Novel Tools for Extraction and Validation of Disease-Related Mutations Applied to Fabry Disease
Novel Tools for Extraction and Validation of Disease-Related Mutations Applied to Fabry Disease
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DOI：
10.1002/humu.21317
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发表时间：
2010-09-01
期刊：
影响因子：
3.9
通讯作者：
Schaap, Peter J.
中科院分区：
文献类型：
--
作者：
Kuipers, Remko;van den Bergh, Tom;Schaap, Peter J.
遗传性疾病通常由与疾病相关的一个或多个基因中的非同义核苷酸变化引起。然而，特定的氨基酸变化可导致表型表达的大变异性。对于许多遗传性疾病，这导致越来越多的出版物描述疾病相关基因中的表型相关突变。跟上这一出版物流对于分子诊断和转化研究目的是必不可少的，但由于时间限制，通常是不可能的：有太多的文章要阅读。为了帮助解决这个问题，我们创建了Mutator，这是一种从全文文章中提取突变的自动化方法。将提取的突变与序列数据交叉引用，并应用评分方法来区分假阳性。为了分析存储的和新的突变数据的（潜在）影响，我们开发了Validator，这是一种专门为DNA诊断设计的基于Web的工具。法布里病，一种GLA基因的单遗传基因疾病，被用作测试案例。使用α-淀粉酶超家族的基于结构的序列比对来验证结果。我们将我们的数据与从HGMD和Swiss-Prot数据库获得的现有Fabry突变数据集进行了比较。与这些数据集相比，Mutator从文献中提取了30%的额外突变。Mutat 31：1026-1032，2010. (c)2010 Wiley-Liss，Inc.
Genetic disorders are often caused by nonsynonymous nucleotide changes in one or more genes associated with the disease. Specific amino acid changes, however, can lead to large variability of phenotypic expression. For many genetic disorders this results in an increasing amount of publications describing phenotype-associated mutations in disorder-related genes. Keeping up with this stream of publications is essential for molecular diagnostics and translational research purposes but often impossible due to time constraints: there are simply too many articles to read. To help solve this problem, we have created Mutator, an automated method to extract mutations from full-text articles. Extracted mutations are crossreferenced to sequence data and a scoring method is applied to distinguish false-positives. To analyze stored and new mutation data for their (potential) effect we have developed Validator, a Web-based tool specifically designed for DNA diagnostics. Fabry disease, a mono-genetic gene disorder of the GLA gene, was used as a test case. A structure-based sequence alignment of the alpha-amylase superfamily was used to validate results. We have compared our data with existing Fabry mutation data sets obtained from the HGMD and Swiss-Prot databases. Compared to these data sets, Mutator extracted 30% additional mutations from the literature. Hum Mutat 31:1026-1032, 2010. (c) 2010 Wiley-Liss, Inc.