investigations spanning bacteria, mammalian spatial cortex, fungi, mosquito vectors, protozoan parasites, and 42 pathogen epidemic alignments, autonomous agents executed reproducible workflows on free public UseGalaxy.org and national ACCESS-CI supercomputing infrastructure.

Biological System & Study Assay & Scale Agent & Infrastructure Stack Forensic Audit or Discovery Finding
Bacillus cereus enterotoxin regulation
Vyklická et al. (2025)
Bacterial RNA-seq
5 libraries, 5,472 loci
Generic CLI agent + Galaxy MCP + Skills Replaced 26 unversioned local glue scripts from 30 unconstrained runs; caught split bacterial CDS rows and switched to Kallisto (38–60s/lib, $r = 0.9622$).
Mouse cortex spatial transcriptomics
Paper2Agent (Miao et al., 2026) / TISSUE
scRNA-seq + spatial
3,405 spatial & 5,613 reference cells
Orbit + 2 UDTs on UseGalaxy.org Exposed that the published benchmark ran on a 1,000-cell tutorial demo file (dropping 82% of cells); reproduced tutorial ($r = 1.0000$) and scaled to all 5,613 cells, tripling accuracy ($r = 0.0861 \to 0.2553$).
Aspergillus fumigatus azole time-course
Hokken et al. (2019)
Fungal RNA-seq
30 libraries (3 isolates × 5 timepoints)
Orbit + Workflow Foundry + BRC-Analytics + 3 UDTs Compiled a 60-step workflow; proved from identical baseMean columns that the authors fitted one pooled 30-sample DESeq2 model (matching counts within 0.3–1.3%, $r \ge 0.9996$).
Anopheles gambiae infection chromatin
Ruiz et al. (2021)
Vector ATAC-seq
4 libraries (midguts & salivary glands)
Orbit + 3 UDTs on UseGalaxy.org Reproduced 90.7–93.2% of published chromatin peaks without free parameters while showing headline region counts came from unmerged replicate rows.
Aedes aegypti midgut single-cell atlas
Wang et al. (2024)
Vector 10x 3' scRNA-seq
6,707 post-QC cells
Orbit + BRC-Analytics on UseGalaxy.org Staged non-model vector reference data, fixed an AAEL mitochondrial gene prefix mismatch that caused standard Scanpy QC to report 0% MT reads, and recovered 20 cell clusters de novo.
Plasmodium vivax VIR phylogenomics
Carlton et al. (2008), Harrison et al. (2020)
Structure-aware phylogenomics
3 genomes, 2,592 proteins
Orbit + 10 UDTs (GPU & CPU) on ACCESS-CI Orchestrated ProstT5, Foldseek, FoldMason, and IQ-TREE 3 on public GPUs, collapsing 146–203 sequence clusters into 73–76 structural classes (>97% in 21 conserved folds across 3 continents, $p = 0.55$).
Pathogen emergence dating
42 BEAST benchmark alignments (37 studies)
Genomic epidemiology
42 viral & bacterial cohorts
Orbit + 2 ChronAeon UDTs on UseGalaxy.org Dated 42 epidemic alignments in seconds per cohort instead of hours/days of Bayesian MCMC, matching Bayesian emergence dates on 61.5–64.1% of scored outbreaks ($0.40\text{ yr}$ median post-1980 error).

Full-Resolution Reference Figures from the Preprint

Figure 1 • 30 Autonomous Agents Propose 18 Incompatible Pipelines for the Same Study

Alluvial diagram tracing 30 reanalysis plans generated by Claude Opus (blue), OpenAI Codex (orange), and Google Gemini (teal) without infrastructure guardrails across the eight pipeline steps of Vyklická et al. (2025).

Alluvial diagram of 30 autonomous agents splintering into 18 incompatible bioinformatics pipelines

Figure 2 • Architecture for Verifiable Agentic Science on Public Infrastructure

Command-line coding agents or the Orbit desktop workbench connect via curated domain skills and the Galaxy Model Context Protocol (MCP) server to execute containerized workflows and User-Defined Tools across free national ACCESS-CI supercomputers, recording every step in a living research notebook.

Architecture for verifiable agentic science on public Galaxy infrastructure

Figure 3 • Structure-Aware Phylogenomics of Plasmodium vivax VIR Antigens on Public GPUs

Orchestrating ProstT5 3Di structural embeddings, Foldseek, FoldMason, and IQ-TREE 3 via unprivileged UDTs on UseGalaxy.org collapses sequence-fragmented VIR surface antigens across Indonesia, Thailand, and Peru into 21 globally shared ancestral folds.

Structure-aware reconstruction of Plasmodium vivax VIR surface antigens across three continents