复旦大学附属儿科医院高通量测序数据分析流程(第二版)对遗传疾病候选变异基因筛选用时和准确性分析

Evaluation of turn around time and diagnostic accuracy of the next generation sequencing data analysis pipeline version 2 of Children's Hospital of Fudan University

目的本研究旨在比较和分析复旦大学附属儿科医院(我院)分子诊断中心(本中心)2015年建立的高通量测序数据分析和临床诊断流程(复旦流程1.0)及其升级后的流程(复旦流程2.0)的临床应用效果。方法以复旦流程1.0和2.0对本中心新生儿重症监护病房送检行二代测序分子诊断的连续样本,进行初步数据分析结果、流程用时和准确性的比较和分析,并以典型病例具体说明复旦流程2.0的主要特点。结果 2017年11月7~14日取得家属的知情同意的、行临床外显子检测的112例进入本文分析,初步数据分析结果的比较,进入人工数据审核的变异数量,复旦流程1.0平均210个,复旦流程2.0平均25个;完成112例从样本送达测序完成到初步报告形成时间,复旦流程1.0为78.8 h,复旦流程2.0为19.8 h;与人工审核后阳性结果判读符合率为63.6%(7/11),阴性结果判读符合率为84.2%(85/101)。结论复旦流程2.0可以更加快速、准确和自动地进行大样本量的数据分析,可以用于临床大样本量的高通量数据分析及解读。

Objective We have upgraded the data analysis pipeline（ Fudan pipeline 1. 0） to Fudan pipeline 2. 0 for high throughput sequencing which established in 2015. The purpose of this study is to compare the turn around time and accuracy of these two pipelines. Methods In this study,112 continuous samples from neonatal intensive care unit were recruited. Both Fudan pipeline 1.0 and 2. 0 were used for the data analysis. We compared the results of preliminary analysis,time-consuming,and the accuracy between these two pipelines. And the main features of the Fudan pipeline 2. 0 are explained in detail. Results On the comparison of preliminary data analysis results,the variations to manual analysis step of Fudan pipeline 2. 0（ an average of 25 variants） was significantly less than that of Fudan pipeline 1.0（ an average of 210 variants）. On the comparison of efficiency,the turn around time of Fudan pipeline 2.0（ 19.8 h） was significantly shorter than that of Fudan pipeline 1.0（ 78.8 h）. The diagnosis coincidence rate of Fudan pipeline 2.0 is 63.6%（ 7/11） for positive cases,and 84.2%（ 85/101） for negative cases with manual review. Conclusion This study clearly shows the efficient,accurate and automated of Fudan pipeline 2.0 for genetic diagnosis with large sample size.