Background Exome- or genome-based panels—also known as slices or virtual panels—are now a popular approach that involves comprehensive genomic sequencing while restricting analysis to subsets of genes based on patients’ phenotypes. This flexible strategy enables frequent gene updates based on novel disease associations as well as reflexing to analyzing other genes up to the whole exome or genome. With recent improvements addressing limitations associated with virtual panels, the advantages of this approach, relative to static custom-based panels, remain to be systematically characterized. Methods Here we perform slice testing on 1014 patients (50.5% females; average age 17 years) referred from multiple pediatric clinics within a single center in the Middle East (83% Arab population). Results Initial analysis uncovered molecular diagnoses for 235 patients for a diagnostic yield of 23% (235/1014). “On the fly” focused analysis in most negative cases (N = 779) identified clinically significant variants correlating with patients’ presentations in genes outside the originally ordered panel for another 35 patients (3.5% or 35/1024) increasing the overall diagnostic yield to 27%. The pathogenic variants underlying the additional cases (13% of all positive cases) were excluded from the original “panel” gene list, mainly as result of issues related to panel selection, novel gene–disease associations, phenotype spectrum broadening, or gene lists variability. The additional findings led to changes in clinical management in most patients (94%). Conclusions Our findings support slice testing as an efficient and flexible platform that facilitates updates to gene lists to achieve high clinical sensitivity and utility.

中文翻译：

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与静态 panel 相比，虚拟基因 panel 对遗传性罕见病的诊断率更高


背景 基于外显子组或基因组的检测组合（也称为切片或虚拟检测组合）现在是一种流行的方法，它涉及全面的基因组测序，同时将分析限制在基于患者表型的基因子集中。这种灵活的策略能够根据新的疾病关联进行频繁的基因更新，并反射性地分析其他基因，直至整个外显子组或基因组。随着最近改进解决了与虚拟面板相关的限制，相对于静态基于自定义的面板，这种方法的优势仍有待系统地描述。方法 在这里，我们对从中东单个中心内的多个儿科诊所转诊的 1014 名患者 （50.5% 为女性;平均年龄 17 岁） 进行切片测试（83% 为阿拉伯人口）。结果 初步分析发现 235 例患者的分子诊断，诊断率为 23% （235/1014）。在大多数阴性病例 （N = 779） 中，“动态”重点分析确定了与另外 35 名患者 （3.5% 或 35/1024） 在最初排序组之外的基因表现相关的临床显着变异，将总体诊断率提高到 27%。其他病例背后的致病性变异 （占所有阳性病例的 13%） 被排除在原始 “面板” 基因列表中，主要是由于与面板选择、新的基因-疾病关联、表型谱拓宽或基因列表变异性相关的问题。额外的发现导致大多数患者 （94%） 的临床管理发生变化。结论 我们的研究结果支持切片检测作为一个高效灵活的平台，有助于更新基因列表以实现高临床敏感性和实用性。