NSW Health Pathology Randwick Genomics, Prince of Wales Hospital, Randwick, New South Wales, Australia.
NSW Health Pathology Randwick Genomics, Prince of Wales Hospital, Randwick, New South Wales, Australia; School of Women's and Children's Health, University of New South Wales Sydney, Kensington, New South Wales, Australia.
J Mol Diagn. 2021 Jul;23(7):894-905. doi: 10.1016/j.jmoldx.2021.04.007. Epub 2021 May 5.
Massively parallel sequencing has markedly improved mendelian diagnostic rates. This study assessed the effects of custom alterations to a diagnostic genomic bioinformatic pipeline in response to clinical need and derived practice recommendations relative to diagnostic rates and efficiency. The Genomic Annotation and Interpretation Application (GAIA) bioinformatics pipeline was designed to detect panel, exome, and genome sample integrity and prioritize gene variants in mendelian disorders. Reanalysis of selected negative cases was performed after improvements to the pipeline. GAIA improvements and their effect on sensitivity are described, including addition of a PubMed search for gene-disease associations not in the Online Mendelian Inheritance of Man database, inclusion of a process for calling low-quality variants (known as QPatch), and gene symbol nomenclature consistency checking. The new pipeline increased the diagnostic rate and reduced staff costs, resulting in a saving of US$844.34 per additional diagnosis. Recommendations for genomic analysis pipeline requirements are summarized. Clinically responsive bioinformatics pipeline improvements increase diagnostic sensitivity and increase cost-effectiveness.
大规模平行测序显著提高了孟德尔诊断率。本研究评估了根据临床需求对诊断基因组生物信息学管道进行定制修改的效果，并就诊断率和效率提出了相关实践建议。基因组注释和解释应用程序 (GAIA) 生物信息学管道旨在检测面板、外显子和基因组样本的完整性，并优先考虑孟德尔疾病中的基因变异。在对管道进行改进后，对选定的阴性病例进行了重新分析。描述了 GAIA 的改进及其对敏感性的影响，包括添加了一个 PubMed 搜索，以查找不在在线孟德尔遗传数据库中的基因疾病关联，纳入了一个用于调用低质量变异的过程（称为 QPatch），以及基因符号命名法一致性检查。新的管道提高了诊断率并降低了人员成本，每增加一个诊断可节省 844.34 美元。总结了基因组分析管道要求的建议。对生物信息学管道的临床响应性改进提高了诊断敏感性并提高了成本效益。
