Abstract:
:Integration of detailed phenotype information with genetic data is well established to facilitate accurate diagnosis of hereditary disorders. As a rich source of phenotype information, electronic health records (EHRs) promise to empower diagnostic variant interpretation. However, how to accurately and efficiently extract phenotypes from heterogeneous EHR narratives remains a challenge. Here, we present EHR-Phenolyzer, a high-throughput EHR framework for extracting and analyzing phenotypes. EHR-Phenolyzer extracts and normalizes Human Phenotype Ontology (HPO) concepts from EHR narratives and then prioritizes genes with causal variants on the basis of the HPO-coded phenotype manifestations. We assessed EHR-Phenolyzer on 28 pediatric individuals with confirmed diagnoses of monogenic diseases and found that the genes with causal variants were ranked among the top 100 genes selected by EHR-Phenolyzer for 16/28 individuals (p < 2.2 × 10-16), supporting the value of phenotype-driven gene prioritization in diagnostic sequence interpretation. To assess the generalizability, we replicated this finding on an independent EHR dataset of ten individuals with a positive diagnosis from a different institution. We then assessed the broader utility by examining two additional EHR datasets, including 31 individuals who were suspected of having a Mendelian disease and underwent different types of genetic testing and 20 individuals with positive diagnoses of specific Mendelian etiologies of chronic kidney disease from exome sequencing. Finally, through several retrospective case studies, we demonstrated how combined analyses of genotype data and deep phenotype data from EHRs can expedite genetic diagnoses. In summary, EHR-Phenolyzer leverages EHR narratives to automate phenotype-driven analysis of clinical exomes or genomes, facilitating the broader implementation of genomic medicine.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Son JH,Xie G,Yuan C,Ena L,Li Z,Goldstein A,Huang L,Wang L,Shen F,Liu H,Mehl K,Groopman EE,Marasa M,Kiryluk K,Gharavi AG,Chung WK,Hripcsak G,Friedman C,Weng C,Wang Kdoi
10.1016/j.ajhg.2018.05.010subject
Has Abstractpub_date
2018-07-05 00:00:00pages
58-73issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(18)30171-Xjournal_volume
103pub_type
杂志文章abstract::Historical and genetic evidences suggest that the recently founded population of Antioquia (Colombia) is potentially useful for the genetic mapping of complex traits. This population was established in the 16th-17th centuries through the admixture of Amerinds, Europeans, and Africans and grew in relative isolation unt...
journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-04-01 00:00:00
abstract::We screened DNA from unrelated individuals for RFLPs in the muscle nicotinic acetylcholine receptor (AcChoR) genes. These RFLP markers can be used for genetic linkage and association studies to test the hypothesis that receptor structure or regulation is involved in the development of myasthenia gravis (MG). The cDNAs...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
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更新日期:2019-08-01 00:00:00
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doi:10.1086/320605
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/321296
更新日期:2001-08-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.03.022
更新日期:2013-05-02 00:00:00
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journal_title:American journal of human genetics
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doi:10.1086/426061
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
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journal_title:American journal of human genetics
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doi:10.1086/302583
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/498175
更新日期:2005-12-01 00:00:00
abstract::The lysosomal hydrolase alpha-L-iduronidase (IDUA) is one of the enzymes in the metabolic pathway responsible for the degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate. In humans a deficiency of IDUA leads to the accumulation of glycosaminoglycans, resulting in the lysosomal storage disorder m...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
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abstract::The two main phenotypes of inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--are chronic intestinal inflammatory disorders with a complex genetic background. Using a three-stage design, we performed a functional candidate-gene analysis of innate immune pathway in IBD. In phase I, we t...
journal_title:American journal of human genetics
pub_type: 杂志文章,多中心研究
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journal_title:American journal of human genetics
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doi:
更新日期:1980-09-01 00:00:00
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journal_title:American journal of human genetics
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doi:
更新日期:1991-08-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1980-09-01 00:00:00
abstract::Centromeric-mapping methods have been used to investigate the association between altered recombination and meiotic nondisjunction in humans. For trisomies, current methods are based on the genotypes from a trisomic offspring and both parents. Because it is sometimes difficult to obtain samples from both parents and b...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302799
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journal_title:American journal of human genetics
pub_type: 杂志文章
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更新日期:2000-03-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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