Clinical Diagnostics in Human Genetics with Semantic Similarity Searches in Ontologies
Clinical Diagnostics in Human Genetics with Semantic Similarity Searches in Ontologies
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DOI：
10.1016/j.ajhg.2009.09.003
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发表时间：
2009-10-09
影响因子：
9.8
通讯作者：
Robinson, Peter N.
中科院分区：
文献类型：
--
作者：
Koehler, Sebastian;Schulz, Marcel H.;Robinson, Peter N.
鉴别诊断过程试图确定最能解释一组临床特征的候选疾病。由于这些特征可能具有不同程度的特异性以及存在与疾病本身无关的特征，这一过程可能会变得复杂。根据医生的经验和实验室检查的可用性，临床异常可能会更详细或更详细地描述。我们已经调整了语义相似性度量来测量查询和使用人类表型本体（HPO）注释的遗传性疾病之间的表型相似性，并且已经开发了一个统计模型来为所得到的相似性分数分配1）值，其可以用于对候选疾病进行排名。我们表明，我们的方法优于简单的术语匹配方法，不考虑术语之间的语义相互关系。我们的方法的优势是更大的查询包含表型噪音或不精确的临床描述。由HPO定义的语义网络可以用于通过建议在候选诊断之间最佳区分的临床特征（如果存在）来细化鉴别诊断。因此，本体中的语义相似性搜索代表了利用人类表型异常的语义结构来帮助鉴别诊断的有用方式。我们已经在人类孟德尔疾病领域的免费网络应用程序中实现了我们的方法。
The differential diagnostic process attempts to identify candidate diseases that best explain a set of clinical features. This process can be complicated by the fact that the features can have varying degrees of specificity as well as by the presence of features unrelated to the disease itself. Depending on the experience of the physician and the availability of laboratory tests, clinical abnormalities may be described in greater or lesser detail. We have adapted semantic similarity metrics to measure phenotypic similarity between queries and hereditary diseases annotated with the use of the Human Phenotype Ontology (HPO) and have developed a statistical model to assign 1) values to the resulting similarity scores, which can be used to rank the candidate diseases. We show that our approach outperforms simpler term-matching approaches that do not take the semantic interrelationships between terms into account. The advantage of our approach was greater for queries containing phenotypic noise or imprecise clinical descriptions. The semantic network defined by the HPO can be used to refine the differential diagnosis by suggesting clinical features that, if present, best differentiate among the candidate diagnoses. Thus, semantic similarity searches in ontologies represent a useful way of harnessing the semantic structure of human phenotypic abnormalities to help with the differential diagnosis. We have implemented Our methods in a freely available web application for the field of human Mendelian disorders.