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Evaluating open LLMs for agentic analysis orchestration in a typical biomedical lab.

Anton Nekrutenko1

  • 1Department of Biochemistry and Molecular Biology Penn State University, University Park, PA 16802.

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Free, open-weight large language models (LLMs) can now perform routine biomedical data analysis at frontier accuracy, matching proprietary models. This breakthrough significantly reduces computational costs for repetitive tasks like variant calling.

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Area of Science:

  • Biomedical Data Analysis
  • Artificial Intelligence
  • Computational Biology

Background:

  • Agentic tools, powered by large language models (LLMs), are poised to dominate routine biomedical data analysis.
  • High per-call inference costs of frontier LLMs currently limit their widespread adoption for these tasks.

Purpose of the Study:

  • To evaluate if free, locally-runnable open-weight LLMs can execute repetitive biomedical data analysis steps with accuracy comparable to frontier models.
  • To identify cost-effective LLM solutions for large-scale biomedical data processing.

Main Methods:

  • Claude's Opus was used to generate detailed execution plans for per-sample variant calling.
  • Six open-weight LLMs (released in 2026) were tested against these plans on desktop GPUs.
  • Performance was validated using a 36-cell error-injection matrix.

Main Results:

  • The open-weight model qwen3.6:27b successfully replicated frontier accuracy across all tested plans.
  • qwen3.6:27b demonstrated cell-for-cell equivalence with Opus on the error-injection matrix.
  • The implementer LLM operated effectively on affordable hardware (sub-$2,000 Jetson or Mac Mini).

Conclusions:

  • Open-weight LLMs are capable of matching frontier accuracy in complex biomedical data analysis tasks.
  • Local execution of open-weight LLMs offers a cost-effective alternative to proprietary models for routine analysis.
  • A framework and associated artifacts are provided for ongoing evaluation of rapidly evolving open-weight LLMs.