Phevor Combines Multiple Biomedical Ontologies for Accurate Identification of Disease-Causing Alleles in Single Individuals and Small Nuclear Families
Phevor Combines Multiple Biomedical Ontologies for Accurate Identification of Disease-Causing Alleles in Single Individuals and Small Nuclear Families
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DOI：
10.1016/j.ajhg.2014.03.010
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发表时间：
2014-04-03
影响因子：
9.8
通讯作者：
Yandell, Mark
中科院分区：
文献类型：
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作者：
Singleton, Marc V.;Guthery, Stephen L.;Yandell, Mark
Phevor将表型、基因功能和疾病信息与个人基因组数据相结合，以提高识别致病等位基因的能力。Phevor通过将驻留在多个生物医学本体中的知识与不同优先级工具的输出相结合来工作。它通过使用一种在本体之间传播信息的算法来实现这一点。这一过程使Phevor能够根据基因功能、疾病和表型知识，准确地重新确定变异优先工具所确定的潜在破坏性等位基因的优先顺序。Phevor特别适用于单外显子和基于家庭三元组的诊断分析，这是最常见的临床情况，也是现有个人基因组诊断工具最不准确和功能不足的情况。在这里，我们提供了一系列基准分析，以说明Phevor的性能特征。还介绍了犹他州基因组计划最近的三个案例研究，在这些案例研究中，Phevor被用来识别致病等位基因。总而言之，这些结果表明，Phevor不仅提高了对已确定疾病表型的个人的诊断准确性，也提高了对那些以前未描述的和非典型疾病表现的人的诊断准确性。重要的是，Phevor并不局限于已知的疾病或已知的致病等位基因。正如我们所展示的，Phevor还可以使用本体论中的潜在信息来发现以前与疾病无关的基因和致病等位基因。
Phevor integrates phenotype, gene function, and disease information with personal genomic data for improved power to identify disease-causing alleles. Phevor works by combining knowledge resident in multiple biomedical ontologies with the outputs of variant-prioritization tools. It does so by using an algorithm that propagates information across and between ontologies. This process enables Phevor to accurately reprioritize potentially damaging alleles identified by variant-prioritization tools in light of gene function, disease, and phenotype knowledge. Phevor is especially useful for single-exome and family-trio-based diagnostic analyses, the most commonly occurring clinical scenarios and ones for which existing personal genome diagnostic tools are most inaccurate and underpowered. Here, we present a series of benchmark analyses illustrating Phevor's performance characteristics. Also presented are three recent Utah Genome Project case studies in which Phevor was used to identify disease-causing alleles. Collectively, these results show that Phevor improves diagnostic accuracy not only for individuals presenting with established disease phenotypes but also for those with previously undescribed and atypical disease presentations. Importantly, Phevor is not limited to known diseases or known disease-causing alleles. As we demonstrate, Phevor can also use latent information in ontologies to discover genes and disease-causing alleles not previously associated with disease.