Phenogenon: Gene to phenotype associations for rare genetic diseases

被引：8

作者：

Pontikos, Nikolas ^{[1
,2
,3
]}

Murphy, Cian ^{[1
,4
]}

Moghul, Ismail ^{[5
]}

Arno, Gavin ^{[2
,3
,6
]}

Fujinami, Kaoru ^{[2
,3
,6
,7
]}

Fujinami, Yu ^{[8
,9
]}

Sumodhee, Dayyanah ^{[10
]}

Downes, Susan ^{[11
,12
]}

Webster, Andrew ^{[2
,3
]}

Yu, Jing ^{[12
]}

机构：

[1] UCL, UCL Genet Inst, London, England

[2] UCL, Inst Ophthalmol, London, England

[3] Moorfields Eye Hosp, London, England

[4] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England

[5] UCL, UCL Canc Inst, London, England

[6] Natl Hosp Org Tokyo Med Ctr, Lab Visual Physiol, Div Vis Res, Natl Inst Sensory Organs, Tokyo, Japan

[7] Keio Univ, Dept Ophthalmol, Sch Med, Tokyo, Japan

[8] Keio Univ, Grad Sch Hlth Management, Tokyo, Japan

[9] Yokokawa Clin, Div Publ Hlth, Osaka, Japan

[10] Queen Mary Univ, Bethnal Green, Mile End Rd, London, England

[11] John Radcliffe Hosp, Oxford Eye Hosp, West Wing, Oxford, England

[12] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, Oxford, England

来源：

PLOS ONE | 2020年 / 15卷 / 04期

基金：

英国惠康基金; 日本学术振兴会; 英国医学研究理事会;

关键词：

MUTATIONS; VARIANTS;

D O I：

10.1371/journal.pone.0230587

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

As high-throughput sequencing is increasingly applied to the molecular diagnosis of rare Mendelian disorders, a large number of patients with diverse phenotypes have their genetic and phenotypic data pooled together to uncover new gene-phenotype relations. We introduce Phenogenon, a statistical tool that combines, Human Phenotype Ontology (HPO) annotated patient phenotypes, gnomAD allele population frequency, and Combined Annotation Dependent Depletion (CADD) score for variant pathogenicity, in order to jointly predict the mode of inheritance and gene-phenotype associations. We ran Phenogenon on our cohort of 3,290 patients who had undergone whole exome sequencing. Among the top associations, we recapitulated previously known, such as "SRD5A3-Abnormal full-field electroretinogram-recessive" and "GRHL2-Nail dystrophy-recessive", and discovered one potentially novel, "RRAGA-Abnormality of the skin-dominant". We also developed an interactive web interface available at https://phenogenon.phenopolis.org to visualise and explore the results.

引用

页数：12

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