AVA：用智能体自动完成癌症测序的读级变异判读

View PDF HTML (experimental)

Abstract:Identifying a tumor's DNA mutations is central to cancer diagnosis and treatment, but distinguishing genuine mutations from sequencing artifacts is error-prone. In practice, genuine mutations are identified using fixed variant-allele-frequency (VAF) and depth thresholds which cannot separate artifacts from genuine mutations in the borderline low-VAF zone where they overlap. A laboratory specialist must manually inspect the read-level sequencing data, a slow step that has high inter-rater variability and causes diagnosis delays. We present AVA: Agentic Variant Adjudication; an agentic framework that automates this read-level inspection with subagents that reason over evidence, generate investigative code, and return a real-or-artifact adjudications with an auditable reasoning trace all without training on existing data. On both the SEQC2 DNA-seq benchmark and patient RNA-seq data, restricted to a subsample of borderline variants where thresholds fail, both closed-source (Claude Sonnet 5) and open-weight (GLM 5.3 Flash and Gemma 4 31b) agents outperform the best achievable VAF/depth thresholds. Ultimately, AVA is suited for privacy-constrained clinical deployment, since the framework can run on locally deployed open-weight models with descriptive reasoning traces to keep specialists in the loop.

Submission history

From: Caleb Chin [view email]
[v1] Thu, 5 Nov 2026 06:41:32 UTC (1,246 KB)