Division of Molecular and Genomic Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Division of Molecular and Genomic Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
J Mol Diagn. 2014 Jan;16(1):11-22. doi: 10.1016/j.jmoldx.2013.08.005. Epub 2013 Nov 9.
A wide repertoire of bioinformatics applications exist for next-generation sequencing data analysis; however, certain requirements of the clinical molecular laboratory limit their use: i) comprehensive report generation, ii) compatibility with existing laboratory information systems and computer operating system, iii) knowledgebase development, iv) quality management, and v) data security. SeqReporter is a web-based application developed using ASP.NET framework version 4.0. The client-side was designed using HTML5, CSS3, and Javascript. The server-side processing (VB.NET) relied on interaction with a customized SQL server 2008 R2 database. Overall, 104 cases (1062 variant calls) were analyzed by SeqReporter. Each variant call was classified into one of five report levels: i) known clinical significance, ii) uncertain clinical significance, iii) pending pathologists' review, iv) synonymous and deep intronic, and v) platform and panel-specific sequence errors. SeqReporter correctly annotated and classified 99.9% (859 of 860) of sequence variants, including 68.7% synonymous single-nucleotide variants, 28.3% nonsynonymous single-nucleotide variants, 1.7% insertions, and 1.3% deletions. One variant of potential clinical significance was re-classified after pathologist review. Laboratory information system-compatible clinical reports were generated automatically. SeqReporter also facilitated quality management activities. SeqReporter is an example of a customized and well-designed informatics solution to optimize and automate the downstream analysis of clinical next-generation sequencing data. We propose it as a model that may envisage the development of a comprehensive clinical informatics solution.
生物信息学应用程序的广泛存在可用于下一代测序数据分析；然而，临床分子实验室的某些要求限制了它们的使用：i）全面的报告生成，ii）与现有实验室信息系统和计算机操作系统的兼容性，iii）知识库开发，iv）质量管理，和 v）数据安全。SeqReporter 是一个使用 ASP.NET 框架版本 4.0 开发的基于网络的应用程序。客户端使用 HTML5、CSS3 和 JavaScript 进行设计。服务器端处理（VB.NET）依赖于与自定义 SQL Server 2008 R2 数据库的交互。总的来说，SeqReporter 分析了 104 个案例（1062 个变异调用）。每个变异调用被分为以下五个报告级别之一：i）已知的临床意义，ii）不确定的临床意义，iii）等待病理学家审查，iv）同义和深内含子，和 v）平台和面板特异性序列错误。SeqReporter 正确注释和分类了 99.9%（860 个中的 859 个）的序列变体，包括 68.7%的同义单核苷酸变体、28.3%的非同义单核苷酸变体、1.7%的插入和 1.3%的缺失。经过病理学家审查后，一个具有潜在临床意义的变体被重新分类。与实验室信息系统兼容的临床报告自动生成。SeqReporter 还促进了质量管理活动。SeqReporter 是一个定制和精心设计的信息学解决方案的示例，用于优化和自动化临床下一代测序数据的下游分析。我们建议将其作为一个模型，可以设想开发一个全面的临床信息学解决方案。
