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Genetics

DeepBD: A Grounded Agentic Workflow for Variant Prioritization and Diagnosis of Genetic Birth Defects

Shiyu Li, Ziqi Yan, Zhihao Wu, Jielong Lu, Weiran Liao, Jiajun Yu, Genjie Li, Zeyu Chu, Jiajun Bu, Haishuai Wang

Featured July 1, 2026

Original Paper

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Simply

A smart computer system called DeepBD helps doctors find the specific faulty gene in babies with birth defects by carefully sorting through many possibilities, using a special engine to rank them and a helpful assistant to explain the findings.

In depth
The paper introduces DeepBD, a system that tackles the challenge of prioritizing genetic variants for birth defects. It employs a grounded agentic workflow where a trainable evidence engine performs the core variant ranking by integrating diverse data, while an LLM-assisted agent handles case structuring, evidence synthesis, and review, ensuring traceability and preventing unconstrained reasoning.

Key Takeaways

  • 1
    DeepBD introduces a grounded agentic workflow that separates variant ranking (via a trainable evidence engine) from diagnostic review and synthesis (via an LLM-assisted agent), ensuring robust and traceable interpretations.
  • 2
    The core evidence engine integrates three distinct evidence streams: explicit clinical rules, variant-intrinsic features (sequence context, variant-effect predictions), and phenotype-conditioned biological context (derived from graph attention).
  • 3
    The system was developed and evaluated on a large, in-house fetal and infant cohort of over 18,000 cases, specifically addressing the unique challenges of incomplete and imaging-derived phenotypes in birth defect diagnosis.

Conceptual Flow

HIGH LEVEL
1
Methodology: How DeepBD Works

DeepBD uses a smart engine to sort gene changes and a helpful assistant to explain why certain changes are important for a baby's health.

Patient Info
Gene Changes
Process & Rank
Top Gene Changes
Diagnosis Help
2
Results: Better Gene Change Finding

DeepBD found the correct faulty gene change much more often in the top few guesses compared to older methods, especially for birth defects.

Old Methods
DeepBD
Find Correct Gene
Fewer Correct Found
More Correct Found