Advancing Clinical Genomic Analysis with a Skill-Centred Agent

Clinical genomic analysis requires experts to integrate evolving guidelines, databases, and computational evidence. As sequencing has become increasingly accessible, this complex and labor-intensive process has become a major bottleneck to the timely use of genomic information in clinical decision-making. To fill this gap, we developed ClinGeX, a large-language-model agent that composes 105 curated executable skills through task-specific retrieval and dependency-aware orchestration. On 223 temporally held-out benchmark cases, ClinGeX achieved 71.7% macro-averaged task-level concordance with expert reference classifications, compared with 45.7% for the strongest comparator. In a three-condition, counterbalanced human-AI collaboration study, 45 clinical genomic professionals assessed 135 clinically derived cases under routine (no AI assistance), DeepSeek-assisted and ClinGeX-assisted conditions. ClinGeX assistance increased raw case-level concordance across criterion-level variant analysis, genomic interpretation in rare disease and molecular oncology decision-making (51.1%, 57.8%, 64.4% versus 15.6%, 31.1%, 20.0% in comparator conditions) and reduced reported interpretation time in all scenarios. During an exploratory one-month real-world non-interventional assessment, 11 experienced professionals submitted feedback on 96 self-selected analysis episodes and reported frequent conclusion adoption and time savings. These findings support executable domain skills as a promising approach to augment specialist genomic interpretation.

Source: arXiv:2610.40556v1 - http://arxiv.org/abs/2610.40556v1 PDF: https://arxiv.org/pdf/2610.40556v1 Original Link: http://arxiv.org/abs/2610.40556v1