State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, Shanghai, China.
Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, Shanghai, China.
Bioinformatics. 2019 Oct 1;35(19):3559-3566. doi: 10.1093/bioinformatics/btz100.
Whole-exome sequencing (WES) is now being used in clinical practice for the diagnosis of the causal genes of Mendelian diseases. In order to make the diagnosis, however, the clinical phenotypes [e.g. Human Phenotype Ontology (HPO) terms] of a patient are needed for prioritizing the variants called from the WES data of the patient. Computational tools are therefore needed to standardize and accelerate this process.
Here, we introduce a tool named PhenoPro for prioritizing the causal gene of Mendelian disease given both the HPO terms assigned to and the variants called from the WES data of a patient. PhenoPro has been benchmarked using both simulated patients and 287 real diagnosed patients of Chinese ancestry, and shows significant improvements over five previous tools. Moreover, the addition of an internal variant data of Chinese ancestry and the variant data from the patients' parents can further improve PhenoPro's performance. To make PhenoPro a fully automated tool, we also include a natural language processing component for automated HPO term assignment from clinical reports, and demonstrate that the natural language processing is as effective as manual HPO assignment using real clinical reports. In conclusion, PhenoPro can be used as a pre-screening tool to assist in the diagnosis of Mendelian disease genes.
The web server of PhenoPro is freely available at http://app.tianlab.cn.
Supplementary data are available at Bioinformatics online.
全外显子测序（WES）现在正被用于临床实践中，以诊断孟德尔疾病的因果基因。然而，为了做出诊断，需要患者的临床表型（例如人类表型本体论[HPO]术语），以便优先考虑从患者 WES 数据中调用的变体。因此，需要计算工具来规范和加速这一过程。
在这里，我们介绍了一种名为 PhenoPro 的工具，用于根据分配给患者的 HPO 术语和从 WES 数据中调用的变体，优先考虑孟德尔疾病的因果基因。使用模拟患者和 287 名具有中国血统的确诊患者对 PhenoPro 进行了基准测试，与之前的五个工具相比，PhenoPro 有显著的改进。此外，添加中国血统的内部变体数据和患者父母的变体数据，可以进一步提高 PhenoPro 的性能。为了使 PhenoPro 成为一个全自动的工具，我们还包括一个自然语言处理组件，用于从临床报告中自动分配 HPO 术语，并证明该自然语言处理与使用真实临床报告的手动 HPO 分配一样有效。总之，PhenoPro 可以作为一种预筛选工具，帮助诊断孟德尔疾病基因。
PhenoPro 的网络服务器可在 http://app.tianlab.cn 免费使用。
补充数据可在《生物信息学》在线获取。
