A pipeline-friendly software tool for genome diagnostics to prioritize genes by matching patient symptoms to literature.
A pipeline-friendly software tool for genome diagnostics to prioritize genes by matching patient symptoms to literature.
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DOI：
10.1002/ggn2.10023
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发表时间：
2020-12
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影响因子：
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通讯作者：
Swertz, Morris A
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作者：
van der Velde, K Joeri;van den Hoek, Sander;van Dijk, Freerk;Hendriksen, Dennis;van Diemen, Cleo C;Johansson, Lennart F;Abbott, Kristin M;Deelen, Patrick;Sikkema-Raddatz, Birgit;Swertz, Morris A
尽管下一代测序数据爆炸式增长，但基因组诊断仅为少数患者提供分子诊断。使用已知的基因-疾病关联根据患者症状对基因进行优先排序的软件工具可以补充变异过滤和解释，以增加成功的机会。然而，这些工具中的许多工具不能在实践中使用，因为它们被嵌入在变体优先级排序算法中，或者作为远程服务存在，由于法律的/道德障碍而不能被依赖或不可接受。此外，许多工具不是为命令行使用而设计的，它们是封闭源代码的、被放弃的或不可用的。我们提出了变异解释使用生物医学文献证据（VIBE），一种工具，优先疾病基因的基础上人类表型本体代码。VIBE是一个本地安装的可执行文件，可确保操作可用性，并建立在DisGeNET‐RDF基础上，这是一个综合知识平台，包含主要来自文献的基因疾病关联和主要来自策展源数据库的变异疾病关联。VIBE的命令行界面和输出旨在轻松整合到生物信息学管道中，为进一步的临床解释注释和优先排序变体。我们在基于305例患者病例以及其他7种工具的基准中评估VIBE。我们的研究结果表明，VIBE提供了一致的性能与少数情况下错过，但我们也发现所有测试工具之间的高度互补性。VIBE是一个强大的，免费的，开源的和本地安装的解决方案，用于根据患者症状优先考虑基因。项目源代码、文档、基准测试和可执行文件可在https://github.com/molgenis/vibe上获得。基因优先级工具输出和所有患者病例的因果基因排名。每个点代表一个患者病例（即，人类表型本体论代码集），其中因果基因由八个基准工具之一优先排序。所示的是因果基因的绝对排名与工具返回的候选基因的总数。彩色标签指示哪个点属于哪个工具，以及显示每个工具的缺失基因的数量，其中因果基因不存在于输出基因列表中。
Despite an explosive growth of next‐generation sequencing data, genome diagnostics only provides a molecular diagnosis to a minority of patients. Software tools that prioritize genes based on patient symptoms using known gene‐disease associations may complement variant filtering and interpretation to increase chances of success. However, many of these tools cannot be used in practice because they are embedded within variant prioritization algorithms, or exist as remote services that cannot be relied upon or are unacceptable because of legal/ethical barriers. In addition, many tools are not designed for command‐line usage, closed‐source, abandoned, or unavailable. We present Variant Interpretation using Biomedical literature Evidence (VIBE), a tool to prioritize disease genes based on Human Phenotype Ontology codes. VIBE is a locally installed executable that ensures operational availability and is built upon DisGeNET‐RDF, a comprehensive knowledge platform containing gene‐disease associations mostly from literature and variant‐disease associations mostly from curated source databases. VIBE's command‐line interface and output are designed for easy incorporation into bioinformatic pipelines that annotate and prioritize variants for further clinical interpretation. We evaluate VIBE in a benchmark based on 305 patient cases alongside seven other tools. Our results demonstrate that VIBE offers consistent performance with few cases missed, but we also find high complementarity among all tested tools. VIBE is a powerful, free, open source and locally installable solution for prioritizing genes based on patient symptoms. Project source code, documentation, benchmark and executables are available at https://github.com/molgenis/vibe. Gene prioritization tool output and causal gene rank for all patient cases. Each dot represents a patient case (ie, set of Human Phenotype Ontology codes) for which the causal gene was prioritized by one of eight benchmarked tools. Shown are the absolute ranks of the causal genes vs the total number of candidate genes returned by a tool. The colored labels indicate which dot belongs to which tool, as well as show the number of missed genes for each tool, where the causal gene was not present in the output gene list.